tbuckley/cabot-search huggingface dataset:
NK-cell Editing Mediates Epithelial-to-Mesenchymal Transition via Phenotypic and Proteomic Changes in Melanoma Cell Lines
Authors: Leticía Huergo-Zapico, Monica Parodi, Claudia Cantoni, Chiara Lavarello, Juan L. Fernández-Martínez, Andrea Petretto, Enrique J. DeAndrés-Galiana, Mirna Balsamo, Alejandro López-Soto, Gabriella Pietra, Mattia Bugatti, Enrico Munari, Marcella Marconi, Maria Cristina Mingari, William Vermi, Lorenzo Moretta, Segundo González, Massimo Vitale
Journal: Cancer Research (2018)

Tumor cell plasticity is a major obstacle for the cure of malignancies as it makes tumor cells highly adaptable to microenvironmental changes, enables their phenotype switching among different forms, and favors the generation of prometastatic tumor cell subsets. Phenotype switching toward more aggressive forms involves different functional, phenotypic, and morphologic changes, which are often related to the process known as epithelial-mesenchymal transition (EMT). In this study, we report natural killer (NK) cells may increase the malignancy of melanoma cells by inducing changes relevant to EMT and, more broadly, to phenotype switching from proliferative to invasive forms. In coculture, NK cells induced effects on tumor cells similar to those induced by EMT-promoting cytokines, including upregulation of stemness and EMT markers, morphologic transition, inhibition of proliferation, and increased capacity for Matrigel invasion. Most changes were dependent on the engagement of NKp30 or NKG2D and the release of cytokines including IFNγ and TNFα. Moreover, EMT induction also favored escape from NK-cell attack. Melanoma cells undergoing EMT either increased NK-protective HLA-I expression on their surface or downregulated several tumor-recognizing activating receptors on NK cells. Mass spectrometry-based proteomic analysis revealed in two different melanoma cell lines a partial overlap between proteomic profiles induced by NK cells or by EMT cytokines, indicating that various processes or pathways related to tumor progression are induced by exposure to NK cells.Significance: NK cells can induce prometastatic properties on melanoma cells that escape from killing, providing important clues to improve the efficacy of NK cells in innovative antitumor therapies. Cancer Res; 78(14); 3913-25. ©2018 AACR.
Soluble urokinase plasminogen activator receptor (suPAR) represents a novel serum biomarker for patients undergoing resection of colorectal liver metastases
Authors: S. Loosen, F. Tacke, M. Binnebösel, C. Klink, T.F. Ulmer, C. Trautwein, C. Roderburg, U. Neumann, T. Lüdde
Journal: Journal of Hepatology (2018)
Correlation of outcome with early metabolic response on FDG-PET in treatment of locally advanced nasopharyngeal carcinoma.
Authors: Dora Lai Wan Kwong, Victor HF Lee, Pek lan Khong
Journal: Journal of Clinical Oncology (2017)

e17555 Background: Skull base changes often persist on CT and MRI after treatment in locally advanced nasopharyngeal carcinoma (NPC) and cannot be differentiated from active tumor. We prospectively evaluated the metabolic response of T3/T4 NPC during treatment with PET scans. Early metabolic response was correlated with outcome after treatment. Methods: 50 patients with T3/T4, N0-3, M0 NPC were recruited. All patients had 3 cycles of induction chemotherapy (IC, physician’s choice of regime) before concurrent chemoradiation (CRT) with cisplatin 100mg/sqm for 3 cycles. PET scans were performed before and after IC and at 30Gy of CRT. For primary tumor that showed complete metabolic response (mCR, defined as SUV max in tumor ≤1.25x liver background activity) on reassessment PET, the dose to tumor stopped at 70Gy. For those who did not achieve mCR, a boost dose was given to the residual tumor to total 76Gy. Results: On post-IC PET scan, 2 patients with extensive intracranial disease showed no response with static and progressive disease respectively and did not proceed to CRT. 48 patients showed regression of tumor and decreased metabolic activity on post-IC PET, 16 of whom achieved mCR. One patient with mCR after IC refused CRT. 47 patients proceeded to CRT. 44 patients had reassessment PET at around 30Gy and 25 patients had mCR during CRT. 47 patients who completed CRT were included in survival analysis. Median follow up after completion of CRT was 28 months. Among the 15 cases who achieved mCR after IC, all patients were disease free without relapse at time of analysis. Among the 32 patients who did not achieve mCR after IC, there was 1 persistent loco-regional disease, 1 local and 1 regional relapse and 6 developed distant metastases. The 3 year NP control, regional control, distant metastases free, progression free survival and overall survival were 89.4%, 96.9%, 79.5%, 49.2% and 81% respectively compared with 100% corresponding survival rates among patients who achieved mCR after IC. The difference in progression-free survival was statistically significant (p = 0.045) Conclusions: Early mCR was observed in 32% patient after IC and 56.8% of patients during CRT. mCR after IC predicts for very favourable outcome.
Endoscopic ultrasound-guided management of bleeding periampullary tumor
Authors: Malay Sharma, Piyush Somani, Tagore Sunkara, Ritesh Prajapati
Journal: Endoscopy (2018)

A 72-year-old man presented with melena and a drop in hemoglobin from 10 g/dL to 5 g/dL. He required three units of blood for hemodynamic stabilization. He had undergone endoscopic retrograde cholangiopancreatography (ERCP) with biliary plastic stenting 4 days previously for a periampullary tumor. On side-viewing endoscopy, a blood clot covering the tumor was found and removed, with 20 mL of 1:10 000 epinephrine injected to achieve hemostasis ([Fig. 1]).
Efficacy and safety of Elbasvir/Grazoprevir in women infected with hepatitis C virus genotype 1 or 4 and co-administered oral contraceptives or hormone replacement therapy
Authors: C. Hezode, P. Kwo, J. Sperl, G. Dore, P. Hwang, J. Long, R. Talwani, M. Robertson, B. Haber
Journal: Journal of Hepatology (2018)
TCTAP A-124 Prognostic Impact of Renal Function On-admission in Diabetic Patients Presenting for Acute ST-elevation Myocardial Infarction: Insights from a Tunisian Single Center Registry
Authors: Walid Jomaa, Zouhair Jnifene, Ikram Chamtouri, Aymen El Hraiech, Khaldoun Ben Hamda, Faouzi Maatouk
Journal: Journal of the American College of Cardiology (2018)
Cardiac recovery via extended cell-free delivery of extracellular vesicles secreted by cardiomyocytes derived from induced pluripotent stem cells
Authors: Bohao Liu, Benjamin W. Lee, Koki Nakanishi, Aranzazu Villasante, Rebecca Williamson, Jordan Metz, Jinho Kim, Mariko Kanai, Lynn Bi, Kristy Brown, Gilbert Di Paolo, Shunichi Homma, Peter A. Sims, Veli K. Topkara, Gordana Vunjak-Novakovic
Journal: Nature Biomedical Engineering (2018)
Early-TIPS improves survival in cirrhotic patients with high-risk varical bleeding: Results of a China multicenter observational study
Authors: Y. LV, L. Zuo, X. Zhu, J. Zhao, H. Xue, Z. Jiang, Y. Zhuge, C. Zhang, J. Sun, P. Ding, W. Ren, Y. Li, K. Zhang, W. Zhang, C. He, J. Zhong, Q. Peng, F. MA, J. Luo, M. Zhang, G. Wang, M. Sun, J. Dong, W. Guo, W. Bai, K. Li, J. Tie, H. Chen, Q. Wang, H. Liu, J. Niu, Z. Wang, B. Luo, X. Li, Y. Zhu, Z. Yin, D. Fan, G. Han
Journal: Journal of Hepatology (2018)
Rubella infection in pregnancy and congenital rubella in United Kingdom, 2003 to 2016
Authors: Antoaneta Bukasa, Helen Campbell, Kevin Brown, Helen Bedford, Mary Ramsay, Gayatri Amirthalingam, Pat Tookey
Journal: Eurosurveillance (2018)

Rubella vaccination has been included in the United Kingdom’s (UK) routine childhood schedule for nearly 30 years. The UK achieved World Health Organization (WHO) elimination status in 2016 and acute rubella infections are rare. In the period 2003–16, 31 rubella infections in pregnancy (0.23 per 100,000 pregnancies) were identified through routine surveillance, of which 26 were in women who were born abroad. Five of the 31 rubella infections led to congenital rubella syndrome in the infant and three had confirmed congenital rubella infection without congenital rubella syndrome. An additional seven babies were identified with congenital rubella syndrome, although rubella infection in pregnancy had not been reported. Place of birth was known for six of these seven mothers, all of whom were born outside the UK, and in five cases maternal infection was acquired abroad. WHO Europe has set targets for measles and rubella elimination and prevention of congenital rubella syndrome by 2015. Vaccination uptake and rubella immunity is high in the UK population and most infections in pregnancy since 2003 were acquired abroad and in unvaccinated women. Every contact with a health professional should be used to check that women are fully immunised according to UK schedule.
Rescuing hepatitis-B-specific T cell responses by modulating cholesterol metabolism
Authors: N. Schmidt, L.J. Pallett, A. Schurich, K. Suveizdyte, O.E. Amin, F. Froghi, B.R. Davidson, R. Gillmore, T. Meyer, W. Rosenberg, M. Maini
Journal: Journal of Hepatology (2018)
Comprehensive in‐hospital monitoring in acute heart failure: applications for clinical practice and future directions for research. A statement from the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)
Authors: Veli‐Pekka Harjola, John Parissis, Hans‐Peter Brunner‐La Rocca, Jelena Čelutkienė, Ovidiu Chioncel, Sean P. Collins, Daniel De Backer, Gerasimos S. Filippatos, Etienne Gayat, Loreena Hill, Mitja Lainscak, Johan Lassus, Josep Masip, Alexandre Mebazaa, Òscar Miró, Andrea Mortara, Christian Mueller, Wilfried Mullens, Markku S. Nieminen, Alain Rudiger, Frank Ruschitzka, Petar M. Seferovic, Alessandro Sionis, Antoine Vieillard‐Baron, Jean Marc Weinstein, Rudolf A. de Boer, Maria G. Crespo‐Leiro, Massimo Piepoli, Jillian P. Riley
Journal: European Journal of Heart Failure (2018)
Relationship Between Relative Skeletal Muscle Mass and Nonalcoholic Fatty Liver Disease: A 7‐Year Longitudinal Study
Authors: Gyuri Kim, Seung‐Eun Lee, You‐Bin Lee, Ji Eun Jun, Jiyeon Ahn, Ji Cheol Bae, Sang‐Man Jin, Kyu Yeon Hur, Jae Hwan Jee, Moon‐Kyu Lee, Jae Hyeon Kim
Journal: Hepatology (2018)

Nonalcoholic fatty liver disease (NAFLD) has been associated with relative skeletal muscle mass in several cross-sectional studies. We explored the effects of relative skeletal muscle mass and changes in relative muscle mass over time on the development of incident NAFLD or the resolution of baseline NAFLD in a large, longitudinal, population-based 7-year cohort study. We included 12,624 subjects without baseline NAFLD and 2943 subjects with baseline NAFLD who underwent health check-up examinations. A total of 10,534 subjects without baseline NAFLD and 2631 subjects with baseline NAFLD were included in analysis of changes in relative skeletal muscle mass over a year. Subjects were defined as having NAFLD by the hepatic steatosis index, a previously validated NAFLD prediction model. Relative skeletal muscle mass was presented using the skeletal muscle mass index (SMI), a measure of body weight-adjusted appendicular skeletal muscle mass, which was estimated by bioelectrical impedance analysis. Of the 12,624 subjects without baseline NAFLD, 1864 (14.8%) developed NAFLD during the 7-year follow-up period. Using Cox proportional hazard analysis, compared with the lowest sex-specific SMI tertile at baseline, the highest tertile was inversely associated with incident NAFLD (adjusted hazard ratio [AHR] = 0.44, 95% confidence interval [CI] = 0.38-0.51) and positively associated with the resolution of baseline NAFLD (AHR = 2.09, 95% CI = 1.02-4.28). Furthermore, compared with the lowest tertile of change in SMI over a year, the highest tertile exhibited a significant beneficial association with incident NAFLD (AHR = 0.69, 95% CI = 0.59-0.82) and resolution of baseline NAFLD (AHR = 4.17, 95% CI = 1.90-6.17) even after adjustment for baseline SMI. Conclusion: Increases in relative skeletal muscle mass over time may lead to benefits either in the development of NAFLD or the resolution of existing NAFLD.
Abstract 19460: Obesity Associates With Heart Failure in Young Adults With Congenital Heart Disease
Authors: Joseph B Lerman, Ira A Parness, Rajesh U Shenoy
Journal: Circulation (2016)

Introduction:  Adults with Congenital Heart Disease (ACHD) are a growing segment of the population, at elevated cardiovascular risk. This risk increases with age, and is primarily attributable to congestive heart failure (CHF). Obesity is an emerging cardiovascular risk factor, associated with CHF in the healthy adult population. To date, however, the relationship between obesity and CHF in ACHD is poorly described.   Hypothesis:  We hypothesized that obesity would independently associate with CHF in young ACHD.   Methods:  Retrospective analysis was performed on all ACHD (identified via ICD-9 coding), ages 19 - 45 years old, seen at a Pediatric Heart Network-affiliated center in 2013. ACHD were classified as having simple or complex congenital heart disease per the Bethesda Conference Criteria. Obesity was defined as body-mass index ≥ 30 kg/m 2 . Statistical analysis included multivariate regression and likelihood ratio testing.   Results:  493 ACHD met inclusion criteria, with 24 identified cases of CHF. CHF patients had a higher prevalence of obesity (p=0.003), diabetes (p  2  4.49, p=0.03), a finding not seen in hypertension, hyperlipidemia, or diabetes mellitus.   Conclusions:  Obesity was independently associated with CHF in this cohort of 493 young ACHD. In the midst of the modern obesity epidemic, these results may indicate a need for improved lifestyle counseling in congenital heart disease patients of all ages. Larger, prospective studies are needed to confirm these findings.
Self-reported Asthma is Associated with Increased Risk of Hospitalization and/or Death Due to Coronary Heart Disease among Never Smoking Men and Women.
Authors: Carlos Iribarren, Mark D Eisner, Alan S Go, Stephen Sidney, Arthur L Klatsky
Journal: Circulation (2001)

P61     Inflammation is thought to play a crucial role in the  pathogenesis of coronary atherosclerosis. Asthma is a chronic  inflammatory disease and a major cause of pulmonary morbidity and  mortality. However, very few prospective studies exist evaluating the  question of whether asthma is related to increased risk of  cardiovascular diseases, and none were restricted to never smokers. We  examined the prospective association between self-reported asthma  diagnosis and risk of hospitalization and/or death due to coronary  heart disease (CHD, ICD-9 codes 410-414) in a large population-based  sample. Data on self-reported health conditions, including asthma, and  cardiovascular risk factors were collected at a health maintenance  organization (HMO) in the San Francisco Bay Area between 1979 and 1985.  The sample included 14,047 never smoking women and 7,989 never smoking  men aged 35-89 years (mean ± SD, 50.4 ± 11.9 years), 56%  Caucasian, who were free of known CHD at baseline. Of those, 652 women  (4.6%) and 410 men (5.1%) self-reported physician-diagnosed asthma.  Follow-up for hospitalization and/or death was available through the  end of 1998 (median=13.4 years). Using Cox proportional hazards  regression, we censored persons leaving the health plan at their last  known date of HMO membership. Compared to subjects with no-known  history of asthma, and after adjustment for age, sex, race, education  level, alcohol consumption, body mass index, serum cholesterol,  systolic blood pressure and diabetes, self-reported asthma was  significantly associated with higher risk of hospitalization and /or  death due to CHD (RR=1.33; 95% CI=1.05-1.67; p=0.02). Also in  multivariate analysis, asthma under treatment at the time of the  baseline examination was more strongly associated with CHD risk  (RR=1.82; 95% CI=1.23-2.69; p=0.003). No interactions were found  between self-reported asthma or asthma under treatment and patient sex.  We conclude that, in a large representative population-based sample of  non-smokers, self-reported asthma was associated with increased risk of  coronary heart disease.
Impact of type 2 diabetes mellitus on short-term and long-term outcomes of patients with esophageal squamous cell cancer undergoing resection: a propensity score analysis
Authors: Wang Yao, Yuqi Meng, Mingjian Lu, Wenzhe Fan, Jinhua Huang, Jiaping Li, Zhihua Zhu
Journal: Cancer Communications (2018)

The association between type 2 diabetes mellitus (T2DM) and the risk of esophageal cancer remains unclear. The present study aimed to evaluate the impact of T2DM on short-term outcomes and long-term survival in patients with esophageal squamous cell cancer (ESCC).The present retrospective study included 862 patients diagnosed with ESCC between January 2001 and December 2010. Among them, 280 patients had T2DM. A 1:1 propensity score-matched cohort consisting of 280 patients with and 280 without T2DM was selected from the 862 patients. The associations between T2DM and clinicopathologic characteristics were assessed using the χ2 or Fisher's exact test. Survival of ESCC patients with and without T2DM was calculated by using the Kaplan-Meier method and compared by using the Cox regression model between the two groups.The occurrence rate of anastomotic leakage was significantly higher in patients with T2DM than in those without T2DM (P < 0.001). In the subgroup with weight loss rate ≤ 5.05%, ESCC patients with T2DM had a significant longer overall survival than did those without T2DM (P = 0.003), whereas in the subgroup with weight loss rate > 5.05%, the patients without T2DM showed a longer survival (P = 0.001). Univariate and multivariate analysis results showed that T2DM was not an independent prognostic factor for patient survival.Type 2 diabetes mellitus is not an independent prognostic factor in patients with ESCC. However, the combination of T2DM with severe weight loss would be a predictor of poor prognosis.
PSMD5 Inactivation Promotes 26S Proteasome Assembly during Colorectal Tumor Progression
Authors: Avi Levin, Adi Minis, Gadi Lalazar, Jose Rodriguez, Hermann Steller
Journal: Cancer Research (2018)

Protein degradation by the ubiquitin-proteasome system (UPS) is central to protein homeostasis and cell survival. The active 26S proteasome is a large protease complex consisting of a catalytic 20S subunit and 19S regulatory particles. Cancer cells are exposed to considerable protein overload due to high metabolic rates, reprogrammed energy metabolism, and aneuploidy. Here we report a mechanism that facilitates the assembly of active 26S proteasomes in malignant cells. Upon tumorigenic transformation of the gut epithelium, 26S proteasome assembly was significantly enhanced, but levels of individual subunits were not changed. This enhanced assembly of 26S proteasomes increased further with tumor progression and was observed specifically in transformed cells, but not in other rapidly dividing cells. Moreover, expression of PSMD5, an inhibitor of proteasome assembly, was reduced in intestinal tumors and silenced with tumor progression. Reexpression of PSMD5 in tumor cells caused decreased 26S assembly and accumulation of polyubiquitinated proteins. These results suggest that inhibition of cancer-associated proteasome assembly may provide a novel therapeutic strategy to selectively kill cancer cells.
Acute‐on‐Chronic Liver Failure: Getting Ready for Prime Time?
Authors: Jasmohan S. Bajaj, Richard Moreau, Patrick S Kamath, Hugo E. Vargas, Vicente Arroyo, K. Rajender Reddy, Gyongyi Szabo, Puneeta Tandon, Jody Olson, Constantine Karvellas, Thierry Gustot, Jennifer C. Lai, Florence Wong
Journal: Hepatology (2018)

Acute on chronic liver failure (ACLF) is the culmination of chronic liver disease and extrahepatic organ failures, which is associated with a high short‐term mortality and immense health care expenditure. There are varying definitions for organ failures and ACLF in Europe, North America, and Asia. These differing definitions need to be reconciled to enhance progress in the field. The pathogenesis of ACLF is multifactorial and related to interactions between the immunoinflammatory system, microbiota, and the various precipitating factors. Individual organ failures related to the kidney, brain, lungs, and circulation have cumulative adverse effects on mortality and are often complicated or precipitated by infections. Strategies to prevent and rapidly treat these organ failures are paramount in improving survival. With the aging population and paucity of organs for liver transplant, the prognosis of ACLF patients is poor, highlighting the need for novel therapeutic strategies. The role of liver transplant in ACLF is evolving and needs further investigation across large consortia. A role for early palliative care and management of frailty as approaches to alleviate disease burden and improve patient‐reported outcomes is being increasingly recognized. Conclusion : ACLF is a clinically relevant syndrome that is epidemic worldwide and requires a dedicated multinational approach focused on prognostication and management; investigations are underway worldwide to prepare ACLF for prime time. (H epatology 2018; 00:000‐000)
Delamanid for rifampicin-resistant tuberculosis: a retrospective study from South Africa
Authors: Erika Mohr, Jennifer Hughes, Anja Reuter, Laura Trivino Duran, Gabriella Ferlazzo, Johnny Daniels, Virginia De Azevedo, Yulene Kock, Sarah Jane Steele, Amir Shroufi, Serge Ade, Natavan Alikhanova, Guido Benedetti, Jeffrey Edwards, Helen Cox, Jennifer Furin, Petros Isaakidis
Journal: European Respiratory Journal (2018)

Experience with delamanid (Dlm) is limited, particularly among HIV-positive individuals. We describe early efficacy and safety data from a programmatic setting in South Africa. This was a retrospective cohort study of patients receiving Dlm-containing treatment regimens between November 2015 and August 2017. We report 12-month interim outcomes, sputum culture conversion (SCC) by months 2 and 6, serious adverse events (SAEs) and QT intervals corrected using the Frederica formula (QTcF). Overall, 103 patients were initiated on Dlm; 79 (77%) were HIV positive. The main indication for Dlm was intolerance to second-line anti-tuberculosis (TB) drugs (n=58, 56%). There were 12 months of follow-up for 46 patients; 28 (61%) had a favourable outcome (cure, treatment completion or culture negativity). Positive cultures were found for 57 patients at Dlm initiation; 16 out of 31 (52%) had SCC within 2 months and 25 out of 31 (81%) within 6 months. There were 67 SAEs reported in 29 patients (28%). There were four instances of QTcF prolongation &gt;500 ms in two patients (2%), leading to permanent discontinuation in one case; however, no cardiac arrhythmias occurred. This large cohort of difficult-to-treat patients receiving Dlm for rifampicin-resistant TB treatment in a programmatic setting with high HIV prevalence had favourable early treatment response and tolerated treatment well. Dlm should remain available, particularly for those who cannot be treated with conventional regimens or with limited treatment options.