tbuckley/cabot-search huggingface dataset:
Upconversion-Magnetic Carbon Sphere for Near Infrared Light-Triggered Bioimaging and Photothermal Therapy
Authors: Jiaxin Wang, Chenjie Yao, Bin Shen, Xiaohui Zhu, Yong Li, Liyi Shi, Yong Zhang, Jinliang Liu, Yanli Wang, Lining Sun
Journal: Theranostics (2019)

Nanoparticle-based theranostics combines tumor imaging and cancer therapy in one platform, but the synthesis of theranostic agents is impeded by chemical groups on the surface and the size and morphology of the components. Strategies to construct a multifunctional platform for bioimaging and photothermal therapy (PTT) are urgently needed. A new upconversion-magnetic agent (FeCUPs) based on hollow carbon spheres, which is both a photothermal agent and a dual carrier of luminescent and magnetic nanoparticles, provides an effective approach for tumor elimination. Methods: The morphology of FeCUPs was characterized for the construction and size adjustment of the theranostic agent using transmission electron microscopy, high-resolution transmission electron microscopy, energy dispersive spectroscopy and high angle annular dark field scanning transmission electron microscopy. The distribution of FeCUPs was tracked under in-situ upconversion luminescence (UCL) imaging and magnetic resonance imaging (MRI) in vivo. Photothermal therapy was carried out on tumor-bearing mice, after which the toxicity of PTT was evaluated by a blood biochemistry test and histological section analysis. Results: Stable and uniform loading of luminescent nanocomposites on three-dimensional carbon materials is reported for the first time. Based on the mechanism of synthesis, the size of the hybrid particles was adjusted from micrometers to nanometers. External magnetic field-enhanced photothermal therapy with multi-model imaging was accomplished using FeCUPs. Moreover, no cancer recurrence was found during 14 days of recovery without PTT. Conclusions: Hollow carbon spheres, photothermal agents loaded with upconversion nanoparticles inside and magnetic nanoparticles outside were prepared for photothermal therapy. The aggregation of FeCUPs in tumors by the local magnetic field was verified by MRI and UCL imaging, and PTT was enhanced.
Abstract 14092: Reduction of Atherosclerosis in Gucy1a3 Deficient Mice
Authors: Maria Segura Puimedon, Evanthia Mergia, Jaafar Al-Hasani, Redouane Aherrahrou, Jennifer Freyer, Cor de Wit, Doris Kösling, Heribert Schunkert, Jeanette Erdmann, Zouhair Aherrahrou
Journal: Circulation (2015)

Introduction: GUCY1A3 encodes the α1 subunit of the soluble guanylate cyclase (sGC) and has been associated with CAD/MI by genome-wide association studies (GWAS) and in a rare extended family with MI. The α1 and the β1 subunit form the heterodimeric sGC, the nitric oxide (NO) receptor. NO plays an important role in the human cardiovascular system. The aim of our study is to define the role of GUCY1A3 in atherosclerosis using a mouse atherogenic model. Methods: Gucy1a3 KO mice were backcrossed on an Ldlr KO atherogenic background. Four groups were used, i.e. C57BL/6 (WT), Gucy1a3 KO, Ldlr KO and Gucy1a3-Ldlr double KO. All groups were fed high fat diet (HFD) or standard diet (SD) starting at the age of 12-14w and for 20 weeks. Blood pressure was studied at the end of the experiment in the HFD. At the start and end of the diet, lipid metabolism parameters (TC, HDLC, LDLC and TG) were analyzed. Plaque lesion size and collagen and macrophages content were studied. As smooth muscle cells play a key role in atherosclerosis, primary mouse aortic smooth muscle cells (maSMC) were isolated from WT and Gucy1a3 KO animals and subjected to proliferation and migration assays. Results: Blood pressure was studied in HFD animals, showing, as expected, an increase of systolic and diastolic blood pressure in double KO animals when compared to Ldlr KO animals. Regarding lipid levels, no differences were found in the double KO to Ldlr KO comparison under HFD, but a reduction in total cholesterol was found in double KO under SD. For atherosclerosis, a significant reduction in plaque area at the aortic root of double KO when compared to the Ldlr KO animals was demonstrated in both SD and HFD. The reduction was further confirmed in an additional independent experiment under SD. Similarly, a significant reduction of plaque lesion was found in the whole aorta of double KO when compared to the Ldlr KO under HFD. Moreover, a reduction in collagen content was found in double KO mice under HFD when compared to Ldlr KO animals. The migration and proliferation assays show a significant reduction in both migration and proliferation of the Gucy1a3 KO maSMC compared to WT. Conclusions: Our results point to an atherogenic role of Gucy1a3 in mice probably induced via smooth muscle migration and proliferation defects.
Assessment of a Personalized Approach to Predicting Postprandial Glycemic Responses to Food Among Individuals Without Diabetes
Authors: Helena Mendes-Soares, Tali Raveh-Sadka, Shahar Azulay, Kim Edens, Yatir Ben-Shlomo, Yossi Cohen, Tal Ofek, Davidi Bachrach, Josh Stevens, Dorin Colibaseanu, Lihi Segal, Purna Kashyap, Heidi Nelson
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Emerging evidence suggests that postprandial glycemic responses (PPGRs) to food may be influenced by and predicted according to characteristics unique to each individual, including anthropometric and microbiome variables. Interindividual diversity in PPGRs to food requires a personalized approach for the maintenance of healthy glycemic levels. <h3>Objectives</h3> To describe and predict the glycemic responses of individuals to a diverse array of foods using a model that considers the physiology and microbiome of the individual in addition to the characteristics of the foods consumed. <h3>Design, Setting, and Participants</h3> This cohort study using a personalized predictive model enrolled 327 individuals without diabetes from October 11, 2016, to December 13, 2017, in Minnesota and Florida to be part of a study lasting 6 days. The study measured anthropometric variables, described the gut microbial composition, and assessed blood glucose levels every 5 minutes using a continuous glucose monitor. Participants logged their food and activity information for the duration of the study. A predictive model of individualized PPGRs to a diverse array of foods was trained and applied. <h3>Main Outcomes and Measures</h3> Glycemic responses to food consumed over 6 days for each participant. The predictive model of personalized PPGRs considered individual features, including the microbiome, in addition to the features of the foods consumed. <h3>Results</h3> Postprandial response to the same foods varied across 327 individuals (mean [SD] age, 45 [12] years; 78.0% female). A model predicting each individual’s responses to food that considers several individual factors in addition to food features had better overall performance (<i>R</i> = 0.62) than current standard-of-care approaches using nutritional content alone (<i>R</i> = 0.34 for calories and<i>R</i> = 0.40 for carbohydrates) to control postprandial glycemic levels. <h3>Conclusions and Relevance</h3> Across the cohort of adults without diabetes who were examined, a personalized predictive model that considers unique features of the individual, such as clinical characteristics, physiological variables, and the microbiome, in addition to nutrient content was more predictive than current dietary approaches that focus only on the calorie or carbohydrate content of foods. Providing individuals with tools to manage their glycemic responses to food based on personalized predictions of their PPGRs may allow them to maintain their blood glucose levels within limits associated with good health.
Insulin Analogues for Type 2 Diabetes
Authors: Kasia J. Lipska
Journal: JAMA (2019)

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Superior Salvage Treatment with Regimen Containing Sorafenib for Relapse of Acute Myeloid Leukemia with FLT3-ITD after Allo-HSCT
Authors: Li Xuan, Yu Wang, Jia Chen, Erlie Jiang, Li Gao, Bingyi Wu, Lan Deng, Xinquan Liang, Fen Huang, Zhiping Fan, Xiaowen Tang, Jing Sun, Xi Zhang, Ming-Zhe Han, De-Pei Wu, Xiao Jun Huang, Qifa Liu
Journal: Blood (2018)
Efficacy and Safety of Ponatinib in CML and Ph+ ALL Patients in Real-World Clinical Practice: Data from a Belgian Registry
Authors: Timothy Devos, Koen Theunissen, Fleur Samantha Benghiat, Alain Gadisseur, Stef Meers, Dominik Selleslag, Gaëtan Vanstraelen, Pierre Zachée, Marc André, Philippe Lewalle, Mia Janssen, Rik Schots, Koen Van Eygen, Alain Kentos, Marie Lejeune, Agnes Triffet, Inge Vrelust, Carolina Kuipers, Violaine Havelange
Journal: Blood (2018)
Abstract 10643: Important Role of Adventitial Vasa Vasorum in the Pathogensis of Coronary Hyperconstricting Responses After Drug-Eluting Stent Implantation in Pigs in Vivo
Authors: Kensuke Nishimiya, Yasuharu Matsumoto, Jun Takahashi, Tomohiko Shindo, Kenichiro Hanawa, Yuhi Hasebe, Ryuji Tsuburaya, Takashi Shiroto, Kenta Ito, Hatsue Ishibashi-Ueda, Satoshi Yasuda, Hiroaki Shimokawa
Journal: Circulation (2013)

Background: We tested our hypothesis that the adventitial vasa vasorum (VV) is substantially involved in coronary vasomotor dysfunction induced by drug-eluting stents (DES) in pigs in vivo. Methods...
Determination of O-6-methylguanine-DNA methyltransferase by immunochemistry and pyrosequencing as a predictive factor of response to temozolomide in pancreatic neuroendocrine tumors.
Authors: Roberto Escala, L Miguel Navarro, Sofía Del Carmen Martínez, Sandra I Malmierca Gonzalez, Julia Ayuso Martín-Romo, Belén Cigarral García, María García Muñoz, Diego Casado Elía, Beatriz Barrios Collado, Juncal Claros Ampuero, Elena Escalera Martín, Juan J. Cruz-Hernández
Journal: Journal of Clinical Oncology (2019)

195 Background: Temozolomide (TMZ) is an alkylating agent that has shown good results in the treatment of neuroendocrine and central nervous system (CNS) tumors. The loss of O-6-methylguanine-DNA methyltransferase (MGMT) expression by pyrosequencing (PSQ) is a predictive factor of response to treatment with TMZ in high-grade gliomas. However, its predictive value in pancreatic neuroendocrine tumors (pNET) is controversial, and there is no consensus on how to best assess MGMT. The aim was to evaluate the objective response rate in pNET according to the state of MGMT, assessed by PSQ for evaluation of promoter methylation and immunohistochemistry (IHC). Methods: Patients with pNET who were treated with TMZ at the center between 2008 and 2017 were studied retrospectively. Ten patients were included in the study. A deficiency of MGMT was determined by IHC and MGMT promoter methylation by PSQ. For IHC, the cut-off was 10%, defined as negative &lt; 10% of tumor cells positive in the tumor tissue. For the PSQ, the cut-off was 8%, defined as methylated who presented &gt; 8%. Results: A deficiency of MGMT was detected in five patients (50%) by IHC. An MGMT promoter methylation by PSQ was observed in three patients (30%). The IHC results were consistent with PSQ results in only six patients (60%); one patient with methylated MGMT had positive IHC, and three patients had unmethylated MGMT by PSQ unmethylated, IHC negative. PSQ had a high positive predictive value of response because the three patients with MGMT promoter methylation by PSQ presented objective responses (OR). Nevertheless, a low negative predictive power (57%) was observed because three of seven patients with unmethylated MGMT presented OR. Of the five patients with MGMT deficiency by IHC, four (80%) presented OR, suggesting positive predictive value of 80%; however, it also presented a low negative predictive power of 60%. Conclusions: Despite having 100% of the patients with MGMT promoter methylation showing OR in this series, the low negative predictive power suggests that the absence of MGMT deficiency by IHC or MGMT unmethylated by PSQ does not contraindicate the use of TMZ in pNET treatment.
Prognostic value of DNA repair gene based on stratification of gastric cancer.
Authors: Jinjia Chang, Midie Xu, Hui Sun, Wenhua Li, Min Ye, Weiwei Weng, Xiaodong Zhu
Journal: Journal of Clinical Oncology (2019)

12 Background: DNA repair genes can be used as prognostic biomarkers in many types of cancer. We aimed to identify prognostic DNA repair genes in patients with gastric cancer (GC) by systematically bioinformatic approaches using web-based database. Methods: Global gene expression profiles from altogether 1,325 GC patients’ samples from six independent datasets were included in the study. Clustering analysis was performed to screen potentially abnormal DNA repair genes related to the prognosis of GC, followed by unsupervised clustering analysis to identify molecular subtypes of GC. Characteristics and prognosis differences were analyzed among these molecular subtypes, and modular key genes in molecular subtypes were identified based on changes in expression correlation. Multivariate Cox proportional hazard analysis was used to find the independent prognostic gene. Kaplan-Meier method and log-rank test was used to estimate correlations of key DNA repair genes with GC patients’overall survival. Results: There were 57 key genes significantly associated to GC patients’ prognosis, and patients were stratified into three molecular clusters based on their expression profiles, in which patients in Cluster 3 showed the best survival (P &lt; 0.05). After a three-phase training, test and validation process, the expression profile of 13 independent key DNA repair genes were identified can classify the prognostic risk of patients. Compared with patients with low-risk score, patients with high risk score in the training set had shorter overall survival (P &lt; 0.0001). Furthermore, we verified equivalent findings by these key DNA repair genes in the test set (P &lt; 0.0001) and the independent validation set (P = 0.0024). Conclusions: Our results suggest a great potential for the use of DNA repair gene profiling as a powerful marker in prognostication and inform treatment decisions for GC patients.
Serum levels of hyaluronic acid are associated with COPD severity and predict survival
Authors: Eleni Papakonstantinou, Ioannis Bonovolias, Michael Roth, Michael Tamm, Desiree Schumann, Florent Baty, Renaud Louis, Branislava Milenkovic, Wim Boersma, Bram Stieltjes, Konstantinos Kostikas, Francesco Blasi, Joachim G. Aerts, Gernot G.U. Rohde, Alicia Lacoma, Antoni Torres, Tobias Welte, Daiana Stolz
Journal: European Respiratory Journal (2019)

Hyaluronic acid (HA) and its degradation products play an important role in lung pathophysiology and airway remodelling in chronic obstructive pulmonary disease (COPD).We investigated if HA and its degrading enzyme hyaluronidase (HYAL)-1 are associated with COPD severity and outcome.Serum HA was assessed in a discovery cohort of 80 COPD patients at stable state and exacerbations. HA, HYAL-1 and HYAL-1 enzymatic activity were evaluated at stable state, exacerbations and 4 weeks after exacerbations in 638 COPD patients from the PROMISE validation cohort.In the discovery cohort, serum HA was higher at exacerbations compared with the stable state (p=0.015). In the validation cohort, HA was higher at moderate and severe exacerbations than at baseline (p<0.001), and remained higher after 4 weeks (p<0.001). HA was strongly predictive for overall survival since it was associated with time to death (p<0.001) independently of adjusted Charlson score, annual exacerbation rate and BODE (body mass, airflow obstruction, dyspnoea, exercise capacity) index. Serum HYAL-1 was increased at moderate (p=0.004) and severe (p=0.003) exacerbations, but decreased after 4 weeks (p<0.001). HYAL-1 enzymatic activity at stable state was inversely correlated with FEV1 % pred (p=0.034) and survival time (p=0.017).Serum HA is associated with COPD severity and predicts overall survival. Degradation of HA is associated with airflow limitation and impairment of lung function.
Ten-Year Follow-Up of the First Megatrial Testing Thrombolytic Therapy in Patients With Acute Myocardial Infarction
Authors: Maria Grazia Franzosi, Eugenio Santoro, Claudio De Vita, Enrico Geraci, Antonio Lotto, Aldo P. Maggioni, Francesco Mauri, Fausto Rovelli, Luigi Santoro, Luigi Tavazzi, Gianni Tognoni
Journal: Circulation (1998)

We conducted a 10-year follow-up of the 11 712 patients with acute myocardial infarction randomized in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto-1 study, the first large trial assessing thrombolytic therapy.Information on survival at 10 years was obtained for the 93% of all randomized patients through the census offices of their towns of residence. The difference in survival produced by streptokinase and sustained up to 1 year was still significant at 10 years (log-rank test, P=0.02), with the absolute benefit of 19 (95% CI 1 to 37) lives saved per 1000 patients treated. The time dependence of the extent of the benefit was confirmed, as the higher mortality rate reductions found in patients treated earlier were still present at 10 years. In the overall population, most of the benefit was obtained before hospital discharge (RR 0.81, 95% CI 0.72 to 0.90), since no difference in survival between thrombolyzed and control patients discharged alive was found at 10 years (RR 0.98, 95% CI 0.90 to 1.06). However, a slight albeit nonsignificant divergence of the survival curves of patients randomized within the first hour was observed [90 (95% CI 34 to 146) lives saved per 1000 at 10 years versus 72 (95% CI 37 to 107) lives saved at hospital discharge].The benefits of a single intravenous infusion of 1.5 million units of streptokinase in prolonging survival of patients with acute myocardial infarction is sustained up to 10 years, with a still-evident trend in favor of the patients admitted earlier.
Abstract 20911: Outcomes Among Patients With Heart Failure With Reduced Ejection Fraction Undergoing TAVR via the Minimalist Approach vs Conventional Approach
Authors: Muhammad S Panhwar, Toral Patel, Jerry Lipinski, Thomas Ladas, Sandeep Patel, Guilherme Attizzani
Journal: Circulation (2017)

Introduction: Patients who undergo transcatheter aortic valve replacement (TAVR) for severe, symptomatic aortic stenosis frequently have heart failure with reduced ejection fraction (HFrEF). TAVR is usually performed via the conventional approach (CA) in a hybrid OR under general anesthesia with transesophageal echocardiographic guidance. We utilize a cost-effective minimalist approach (MA), whereby TAVR is performed in a standard catheterization lab, with local anesthesia, conscious sedation and a surface echocardiogram, thus reducing invasiveness and the hemodynamic burden of general anesthesia. There are scant data on outcomes of HFrEF patients undergoing TAVR via MA vs CA. Hypothesis: We hypothesize that HFrEF patients undergoing TAVR via the MA approach have similar or better outcomes compared to those done via CA due to the reduced invasiveness and exposure to anesthesia in the MA approach. Methods: We retrospectively assessed 608 patients undergoing transfemoral TAVR at our institution. 174 patients had HFrEF (defined as pre-TAVR EF &lt;50%). 34 patients underwent TAVR via CA while 140 patients underwent TAVR via MA. These patients were followed for 1 year. Primary outcome was survival at 1 year. Secondary outcomes were heart-failure and all-cause readmissions at 1 year. Outcomes were defined per the Valve Academic Research Consortium-2 (VARC-2) consensus statement. Results: Of the 174 patients studied, the median age was 83 years (77-87), Society of Thoracic Surgery score of 8 (5-12), and 67% were male. At 1 year, there were no significant differences in mortality (CA 24% vs MA 26%; P=0.308, Fig 1), heart failure readmissions (CA 29% vs MA 29%; P=0.419), or all-cause readmissions (CA 41% vs MA 36%; P= 0.692). Conclusion: We show that in patients with HFrEF, TAVR via the MA does not have worse outcomes compared to CA. TAVR via MA may be a viable cost-effective alternative in patients at risk for hemodynamic alterations from general anesthesia exposure.
Housing-Based Socioeconomic Status (HOUSES) Index as a Recruitment Tool for Integrating Under-represented Populations in Clinical Research
Authors: Chung-Il Wi, Euijung Ryu, Sunghwan Sohn, Hongfang Liu, Miguel A. Park, Christi A. Patten, Robert J. Pignolo, Richard J. Bram, Young J. Juhn
Journal: Journal of Allergy and Clinical Immunology (2019)
Prognosis of gastric dysplasia after complete resection with endoscopic procedures.
Authors: Junseok Park, Joon Seong Lee, Jin-Oh Kim, Seong Ran Jeon, Hyun Gun Kim, Tae Hee Lee, Jun-Hyung Cho
Journal: Journal of Clinical Oncology (2019)

27 Background: Gastric adenomas are considered premalignant, and some can be interpreted as cancer according to different pathologic guidelines. The dysplastic lesions share histologic characteristics including mucin phenotype that are related prognosis. The prognosis of the lesions has been studied but tends to be researched separately. Moreover, the proposed prognostic factors are mostly derived from the study of surgical specimens, and most of them did not consider the anatomical changes after surgery. Previously researched prognostic factors of gastric dysplasia were evaluated on the recurrence after complete resection with endoscopic procedure. Methods: From 2005 to 2016, 1678 gastric dysplasia were endoscopically removed in Soonchunhyang university hospital, Seoul. They were followed up with endoscopy under a standardized protocol. For the 716 lesions were histologically evaluated including mucin phenotype with immunohistochemical stain of MUC5AC, MUC6, MUC2, and CD10. Recurrence of dysplastic lesions were analyzed for the 688 lesions with at least 1 year’s follow-up. Results: Five-hundred and forty-three malignant lesions including in situ lesions were completely resected with endoscopic procedures. Endoscopic submucosal dissection was performed on 603 lesions and other lesions were removed with endoscopic mucosal resection. Submucosal invasion was on 83 lesions of carcinoma. The mucin phenotype of lesions was immunohistochemically evaluated. During median 40 months of follow-up, there was 89 cases of recurrence (12.9%). Kaplan-Meier analysis of the recurrence-free survival were estimated and the elderly over 65 years of age showed statistical significance (p = 0.039). Conclusions: Completely resected early stage of gastric dysplasia showed relatively low recurrence rate. Previously proposed histologic features did not affect prognosis. However, the age of patient showed statistical significance on recurrence-free survival. Regular surveillance on elderly patients is important to improve the clinical outcome of gastric dysplasia.