tbuckley/cabot-search huggingface dataset:
Detection of circulating tumor cells in the peripheral blood of patients with small cell lung cancer (SCLC) using both the CellSearch platform and immunofluorescence: Correlation with clinicopathological features.
Authors: Ippokratis Messaritakis, Dimitrios Stoltidis, Eleni Politaki, Stella Apostolaki, Eleftheria- Kleio Dermitzaki, Maria Sfakianaki, Athanasios Kotsakis, Sofia Agelaki, Lampros Vamvakas, Kostas Kalbakis, Eleni Lagoudaki, Dimitrios Mavroudis, Vassilis Georgoulias, Ioannis Souglakos
Journal: Journal of Clinical Oncology (2015)

7573 Background: The diagnosis of SCLC is based on morphology and immunocytochemistry using cytokeratins and neuroendocrine markers. We aimed to evaluate the clinical significance of the detection of Circulating Tumor Cells (CTCs) in patients with SCLC using the CellSearch system (CS) and immunofluorescence (IF). Methods: Peripheral blood was obtained from 101 patients with SCLC before treatment, 68 patients after one cycle of 1st line chemotherapy (etoposide/platinum) and 52 patients at the time of disease progression. CTCs were detected by double immunofluorescent staining of one million PBMC’s on cytospins using anti-TTF1 and anti-CD56 antibodies, and by the CS using anti-CK antibody. Results: Prior to the initiation of 1st line treatment, 61% of patients had detectable CTCs by IF and 78% with the CS (range: 1-169 and 2-10000 CTCs, respectively). After 1 cycle of chemotherapy, the positivity of CTC detection decreased to 44% (range: 1-56 CTCs) and 45% (range: 1-4882 CTCs) using IF and CS, respectively; at the time of disease progression (PD) the detection of CTCs almost reached the baseline levels (60% and 74%; range: 2-186 and 1-11143 CTCs for IF and CS, respectively). The detection of CTCs at baseline, after 1 cycle of chemotherapy and on PD was significantly associated with decreased PFS (7.0 vs 8.5 months, p = 0.021; 5.6 vs 8.1 months, p = 0.018; 5.7 vs 7.6 months, p = 0.014, respectively) and OS (11.0 vs 26.0 months, p = 0.021; 8.9 vs 17.0 months, p = 0.009; 10.0 vs 17.0 months, p = 0.021, respectively) compared to the patients with undetectable CTCs. Multivariate analysis revealed that performance status, disease stage and the detection of CTCs after 1 cycle of chemotherapy and at the time of progression emerged as independent factors associated with reduced PFS and OS. Conclusions: Detection of CTCs using either immunofluorescence or the CellSearch is an adverse prognostic factor correlated with poor clinical outcome in patients with SCLC receiving 1st line chemotherapy.
Abstract P094: Genetic Risk, Incident Coronary Heart Disease Events, and the Benefits of a Healthy Lifestyle: Joint and Interacting Effects Across Four US Cohorts
Authors: Liana C Del Gobbo, Elias Salfati, Jin Li, Christopher D Gardner, John P Ioannidis, Themistocles L Assimes
Journal: Circulation (2017)

Background: Recent GWAS revealed single nucleotide polymorphisms (SNPs) that cumulatively increase risk of CHD in those of European ancestry. We quantified the magnitude of preventive effects of healthy lifestyle against the countervailing effects of genetic risk on incident CHD, and assessed potential interactions. Methods: We extracted SNPs of genome-wide significance (&lt;5 x 10 -8 ) for CHD from CARDIoGRAMplusC4 GWAS, and created a weighted 57-SNP genetic risk score (GRS). Baseline covariates, healthy lifestyle score (including diet pattern, physical activity, smoking and BMI), and incident CHD were harmonized across 4 US cohorts (WHI, ARIC, CHS, and MESA) using dbGaP data. Pooled analyses were run using one-step individual participant data multivariate regressions in Caucasians without prevalent CVD. Results: Among 22,412 adults, the GRS was associated with incident CHD (n = 3001 cases) across each cohort (pooled GRS quintile (Q)5 vs Q1, RR (95% CI): 1.59 (1.41-1.79)), independent of all demographic and lifestyle variables. The lifestyle score was more strongly associated with CHD (pooled Q1 vs Q5, RR: 1.94 (1.71-2.20)) than the GRS, and better discriminated those who had a CHD event ( P =0.025 for difference in AUROC curves). When compared to population-level analysis, joint effects analysis revealed significant heterogeneity within quartiles of lifestyle score on risk of incident CHD ( Table ). Interactions between the GRS and diet pattern ( P =0.022) and trans fats ( P =0.046) were observed. Effects of trans fats on CHD risk appear to be concentrated in those with a higher GRS: for trans fats &gt;2.4% of energy, RRs for increasing GRS quartiles are 0.92 (0.62-1.36), 1.13 (0.79-1.62), 1.43 (1.01-2.01), and 1.84 (1.30-2.61), compared to those in the lowest quartile of trans fat (&lt;1.3% of energy) and lowest GRS quartile. Conclusion: A joint effects approach reveals significant inter-individual variability in lifestyle on CHD risk by underlying genetic risk that is obscured by a conventional population-level effects approach.
FRI-132-In vitro modulation by TLR8 agonist GS-9688 of multiple regulatory cell types in patients with chronic hepatitis B
Authors: Oliver E Amin, Emily Colbeck, Stephane Daffis, Divya Pattabiraman, Colette Sitali, William Rosenberg, Simon Fletcher, Mala Maini, Laura J Pallett
Journal: Journal of Hepatology (2019)
TCTAP A-059 Intrahospital and Long-term Outcomes After True Bifurcation Stenting
Authors: Arnis Laduss, Evija Camane, Andrejs Erglis, Karlis Trusinskis, Dace Sondore, Gustavs Latkovskis, Inga Narbute, Andis Dombrovskis, Kristine Dombrovska, Aigars Lismanis, Ieva Briede, Ainars Rudzitis, Sandra Jegere, Indulis Kumsars
Journal: Journal of the American College of Cardiology (2019)
FRI-227-Interleukin-6 −174G/C genotype and interleukin-10 ATA haplotype are associated with clinical comorbidities in chronic hepatitis C patients
Authors: Cliviany Borges da Silva, Diego Alves Vieira, Luciana Rodrigues da Cunha, Adriana Dias Gomes, César Lúcio Lopes de Faria, Rosângela Teixeira, Gifone Aguiar Rocha, Dulciene Maria Magalhães Queiroz, Juliana Maria Trindade Bezerra, Luciana Diniz Silva
Journal: Journal of Hepatology (2019)
Gender disparity in HCC: Is it the fat and not the sex?
Authors: Tim F. Greten
Journal: The Journal of Experimental Medicine (2019)

Men are more likely to develop hepatocellular carcinoma (HCC) than women, but it is not clear why. In this issue of JEM, Manieri et al. (https://doi.org/10.1084/jem.20181288) identify reduced adiponectin levels as responsible for the increased incidence of HCC in males.
Enasidenib, an inhibitor of mutant IDH2 proteins, induces durable remissions in older patients with newly diagnosed acute myeloid leukemia
Authors: Daniel A. Pollyea, Martin S. Tallman, Stéphane de Botton, Hagop M. Kantarjian, Robert Collins, Anthony S. Stein, Mark G. Frattini, Qiang Xu, Alessandra Tosolini, Wendy L. See, Kyle J. MacBeth, Samuel V. Agresta, Eyal C. Attar, Courtney D. DiNardo, Eytan M. Stein
Journal: Leukemia (2019)

Older adults with acute myeloid leukemia (AML) who are not fit for standard chemotherapy historically have poor outcomes. Approximately 12-15% of older patients with AML harbor isocitrate dehydrogenase 2 (IDH2) gene mutations. Enasidenib is an oral inhibitor of mutant IDH2 proteins. Among 39 patients with newly diagnosed mutant-IDH2 AML who received enasidenib monotherapy in this phase I/II trial, median age was 77 years (range 58-87) and 23 patients (59%) had had an antecedent hematologic disorder. The median number of enasidenib treatment cycles was 6.0 (range 1-35). The most common treatment-related adverse events were indirect hyperbilirubinemia (31%), nausea (23%), and fatigue, decreased appetite, and rash (18% each). Treatment-related grade 3-4 cytopenias were reported for eight patients (21%); there was no treatment-related grade 3-4 infections. Twelve patients achieved a response (overall response rate 30.8% [95% CI 17.0%, 47.6%]), including seven patients (18%) who attained complete remission. At a median follow-up of 8.4 months, the median duration of any response was not reached (NR). Median overall survival for all patients was 11.3 months (95% CI 5.7, 15.1), and was NR for responders. Oral, outpatient targeted treatment with enasidenib may benefit older adults with newly diagnosed mutant-IDH2 AML who are not candidates for cytotoxic regimens.
PS-138-PD-1 targeted immunotherapy in advanced hepatocellular carcinoma: Efficacy and safety data from an international multicenter real-world cohort
Authors: Bernhard Scheiner, Martha Kirstein, Florian Hucke, Fabian Finkelmeier, Kornelius Schulze, Johann von Felden, Sandra Koch, Philipp Schwabl, Jan Hinrichs, Oliver Waidmann, Thomas REIBERGER, Christian Müller, Wolfgang Sieghart, Michael Trauner, Arndt Weinmann, Henning Wege, Jörg Trojan, Markus Peck, Arndt Vogel, Matthias Pinter
Journal: Journal of Hepatology (2019)
Hierarchical prediction errors in midbrain and basal forebrain during sensory learning (Correction to: vol 80, pp. 519-530, 2013)
Authors: S. Iglesias, C.D. Mathys, K.H. Brodersen, L. Kasper, M. Piccirelli, H.E.M. den Ouden, K.E. Stephan
Journal: Neuron (2019)
miRNA expression in breast cancer variance with lymph node metastasis and other clinicpathologic features.
Authors: Yabing Zheng, Xiying Shao, Xiping Zhang, Xiaojia Wang
Journal: Journal of Clinical Oncology (2015)

e22084 Background: Breast carcinoma is the most common malignant tumor in females, lymph node status is one of the most important prognostic factors in patients with breast cancer. MiRNAs have been shown to have important role in oncogenesis, invasion, and metastasis via epigenetic posttranscriptional gene regulation. However, lymphatic metastasis related miRNAs of breast cancer has not been well documented. The aim of this study was to identify and evaluate miRNAs related to breast cancer lymph node metastasis, and explore the clinical significance of the differential expressed miRNAs in breast cancer patients. Methods: The expression of miRNAs in primary breast cancer patients with lymph node metastasis and that without lymph node metastases was compared by miRNA microarray. We further validated the miRNAs (miR-185-5p, miR-339-5p, miR-542-5p, miR-3923) between lymph node (n = 31) and non-lymph node (n = 42) group using real-time reverse transcriptase polymerase chain reaction. Furthermore, the relationship between miRNA expression and clinical pathological features was analyzed. Results: The miRNA microarray initially identified that 8 miRNAs (miR-206, miR-3923, miR-181a, miR-92a, miR-421, miR-339-5p, miR-3196, and miR-29b) were down-regulated in lymph node metastasis group, whereas 5 (miR-542-5p, miR-200a, miR-564, miR-451, miR-30c, miR-200b, miR-191-3p, miR-142-5p, and miR-185-5p) were up-regulated in lymph node group when compared with those in non-lymph node group. In the validation cohort, the expression levels of miR-185-5p and miR-542-5p were significantly higher expressed in lymph node group (P= 0.002, and P= 0.000, respectively), the expression levels of miR-339-5p and miR-3923 were significantly lower expressed in lymph node group (P= 0.000, and P= 0.000, respectively). Conclusions: Our results indicated the potential role of miR-185-5p, miR-542-5p, miR-339-5p and miR-3923 in predicting metastasis to the lymph node and prognosis in breast cancers.
Efficacy of pharmacological therapies in patients with IBS with diarrhoea or mixed stool pattern: systematic review and network meta-analysis
Authors: Christopher J Black, Nicholas E Burr, Michael Camilleri, David L Earnest, Eamonn MM Quigley, Paul Moayyedi, Lesley A Houghton, Alexander C Ford
Journal: Gut (2019)

Objective Over half of patients with IBS have either diarrhoea (IBS-D) or a mixed stool pattern (IBS-M). The relative efficacy of licenced pharmacological therapies is unclear in the absence of head-to-head trials. We conducted a network meta-analysis to resolve this uncertainty. Design We searched MEDLINE, Embase, Embase Classic, the Cochrane central register of controlled trials, and Clinicaltrials.gov through January 2019 to identify randomised controlled trials (RCTs) assessing the efficacy of licenced pharmacological therapies (alosetron, eluxadoline, ramosetron and rifaximin) in adults with IBS-D or IBS-M. Trials included in the analysis reported a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Efficacy and safety of all pharmacological therapies were reported as a pooled relative risk with 95% CIs to summarise the effect of each comparison tested. Treatments were ranked according to their p score. Results We identified 18 eligible RCTs (seven alosetron, five ramosetron, two rifaximin and four eluxadoline), containing 9844 patients. All were superior to placebo for the treatment of IBS-D or IBS-M at 12 weeks, according to the Food and Drug Administration (FDA)-recommended endpoint for trials in IBS. Alosetron 1 mg twice daily was ranked first for efficacy, based on the FDA-recommended composite endpoint of improvement in both abdominal pain and stool consistency, effect on global symptoms of IBS and effect on stool consistency. Ramosetron 2.5µg once daily was ranked first for effect on abdominal pain. Total numbers of adverse events were significantly greater with alosetron 1 mg twice daily and ramosetron 2.5µg once daily, compared with placebo. Rifaximin 550 mg three times daily ranked first for safety. Constipation was significantly more common with all drugs, except rifaximin 550 mg three times daily. Conclusion In a network meta-analysis of RCTs of pharmacological therapies for IBS-D and IBS-M, we found all drugs to be superior to placebo, but alosetron and ramosetron appeared to be the most effective.
Oral allergen immunotherapy by targeting Peyer’s patches
Authors: Franziska Roth‐Walter
Journal: Allergy (2019)

FRW is inventor of patent “Antigen-containing microspheres for the treatment of allergies” and “Method and means for diagnosing and treating allergies” owned by Biomedical International GmbH R&D. She reports financial support from Bencard Allergie GmbH outside the submitted work.
PS-082-Plasma metabolomic changes modulate the impact of Middle Eastern versus Western Diet in an international cirrhosis cohort
Authors: I. Jane Cox, Ramazan Idilman, Andrew Fagan, Dilara Turan, Lola Ajayi, Fatih Karakaya, Roger Williams, Edith Gavis, Andrew Atkinson, Adrien Le Guennec, Simon Taylor-Robinson, Masoumeh Sikaroodi, Patrick Gillevet, Jasmohan S Bajaj
Journal: Journal of Hepatology (2019)
Trends and Costs Associated With Suboptimal Physical Activity Among US Women With Cardiovascular Disease
Authors: Victor Okunrintemi, Eve-Marie A. Benson, Martin Tibuakuu, Di Zhao, Oluseye Ogunmoroti, Javier Valero-Elizondo, Martha Gulati, Khurram Nasir, Erin D. Michos
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Cardiovascular disease (CVD) is the leading cause of death and disability among women. Achievement of recommended physical activity (PA) levels is an essential component of CVD management. <h3>Objective</h3> To describe trends, sociodemographic factors, and health care expenditures associated with suboptimal PA among a nationally representative sample of US women with CVD. <h3>Design, Setting, and Participants</h3> This cross-sectional study used serial data from the Medical Expenditure Panel Survey from 2006 through 2015. The analyses were conducted in August 2018. Women who had self-reported and/or<i>International Classification of Diseases, Ninth Revision</i>, diagnosis of CVD were included. <h3>Main Outcomes and Measures</h3> <i>Recommended PA</i>was defined as 30 minutes or more of moderate- to vigorous-intensity exercise, 5 or more days per week. Weighted logistic regression was used to examine the associations of various sociodemographic factors with suboptimal PA, adjusted for comorbidities. A 2-part econometric model was used to assess health care expenditures. <h3>Results</h3> A total of 18 027 women were included in this study. The results were weighted to provide estimates for approximately 19.5 million adult women in the United States with CVD (mean [SD] age, 60.4 [16.9] years). More than half of the women with CVD reported suboptimal PA, a trend that increased during the 10-year period, with 58.2% (95% CI, 55.9%-60.5%) of participants reporting suboptimal PA in 2006-2007 vs 61.9% (95% CI, 59.7%-64.2%) in 2014-2015 (<i>P</i> = .004). The proportion of women with suboptimal PA differed by sociodemographic factors. In adjusted models, compared with non-Hispanic white women, African American women (odds ratio, 1.22; 95% CI, 1.08-1.38) and Hispanic women (odds ratio, 1.33; 95% CI, 1.13-1.58) were more likely to have suboptimal PA. Women from low- or very low-income strata (compared with high-income strata), enrolled in public insurance (compared with private insurance), and with less than high school education (compared with at least some college education) were more likely to have suboptimal PA. Health care costs among women with CVD with suboptimal PA were higher compared with those among women who met the recommended PA, and this increased through time, from a mean total health care expenditure of $12 724 (95% CI, $11 627-$13 821) in 2006-2007 to $14 820 (95% CI, $13 521-$16 119) in 2014-2015. <h3>Conclusions and Relevance</h3> The proportion of women with CVD not meeting recommended PA is high and increasing, particularly among certain racial/ethnic and socioeconomic groups, and is associated with significant health care costs. More must be done to improve PA for secondary prevention and reduction of expenditures among women with CVD.
Postchemotherapy Histiocyte-Rich Pseudotumor of the Spleen Simulating Residual Disease in a Patient With Non-Hodgkin Lymphoma on FDG PET/CT
Authors: Nir Hod, Sophie Lantsberg, Reut Anconina, Daniel Levin, Karen Nalbandyan, Itai Levi
Journal: Clinical Nuclear Medicine (2019)

A 64-year-old man was treated with multiagent chemotherapy owing to high-grade non-Hodgkin lymphoma presenting as a bulky disease involving the spleen. Interim and posttreatment sequential FDG PET/CT scans revealed a residual splenic mass showing markedly intense FDG uptake suspected of a residual viable lymphoma. To definitely decide about the appropriate treatment, a laparoscopic splenectomy was performed. Histopathologic specimen was compatible with the rare diagnosis of postchemotherapy histiocyte-rich pseudotumor of the spleen, a potential pitfall simulating viable disease on FDG PET/CT.
Regional differences in admissions and treatment outcomes for patients with hepatocellular carcinoma (HCC) in Thailand: data from the national universal health care
Authors: T Kitiyakara, A Leerapun, C Sutthivanan, K Poovorawan, W Pan-ngum, N Soonthornworasiri, R Chaiteerakij, S Treeprasertsuk, K Phaosawasdi, P Mairiang, C Kositchaiwat
Journal: Hepatology (2016)
Annals Story Slam - Student Doctor
Authors: Garshasb Soroosh
Journal: Annals of Internal Medicine (2019)

Web Exclusives7 May 2019Annals Story Slam - Student DoctorFREEGarshasb Soroosh, BSGarshasb Soroosh, BSSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W19-0010 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Student Doctor "Student Doctor," by Garshasb Soroosh (Duration 5:18)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: This article was published at Annals.org on 12 April 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 May 2019Volume 170, Issue 9Page: SS1 ePublished: 12 April 2019 Issue Published: 7 May 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.Loading ...
THU-395-Hepatitis C elimination by enhancing care and treatment among HIV co-infected individuals (the co-EC study): Real world evidence of decreasing HCV incidence and prevalence
Authors: Joseph Doyle, Daniela van Santen, David lser, Joe Sasadeusz, Mark O’reilly, Brendan Harney, Janine Roney, Julia Cutts, Anna Bowring, Rebecca Winter, Nick Medland, Christopher Fairley, Richard Moore, Tee Bk, Jennifer Hoy, Edward Gane, Gail Matthews, Maria Prins, Mark Stoove, Margaret Hellard
Journal: Journal of Hepatology (2019)
YYEI motif and oncogenicity of 14-3-3 proteins.
Authors: Wen-Hsin Chang, Kang-Yi Su, Sung-Liang Yu
Journal: Journal of Clinical Oncology (2015)

e22232 Background: 14-3-3 family is implicated with many biological activities by binding to other proteins. It consists of seven highly conserved isoforms (β, γ, ε, ζ, η, σ, and τ) and most of them are identified as oncogenes in various types of cancer except 14-3-3σ, a well-known tumor suppressor. However, their biological and molecular mechanism as well as clinical application in lung cancer had not been clarified. Methods: The in vitro cell functions of 14-3-3 proteins were performed by transwell invasion assay and MTT assay. Next, we used protein alignment and genetic approaches to verify the functionality and molecular mechanism of 14-3-3. Finally, we clarified the clinical relevance and pharmacological application of 14-3-3 by correlating with lung cancer patient outcome. Results: Six of 14-3-3 proteins increased cell growth besides 14-3-3σ, which inhibited cancer cell viability. Higher mRNA levels of 14-3-3ζ, 14-3-3η and 14-3-3τ were correlated with shorter overall survival of lung cancer patients. We found that the major difference between six oncogenic members and 14-3-3σ was a substitution at amino acid 180 from Tyr to His resulting in SH2-binding motif (YYEI) alteration according to amino acid sequence alignment. Therefore, we generated seven 14-3-3 constructs and 14-3-3σ H180Y mutant as well as 14-3-3ζ Y178F mutant to investigate the impact of YYEI motif on tumorigenicity. Src can interact with 14-3-3 proteins which carried YYEI motif (14-3-3ζ and 14-3-3σ H180Y mutant), while the interaction disappeared when 14-3-3 proteins lost YYEI motif (14-3-3σ and 14-3-3ζ Y178F). In addition, overexpression of 14-3-3β, γ, ε, ζ, η, τ, and 14-3-3σ H180Y mutant, but not wild type of 14-3-3σ, increased Src activity. In in vitro cell functions, YYEI motif-carrying 14-3-3 proteins promoted cancer growth and invasion. Blockage of Src via dasatinib impeded 14-3-3-induced oncogenic functions. Furthermore, YYEI motif-carrying 14-3-3 proteins enhanced tumorigenesis in vivo. Conclusions: YYEI motif is essential for 14-3-3 proteins to interact with Src and regulate Src activity and Src-mediated cellular functions in lung cancer. Effective blockage of the interaction may raise a novel therapeutic strategy to eliminate or control the cancer progression in the future.