tbuckley/cabot-search huggingface dataset:
Confocal microscopy and dermoscopy for the monitoring of BRAF inhibitor therapy of melanoma skin metastases
Authors: S. Ribero, E. Marra, C.F. Tomasini, M.T. Fierro, C. Bombonato, C. Longo
Journal: British Journal of Dermatology (2016)

Herein we demonstrated the utility of dermoscopy and RCM in the monitoring of BRAF inhibitore therapy for melanoma skin metastases. Dermoscopically, after therapy all nodules and papules were typified by the presence of bluish colour with crystalline structures and peppering feature. RCM revealed a honeycombed pattern as typical finding of healthy skin; at dermal level, grossly arranged collagen fibers were detected along with small bright particles corresponding to inflammatory cells. Notably, no atypical melanocytes or any other malignant features were seen at all skin levels.

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Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging
Authors: Livia S. Eberlin, Katherine Margulis, Ivette Planell-Mendez, Richard N. Zare, Robert Tibshirani, Teri A. Longacre, Moe Jalali, Jeffrey A. Norton, George A. Poultsides
Journal: PLoS Medicine (2016)

Background Surgical resection with microscopically negative margins remains the main curative option for pancreatic cancer; however, in practice intraoperative delineation of resection margins is challenging. Ambient mass spectrometry imaging has emerged as a powerful technique for chemical imaging and real-time diagnosis of tissue samples. We applied an approach combining desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with the least absolute shrinkage and selection operator (Lasso) statistical method to diagnose pancreatic tissue sections and prospectively evaluate surgical resection margins from pancreatic cancer surgery. Methods and Findings Our methodology was developed and tested using 63 banked pancreatic cancer samples and 65 samples (tumor and specimen margins) collected prospectively during 32 pancreatectomies from February 27, 2013, to January 16, 2015. In total, mass spectra for 254,235 individual pixels were evaluated. When cross-validation was employed in the training set of samples, 98.1% agreement with histopathology was obtained. Using an independent set of samples, 98.6% agreement was achieved. We used a statistical approach to evaluate 177,727 mass spectra from samples with complex, mixed histology, achieving an agreement of 81%. The developed method showed agreement with frozen section evaluation of specimen margins in 24 of 32 surgical cases prospectively evaluated. In the remaining eight patients, margins were found to be positive by DESI-MSI/Lasso, but negative by frozen section analysis. The median overall survival after resection was only 10 mo for these eight patients as opposed to 26 mo for patients with negative margins by both techniques. This observation suggests that our method (as opposed to the standard method to date) was able to detect tumor involvement at the margin in patients who developed early recurrence. Nonetheless, a larger cohort of samples is needed to validate the findings described in this study. Careful evaluation of the long-term benefits to patients of the use of DESI-MSI for surgical margin evaluation is also needed to determine its value in clinical practice. Conclusions Our findings provide evidence that the molecular information obtained by DESI-MSI/Lasso from pancreatic tissue samples has the potential to transform the evaluation of surgical specimens. With further development, we believe the described methodology could be routinely used for intraoperative surgical margin assessment of pancreatic cancer.
Differential Effects of Fructose and Glucose on Cerebral Blood Flow—Reply
Authors: Kathleen A. Page, Rajita Sinha, Robert S. Sherwin
Journal: JAMA (2013)

In Reply: Dr Hertzler points out that peak levels of plasma fructose following fructose ingestion were much less than the peak levels of plasma glucose following glucose ingestion and suggests such differences would be expected to lead to differential brain responses. We agree that this is likely to be one important factor contributing to the diminished ability of fructose vs glucose to suppress human brain activity in regions that control feeding behavior, particularly in the hypothalamus, which contains specific glucose-sensing neurons.1
Defibrotide for Prophylaxis of Hepatic Veno-Occlusive Disease in Autologous, Non-Purged Peripheral Stem Cell Transplantation for High Risk Neuroblastoma Patients
Authors: Emel Unal, Nurdan Tacyildiz, Gulsan Yavuz, Handan Dincaslan, Gulsah Tanyildiz, Erol Ayyildiz, Muhit Ozcan
Journal: Blood (2014)
Diagnostic Pathway with Multiparametric Magnetic Resonance Imaging Versus Standard Pathway: Results from a Randomized Prospective Study in Biopsy-naïve Patients with Suspected Prostate Cancer
Authors: Francesco Porpiglia, Matteo Manfredi, Fabrizio Mele, Marco Cossu, Enrico Bollito, Andrea Veltri, Stefano Cirillo, Daniele Regge, Riccardo Faletti, Roberto Passera, Cristian Fiori, Stefano De Luca
Journal: European Urology (2016)
Toward the Reliable Diagnosis of DSM-5 Premenstrual Dysphoric Disorder: The Carolina Premenstrual Assessment Scoring System (C-PASS)
Authors: Tory A Eisenlohr-Moul, Susan S Girdler, Katja M Schmalenberger, Danyelle N Dawson, Pallavi Surana, Jacqueline L Johnson, David R Rubinow
Journal: American Journal of Psychiatry (2016)

Objective: Despite evidence for the validity of premenstrual dysphoric disorder (PMDD) and the inclusion of the disorder in DSM-5, variable diagnostic practices compromise the construct validity of the diagnosis and threaten the clarity of efforts to understand and treat its underlying pathophysiology. In an effort to hasten and streamline the translation of the DSM-5 criteria for PMDD into terms compatible with existing research practices, the authors present the development and initial validation of the Carolina Premenstrual Assessment Scoring System (C-PASS). The C-PASS (available as a worksheet, Excel macro, and SAS macro) is a standardized scoring system for making DSM-5 PMDD diagnoses using two or more months of daily symptom ratings with the Daily Record of Severity of Problems (DRSP). Method: Two hundred women recruited for retrospectively reported premenstrual emotional symptoms provided two to four months of daily symptom ratings on the DRSP. Diagnoses made by expert clinician and by the C-PASS were compared. Results: Agreement of C-PASS diagnosis with expert clinical diagnosis was excellent; overall correct classification by the C-PASS was estimated at 98%. Consistent with previous evidence, retrospective reports of premenstrual symptom increases were a poor predictor of prospective C-PASS diagnosis. Conclusions: The C-PASS is a reliable and valid companion protocol to the DRSP that standardizes and streamlines the complex, multilevel diagnosis of DSM-5 PMDD. Consistent use of this robust diagnostic method would result in more clearly defined, homogeneous samples of women with PMDD, thereby improving the clarity of studies seeking to characterize and treat the underlying pathophysiology of the disorder.
A novel statistical methodology to detect gene fusions in RNA-Seq data.
Authors: Gillian Hsieh, Linda Szabo, Julia Salzman
Journal: Journal of Clinical Oncology (2016)

11575 Background: Current gene fusion detection algorithms have high false positive and unknown false negative rates, especially when applied to tumors with complex rearrangements. Available methods are inadequate at unbiased identification of potentially targetable fusions or fusions that may serve as biomarkers through their detection in circulating biofluids. Methods: We present a novel algorithm developed using statistically intensive methods. Publicly available paired-end RNA-Seq data sets from the CML cell line K-562 and five malignant prostate adenocarcinoma patient samples were obtained from the Sequence Read Archive (SRA) and The Cancer Genome Atlas (TCGA) databases. RNA-Seq reads were aligned to the UCSC HG19 human genome. Samples were analyzed for known gene fusions using our algorithm and compared to previously published results to assess our ability to prioritize validated and invalidated fusion events. Results: Our algorithm successfully stratified fusions by confidence level. In CML RNA-seq data, it assigned the greatest likelihood to the BCR-ABL1 and NUP214-XKR3 fusions, both of which are experimentally validated. Unbiased statistical filters removed other putative but almost certainly spurious fusions. Similarly, in prostate cancer data sets, the three top-scoring fusions, TMPRSS2-ERG,TMPRSS-ZFAT and ZFAT:CRLS1, are all experimentally validated. Unlike prior fusion detection software, which found more than 6,000 fusions in the same prostate samples and did not offer a way to stratify them into levels of importance, our algorithm provides more clinically and experimentally actionable results. Conclusions: Our statistical algorithm identifies gene fusions from RNA-Seq data, uses statistical models to estimate probabilities that these fusion events are real and stratifies fusions by statistical confidence. Current work includes continued development and application of this methodology to other cancer subtypes and large-scale cancer genomics datasets to help scientists target fusions of clinical significance.
Imatinib Mesylate Treatment of Patients with Chronic Myeloid Leukaemia Relapsing Following Allogeneic Stem Cell Transplantation.
Authors: Eibhlin Conneally, Peig Carroll, Michael Neat, Karl Haslam, Kathy Gately, Jacqui Ryan, Mark Lawler, Shaun McCann
Journal: Blood (2004)
Antitrust and Medical Ethics
Authors: D. J. Canale
Journal: JAMA (1984)

To the Editor.—  Bernard D. Hirsh's excellent article Antitrust and Medical Ethics is must reading for all of those in organized medicine who may be called on to explain our position in regard to contemporary medical ethics.  The question of advertising, minimum fee schedules, and prohibition of competitive bidding is not the real issue with medical society peer review activities. It is, rather, the unethical unconscionable fees of a few practitioners. The dilemma lies in the fact that the third-party payers, including medicare and other federally funded programs, do in fact maintain fee schedules including maximum allowable charges and profiles while organized medicine is forbidden to use this information in what Mr Hirsh has described as carefully controlled disciplinary proceedings.  Mr Hirsh is to be commended on pointing out how the courts narrowly, by a divided vote, have restrained organized medicine in one of its ethical pursuits.
Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) In Adults With Philadelphia Chromosome (Ph)-Negative Acute Lymphoblastic Leukemia (ALL): Results From The Group For Research On Adult ALL (GRAALL)
Authors: Nathalie Dhédin, Anne Huynh, Sébastien Maury, Reza Tabrizi, Xavier Thomas, Patrice Chevallier, Stéphanie Nguyen, Valérie Coiteux, Mathilde Hunault, Stéphane de Botton, Yosr Hichri, Martine Escoffre-Barbe, Oumedaly Reman, Yves Chalandon, Didier Blaise, Nicole Raus, Véronique Lhéritier, Jean-Yves Cahn, Hervé Dombret, Norbert Ifrah
Journal: Blood (2013)
Safety, Antitumor Activity, and Immune Activation of Pegylated Recombinant Human Interleukin-10 (AM0010) in Patients With Advanced Solid Tumors
Authors: Aung Naing, Kyriakos P. Papadopoulos, Karen A. Autio, Patrick A. Ott, Manish R. Patel, Deborah J. Wong, Gerald S. Falchook, Shubham Pant, Melinda Whiteside, Drew R. Rasco, John B. Mumm, Ivan H. Chan, Johanna C. Bendell, Todd M. Bauer, Rivka R. Colen, David S. Hong, Peter Van Vlasselaer, Nizar M. Tannir, Martin Oft, Jeffrey R. Infante
Journal: Journal of Clinical Oncology (2016)

Purpose Interleukin-10 (IL-10) stimulates the expansion and cytotoxicity of tumor-infiltrating CD8+ T cells and inhibits inflammatory CD4+ T cells. Pegylation prolongs the serum concentration of IL-10 without changing the immunologic profile. This phase I study sought to determine the safety and antitumor activity of AM0010. Patients and Methods Patients with selected advanced solid tumors were treated with AM0010 in a dose-escalation study, which was followed by a renal cell cancer (RCC) dose-expansion cohort. AM0010 was self-administered subcutaneously at doses of 1 to 40 μg/kg once per day. Primary end points were safety and tolerability; clinical activity and immune activation were secondary end points. Results In the dose-escalation and -expansion cohorts, 33 and 18 patients, respectively, were treated with daily subcutaneous injection of AM0010. AM0010 was tolerated in a heavily pretreated patient population. Treatment-related adverse events (AEs) included anemia, fatigue, thrombocytopenia, fever, and injection site reactions. Grade 3 to 4 nonhematopoietic treatment-related AEs, including rash (n = 2) and transaminitis (n = 1), were observed in five of 33 patients. Grade 3 to 4 anemia or thrombocytopenia was observed in five patients. Most treatment-related AEs were transient or reversible. AM0010 led to systemic immune activation with elevated immune-stimulatory cytokines and reduced transforming growth factor beta in the serum. Partial responses were observed in one patient with uveal melanoma and four of 15 evaluable patients with RCC treated at 20 μg/kg (overall response rate, 27%). Prolonged stable disease of at least 4 months was observed in four patients, including one with colorectal cancer with disease stabilization for 20 months. Conclusion AM0010 has an acceptable toxicity profile with early evidence of antitumor activity, particularly in RCC. These data support the further evaluation of AM0010 both alone and in combination with other immune therapies and chemotherapies.
Response-Adapted Sequential Immuno-Chemotherapy of Post-Transplant Lymphoproliferative Disorders in Pediatric Solid Organ Transplant Recipients: Results from the Prospective Ped-PTLD 2005 Trial
Authors: Britta Maecker-Kolhoff, Rita Beier, Martin Zimmermann, Brigitte Schlegelberger, Ulrich Baumann, Carsten Mueller, Lars Pape, Alfred Reiter, Claudia Rossig, Stephan Schubert, Burkhard Toenshoff, Anne-Margret Wingen, Barbara Meissner, Christian Kebelmann-Betzing, Guenter Henze, Hans H. Kreipe, Christoph Klein
Journal: Blood (2014)
International patient and physician consensus on a psoriatic arthritis core outcome set for clinical trials
Authors: Ana-Maria Orbai, Maarten de Wit, Philip Mease, Judy A Shea, Laure Gossec, Ying Ying Leung, William Tillett, Musaab Elmamoun, Kristina Callis Duffin, Willemina Campbell, Robin Christensen, Laura Coates, Emma Dures, Lihi Eder, Oliver FitzGerald, Dafna Gladman, Niti Goel, Suzanne Dolwick Grieb, Sarah Hewlett, Pil Hoejgaard, Umut Kalyoncu, Chris Lindsay, Neil McHugh, Bev Shea, Ingrid Steinkoenig, Vibeke Strand, Alexis Ogdie
Journal: Annals of the Rheumatic Diseases (2016)

Objective To identify a core set of domains (outcomes) to be measured in psoriatic arthritis (PsA) clinical trials that represent both patients' and physicians' priorities. Methods We conducted (1) a systematic literature review (SLR) of domains assessed in PsA; (2) international focus groups to identify domains important to people with PsA; (3) two international surveys with patients and physicians to prioritise domains; (4) an international face-to-face meeting with patients and physicians using the nominal group technique method to agree on the most important domains; and (5) presentation and votes at the Outcome Measures in Rheumatology (OMERACT) conference in May 2016. All phases were performed in collaboration with patient research partners. Results We identified 39 unique domains through the SLR (24 domains) and international focus groups (34 domains). 50 patients and 75 physicians rated domain importance. During the March 2016 consensus meeting, 12 patients and 12 physicians agreed on 10 candidate domains. Then, 49 patients and 71 physicians rated these domains' importance. Five were important to &gt;70% of both groups: musculoskeletal disease activity, skin disease activity, structural damage, pain and physical function. Fatigue and participation were important to &gt;70% of patients. Patient global and systemic inflammation were important to &gt;70% of physicians. The updated PsA core domain set endorsed by 90% of OMERACT 2016 participants includes musculoskeletal disease activity, skin disease activity, pain, patient global, physical function, health-related quality of life, fatigue and systemic inflammation. Conclusions The updated PsA core domain set incorporates patients' and physicians' priorities and evolving PsA research. Next steps include identifying outcome measures that adequately assess these domains.
Sulfation of Glycosaminoglycans and Its Implications in Human Health and Disorders
Authors: Diana Soares da Costa, Rui L. Reis, Iva Pashkuleva
Journal: Annual Review of Biomedical Engineering (2017)

Sulfation is a dynamic and complex posttranslational modification process. It can occur at various positions within the glycosaminoglycan (GAG) backbone and modulates extracellular signals such as cell-cell and cell-matrix interactions; different sulfation patterns have been identified for the same organs and cells during their development. Because of their high specificity in relation to function, GAG sulfation patterns are referred to as the sulfation code. This review explores the role of GAG sulfation in different biological processes at the cell, tissue, and organism levels. We address the connection between the sulfation patterns of GAGs and several physiological processes and discuss the misregulation of GAG sulfation and its involvement in several genetic and metabolic disorders. Finally, we present the therapeutic potential of GAGs and their synthetic mimics in the biomedical field.
Estimating the economic impact of a possible equine and human epidemic of West Nile virus infection in Belgium
Authors: M. Humblet, S. Vandeputte, F. Fecher-Bourgeois, P. Leonard, C. Gosset, Thomas Balenghien, B. Durand, C. Saegerman
Journal: Eurosurveillance (2016)

This study aimed at estimating, in a prospective scenario, the potential economic impact of a possible epidemic of WNV infection in Belgium, based on 2012 values for the equine and human health sectors, in order to increase preparedness and help decision-makers. Modelling of risk areas, based on the habitat suitable for Culex pipiens, the main vector of the virus, allowed us to determine equine and human populations at risk. Characteristics of the different clinical forms of the disease based on past epidemics in Europe allowed morbidity among horses and humans to be estimated. The main costs for the equine sector were vaccination and replacement value of dead or euthanised horses. The choice of the vaccination strategy would have important consequences in terms of cost. Vaccination of the country's whole population of horses, based on a worst-case scenario, would cost more than EUR 30 million; for areas at risk, the cost would be around EUR 16-17 million. Regarding the impact on human health, short-term costs and socio-economic losses were estimated for patients who developed the neuroinvasive form of the disease, as no vaccine is available yet for humans. Hospital charges of around EUR 3,600 for a case of West Nile neuroinvasive disease and EUR 4,500 for a case of acute flaccid paralysis would be the major financial consequence of an epidemic of West Nile virus infection in humans in Belgium.
Conditional survival nomogram after an R0 resection for gastric cancer.
Authors: J. L. Dikken, C. J. Van De Velde, M. Verheij, R. Baser, M. Gonen, M. W. Kattan, M. A. Shah, M. F. Brennan, D. G. Coit
Journal: Journal of Clinical Oncology (2011)

11 Background: The risk of dying of cancer is highest in the first two years after a curative resection for gastric cancer. Therefore, the prognosis of patients who did not recur in the first two years is improved because they survived this critical period, a phenomenon called conditional survival. The US-derived gastric cancer nomogram predicts disease-specific survival (DSS) based on pathological variables. However, a disease-free interval after surgery, which improves the prognosis, is not captured by the nomogram. Therefore, it has only been used directly after surgery and not in the follow-up setting. The purposes of this study were to develop a conditional survival nomogram for 1, 2 and 3-year survivors (step 1) and to test if the introduction of follow-up variables would improve predictive accuracy of the nomogram in the follow-up setting (step 2). Methods: In a combined US-Dutch population of 1642 patients who underwent an R0 resection for gastric cancer and for whom the old nomogram variables were available, a conditional survival nomogram based on the original variables was developed for one (N=1147), two (N=879) and three (N=721) year survivors (step 1). To improve predictive accuracy in the follow-up setting, weight loss, performance status (PS), hemoglobin (HGB), and albumin (ALB) at one year after resection were retrospectively collected and added to the baseline variables in a new nomogram (step 2). Results: The conditional survival nomograms for 1, 2 and 3-year survivors (step 1) showed a high predictive accuracy in the calibration plots. Surviving one, two and three years shows a median improvement of 5-year DSS of 4%, 9% and 14% respectively. The introduction of weight loss, PS, HGB, and ALB at one year after surgery (step 2) did not improve this nomogram, but availability of these variables was limited. Conclusions: A strongly predictive conditional survival nomogram was developed, giving an improved prognosis for 1, 2 and 3-year survivors of gastric cancer. Introduction of variables available at one year after resection did not further improve this nomogram. This might be caused by the limited availability of follow-up data, as well as the strong predictive accuracy of the original variables. No significant financial relationships to disclose.
The Transcripts Of Platelet-Endothelial Adhesion Molecules and Inflamatory Chemokine Activation Pathway Molecules Are Hyperexpressed In The Bone Marrow Of Acute Promyelocytic Leukemia Patients Presenting Severe Coagulopathy
Authors: Priscila S Scheucher, Guilherme A. dos Santos, Rodrigo Alexandre Panepucci, Amelia Goes de Araujo, Roberto P. Falcao, Eduardo M. Rego
Journal: Blood (2013)
Clofarabine, Idarubicin, and Cytarabine (CIA) As Frontline Therapy for Patients &lt;= 60 Years with Newly Diagnosed Acute Myeloid Leukemia (AML)
Authors: Aziz Nazha, Farhad Ravandi, Hagop M. Kantarjian, Xuelin Huang, Sangbum Choi, Guillermo Garcia-Manero, Elias J. Jabbour, Gautam Borthakur, Tapan M. Kadia, Marina Konopleva, Jorge E. Cortes, Alessandra Ferrajoli, Steven M. Kornblau, Michael Andreeff, Zeev Estrov, Naval G. Daver, Naveen Pemmaraju, Min Du, Mark Brandt, Stefan Faderl
Journal: Blood (2012)
Epidemiological trends in Merkel cell carcinoma in southern France: a registry-based study
Authors: M. Fondain, A. Du Thanh, F. Bessaoud, O. Dereure, B. Tretarre, B. Guillot
Journal: British Journal of Dermatology (2016)

Merkel cell carcinoma (MCC) is a cutaneous malignancy derived from Merkel cells. The crude incidence of MCC has increased from 0.2 to 0.6 per 100,000 persons between 1990 and 2006 in the United States (1).

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