tbuckley/cabot-search huggingface dataset:
Clinical prognostic score of <i>BRAF</i> V600E mutated (BM) metastatic colorectal cancer (mCRC): Results from the “BRAF, BeCool” platform.
Authors: Rossana Intini, Fotios Loupakis, Chiara Cremolini, Andrea Sartore-Bianchi, Filippo Pietrantonio, Nicoletta Pella, Daniele Santini, Lorenza Rimassa, Vincenzo Formica, Lorenzo Calvetti, Lisa Salvatore, Lorenzo Antonuzzo, Emmanuele De Luca, Federica Morano, Federica Tosi, Roberto Moretto, Matteo Fassan, Giovanna De Maglio, Vittorina Zagonel, Massimo Di Maio
Journal: Journal of Clinical Oncology (2018)

639 Background: BM mCRCs account around 10% of mCRCs, with a dismal prognosis. Intra-group heterogeneity has been recently studied, however, an extensive prognostic clinical analysis has not been provided yet. Methods: BM mCRCs tested on primary tumor (T) or on metastases (mets) were collected from 13 Italian Oncology Units. A prognostic score was derived by an internal cross-validation procedure: the whole population was splitted in a training (67%) and in a testing (33%) sample; this process was repeated 10 times. Primary endpoint was OS. Multivariate analysis (MA) was performed on each training sample, and covariates with independent prognostic value were included in the scoring system, assigning rounded scores to the covariates. Results: A total of 395 BM mCRC patients were included. At MA, independent prognosticators for OS were ECOG PS (1 vs 0; 2-3 vs 0), Ca19.9 (high vs normal); LDH (≥300 vs low); neutrophil/lymphocyte ratio ( &gt; 3 vs low); T grading (3-4 vs 1-2); liver mets (yes vs no); lung mets (yes vs no); lymphnode mets (yes vs no). Two different scoring systems were built: a «complete» score (0-18) with all significant covariates; a «simplified» score (0-11), selecting only significant clinico-pathological covariates, excluding laboratory values. With «complete» score, proportion of patients with low (0-4), intermediate (5-8) and high (9-18) score was 39%, 46% and 15%, respectively. Median OS was 27.6, 18.7 (HR interm. vs low 1.89, 95%CI 1.25 – 2.86, p = 0.003) and 6.6 months (HR high vs low 4.95, 95%CI 2.89 – 8.47, p &lt; 0.0001), respectively. Similar results were observed adjusting for type of first-line treatment. Median PFS was 11.1, 8.6 (HR interm. vs low 1.36, 95%CI 0.94 – 1.97, p = 0.11) and 4.1 months (HR high vs low 3.50, 95%CI 1.98 – 6.20, p &lt; 0.0001). Similar results were obtained with the «simplified» score. Conclusions: A simple and ready-to-use prognostic score for BM mCRC was developed. The robustness of the internal cross-validation justifies the effort of a validation study. Identification of specific prognostic factors in distinct molecular subgroups is crucial for adjusting exploratory translational analyses and future clinical trial design.
Long-Term Triple Therapy De-escalation to Indacaterol/Glycopyrronium in Patients with Chronic Obstructive Pulmonary Disease (SUNSET): A Randomized, Double-Blind, Triple-Dummy Clinical Trial
Authors: Kenneth R. Chapman, John R. Hurst, Stefan-Marian Frent, Michael Larbig, Robert Fogel, Tadhg Guerin, Donald Banerji, Francesco Patalano, Pankaj Goyal, Pascal Pfister, Konstantinos Kostikas, Jadwiga A. Wedzicha
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

There are no studies on withdrawal of inhaled corticosteroids in patients on long-term triple therapy in the absence of frequent exacerbations.To evaluate the efficacy and safety of direct de-escalation from long-term triple therapy to indacaterol/glycopyrronium in nonfrequently exacerbating patients with chronic obstructive pulmonary disease (COPD).This 26-week, randomized, double-blind, triple-dummy study assessed the direct change from long-term triple therapy to indacaterol/glycopyrronium (110/50 μg once daily) or continuation of triple therapy (tiotropium [18 μg] once daily plus combination of salmeterol/fluticasone propionate [50/500 μg] twice daily) in nonfrequently exacerbating patients with moderate-to-severe COPD. Primary endpoint was noninferiority on change from baseline in trough FEV1. Moderate or severe exacerbations were predefined secondary endpoints.A total of 527 patients were randomized to indacaterol/glycopyrronium and 526 to triple therapy. Inhaled corticosteroids withdrawal led to a reduction in trough FEV1 of -26 ml (95% confidence interval, -53 to 1 ml) with confidence limits exceeding the noninferiority margin of -50 ml. The annualized rate of moderate or severe COPD exacerbations did not differ between treatments (rate ratio, 1.08; 95% confidence interval, 0.83 to 1.40). Patients with ≥300 blood eosinophils/μl at baseline presented greater lung function loss and higher exacerbation risk. Adverse events were similar in the two groups.In patients with COPD without frequent exacerbations on long-term triple therapy, the direct de-escalation to indacaterol/glycopyrronium led to a small decrease in lung function, with no difference in exacerbations. The higher exacerbation risk in patients with ≥300 blood eosinophils/μl suggests that these patients are likely to benefit from triple therapy. Clinical trial registered with www.clinicaltrials.gov (NCT 02603393).
Inhaled Combined Budesonide–Formoterol as Needed in Mild Asthma
Authors: Paul M. O’Byrne, J. Mark FitzGerald, Eric D. Bateman, Peter J. Barnes, Nanshan Zhong, Christina Keen, Carin Jorup, Rosa Lamarca, Stefan Ivanov, Helen K. Reddel
Journal: New England Journal of Medicine (2018)

In patients with mild asthma, as-needed use of an inhaled glucocorticoid plus a fast-acting β2-agonist may be an alternative to conventional treatment strategies.We conducted a 52-week, double-blind trial involving patients 12 years of age or older with mild asthma. Patients were randomly assigned to one of three regimens: twice-daily placebo plus terbutaline (0.5 mg) used as needed (terbutaline group), twice-daily placebo plus budesonide-formoterol (200 μg of budesonide and 6 μg of formoterol) used as needed (budesonide-formoterol group), or twice-daily budesonide (200 μg) plus terbutaline used as needed (budesonide maintenance group). The primary objective was to investigate the superiority of as-needed budesonide-formoterol to as-needed terbutaline with regard to electronically recorded weeks with well-controlled asthma.A total of 3849 patients underwent randomization, and 3836 (1277 in the terbutaline group, 1277 in the budesonide-formoterol group, and 1282 in the budesonide maintenance group) were included in the full analysis and safety data sets. With respect to the mean percentage of weeks with well-controlled asthma per patient, budesonide-formoterol was superior to terbutaline (34.4% vs. 31.1% of weeks; odds ratio, 1.14; 95% confidence interval [CI], 1.00 to 1.30; P=0.046) but inferior to budesonide maintenance therapy (34.4% and 44.4%, respectively; odds ratio, 0.64; 95% CI, 0.57 to 0.73). The annual rate of severe exacerbations was 0.20 with terbutaline, 0.07 with budesonide-formoterol, and 0.09 with budesonide maintenance therapy; the rate ratio was 0.36 (95% CI, 0.27 to 0.49) for budesonide-formoterol versus terbutaline and 0.83 (95% CI, 0.59 to 1.16) for budesonide-formoterol versus budesonide maintenance therapy. The rate of adherence in the budesonide maintenance group was 78.9%. The median metered daily dose of inhaled glucocorticoid in the budesonide-formoterol group (57 μg) was 17% of the dose in the budesonide maintenance group (340 μg).In patients with mild asthma, as-needed budesonide-formoterol provided superior asthma-symptom control to as-needed terbutaline, assessed according to electronically recorded weeks with well-controlled asthma, but was inferior to budesonide maintenance therapy. Exacerbation rates with the two budesonide-containing regimens were similar and were lower than the rate with terbutaline. Budesonide-formoterol used as needed resulted in substantially lower glucocorticoid exposure than budesonide maintenance therapy. (Funded by AstraZeneca; SYGMA 1 ClinicalTrials.gov number, NCT02149199 .).
Time to sustained improvement in bowel movement frequency with telotristat ethyl: Analysis of the phase III telecast study.
Authors: Joseph Dillon, Pablo Lapuerta, Chad McKee
Journal: Journal of Clinical Oncology (2018)

395 Background: Telotristat ethyl (TE) is approved to treat inadequately controlled carcinoid syndrome (CS) diarrhea in combination with somatostatin analog (SSA) therapy. Understanding the time to onset of sustained BM frequency improvement is important when considering the use of TE in patients with CS diarrhea. We present data on time to sustained improvement and worsening in BM frequency during the double-blind treatment (DBT) period of TELECAST, a phase 3, randomized, placebo-controlled, double-blind study in patients with CS that required additional treatment, primarily due to gastrointestinal symptoms. Methods: Stable dose SSA was not required. Patients were treated with TE 250 mg 3 times per day (tid), TE 500 mg tid, or placebo tid. Sustained response was defined as the time from the first double-blind dose date to the first day of 2 consecutive weeks with BM frequency change of at least 30% from baseline. The time to the first sustained response in the TELECAST study was examined among treatment groups and analyzed using Cox regression. Results: There were 26 patients on placebo and 25 patients on either 250 mg or 500 mg telotristat groups. Sustained improvement in BM frequency over the 12-week DBT period was achieved in 6, 16, and 16 patients on placebo, TE 250 mg, and TE 500 mg treatment groups. Median time to sustained ≥ 30% improvement was 4-5 weeks with TE at both dosing levels, with no median reached on placebo. First occurrence of sustained improvements in BM frequency occurred within 4-68 days. Time to sustained worsening was delayed on the 500-mg dose of TE (no percentile reached) and is statistically significant (p = 0.021, HR: 0.25) Conclusions: Treatment with telotristat ethyl may provide sustained BM frequency reduction within 4-5 weeks (median) of initiating therapy. No median was reached on placebo due to fewer patients with sustained improvement. Additionally, TE 500 mg tid may also offer additional clinical benefit by reducing sustained BM worsening. Clinical trial information: NCT02063659.
META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS SHOWS THAT ENDOCUFF INCREASES COLONOSCOPY ADENOMA DETECTION RATE
Authors: K Triantafyllou, P Gkolfakis, G Tziatzios, L Fuccio, C Hassan
Journal: Endoscopy (2018)

Endocuff -a plastic device with flexible projections- mounted on the distal tip of the colonoscope, promises improved colonic mucosa inspection. Since data from individual studies are controversial, we aimed to elucidate the effect of Endocuff on adenoma detection rate (ADR) and on advanced ADR (AADR).
FOCS: a novel method for analyzing enhancer and gene activity patterns infers an extensive enhancer–promoter map
Authors: Tom Aharon Hait, David Amar, Ron Shamir, Ran Elkon
Journal: Genome biology (2018)

Recent sequencing technologies enable joint quantification of promoters and their enhancer regions, allowing inference of enhancer–promoter links. We show that current enhancer–promoter inference methods produce a high rate of false positive links. We introduce FOCS, a new inference method, and by benchmarking against ChIA-PET, HiChIP, and eQTL data show that it results in lower false discovery rates and at the same time higher inference power. By applying FOCS to 2630 samples taken from ENCODE, Roadmap Epigenomics, FANTOM5, and a new compendium of GRO-seq samples, we provide extensive enhancer–promotor maps ( http://acgt.cs.tau.ac.il/focs ). We illustrate the usability of our maps for deriving biological hypotheses.
Hepatocellular Carcinoma with Irregular Rim-Like Arterial Phase Hyperenhancement: More Aggressive Pathologic Features
Authors: Hyungjin Rhee, Chansik An, Hye-Young Kim, Jeong Eun Yoo, Young Nyun Park, Myeong-Jin Kim
Journal: Liver Cancer (2018)

The purpose of our study was to examine the histopathologic characteristics of hepatocellular carcinoma (HCC) with irregular rim-like arterial phase enhancement (IRE), which has been reported to be associated with more aggressive tumor behavior.We investigated 84 pathologically confirmed HCCs in 84 patients who underwent curative hepatic resection after gadoxetate-enhanced magnetic resonance imaging between January 2008 and February 2013. Two abdominal radiologists independently reviewed these images and classified HCCs into two categories: HCC showing IRE (IRE-HCC) and HCC showing hypoenhancement or diffuse arterial enhancement (non-IRE-HCC). Twenty-two HCCs were classified as IRE-HCCs, and 51 were classified as non-IRE-HCCs concordantly by both reviewers. The remaining 11 HCCs, on whose radiologic classifications the reviewers disagreed, were classified as HCCs with intermediate enhancement patterns. The HCC clinicopathologic characteristics and patient outcomes were then compared.IRE-HCCs showed more frequent microvascular invasion (91 vs. 35%), lower microvascular density (246.5 vs. 426.5/mm2), higher proportions of sinusoid-like microvascular pattern (55 vs. 0%) and macrotrabecular pattern (45 vs. 0%), and larger areas of tumor necrosis (15 vs. 0%) and fibrous stroma (8.3 vs. 2.1%) than non-IRE-HCCs. IRE-HCCs also expressed higher levels of immunomarkers of hypoxia (carbonic anhydrase IX, 64 vs. 8%) and stemness (EpCAM, 50 vs. 20%). p values were < 0.001 for all comparisons except for EpCAM (p = 0.026). HCCs with intermediate enhancement patterns showed mixed/intermediate pathologic features from both IRE- and non-IRE-HCCs. IRE-HCC patients showed poorer 5-year disease-free survival after curative resection than non-IRE-HCC patients (p = 0.005).IRE-HCCs demonstrate aggressive histopathologic features, including more hypoxic and fibrotic tumor microenvironments and increased stemness, compared to non-IRE-HCCs. IRE might therefore serve as a noninvasive imaging biomarker for aggressive HCC.
Prognostic factors in duodenal adenocarcinoma.
Authors: Brandon M Huffman, Zhaohui Jin, Cristobal T. Sanhueza, Mindy L. Hartgers, Benny Johnson, Christopher R. Shubert, Amit Mahipal
Journal: Journal of Clinical Oncology (2017)

e15797 Background: Duodenal adenocarcinoma is a rare tumor representing approximately 0.3% of all gastrointestinal tract cancers. Prognostic factors in relation to survival outcomes for these patients are sporadically reported in the medical literature. We aimed to evaluate outcomes of patients with duodenal adenocarcinoma who underwent pancreaticojejunostomy treated at Mayo Clinic Rochester from January 1, 2006 to December 31, 2016. Methods: Clinicopathological data of 52 duodenal cancer patients were collected. JMP software was used for statistical analysis. Kaplan-Meier method and log-rank tests were used for survival analysis, and multivariate cox proportional hazards model was used to evaluate the prognostic effect of pertinent clinical variables. All tests were two sided and a P value of &lt; 0.05 was considered significant. Results: The median age at diagnosis was 65.9 years (range 39-81). The median overall survival was 51 months (95% CI 31.3-105.4) and the median progression free survival was 30.4 months with median follow up of 73.4 months. There were 3, 9, 21, and 19 patients with stage I, II, III, and IV disease, respectively. Depth of tumor invasion (p = 0.0156) and lymph node metastasis (p = 0.0441) were associated with overall survival on multivariate analysis. Advanced clinical staging influenced overall survival in univariate analysis, but lost prognostic significance in multivariate analysis. Age, gender, surgical technique, presence of metastases, tumor size, number of lymph nodes removed, location of duodenal segment involvement, and adjuvant treatment had no significant impact on overall survival. Laparoscopic approach did not influence survival but was associated with less hospital days (p = 0.0437). Conclusions: Depth of tumor invasion and lymph node status were associated with improved overall survival in patients with duodenal adenocarcinoma. Laparoscopic procedure decreased the hospital stay without affecting outcomes.
Abstract 18101: Examining Self-Efficacy and Patient Activation Mechanisms in a Weight Management Intervention for Overweight and Obese Cardiac Rehabilitation Patients
Authors: Susan A Barnason, Lufei Young, Kevin Kupzyk, Lani Zimmerman, Carol Pullen
Journal: Circulation (2016)

Introduction: Approximately 80% of cardiac patients in cardiac rehabilitation (CR) are overweight. Although weight loss interventions are effective in reducing weight in the short-term, they fail t...
Untangling the Factors Contributing to Functional Outcome in Schizophrenia
Authors: Michal Hajduk, Amy E. Pinkham
Journal: JAMA Psychiatry (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Evolution and Uptake of the Endoscopic Stone Treatment Step 1 (EST-s1) Protocol: Establishment, Validation, and Assessment in a Collaboration by the European School of Urology and the Uro-Technology and Urolithiasis Sections
Authors: Domenico Veneziano, Achilles Ploumidis, Silvia Proietti, Theodoros Tokas, Guido Kamphuis, Giovanni Tripepi, Ben Van Cleynenbreugel, Ali Gozen, Alberto Breda, Joan Palou, Kemal Sarica, Evangelos Liatsikos, Kamran Ahmed, Bhaskar K. Somani
Journal: European Urology (2018)
Dual-functional protein for one-step production of a soluble and targeted fluorescent dye
Authors: Yunjie Xiao, Qian Zhang, Yanyan Wang, Bin Wang, Fengnan Sun, Ziyu Han, Yaqing Feng, Haitao Yang, Shuxian Meng, Zefang Wang
Journal: Theranostics (2018)

Low water solubility and poor selectivity are two fundamental limitations that compromise applications of near-infrared (NIR) fluorescent probes.Methods: Here, a simple strategy that can resolve these problems simultaneously was developed by using a novel hybrid protein named RGD-HFBI that is produced by fusion of hydrophobin HFBI and arginine-glycine-aspartic acid (RGD) peptide.This unique hybrid protein inherits self-assembly and targeting functions from HFBI and RGD peptide respectively.Results: Boron-dipyrromethene (BODIPY) used as a model NIR dye can be efficiently dispersed in the RGD-HFBI solution by simple mixing and sonication for 30 min.The data shows that self-assembled RGD-HFBI forms a protein nanocage by using the BODIPY as the assembly template.Cell uptake assay proves that RGD-HFBI/BODIPY can efficiently stain αvβ3 integrin-positive cancer cells.Finally, in vivo affinity tests fully demonstrate that the soluble RGD-HFBI/BODIPY complex selectively targets and labels tumor sites of tumor-bearing mice due to the high selectivity of the RGD peptide.Conclusion: Our one-step strategy using dual-functional RGD-HFBI opens a novel route to generate soluble and targeted NIR fluorescent dyes in a very simple and efficient way and may be developed as a general strategy to broaden their applications.
Novel prep-less X-ray imaging capsule for colon cancer screening: a feasibility study
Authors: Nathan Gluck, Elizabeth E Half, Vered Bieber, Doron Schwartz, Yulia Ron, Ian Gralnek, Amir Klein, Jesse Lachter, Moshe Shoni Levy, Menachem Moshkowitz, Nadir Arber
Journal: Gut (2018)

The X-ray imaging capsule overcomes the requirement for bowel preparation, a major deterrent for colorectal cancer (CRC) screening. This prospective multicentre study examined capsule safety and efficacy (compared with fecal immunochemical test (FIT)) for polyp detection confirmed by ensuing colonoscopy. In 45 analysed patients, capsule and FIT sensitivity for polyps was 44% and 37%, respectively. Capsule sensitivity increased to 78% when >50% of the colon surface area was imaged, with a linear correlation between imaged area and sensitivity. An updated scanning algorithm, retrospectively implemented on these study data, dramatically increased numbers of subjects with imaged area >50%, from 21 to 41/45 (46% to 91%). Capsule specificity for polyps approached 90%. Transit time was 52±32 hours. No device-related serious adverse events occurred. Average X-ray dose was 0.05 mSv.

Many patients forego screening by colonoscopy due to the need for cathartic preparation,1 2 posing a major obstacle to implementation of current screening programmes.3 4 A test not requiring laxative preparation could increase adherence with screening.1 Moreover, inadequate preparation for colonoscopy impairs adenoma and cancer detection rates and often necessitates repeating of the procedure.5 A prep-less modality would not suffer from these limitations. In a previous proof-of-concept study, a prep-less screening capsule was shown to be safe, capable of 3D reconstruction of the colonic wall and lumen and identifying adenomatous polyps.6 In a prospective multicentre comparative study, we studied the safety and efficacy of a first version of the capsule for identifying colonic polypoid lesions and masses compared with FIT and colonoscopy.

The system has …
Cancer-Associated Fibroblasts Drive Glycolysis in a Targetable Signaling Loop Implicated in Head and Neck Squamous Cell Carcinoma Progression
Authors: Dhruv Kumar, Jacob New, Vikalp Vishwakarma, Radhika Joshi, Jonathan Enders, Fangchen Lin, Sumana Dasari, Wade R. Gutierrez, George Leef, Sivapriya Ponnurangam, Hemantkumar Chavan, Lydia Ganaden, Mackenzie M. Thornton, Hongying Dai, Ossama Tawfik, Jeffrey Straub, Yelizaveta Shnayder, Kiran Kakarala, Terance Ted Tsue, Douglas A. Girod, Bennett Van Houten, Shrikant Anant, Partha Krishnamurthy, Sufi Mary Thomas
Journal: Cancer Research (2018)

Despite aggressive therapies, head and neck squamous cell carcinoma (HNSCC) is associated with a less than 50% 5-year survival rate. Late-stage HNSCC frequently consists of up to 80% cancer-associated fibroblasts (CAF). We previously reported that CAF-secreted HGF facilitates HNSCC progression; however, very little is known about the role of CAFs in HNSCC metabolism. Here, we demonstrate that CAF-secreted HGF increases extracellular lactate levels in HNSCC via upregulation of glycolysis. CAF-secreted HGF induced basic FGF (bFGF) secretion from HNSCC. CAFs were more efficient than HNSCC in using lactate as a carbon source. HNSCC-secreted bFGF increased mitochondrial oxidative phosphorylation and HGF secretion from CAFs. Combined inhibition of c-Met and FGFR significantly inhibited CAF-induced HNSCC growth in vitro and in vivo (P < 0.001). Our cumulative findings underscore reciprocal signaling between CAF and HNSCC involving bFGF and HGF. This contributes to metabolic symbiosis and a targetable therapeutic axis involving c-Met and FGFR.Significance: HNSCC cancer cells and CAFs have a metabolic relationship where CAFs secrete HGF to induce a glycolytic switch in HNSCC cells and HNSCC cells secrete bFGF to promote lactate consumption by CAFs. Cancer Res; 78(14); 3769-82. ©2018 AACR.