tbuckley/cabot-search huggingface dataset:
Relationship of Ki67 to tumor size and lymph node metastasis in breast cancer.
Authors: Ioana Bonta, Dacian Bonta, Michelle Marie Loch, Ann Eapen, Rita A. Blanchard
Journal: Journal of Clinical Oncology (2012)

e21076 Background: Ki67, a tumor proliferation marker, has demonstrated usefulness in breast cancer prognosis. Prior work with BrdU labeling for cell proliferation in breast cancer has not settled the question whether cell proliferation labeling is independent of other tumor features like tumor size and presence of axillary metastases, see Rew (1992) vs. Thor et al (1999). Methods: We analyzed retrospectively our database of 379 patients for correlation between the and tumor size, presence of axillary lymph node metastases and the percentage of Ki67 positve cells. We used linear and parabolic regression to correlate tumor size with the Ki67 index and receiver operator characteristics curve to correlate the presence of axillary lymph node metastases with the Ki67 index. Results: A very weak linear relationship was detected between tumor size and Ki67 index. The R-squared coefficient was 0.03, indicating that tumor size explained only 3% of the variability in measured Ki67 indexes. The ROC analysis, looking at the correlation between Ki67 and lymph node metastasis, yielded an area under the curve (Az) of 0.53. This indicates a very weak correlation. No relationship between axillary lymph node metastasis would yield an Az of 0.5 and a perfect correlation would yield an Az of 1. Conclusions: Tumor size and axillary lymph node metastasis explain less than 10% of observed Ki67 index variability. Therefore, in breast cancer, the prognostic value of Ki67 is additive to that of tumor size and lymph node involvement.
Adverse reactions of direct-acting antiviral agents in HCV patients: Our experience
Authors: D. Padovani, S. Colla, F. Masutti, C. Abazia, K. Parenzan, R. Patti, M.R. Buonocore, D. Macor, V. Lanzillotti, S. Paolo, S.L. Croce
Journal: Journal of Hepatology (2018)
Transcript-indexed ATAC-seq for precision immune profiling
Authors: Ansuman T. Satpathy, Naresha Saligrama, Jason D. Buenrostro, Yuning Wei, Beijing Wu, Adam J. Rubin, Jeffrey M. Granja, Caleb A. Lareau, Rui Li, Yanyan Qi, Kevin R. Parker, Maxwell R. Mumbach, William S. Serratelli, David G. Gennert, Alicia N. Schep, M. Ryan Corces, Michael S. Khodadoust, Youn H. Kim, Paul A. Khavari, William J. Greenleaf, Mark M. Davis, Howard Y. Chang
Journal: Nature Medicine (2018)
Fibroblast Growth Factor 15–Dependent and Bile Acid–Independent Promotion of Liver Regeneration in Mice
Authors: Bo Kong, Runbin Sun, Mingxing Huang, Monica D. Chow, Xiao‐Bo Zhong, Wen Xie, Yi‐Horng Lee, Grace L. Guo
Journal: Hepatology (2018)

The role of intestine‐derived factors in promoting liver regeneration after partial hepatectomy (PHx) are not entirely known, but bile acids (BAs) and fibroblast growth factor 15 (Fgf15) that is highly expressed in the mouse ileum could promote hepatocyte proliferation. Fgf15 strongly suppresses the synthesis of BAs, and emerging evidence indicates that Fgf15 is important for liver regeneration. The mechanisms by which Fgf15 promotes liver regeneration are unclear, but Fgf15 may do so indirectly by reducing BA levels and/or directly by promoting cell proliferation. However, it remains undetermined whether these two mechanisms are independent or integrated. In this study, we aimed to clarify these relationships by generating Fgf15 Tet‐Off, transgenic mice ( Fgf15 Tg) that had very low BA levels as a result from overexpressed Fgf15‐mediated suppression of BA synthesis. Compared with wild‐type mice, the Fgf15 Tg mice showed increased hepatocyte proliferation even without surgery, and a further induction of the genes in cell‐cycle progression after PHx. Moreover, overexpression of Fgf15 by adeno‐associated virus (AAV)‐ Fgf15 transduction or treatment with the recombinant Fgf15 protein led to increased cell proliferation in vivo . Furthermore, Fgf15 Tg mice exhibited an earlier and greater activation of mitogen‐activated protein kinase, signal transducer and activator of transcription 3, and NF‐κB signaling pathways in the priming stage, and a disruption of the hippo signaling pathway in the termination stage of liver regeneration. Conclusion: Direct in vivo evidence demonstrates that Fgf15 is critical in stimulating the phases of priming and termination of liver regeneration that are critical for cell survival and liver‐size determination, independent of BA levels. (H epatology 2018; 00:000‐000).
Hepatocyte-specific overexpression of FoxM1 transcription factor leads to spontaneous liver inflammation, fibrosis, and tumorigenesis in mice
Authors: T. Kurahashi, Y. Yoshida, S. Ogura, M. Egawa, K. Furuta, Y. Kamada, S. Kiso, T. Kodama, H. Hikita, R. Sakamori, T. Tatsumi, T. Takehara
Journal: Journal of Hepatology (2018)
The Relationship of Health Insurance and Mortality
Authors: Michael R. Grey
Journal: Annals of Internal Medicine (2018)

Letters17 April 2018The Relationship of Health Insurance and MortalityMichael R. Grey, MD, MPHMichael R. Grey, MD, MPHSaint Francis Hospital and Medical Center, Hartford, Connecticut (M.R.G.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L17-0703 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:C.S. Lewis wrote, “If you look for truth, you may find comfort in the end; if you look for comfort you will not get either comfort or truth—only soft soap and wishful thinking to begin with and, in the end, despair.” Woolhandler and Himmelstein's article (1) is as well-grounded in empirical evidence as we are likely to get and clearly comes out in favor of what both authors have long articulated with passion and reason: the benefits of a single-payer system. Supporters of such a system have not been completely transparent about the simple truth that we ...Reference1. Woolhandler S, Himmelstein DU. The relationship of health insurance and mortality: is lack of insurance deadly? Ann Intern Med. 2017;167:424-31. [PMID: 28655034]. doi:10.7326/M17-1403 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Saint Francis Hospital and Medical Center, Hartford, Connecticut (M.R.G.)Disclaimer: Dr. Grey was an intern in the same program in which Dr. Woolhandler was a junior resident and Dr. Himmelstein was a faculty member.Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L17-0703. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Relationship of Health Insurance and Mortality: Is Lack of Insurance Deadly? Steffie Woolhandler and David U. Himmelstein The Relationship of Health Insurance and Mortality Steffie Woolhandler and David U. Himmelstein Metrics 17 April 2018Volume 168, Issue 8Page: 604-605KeywordsConflicts of interestDisclosureHealth careHealth insuranceMedicareMortalitySoaps ePublished: 17 April 2018 Issue Published: 17 April 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Tumor-secreted Pros1 inhibits macrophage M1 polarization to reduce antitumor immune response
Authors: Eric Ubil, Laura Caskey, Alisha Holtzhausen, Debra Hunter, Charlotte Story, H. Shelton Earp
Journal: Journal of Clinical Investigation (2018)

Tyro3, Axl, Mer (TAM) receptor tyrosine kinases reduce inflammatory, innate immune responses. We demonstrate that tumor-secreted protein S (Pros1), a Mer/Tyro3 ligand, decreased macrophage M1 cytokine expression in vitro and in vivo. In contrast, tumor cells with CRISPR-based deletion of Pros1 failed to inhibit M1 polarization. Tumor cell-associated Pros1 action was abrogated in macrophages from Mer- and Tyro3- but not Axl-KO mice. In addition, several other murine and human tumor cell lines suppressed macrophage M1 cytokine expression induced by IFN-γ and LPS. Investigation of the suppressive pathway demonstrated a role for PTP1b complexing with Mer. Substantiating the role of PTP1b, M1 cytokine suppression was also lost in macrophages from PTP1b-KO mice. Mice bearing Pros1-deficient tumors showed increased innate and adaptive immune infiltration, as well as increased median survival. TAM activation can also inhibit TLR-mediated M1 polarization. Treatment with resiquimod, a TLR7/8 agonist, did not improve survival in mice bearing Pros1-secreting tumors but doubled survival for Pros1-deleted tumors. The tumor-derived Pros1 immune suppressive system, like PD-L1, was cytokine responsive, with IFN-γ inducing Pros1 transcription and secretion. Inhibition of Pros1/TAM interaction represents a potential novel strategy to block tumor-derived immune suppression.
Reevaluating Fasting for Procedural Sedation
Authors: Steven M. Green, Baruch S. Krauss, Keira P. Mason
Journal: JAMA Pediatrics (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Endoscopic full-thickness resection for diagnosis of Hirschsprung’s disease
Authors: Alvaro Martínez-Alcalá, Felipe Martínez-Alcalá García, Klaus Mönkemüller, Helmut Neumann, Felipe Martínez-Alcalá
Journal: Endoscopy (2018)

Endoscopic full-thickness resection (EFTR) is beneficial for treating a variety of conditions of the lower gastrointestinal tract such as early cancers, polyps, and fistulas [1] [2]. Whereas the role of EFTR in the therapy for these conditions has been proven to be effective and safe, there is a paucity of data about its potential utility as a diagnostic intervention in patients with gastrointestinal tract dysmotility disorders [3]
FDA analysis of enrollment of older adults in clinical trials for cancer drug registration: A 10-year experience by the U.S. Food and Drug Administration.
Authors: Harpreet Singh, Bindu Kanapuru, Che Smith, Lola A. Fashoyin-Aje, Adrian Myers, Geoffrey Kim, Richard Pazdur
Journal: Journal of Clinical Oncology (2017)

10009 Background: Older adults are a growing segment of our oncology population, with an expected increase in cancer incidence of 67% from 2010 to 2030 in people age 65 and older. However, older adults have been proportionally underrepresented in clinical trials. We sought to analyze the age-related enrollment of cancer patients onto trials supporting registration of new drugs or new indications approved by the US Food and Drug Administration from 2005 to 2015. Methods: This study involved retrospective analyses of demographic data of cancer patients enrolled onto trials supporting registration from 2005-2015. The data on 224,766 cancer patients supporting 105 drug applications were analyzed according to age distributions of &lt;65, 65-69, 70-74, 75-79, and ≥80 years. The rates of enrollment were compared with the corresponding rates in the US cancer population. The age distributions of the US cancer population were derived from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute for the year 2013 based on the 2010 US Census. Conclusions: Older adults were under-represented in the registration trials of new cancer therapies, especially those over age 75. Various strategies may be needed to evaluate cancer therapies for older adults in prospective clinical trials and to improve cancer care in adults over age 75. These include re-evaluating what may be considered restrictive eligibility criteria so as not to exclude older adults. Incorporating elements from geriatric assessment tools may help identify older adults most likely to benefit from treatment. More detailed labeling information that reflects the clinical experience with older adults could be considered. The FDA encourages drug sponsors as well as clinical trial cooperative groups to devise strategies to recruit patients that are reflective of their intended population. [Table: see text]
Directly acting antiviral HCV therapy is safe and effective in patients with advanced cirrhosis: real world experience from the HCV-TARGET Cohort
Authors: E. Verna, G. Morelli, N. Terrault, A. Lok, J. Lim, A.M. DI Bisceglie, S. Zeuzem, C. Landis, G. Lutchman, M. Hassan, M.P. Manns, M. Vainorius, L. Akushevich, D.R. Nelson, M.W. Fried, R. Reddy
Journal: Journal of Hepatology (2018)
Multimodality reporter gene imaging: Construction strategies and application
Authors: Mengting Li, Yichun Wang, Mei Liu, Xiaoli Lan
Journal: Theranostics (2018)

Molecular imaging has played an important role in the noninvasive exploration of multiple biological processes. Reporter gene imaging is a key part of molecular imaging. By combining with a reporter probe, a reporter protein can induce the accumulation of specific signals that are detectable by an imaging device to provide indirect information of reporter gene expression in living subjects. There are many types of reporter genes and each corresponding imaging technique has its own advantages and drawbacks. Fused reporter genes or single reporter genes with products detectable by multiple imaging modalities can compensate for the disadvantages and potentiate the advantages of each modality. Reporter gene multimodality imaging could be applied to trace implanted cells, monitor gene therapy, assess endogenous molecular events, screen drugs, etc. Although several types of multimodality imaging apparatus and multimodality reporter genes are available, more sophisticated detectors and multimodality reporter gene systems are needed.
Genome-wide association meta-analysis of individuals of European ancestry identifies new loci explaining a substantial fraction of hair color variation and heritability
Authors: Pirro G. Hysi, Ana M. Valdes, Fan Liu, Nicholas A. Furlotte, David M. Evans, Veronique Bataille, Alessia Visconti, Gibran Hemani, George McMahon, Susan M. Ring, George Davey Smith, David L. Duffy, Gu Zhu, Scott D. Gordon, Sarah E. Medland, Bochao D. Lin, Gonneke Willemsen, Jouke Jan Hottenga, Dragana Vuckovic, Giorgia Girotto, Ilaria Gandin, Cinzia Sala, Maria Pina Concas, Marco Brumat, Paolo Gasparini, Daniela Toniolo, Massimiliano Cocca, Antonietta Robino, Seyhan Yazar, Alex W. Hewitt, Yan Chen, Changqing Zeng, Andre G. Uitterlinden, M. Arfan Ikram, Merel A. Hamer, Cornelia M. van Duijn, Tamar Nijsten, David A. Mackey, Mario Falchi, Dorret I. Boomsma, Nicholas G. Martin, David A. Hinds, Manfred Kayser, Timothy D. Spector
Journal: Nature Genetics (2018)
Secukinumab shows high efficacy irrespective of<i>HLA-Cw6</i>status in patients with moderate-to-severe plaque-type psoriasis: SUPREME study
Authors: A. Costanzo, L. Bianchi, M.L. Flori, G. Malara, L. Stingeni, M. Bartezaghi, L. Carraro, G. Castellino
Journal: British Journal of Dermatology (2018)

Understanding genetic variations is important in predicting treatment response and forms the basis for identifying new pharmacogenetic and pharmacogenomic targets for psoriasis treatment. There are limited data on the efficacy of secukinumab in relation to genetic markers.To evaluate the efficacy and safety of secukinumab 300 mg in HLA-Cw6-positive (Cw6-POS) and HLA-Cw6-negative (Cw6-NEG) patients with moderate-to-severe chronic plaque-type psoriasis.SUPREME was a 24-week, phase IIIb study with an extension period up to 72 weeks. Primary end point was Psoriasis Area Severity Index (PASI) 90 response rate after 16 weeks.In total, 434 patients were recruited: 185 (42·6%) were Cw6-POS and 246 (56·7%) were Cw6-NEG (three not assessed). Mean ± SD age was 45·2 ± 13·2 years (Cw6-POS 42·7 ± 13·1; Cw6-NEG 47·2 ± 12·9). The baseline PASI score was comparable between the cohorts [Cw6-POS 20·7 ± 8·99; Cw6-NEG 21·5 ± 9·99 (P = 0·777)]. At week 16, PASI 90 was achieved in 80·4% of Cw6-POS and 79·7% of Cw6-NEG patients (difference 0·76; 95% confidence interval -7·04 to 8·23). No differences in absolute PASI at week 16 (Cw6-POS 1·36 ± 3·58; Cw6-NEG 1·18 ± 2·29) were observed. The overall safety profile of secukinumab was consistent with that previously reported. No statistically significant difference was detected in the rate of treatment-emergent adverse events [Cw6-POS 42·7%; Cw6-NEG 49·6% (P = 0·295)]. A high PASI 90 response was achieved with secukinumab with a fast reduction in absolute PASI.Determination of HLA-Cw6 status for secukinumab therapy is unnecessary, as it is highly effective regardless of HLA-Cw6 status.
Estimating 1- and 5-year relative survival trends in colorectal cancer (CRC) in the United States: 2004 to 2014.
Authors: Hannah Crooke, Monica Kobayashi, Brian Mitchell, Esmond Nwokeji, Melissa Laurie, Shital Kamble, Mike McKenna, Ashiq Masood, Beata Korytowsky
Journal: Journal of Clinical Oncology (2018)

587 Background: Patient survival is impacted by several factors, one of which is stage at diagnosis. From 1976 to 2014, CRC death rate in the United States (US) declined by 51%. This retrospective study was conducted using US Surveillance, Epidemiology and End Results (SEER) data to evaluate 1- and 5-year relative survival for patients with CRC by American Joint Committee on Cancer (AJCC) stage, age and sex at diagnosis. Methods: The study included adults (age ≥20 years) in the SEER-18 registry diagnosed with CRC in 2004-2014. One- and 5-year relative survival rates were stratified by AJCC stage, age group (20-64 vs. ≥65 years) and sex. Results: One- and 5-year survival was calculated by age and stage at diagnosis (Table), and by sex (data not shown). Overall, 5-year survival rates declined compared to 1-year rates, with the biggest decline observed in stage IV patients. Survival was higher in the younger cohort than in patients ≥65 years of age regardless of stage. Both men and women diagnosed with stage IIB CRC had lower 1- and 5-year survival compared to stage IIIA and IIIB groups, consistent with previous findings. Patients with stage IV had the lowest survival irrespective of age or sex. Conclusions: Overall trends in 1- and 5-year relative survival for CRC varied by AJCC stage, age and sex. Since survival is lowest among CRC patients diagnosed at stage IV, particularly in elderly patients, it reinforces the need for early diagnosis and availability of innovative late stage therapies in this population. [Table: see text]
Effectiveness of 8 vs. 12 week ledipasvir-sofosbuvir (LDV/SOF) in black, treatment naive patients with non-cirrhotic, genotype 1 HCV and baseline viral load
Authors: M. Curry, B. Bacon, S. Flamm, A. Landen, S. Milligan, N. Tsai, Z. Younossi, N. Afdhal
Journal: Journal of Hepatology (2018)
New insights from the widening homogeneity perspective to target intratumor heterogeneity
Authors: Mengying Tong, Ziqian Deng, Xiaolong Zhang, Bin He, Mengying Yang, Wei Cheng, Quentin Liu
Journal: Cancer Communications (2018)

Abstract Precision medicine has shed new light on the treatment of heterogeneous cancer patients. However, intratumor heterogeneity strongly constrains the clinical benefit of precision medicine. Thus, rethinking therapeutic strategies from a different facet within the precision medicine framework will not only diversify clinical interventions, but also provide an avenue for precision medicine. Here, we explore the current approaches for targeting intratumor heterogeneity and their limitations. Furthermore, we propose a theoretical strategy with a “homogenization” feature based on iatrogenic evolutionary selection to target intratumor heterogeneity.
Bioreactors for Cardiac Tissue Engineering
Authors: Jesus Paez‐Mayorga, Gustavo Hernández‐Vargas, Guillermo U. Ruiz‐Esparza, Hafiz M. N. Iqbal, Xichi Wang, Yu Shrike Zhang, Roberto Parra‐Saldivar, Ali Khademhosseini
Journal: Advanced Healthcare Materials (2018)

Abstract The advances in biotechnology, biomechanics, and biomaterials can be used to develop organ models that aim to accurately emulate their natural counterparts. Heart disease, one of the leading causes of death in modern society, has attracted particular attention in the field of tissue engineering. To avoid incorrect prognosis of patients suffering from heart disease, or from adverse consequences of classical therapeutic approaches, as well as to address the shortage of heart donors, new solutions are urgently needed. Biotechnological advances in cardiac tissue engineering from a bioreactor perspective, in which recapitulation of functional, biochemical, and physiological characteristics of the cardiac tissue can be used to recreate its natural microenvironment, are reviewed. Detailed examples of functional and preclinical applications of engineered cardiac constructs and the state‐of‐the‐art systems from a bioreactor perspective are provided. Finally, the current trends and future directions of the field for its translation to clinical settings are discussed.
Abstract 14054: Pre-operative Severe Pulmonary Hypertension is an Independent Predictor of Adverse Short and Long-term Outcomes in Cardiac Surgery
Authors: Priyadharshanan Ariyaratnam, Mahmoud Loubani
Journal: Circulation (2016)

Introduction:  Right heart catheterisation remains the gold standard in diagnosing patients with pulmonary hypertension but is not employed routinely in cardiac surgery. Unlike, in the EuroSCORE, the Society of Thoracic Surgeons does not at present recognize pulmonary hypertension as part of their risk stratification. Severe pulmonary hypertension (SPH) is defined as a systolic pulmonary artery pressure of >55mm Hg according to the EuroSCORE criteria.   Hypothesis:  Short and long-term outcomes of pre-operative SPH are compromised following cardiac surgery.   Methods:  Of the 13,556 consecutive patients who underwent cardiac surgery at our institution between July 1999 and July 2015, 1558 patients had right heart catheterisation studies pre-operatively. We analysed all pre-operative factors in the EuroSCORE.   Results:  The mean logistic EuroScore in these patients was 9.4 +/- 12.8 demonstrating that these were a high risk cohort. The mean pulmonary artery pressure measured was 36.2mm Hg (+/- 17.2). whilst 16.6% (234/1588) had SPH. Multivariate logistic analysis revealed SPH to be an important predictor of in-hospital mortality (Hazard Ratio 2.400, p=0.001), post-operative renal failure (Hazard Ratio 1.920, p=0.005) and gastro-intestinal complications (Hazard Ratio 2.342, p   Conclusions:  We have shown that patients with SPH have compromised post-operative complications and long-term survival. This appears to be independent of preoperative factors including the primary cardiac pathology. Greater emphasis should be made in optimising pulmonary artery pressures pre-operatively as well as including PAH in American risk stratification models.
Presepsin, C reactive protein and procalcitonin have similar accuracy for bacterial infection and sepsis in decompensated cirrhosis
Authors: P. Fischer, C. Grigoras, A. Bugariu, O. Farcau, A. Benea, H. Stefanescu, I.M. Gabriela, S. Pascalau, D. Matei, D. Ionescu, M. Tantau, B. Procopet
Journal: Journal of Hepatology (2018)