tbuckley/cabot-search huggingface dataset:
Prognostic significance of MAGE-A10 and NY-ESO-1 cancer-testis antigen in breast cancer.
Authors: Tanja Badovinac Crnjevic, Jasminka Jakic Razumovic, Giulio C Spagnoli, Paula Podolski, Nera Saric, Martina Basic Koretic, Antonio Juretic
Journal: Journal of Clinical Oncology (2012)

e21126 Background: Cancer testis antigens (CTAs) are expressed in a variety of malignant tumors. In normal adult tissues CTA expression is restricted predominantly to germs cells of the adult testis and placenta. Based on their tumor-restricted expression pattern, CTAs are regarded as valuable targets for cancer immunotherapy. The prognostic significance of CTAs in breast cancer has not been analyzed previously. Methods: To evaluate the potential prognostic significance of two member of this family, MAGE-A10 and NY-ESO-1 antigens, we examined their expression in breast cancer patients who underwent curative surgery at our hospital between 2002 and 2003. Paraffin embedded tumor sections were collected retrospectively from 165 breast cancer patients and immunohistochemical staining for MAGE-A10 and NY-ESO-1 was performed. Impact of MAGE-A10 and NY-ESO-1 expression on disease free survival (DFS) and overall survival (OS) was analyzed by the Kaplan-Meier method using 8-year follow up data. Results: MAGE-A10 expression (score ≥2+) was detected in 105/164 (64%) and NY-ESO-1 expression (score ≥2+) was observed in 14/164 (8.5%) patients. 8-year DFS for MAGE-A10 positive patients was 69% and 73% for MAGE-A10 negative (p=0.452). 8-year OS for MAGE-A10 positive patients was 80% and 90% for MAGE-A10 negative (p=0.134). For NY-ESO-1 positive patients 8-year DFS was 67% and 70% for NY-ESO-1 negative patients (p=0.837). 8-year OS for NY-ESO-1 positive patients was 83% and 84% for NY-ESO-1 negative patients. (p=0.991) Conclusions: To our knowledge this is the first study analyzing prognostic significance CTAs in breast cancer. In this retrospective study we did not show statistically significant correlation between MAGE-A10 and NY-ESO-1 expression and clinical outcome. Additional studies are warranted to determine weather this antigens might have prognostic value in breast cancer patients.
All-Cause and Cause-Specific Mortality Among Major League Baseball Players
Authors: Vy T. Nguyen, Ross D. Zafonte, Kale Z. Kponee-Shovein, Sabrina Paganoni, Marc G. Weisskopf
Journal: JAMA Internal Medicine (2019)

ings suggest an association between disproportionately high SNF discharge rates of vulnerable patients and existing Medicare payment policies.Although the clinical implications of these discharge patterns are unknown, payment policies should be designed with consideration of the potential for such unintended consequences, and any potential consequences should be mitigated by balancing existing payment structures with incentives to provide optimal patient care.
Effect of cryopreservation, type of antigen, and route of administration on in vivo migration of human monocyte-derived dendritic cells.
Authors: Andrew John Nicol, Andrea Tazbirkova, David Macfarlane, Mie Nieda
Journal: Journal of Clinical Oncology (2012)

e13128 Background: Immunotherapy strategies using antigen loaded dendritic cells are being widely utilized in clinical trials for patients with malignancies. To induce effective immune responses against tumors, dendritic cells need to traffic into areas rich in immune effector cells such as T cells and natural killer T cells. In our study, we investigated localization of monocyte derived dendritic cells (MoDC) following different routes of administration, and whether cryopreservation or type of antigen has an impact on MoDC trafficking properties. Methods: Twelve patients with metastatic malignancies received 111 Indium-oxine labeled MoDC pulsed with peptide/protein based antigen or glycolipid antigen, which was administered intradermally, subcutaneously or intravenously, and fresh or after a cryopreservation step. Results: Following intravenous administration, MoDC rapidly distributed into lungs, followed by liver and spleen. In nine of twelve cases intradermally administered MoDC migrated to regional lymph nodes but this was true only for one of nine MoDC injections administered subcutaneously. Cryopreservation and type of antigen did not influence migration capabilities of MoDC. Conclusions: Our data confirms that MoDC trafficking is markedly dependent on the mode of delivery. There is no difference in trafficking of MoDC administered fresh or after cryopreservation and the type of antigen does not have impact on MoDC distribution in the human body.
Impaired expression of ketone metabolizing enzymes in malignant gliomas: Implication for ketogenic diet therapy.
Authors: Howard T. Chang, Lawrence Karl Olson, Kenneth A. Schwartz
Journal: Journal of Clinical Oncology (2012)

2056 Background: Malignant glial cells may have altered expression of mitochondrial enzymes that are key for deriving energy from ketones. The novel strategy of treating malignant gliomas with a ketogenic diet has been tested in animal models with promising results. To evaluate the applicability of these findings to human patients we tested the hypothesis that high grade human gliomas may lack or have decreased expression of mitochondrial enzymes that are important for metabolizing ketones. Methods: We evaluated the expression of 2 key mitochondrial enzymes involved in ketone metabolism in 22 patients (17 males and 5 females, mean age 55,range 30-85) with either glioblastoma (GBM, WHO grade IV) or anaplastic glioma (WHO grade III) (Table). Immunohistochemistry reactions were performed on formalin-fixed paraffin-embedded sections from brain biopsies, using antibodies raised against succinyl CoA: 3-oxoacid CoA transferase (OXCT1) and 3-hydroxybutyrate dehydrogenase 1 (BDH1). Immunoreactivities were graded using a semi-quantitative scale based on the percentage of positive cells: negative (NEG) ≤ 5%; intermediate (INT) 5-20%; and positive (POS) more than 20%. Focal non-neoplastic “normal” brain tissue present within the specimens expressed both enzymes and served as an internal positive control. Results: Either absent or marked decreased expression of OXCT1 and BDH1 were observed in most GBM and anaplastic glioma. Concordance for absent or marked decrease expression of both OXCT1 and BDH1 was observed in 14 of the 17 (82%) GBM’s, and 1 of 5 (20%) anaplastic gliomas. Conclusions: These data support the rationale for a pilot clinical study investigating the therapeutic utility of a ketogenic diet in selected glioma patients. Malignant gliomas with diminished expression of key enzymes (e.g., OXCT1, BDH1) may benefit from the ketogenic diet therapy, whereas those with positive expression of these enzymes likely will not. [Table: see text]
Enrichment of CD146<sup>+</sup> Adipose-Derived Stem Cells in Combination with Articular Cartilage Extracellular Matrix Scaffold Promotes Cartilage Regeneration
Authors: Xu Li, Weimin Guo, Kangkang Zha, Xiaoguang Jing, Mingjie Wang, Yu Zhang, Chunxiang Hao, Shuang Gao, Mingxue Chen, Zhiguo Yuan, Zhenyong Wang, Xueliang Zhang, Shi Shen, Haojiang Li, Bin Zhang, Hai Xian, Yuan Zhang, Xiang Sui, Ling Qin, Jiang Peng, Shuyun Liu, Shibi Lu, Quanyi Guo
Journal: Theranostics (2019)

Heterogeneity of mesenchymal stem cells (MSCs) influences the cell therapy outcome and the application in tissue engineering.Also, the application of subpopulations of MSCs in cartilage regeneration remains poorly characterized.CD146+ MSCs are identified as the natural ancestors of MSCs and the expression of CD146 are indicative of greater pluripotency and self-renewal potential.Here, we sorted a CD146 + subpopulation from adipose-derived mesenchymal stem cells (ADSCs) for cartilage regeneration.Methods: CD146 + ADSCs were sorted using magnetic activated cell sorting (MACS).Cell surface markers, viability, apoptosis and proliferation were evaluated in vitro.The molecular signatures were analyzed by mRNA and protein expression profiling.By intra-articular injections of cells in a rat osteochondral defect model, we assessed the role of the specific subpopulation in cartilage microenvironment.Finally, CD146 + ADSCs were combined with articular cartilage extracellular matrix (ACECM) scaffold for long term (3, 6 months) cartilage repair.Results: The enriched CD146 + ADSCs showed a high expression of stem cell and pericyte markers, good viability, and immune characteristics to avoid allogeneic rejection.Gene and protein expression profiles revealed that the CD146 + ADSCs had different cellular functions especially in regulation inflammation.In a rat model, CD146 + ADSCs showed a better inflammation-modulating property in the early stage of intra-articular injections.Importantly, CD146 + ADSCs exhibited good biocompatibility with the ACECM scaffold and the CD146 + cell-scaffold composites produced less subcutaneous inflammation.The combination of CD146 + ADSCs with ACECM scaffold can promote better cartilage regeneration in the long term.Conclusion: Our data elucidated the function of the CD146 + ADSC subpopulation, established their role in promoting cartilage repair, and highlighted the significance of cell subpopulations as a novel therapeutic for cartilage regeneration.
Multiscale Experimental and Computational Modeling Approaches to Characterize Therapy Delivery to the Heart from an Implantable Epicardial Biomaterial Reservoir
Authors: Reyhaneh Neghabat Shirazi, Shahrin Islam, Fiona M. Weafer, William Whyte, Claudia E. Varela, Agnes Villanyi, William Ronan, Peter McHugh, Ellen T. Roche
Journal: Advanced Healthcare Materials (2019)

Delivery of therapeutic-laden biomaterials to the epicardial surface of the heart presents a promising method of treating a variety of diseased conditions by offering targeted, localized release with limited systemic recirculation and enhanced myocardial tissue uptake. A vast range of biomaterials and therapeutic agents using this approach been investigated. However, the fundamental factors that govern transport of the drug molecules from the biomaterials to the tissue are not well understood. Here, the transport of a drug analog from a biomaterial reservoir to the epicardial surface is characterized using experimental techniques and microscale modeling. Using the experimentally determined parameters, a multiscale model of transport is developed. The model is then used to study the effect of important design parameters such as loading conditions, biomaterial geometry, and orientation relative to the cardiac fibers on drug delivery to the myocardium. The simulations highlight the significance of the cardiac fiber anisotropy as a crucial factor in governing drug distribution on the epicardial surface and limiting factor for penetration into the myocardium. The multiscale model can be useful for rapid iteration of different device concepts and for determination of designs for epicardial drug delivery that may be optimal and most promising for the ultimate therapeutic goal.
Abstract 19736: Photoplethysmography Based Vital Sign Measurements Underestimates Heart Rate in Atrial Fibrillation and Tachycardia
Authors: Anoop N Koshy, Jithin K Sajeev, Kevin Rajakariar, Mark Zureik, Christopher Pham, Michael Wong, Maryann Street, Louise Roberts, Jennifer Cooke, Andrew W Teh
Journal: Circulation (2017)

Background: Photoplethysmography (PPG) based pulse oximeters are routinely used to record Heart Rate (HR) among hospital inpatients not on cardiac monitoring. Although PPG-HR monitoring has shown s...
Efficacy of ramucirumab and docetaxel given either before or after immune checkpoint inhibitors in patients with lung cancers.
Authors: Michael Offin, Chongrui Xu, Harsh Jain, Alex Makhnin, Sara A. Hayes, Andrew J. Plodkowski, Darragh Halpenny, Charles M. Rudin, Mark G. Kris, Alexander E. Drilon, Bob T. Li, Paul K. Paik
Journal: Journal of Clinical Oncology (2019)

9078 Background: Ramucirumab and docetaxel (RamDoce) is a treatment for lung cancer patients after platinum-based therapy regardless of histology, the presence of oncogenic drivers, or prior immune checkpoint inhibition (ICI). Past data has shown a possible differential response to chemotherapy based on ICI exposure. We determined the activity of RamDoce given to patients before or after ICI. Methods: We evaluated patients with stage IV lung cancers who received RamDoce at MSK from 1/2015 - 6/2018. We grouped them based on timing of RamDoce: Before (including never receiving ICI) or After ICI. Ram was given at 8-10mg/kg with Doce 60-75mg/m2 every 2-3 weeks. Demographics, oncogene status and histologic comparisons were done with Mann-Whitney and Fisher’s exact tests. Time to treatment discontinuation (TTD) and overall survival (OS), were compared by long-rank test. Results: 194 patients received RamDoce: 78 Before and 116 After ICI. Median line of therapy for RamDoce in both cohorts was 3. Demographics in the Before and After ICI respectively included: 45 vs 53 female (p = 0.56), 50 vs 96 ever-smokers (p = 0.004), 59 vs 64 years old (p = 0.003), 73 vs 103 adenocarcinoma (p = 0.30). 83% (64/77) of patients with available tissue were PD-L1 negative. TMB was similar between cohorts (7.8 vs 6.1 mut/Mb, p = 0.68). Before ICI had a greater proportion of oncogenes present (64% vs 47%, p = 0.02). Combining Cohorts, TTD for EGFR-mutant (n = 41) and KRAS-mutant (n = 45) lung cancers was 4.0 and 3.9 months respectively vs 2.3 months for EGFR/KRAS-WT (p = 0.051). There was no difference in TTD for adenocarcinoma (n = 176) vs squamous cancers (n = 15, 2.6 vs. 3.1 months respectively; HR 0.8, 95% CI 0.4-1.7, p = 0.51). We saw no difference in TTD between Before (1.5 months) and After ICI (3.0 months, HR 0.88, 95% CI 0.7-1.2, p = 0.39). There was no difference in OS: Before ICI (1.6 years) and After ICI (2.0 years; HR 1.1, 95% CI 0.8-1.5, p = 0.49). Conclusions: There was no difference in TTD or OS for RamDoce when given before or after ICI. There was a trend toward prolonged benefit from RamDoce in EGFR/KRAS-mutant lung cancers. Data on the efficacy of RamDoce in oncogene-driven groups can help guide care and serve as a benchmark for new drug evaluations.
The Rise of Citizen Science in Health and Biomedical Research
Authors: Andrea Wiggins, John Wilbanks
Journal: The American Journal of Bioethics (2019)

Citizen science models of public participation in scientific research represent a growing area of opportunity for health and biomedical research, as well as new impetus for more collaborative forms of engagement in large-scale research. However, this also surfaces a variety of ethical issues that both fall outside of and build upon the standard human subjects concerns in bioethics. This article provides background on citizen science, examples of current projects in the field, and discussion of established and emerging ethical issues for citizen science in health and biomedical research.
Abstract 19935: MicroRNA-21 Regulates Transforming Growth Factor Beta-1 Release From Platelets: A Novel Mechanism for the Anti-Fibrotic Effects of MicroRNA-21 Inhibition
Authors: Temo Barwari, Seda Eminaga, Paul C Armstrong, Melissa V Chan, Ruifang Lu, Javier Barallobre-Barreiro, Xiaoke Yin, Raimund Pechlaner, Sarah R Langley, Anna Zampetaki, Peter Santer, Timothy D Warner, Stefan Kiechl, Johann Willeit, Ajay M Shah, Manuel Mayr
Journal: Circulation (2017)

Introduction: Fibrosis is a major contributor to cardiac disease. No specific anti-fibrotic therapy is currently available. MicroRNA-21 (miR-21) has been implicated as a regulator of fibrosis with ...
Au Hollow Nanorods-Chimeric Peptide Nanocarrier for NIR-II Photothermal Therapy and Real-time Apoptosis Imaging for Tumor Theranostics
Authors: Weiyun Zhang, Kai Cai, Xuyu Li, Jin Zhang, Zhaoyu Ma, Mohamed F Foda, Yongli Mu, Xinxin Dai, Heyou Han
Journal: Theranostics (2019)

The strategy that combines photodynamic therapy (PDT) and photothermal therapy (PTT) is widely used to achieve strong antitumor efficiency.Since light in the NIR-II window possesses ideal penetration ability, developing NIR-II PTT and NIR-II light triggered photosensitizer release for combined PDT and PTT is very promising in nanomedicine.Methods: We develop a novel nanocarrier (termed AuHNRs-DTPP) by conjugating photosensitizer contained chimeric peptide (DTPP) to Au hollow nanorods (AuHNRs).AuHNRs was obtained by a Te-templated method with the assistance of L-cysteine.The chimeric peptide PpIX-PEG8-GGK(TPP)GRDEVDGC (DTPP) was obtained through a solid-phase peptide synthesis (SPPS) method.Results: Under the 1064 nm laser irradiation, the nanocarrier can accumulate heat quickly for efficient PTT, and then release activated photosensitizer for real-time apoptosis imaging.Thereafter, supplementary PDT can be conducted to kill tumor cells survived from the PTT, and meanwhile the normal tissue can be protected from photo-toxicity.Conclusion: This designed AuHNRs-DTPP nanocarrier with remarkable therapy effect, real-time apoptosis imaging ability and reduced skin damage is of great potential in nanomedicine application.
Fatal Anti-Ma2 Encephalitis Related to Treatment of Malignant Pleural Mesothelioma With a Combination of Anti-Programmed Death 1 and Anti–Cytotoxic T-Lymphocyte Associated Protein 4 Antibodies
Authors: Pauline Du Rusquec, Arnaud Peyre, Frederique Toulgoat, Jerome Honnorat, Judith Raimbourg
Journal: Journal of Thoracic Oncology (2019)
Systematic Review and Meta-analysis of the Impact of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) on Cytological Diagnosis and Thyroid Cancer Prevalence
Authors: Darin Ruanpeng, Wisit Cheungpasitporn, Charat Thongprayoon, James V. Hennessey, Rupendra T. Shrestha
Journal: Endocrine Pathology (2019)
Neck swelling and enlarged tonsils
Authors: Charn Gill, Max Sallis Osborne, Lisha McClelland
Journal: BMJ (2019)

An 18 year old man presented with a seven day history of gradually worsening throat pain, malaise, vomiting, neck swelling, odynophagia, and pyrexia. He had no history of weight loss, foreign travel, or night sweats; no notable medical history; and he was not a smoker. Examination revealed bilateral tender swellings in the upper jugular node region that became more obvious on rotation of the neck. He spoke with …
High-Throughput Analysis of Ovarian Cycle Disruption by Mixtures of Aromatase Inhibitors
Authors: Frederic Y. Bois, Nazanin Golbamaki-Bakhtyari, Simona Kovarich, Cleo Tebby, Henry A. Gabb, Emmanuel Lemazurier
Journal: Environmental Health Perspectives (2017)

Background: Combining computational toxicology with ExpoCast exposure estimates and ToxCast™ assay data gives us access to predictions of human health risks stemming from exposures to chemical mixtures. Objectives: We explored, through mathematical modeling and simulations, the size of potential effects of random mixtures of aromatase inhibitors on the dynamics of women's menstrual cycles. Methods: We simulated random exposures to millions of potential mixtures of 86 aromatase inhibitors. A pharmacokinetic model of intake and disposition of the chemicals predicted their internal concentration as a function of time (up to 2 y). A ToxCast™ aromatase assay provided concentration–inhibition relationships for each chemical. The resulting total aromatase inhibition was input to a mathematical model of the hormonal hypothalamus–pituitary–ovarian control of ovulation in women. Results: Above 10% inhibition of estradiol synthesis by aromatase inhibitors, noticeable (eventually reversible) effects on ovulation were predicted. Exposures to individual chemicals never led to such effects. In our best estimate, ∼10% of the combined exposures simulated had mild to catastrophic impacts on ovulation. A lower bound on that figure, obtained using an optimistic exposure scenario, was 0.3%. Conclusions: These results demonstrate the possibility to predict large-scale mixture effects for endocrine disrupters with a predictive toxicology approach that is suitable for high-throughput ranking and risk assessment. The size of the effects predicted is consistent with an increased risk of infertility in women from everyday exposures to our chemical environment. https://doi.org/10.1289/EHP742
Targeting cell membrane HDM2: A novel therapeutic approach for acute myeloid leukemia
Authors: Huafeng Wang, Dandan Zhao, Le Xuan Nguyen, Herman Wu, Ling Li, Dan Dong, Estelle Troadec, Yinghui Zhu, Dinh Hoa Hoang, Anthony S. Stein, Monzr Al Malki, Ibrahim Aldoss, Allen Lin, Lucy Y. Ghoda, Tinisha McDonald, Flavia Pichiorri, Nadia Carlesso, Ya-Huei Kuo, Bin Zhang, Jie Jin, Guido Marcucci
Journal: Leukemia (2019)
Predictive value of VEGF gene polymorphisms in metastatic colorectal cancer patients treated with a bevacizumab-based chemotherapy.
Authors: Paola Ulivi, Giorgia Marisi, Emanuela Scarpi, Alessandro Passardi, Angela Ragazzini, Giovanni Luca Frassineti, Wainer Zoli, Martina Valgiusti, Oriana Nanni, Daniele Calistri, Fabio Casacci, Dino Amadori
Journal: Journal of Clinical Oncology (2013)

e14512 Background: Bevacizumab (B) + chemotherapy (CT) is a common choice for first-line treatment of metastatic colorectal cancer (mCRC). However, molecular predictors of B efficacy have still not been identified. In this study we verified the role of specific VEGF polymorphisms as predictive markers of the efficacy of B in mCRC patients. Methods: One hundred and forty-nine patients enrolled onto the phase III prospective multicentric randomized “Italian Trial in Advanced Colorectal Cancer (ITACa)” trial were considered for this study. Seventy-four patients received FOLFIRI or FOLFOX plus B and 75 patients received only CT. A peripheral blood sample was collected from each patients and submitted to genomic DNA extraction. Five single nucleotide polymorphisms (SNPs) were analyzed by direct sequencing: VEGF -2578 C/A, -1498 C/T, -1154 G/A, -634 G/C, +936 C/T. All candidate genotypes were evaluated for a potential correlation with objective response rate (ORR) (Chi-square test). Results: In the B-treated group, the presence of VEGF -2578 AA, -634 GG or -1498 CC polymorphisms was associated with a better ORR compared to the other genotypes. In particular, of the 17 patients carrying the VEGF -2578 AA genotype, 14 (82.4%) showed a response, whereas only 30 (54.6%) of the 55 patients carrying -2578 CC or CA responded to therapy (p=0.05). Similarly, of 30 patients with VEGF -634 GG, 23 (76.7%) responded to therapy, whereas only 21 (50%) of the 42 patients with VEGF -634 GC or CC were responders (p=0.03). Moreover, 13 (81.3%) of the 16 patients carrying VEGF -1498 CC were responders, whereas of the 56 patients with VEGF -1498 CT or TT, only 31 (55.4%) showed a response (p=0.07). No differences in terms of ORR were observed in patients receiving only chemotherapy. However, as a result of the low power of the interaction test, the relation between ORR and treatment was very close to statistical significance for VEGF -2578 only (p=0.07). Conclusions: VEGF -2578 C/A seems to be a potential predictive marker for B-based CT in mCRC patients. Further studies on larger case series are now needed to confirm this finding.
Association Between Spending and Survival of Chronic Heart Failure Across Veterans Affairs Medical Centers
Authors: Peter W. Groeneveld, Elina L. Medvedeva, Lorrie Walker, Andrea G. Segal, Diane M. Menno, Andrew J. Epstein
Journal: JAMA Network Open (2019)

The US Department of Veterans Affairs (VA) provides health care to more than 2 000 000 veterans with chronic cardiovascular disease, yet little is known about how expenditures vary across VA Medical Centers (VAMCs), or whether VAMCs with greater health expenditures are associated with better health outcomes.