tbuckley/cabot-search huggingface dataset:
Early Diagnosis of Myocardial Infarction in Patients With a History of Coronary Artery Bypass Grafting
Authors: Luca Koechlin, Jasper Boeddinghaus, Thomas Nestelberger, Desiree Wussler, Joan Walter, F. Javier Martin-Sanchez, Nicolas Geigy, Dagmar I. Keller, Raphael Twerenbold, Christian Mueller, Tobias Reichlin, Tobias Zimmermann, Mario Meier, Valentina Troester, Jeffrey Huber, Michael Christ, Patrick Badertscher, Karin Wildi, Christian Puelacher, Jeanne du Fay de Lavallaz, Maria Rubini Giménez, Ivo Strebel, Nikola Kozhuharov, Danielle M. Gualandro, Eliska Potlukova, Katharina Rentsch, Òscar Miró, Carolina Fuenzalida, Samyut Shrestha, Damian Kawecki, Beata Morawiec, Piotr Munzk, Tobias Breidthardt, Dayana Flores, Michael Freese, Claudia Stelzig, Caroline Kulangara, Kathrin Meissner, Gregor Fahrni, Eleni Michou, Stefan Osswald, Raban Jeger, Christoph Kaiser, Beatriz López, Sofia Calderón, Esther Rodriguez Adrada, Eva Ganovská, Jiri Parenica, Arnold von Eckardstein, Isabel Campodarve, Joachim Gea, Oliver Reuthebuch, Martin Grapow, Friedrich Eckstein
Journal: Journal of the American College of Cardiology (2019)
Abstract 16882: Temporal Changes in the Peripheral Blood Mononuclear Cell Populations After Acute Myocardial Infarction and Prediction of Improvement in Left Ventricular Function in the Cardiovascular Cell Therapy Research Network (CCTRN) TIME and Late-TIME Trials
Authors: Micheline T Resende, Amir Gahremanpour, Emerson C Perin, Lourdes I Chacon, Luiz C Sampaio, Lem Moye, James T Willerson, Doris A Taylor
Journal: Circulation (2018)

Background: Despite many cell-mediated attempts to promote myocardial repair after myocardial infarction (MI), no cell treatments are currently available. Instead, cell therapy clinical results remain mixed. We hypothesized that by evaluating changes in circulating cells in improvers and non-improvers in an MI cell therapy study, we could identify cells associated with repair that might be candidates for future cell therapy studies. Methods: In this study, peripheral blood (PB) was evaluated by flow cytometry at baseline and days 1, 30, 90 and 180 after bone marrow mononuclear cell (BMMNC) or placebo therapy from 207 consented patients in the CCTRN TIME (n=120) and Late-TIME (n=87) studies. A linear mixed model was used to determine changes over time in cell frequency. Multiple regression and discriminatory analyses were used to identify if changes in circulating cells predict changes in left ventricular ejection fraction (LVEF). Results: Changes in circulating cells were observed independent of treatment group. In TIME, a progressive decrease of CD11b+ cells started at day 30 (91.69±4.57 vs. 93.23±3.97%, p&lt;0.05) and CD14+ cells began at day 90 (73.53±10.82 vs. 79.17±10.97%, p&lt;0.05) compared to baseline. In Late-TIME, there was an increase in CD11b+ (94.01±3.82 vs. 92.81±3.98%, p&lt;0.05) and CD14+ (81.70±6.64 vs. 77.94±9.29%, p&lt;0.05) cells at day 1 when compared to baseline followed by a progressive decrease in the follow-up visits. A progressive decline in CXCR4+ cells started at day 30 in TIME (35.39 ±14.81 vs. 42.86±13.83%, p&lt;0.05) and at day 1 in Late-TIME (42.81±14.33 vs. 47.74±15.13%, p&lt;0.05). In TIME, a decrease of CXCR4+ cells at day 90 was a negative predictor of changes in LVEF from baseline to six months. Conclusion: Although multiple cell frequencies changed after treatment, only one cell frequency predicted changes in LVEF from baseline to six months. A significant reduction in CXCR4+ circulatory cells at day 90 after treatment is associated with improvement in LVEF. Further studies will be necessary to confirm the changes in circulatory cells and its impact on the regenerative capacity of patients with AMI.
Patterns of Surveillance Advanced Imaging and Serum Tumor Biomarker Testing Following Launch of the Choosing Wisely Initiative
Authors: Randy C. Miles, Christoph I. Lee, Qin Sun, Aasthaa Bansal, Gary H. Lyman, Jennifer M. Specht, Catherine R. Fedorenko, Mikael Anne Greenwood-Hickman, Scott D. Ramsey, Janie M. Lee
Journal: Journal of the National Comprehensive Cancer Network (2019)

The purpose of this study was to assess advanced imaging (bone scan, CT, or PET/CT) and serum tumor biomarker use in asymptomatic breast cancer survivors during the surveillance period.Cancer registry records for 2,923 women diagnosed with primary breast cancer in Washington State between January 1, 2007, and December 31, 2014, were linked with claims data from 2 regional commercial insurance plans. Clinical data including demographic and tumor characteristics were collected. Evaluation and management codes from claims data were used to determine advanced imaging and serum tumor biomarker testing during the peridiagnostic and surveillance phases of care. Multivariable logistic regression models were used to identify clinical factors and patterns of peridiagnostic imaging and biomarker testing associated with surveillance advanced imaging.Of 2,923 eligible women, 16.5% (n=480) underwent surveillance advanced imaging and 31.8% (n=930) received surveillance serum tumor biomarker testing. Compared with women diagnosed before the launch of the Choosing Wisely campaign in 2012, later diagnosis was associated with lower use of surveillance advanced imaging (odds ratio [OR], 0.68; 95% CI, 0.52-0.89). Factors significantly associated with use of surveillance advanced imaging included increasing disease stage (stage III: OR, 3.65; 95% CI, 2.48-5.38), peridiagnostic advanced imaging use (OR, 1.76; 95% CI, 1.33-2.31), and peridiagnostic serum tumor biomarker testing (OR, 1.35; 95% CI, 1.01-1.80).Although use of surveillance advanced imaging in asymptomatic breast cancer survivors has declined since the launch of the Choosing Wisely campaign, frequent use of surveillance serum tumor biomarker testing remains prevalent, representing a potential target for further efforts to reduce low-value practices.
Abstract 15425: Distance to Percutaneous Coronary Intervention Care Impacts Treatment for ST-Elevation Myocardial Infarction
Authors: Matthew W Watkins, Samip Vasaiwala, Peter N Ver Lee, John E Jayne, Richard A Boss, James M Flynn, David Butzel, Prospero Gogo, Thomas J Ryan, John F Robb, Yi-Ling Huang, David J Malenka
Journal: Circulation (2017)

Hypothesis: Distance to a PCI hospital will impact the treatment and outcome of patients presenting with ST elevation myocardial infarction (STEMI). Methods: We studied all STEMI patients treated w...
Preliminary results for the combination of docetaxel, oxaliplatin and capecitabine as a first-line treatment for metastatic oesophagogastric cancer
Authors: S. Viteri, J. Rodríguez, M. González Cao, J. De La Cámara, A. Chopitea, A. Viudez, C. Reyna, C. Olier, J. García-Foncillas
Journal: Journal of Clinical Oncology (2006)

14076 Background: Chemotherapy remains the main treatment option for metastatic oesopagogastric cancer (MOC) patients (Pts). First-line regimens have proved a slight but significant increase in quality of life and survival, but a standard regimen has not been defined yet. Several new drugs, as Docetaxel (D), Oxaliplatin (O) and Capecitabine (C) have demostrated activity in MOC. They have shown synergy in preclinical models and activity in previous phase II trials. The purpose of our study is to asses activity and feasibility of the combination of D, O and C as first-line chemotherapy in MOC patients. Methods: MOC patients, with good ECOG performance status and chemonaive are eligible. Pts receive D 60 mg/m 2 day 1, O 85 mg/m 2 day 1 and oral C 650mg/m 2 bid d1–14 every 3 weeks. Primary endpoints are response according to WHO criteria and toxiciy assesment according to NCI.CTCAE v3.0. Results: From November 2004 to December 2005, 17 Pts have been enrolled. Median ECOG PS is 1 (0–2) M/F:9/8. Median age is 57 years (38–68) Primary tumor are gastric carcinomas (82%) and lower oesofagus carcinomas (18%). Metastatic sites included peritoneum 58%, liver 23% and lung 23%. Median number of cycles is 5 (1–7) Treatment is well tolerated with no toxic deaths. NCI grade 3–4 toxicities include 2 Pts (11.8%) with grade 4 neutropenia and one of them developed septic shock; 2 Pts with grade 3 asthenia, 1 Pt with grade 3 vomiting and 1 patient with grade 3 neurotoxicity. Main NCI grade 2 toxicities are dhiarrea (35.3%) and neurotoxicity (23.5%). 13 Pts have been evaluated for response until now: 9 Pts have a confirmed Partial Response (69.2%) and 2 of them underwent salvage surgery; 3 Pts have Stabilized Disease and 1 Pt Progression Disease. Median time to progression and median overall survival have not been reached yet and the study is still ongoing. Conclusions: The combination of D, O and C at the dosses and schedule used in this trial is effective in MOC with a manageable toxicity profile No significant financial relationships to disclose.
Neoadjuvant carboplatin/paclitaxel with concurrent radiotherapy followed by surgery for esophageal/gastroesophageal junction adenocarcinoma: A single-institution experience.
Authors: Timothy Alan Platz, Steven J. Nurkin, Mei Ka Fong, Usha Malhotra, Saikrishna S. Yendamuri, Hector R. Nava, Graham Walter Warren, Kilian Salerno May
Journal: Journal of Clinical Oncology (2012)

e14712 Background: Esophageal and gastroesophageal junction (GEJ) adenocarcinoma is increasingly treated with trimodality therapy. We present our experience using carboplatin/paclitaxel and radiotherapy followed by surgery. Methods: Consecutive patients with distal esophageal/GEJ adenocarcinoma (≥T2 or N+) treated from July 2010 to October 2011 were identified. All patients received neoadjuvant carboplatin/paclitaxel with concurrent radiotherapy (CRT) to 50.4 Gy using an IMRT technique and then Ivor Lewis esophagogastrectomy. PET/CT was performed prior to and after CRT. Patient/treatment characteristics and tumor response were analyzed. Results: Over this timeframe,17 patients completed trimodality therapy using this regimen. All were male with a median age of 59 years (45-72). All tumors were grade 2-3 adenocarcinoma with mean tumor length of 4.4 cm (1-9). A median of 6 cycles (5-9) neoadjuvant carboplatin/paclitaxel were administered, 3 patients received additional adjuvant therapy. Average time from diagnosis to CRT completion was 78 days (44-141) and from CRT end to surgery was 62 days (35-92). Neoadjuvant CRT was well tolerated with mean weight loss of 3.5 kg. All pts had R0 resections. No anastomotic leaks or perioperative mortality occurred. Mean hospital stay was 13.6 days (8-28). Pathologic complete response (pCR) was seen in 41% of patients, microscopic residual disease (isolated tumor cells or &lt;2mm) in 29%, and macroscopic residual disease remained in 29%. Mean SUV reduction was 41% (0-100). Of 12 patients with ≥35% SUV decrease, 50% had pCR and 25% had microscopic residual disease. Three patients had signet ring features; of these 2 had no SUV reduction and all had gross residual disease, including the only patient with pN disease. Conclusions: Trimodality therapyutilizing carboplatin/paclitaxel and CRT to 50.4 Gy IMRT followed by Ivor Lewis esophagogastrectomy was well tolerated and resulted in significant pathologic complete response or minimal residual disease. Further investigation of predictive factors for response is needed to best tailor therapy in the management of esophageal/GEJ adenocarcinoma.
Challenges to the social motivation theory of autism: The dangers of counteracting an imprecise theory with even more imprecision
Authors: Mirko Uljarević, Giacomo Vivanti, Susan R. Leekam, Antonio Y. Hardan
Journal: Behavioral and Brain Sciences (2019)

Abstract The arguments offered by Jaswal &amp; Akhtar to counter the social motivation theory (SMT) do not appear to be directly related to the SMT tenets and predictions, seem to not be empirically testable, and are inconsistent with empirical evidence. To evaluate the merits and shortcomings of the SMT and identify scientifically testable alternatives, advances are needed on the conceptualization and operationalization of social motivation across diagnostic boundaries.
Ratiometric delivery of doxorubicin and berberine by liposome enables superior therapeutic index than DoxilⓇ
Authors: Ruoshi Zhang, Yingxi Zhang, Yue Zhang, Xin Wang, Xuanming Gao, Yuyan Liu, Xuanbo Zhang, Zhonggui He, Dun Wang, Yongjun Wang
Journal: Asian Journal of Pharmaceutical Sciences (2019)

Although the appearance of Doxil alleviated the cardiotoxicity of DOX, the progression-free survival of patients was not prolonged compared with traditional medication regimens, and side effects such as hand-foot syndrome has occurred. In order to solve this dilemma, we have designed a novel co-delivery strategy to construct a co-loaded liposome of berberine (BER) and doxorubicin (DOX), which was called LipoBeDo. The optimal synergistic ratio of the two drugs was screened by cell cytotoxicity experiments in vitro, and the optimal attenuation ratio was further determined by in vivo cardiac H&E staining pathological sections. The optimal combination treatment caused a robust increase in apoptotic cells of 4T1, as compared to drug alone treatment. The prepared co-loaded liposome, LipoBeDo, had high encapsulation efficiency and good stability. The nanoliposome carrier controlled the biological fate of the drugs and maintained a pre-defined optimal ratio in vivo. The LipoBeDo significantly inhibited tumor growth in 4T1 murine mammary carcinoma model compared with Doxil (P < 0.05), and completely overcame the myocardial rupture toxicity caused by Doxil in mice. Our co-loaded liposome delivery platform technology provided a new direction for the clinical treatment of triple-negative breast cancer and the safe application of DOX.
Different Histopathologic Diagnoses in Patients With Clinically Diagnosed Hypertrophic Cardiomyopathy After Surgical Myectomy
Authors: Alaa Alashi, Ria M. Desai, Tamanna Khullar, Kevin Hodges, E. Rene Rodriguez, Carmela Tan, Zoran B. Popovic, Maran Thamilarasan, Per Wierup, Harry M. Lever, Nicholas G. Smedira, Milind Y. Desai
Journal: Circulation (2019)
Differentiation of Rat Mesenchymal Stem Cells toward Osteogenic Lineage on Extracellular Matrix Protein Gradients
Authors: Soraya Rasi Ghaemi, Bahman Delalat, Alex Cavallaro, Agnieszka Mierczynska‐Vasilev, Krasimir Vasilev, Nicolas H. Voelcker
Journal: Advanced Healthcare Materials (2019)

Abstract This report addresses the issue of optimizing extracellular matrix protein density required to support osteogenic lineage differentiation of mesenchymal stem cells (MSCs) by culturing MSCs on surface‐bound density gradients of immobilized collagen type I (COL1) and osteopontin (OPN). A chemical surface gradient is prepared by tailoring the surface chemical composition from high hydroxyl groups to aldehyde groups using a diffusion‐controlled plasma polymerization technique. Osteogenesis on the gradient surface is determined by immunofluorescence staining against Runx2 as an early marker and by staining of calcium phosphate deposits as a late stage differentiation marker. The Runx2 intensity and calcified area increase with increasing COL1 density up to a critical value corresponding to 124.2 ng cm −2 , above which cell attachment and differentiation do not rise further, while this critical value for OPN is 19.0 ng cm −2 . This gradient approach may facilitate the screening of an optimal biomolecule surface density on tissue‐engineered scaffolds, implants, or tissue culture ware to obtain the desired cell response, and may generate opportunities for more cost‐effective regenerative medicine.
Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study
Authors: Esther Conde, Susana Hernandez, Rebeca Martinez, Barbara Angulo, Javier De Castro, Ana Collazo-Lorduy, Beatriz Jimenez, Alfonso Muriel, Jose Luis Mate, Teresa Moran, Ignacio Aranda, Bartomeu Massuti, Federico Rojo, Manuel Domine, Irene Sansano, Felip Garcia, Enriqueta Felip, Nuria Mancheño, Oscar Juan, Julian Sanz, Jose Luis Gonzalez-Larriba, Lidia Atienza-Cuevas, Esperanza Arriola-Arellano, Ihab Abdulkader, Jorge Garcia-Gonzalez, Carmen Camacho, Delvys Rodriguez-Abreu, Cristina Teixido, Noemi Reguart, Ana Gonzalez-Piñeiro, Martin Lazaro-Quintela, Maria Dolores Lozano, Alfonso Gurpide, Javier Gomez-Roman, Marta Lopez-Brea, Lara Pijuan, Marta Salido, Edurne Arriola, Amparo Company, Amelia Insa, Isabel Esteban-Rodriguez, Monica Saiz, Eider Azkona, Ramiro Alvarez, Angel Artal, Maria Luz Plaza, David Aguiar, Ana Belen Enguita, Amparo Benito, Luis Paz-Ares, Pilar Garrido, Fernando Lopez-Rios
Journal: Journal of Thoracic Oncology (2019)

IntroductionThe ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data.MethodsA total of 43 ROS1 FISH–positive and 193 ROS1 FISH–negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific).ResultsAn H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively).ConclusionsThe new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm.
De-bugging the system: could antibiotics improve liver transplant outcomes?
Authors: Jonathan S. Bromberg, Joseph R. Scalea, Emmanuel F. Mongodin
Journal: Journal of Clinical Investigation (2019)

Organ transplantation is now a preferred treatment for end-stage organ failure. Among the challenges for ensuring excellent clinical outcomes for transplant recipients is good initial allograft function at the time of organ implantation. This is determined in part by the functional status of the donor and donor organ, functional status of the recipient, and conduct of the operative procedure. Despite optimization of these variables, organ transplantation is still often plagued by substantial initial dysfunction, variably referred to as slow or delayed graft function, or in the most extreme cases, primary graft nonfunction necessitating urgent regrafting. In this issue of the JCI, Nakamura, Kageyama, Ito, Hirao, and colleagues investigate a potential role for the recipient's microbiome in determining graft function after liver transplantation and demonstrate the benefits of antibiotic pretreatment in both a mouse model and in human patients.
Metabolic intervention targeting 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) using a structure-based design.
Authors: Lars Ährlund-Richter, Katarina Färnegårdh, Elisee Wiita, Mattias Jönsson, Carina Norström, Jessica Martinsson, Kenth Hallberg, Rune Ringom, Hakan Mellstedt
Journal: Journal of Clinical Oncology (2012)

e13518 Background: By producing fructose-2,6-bisphosphate, PFKFB3 functions as an activator of anaerobic glycolysis. PFKFB3 is both over expressed and over activated in many of the types of human cancer. Specific inhibition of the PFKFB3 enzyme results in a reduction in metabolism and cell growth in oxygen-deficient cancer environments. Methods: High-throughput screening. Medicinal Chemistry. Structure-Based Drug Design, X-ray Crystallography. NMR. Isothermal Calorimetry. Dynamic Light Scatttering. ADME. Results: A high-throughput screening of 50.000 selected compounds, by means of a biochemical assay, generated 105 hits including both ATP-and non-ATP competitive hits as identified by NMR binding experiments. The latter type was prioritized and two hits with a similar “ring-linker-ring structure” were selected for further expansions. Interestingly, although structurally similar, the two hits were found by means of X-ray crystallography to exhibit different binding modes within the fructose pocket. Based on their respective binding mode, two chemical series were developed displaying different ADME properties and PFKFB isoenzyme selectivity. Calorimetry verified a reversible strong enthalpy driven, direct binding for both chemical series. A third chemical series was developed towards yet another unoccupied binding pocket within the fructose-site, yielding a 5-fold increase in potency. Strong interactions within the new pocket were confirmed using X-ray crystallography. Our PFKFB3 inhibitors were shown to reduce tumor cell growth in vitro and to exhibit combinatory effects with Cisplatin. Conclusions: We have targeted the fructose-binding pocket of PFKFB3, developed compounds with nM binding potency and have gained a detailed understanding of SAR via structural information. The structure-based analysis has provided a good understanding of the molecular interactions, which is important for further biological/clinical positioning: e.g., combination with chemotherapy, optimization of PK properties and proof of principle in vivo.
Non-prescription antibiotic use is “public health problem” in US, finds study
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Use of antibiotics that have not been prescribed occurs throughout the US population and is a public health problem, but research into the effects on antimicrobial resistance is lacking, a study concludes.1

Researchers analysed 31 studies conducted in the US between 2000 and 2019 that reported non-prescription use of antibiotics and influencing factors. They found that the prevalence of use varied from …
The good, the bad, and the ugly: hyperprogression in cancer patients following immune checkpoint therapy
Authors: Erich Sabio, Timothy A. Chan
Journal: Genome Medicine (2019)

Immune checkpoint blockade therapy can elicit robust and durable responses in a variety of cancer types. While many patients do not respond, recent reports highlight a distinct group of patients whose tumors undergo rapid growth, leading to progressive disease and poor outcome. In this perspective, we synthesize and summarize some important issues surrounding hyperprogression, defining characteristics, prognostic implications, and controversies.