tbuckley/cabot-search huggingface dataset:
Single-center, prospective pilot study to evaluate advance care planning implementing the 3 Questions and 3 Elements to identify an informed health care proxy in an outpatient oncology palliative care clinic.
Authors: Eric Roeland, Sean Heavey, Carolyn Revta, Rabia S. Atayee, Joseph D. Ma, Melanie Benn
Journal: Journal of Clinical Oncology (2014)

TPS9655 Background: Despite the growing cancer therapeutics arsenal, the vast majority of advanced cancer patients will die. Consequently, understanding and communicating their end-of-life (EoL) care wishes is critical. Advance care planning (ACP) should occur in the non-emergent outpatient setting. However, given social and pragmatic challenges, these discussions are delayed until moments of crisis. In order to increase the probability that patients receive care consistent with their EoL wishes, health care providers require simple, effective, and efficient tools to initiate and complete meaningful ACP discussions. Methods: This is a single center, prospective, pilot study sponsored by the American Cancer Society to evaluate the average identification rate of an informed health care proxy by advanced cancer patients implementing a novel ACP tool in an academic oncology palliative care clinic over one year. Eligible subjects must have a known cancer diagnosis and a prognosis of less than 1 year. Consented subjects engage in a 1-hour ACP discussion initiated by the 3 Questions which include: 1) the identification of potential health care proxy; 2) proxy’s awareness about being designated as a health care proxy; 3) proxy’s understanding of patient’s wishes. The 3 Elements define a meaningful ACP discussion and include: 1) the patient’s personal definition of quality of life (QoL) 2) a specific plan if that personal QoL definition is not achieved 3) the patient’s preferred location of death. Details of this ACP conversation are documented in the electronic medical record. The primary aim is to determine the proportion of advanced cancer patients who identify a health care proxy implementing the 3 Questions and 3 Elements versus a historical standard. Secondary aims include: 1) to determine the location of death of the subject 2) to determine if the subject’s desired code status was honored. 3) to evaluate the health care proxy’s satisfaction in understanding subject’s wishes for EoL care after the subject’s death.
Minimal Residual Disease (MRD) Detection By Flow Cytometry during Aplasia and Post-Induction Is an Independent Prognostic Parameter for Relapse-Free Survival in AML
Authors: Veit Bücklein, Thomas Koehnke, Sandra Rechkemmer, Frauke Schnorfeil, Stephanie Schneider, Maja Rothenberg-Thurley, Klaus H. Metzeler, Cristina Sauerland, Wolfgang Hiddemann, Karsten Spiekermann, Marion S. Subklewe
Journal: Blood (2017)
The immunoregulatory molecule B7H3 regulates tumor cell adhesion, migration and invasion, but not proliferation
Authors: Yih-Wen Chen, Oystein Fodstad
Journal: Cancer Research (2007)

3946  Specific cancer markers are powerful tools for early cancer diagnosis, prognosis prediction and monitoring of disease progression. To date, no general cancer marker is available for different cancer types. Monoclonal antibody (mAb) 376.96 has been used for detection of micrometastatic tumor cells for its ability to recognize a wide range of tumor cells, but not to most normal cells. Yet, the cellular antigen for 376.96 mAb is still unknown. In this study, using immunoprecipitation, immunoblotting, and siRNA technologies, we discovered that the antigen is human immunoregulatory molecule 4Ig-B7H3 (4Ig-hB7H3). ELISA data demonstrated that 376.96 mAb has a high specificity and sensitivity to 4Ig-hB7H3. Furthermore, immunoblot results from subcellular fractionation and tunicamycin treatment indicated that 4Ig-hB7H3 is a ~100-kDa N-linked glycoprotein that is expressed only on the cell membrane of many different cancer types. These data indicates that 4Ig-hB7H3 presents as a valuable cancer marker to discriminate between tumor cells and normal cells.  Interestingly, tumor promoter phorbol 12-myristate 13-acetate (PMA) significantly enhanced the expression of 4Ig-hB7H3 in FEMX-I (melanoma), MA11 (breast cancer), and OHS (osteosarcoma) cells, suggesting a relationship between 4Ig-hB7H3 and tumor biological functions. Functional studies showed that in both melanoma and breast cancer cells down-regulation of 4Ig-hB7H3 by siRNA-hB7H3 reduced cell adhesion ability 2-fold. Down-regulation also significantly inhibited migration and matrigel-invasion by more than 3-fold, while no apparent impact on cell proliferation and on sensitivity of the tumor cells to NK cell-mediated cytoxicity was observed. In summary, these data indicate that 4Ig-hB7H3 is an important cancer marker. The results shed new light on the novel role of the immunoregulatory molecule 4Ig-hB7H3 in tumor metastasis and progression and it is critical for improving the cancer diagnosis and cancer treatment in the future.
A hospital-wide intervention replacing ceftriaxone with cefotaxime to reduce rate of healthcare-associated infections caused by extended-spectrum β-lactamase-producing Enterobacteriaceae in the intensive care unit
Authors: Boun Kim Tan, Emmanuel Vivier, Karim Ait Bouziad, Jean-Ralph Zahar, Christian Pommier, Laurence Parmeland, Caroline Pariset, Pauline Misslin, Catherine Haond, Philippe Poirié, Laura Temime, Mounia N. Hocine
Journal: Intensive Care Medicine (2018)
Inflammatory Myofibroblastic Tumor Driven by Novel <i>NUMA1-ALK</i> Fusion Responds to ALK Inhibition
Authors: Nisha Rao, Hans Iwenofu, Bingfeng Tang, Jennifer Woyach, David A. Liebner
Journal: Journal of the National Comprehensive Cancer Network (2018)

Inflammatory myofibroblastic tumors (IMTs) are soft tissue neoplasms with rare metastatic potential. Approximately half of IMTs are positive for an ALK rearrangement, and ALK inhibitors have been used successfully in the treatment of IMTs with a variety of ALK fusions. This report describes a 21-year-old woman with an aggressive, metastatic IMT with a novel NUMA1-ALK fusion that showed a dramatic response to the ALK inhibitors crizotinib and alectinib. To our knowledge, this report provides the first published description of an IMT with a NUMA1-ALK fusion. The patient's aggressive IMT responded favorably to crizotinib and alectinib, suggesting that ALK inhibitors may be effective in IMT with NUMA1-ALK fusions. We review published reports of ALK-driven IMTs that have received ALK inhibitor therapy and suggest characteristics that may be associated with favorable response to treatment. We also discuss the strengths and limitations of immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing in the diagnosis and management of IMTs.
Epidermiological, diagnostic, therapeutic and prognostic aspects of essential thrombocithemia in a retrospective study of the GIMMC group in two thousand patients.
Authors: L Gugliotta, R Marchioli, M Fiacchini, N Vianelli, S Baravelli, L Valdrè, A De vivo, R Marfisi, F Radaelli, L Garantini, A Ambrosetto, Mg Mazzucconi, D Russo, M Bazzan, A Zaccaria, G Finazzi, A Grossi, M Ruggeri, E Pogliani, S Sacchi, Martelli, T Barbui, M. Lazzarino
Journal: Blood (1997)
Reply to Mustafa Z. Temiz and Huseyin Besiroglu's Letter to the Editor re: Giorgio Gandaglia, Stephen A. Boorjian, William P. Parker, et al. Impact of Postoperative Radiotherapy in Men with Persistently Elevated Prostate-specific Antigen After Radical Prostatectomy for Prostate Cancer: A Long-term Survival Analysis. Eur Urol 2017;72:910–7
Authors: Giorgio Gandaglia, Nicola Fossati, Francesco Montorsi, Alberto Briganti
Journal: European Urology (2018)
Flow Cytometric Minimal Residual Disease As Risk Stratification Tool in Younger Adults with NPM1 Wild Type Standard Risk Acute Myeloid Leukemia
Authors: Sylvie D Freeman, Robert K. Hills, Paul Virgo, Naeem Khan, Stephen Couzens, Richard James Dillon, Laura Upton, Lars Kjeldsen, Ian Thomas, David Grimwade, Alan K. Burnett, Nigel H. Russell
Journal: Blood (2017)
Hypoglycemia unawareness in type 1 diabetes suppresses brain responses to hypoglycemia
Authors: Janice Jin Hwang, Lisa Parikh, Cheryl Lacadie, Dongju Seo, Wai Lam, Muhammad Hamza, Christian Schmidt, Feng Dai, Anne-Sophie Sejling, Renata Belfort-DeAguiar, R. Todd Constable, Rajita Sinha, Robert Sherwin
Journal: Journal of Clinical Investigation (2018)

Among nondiabetic individuals, mild glucose decrements alter brain activity in regions linked to reward, motivation, and executive control. Whether these effects differ in type 1 diabetes mellitus (T1DM) patients with and without hypoglycemia awareness remains unclear.Forty-two individuals (13 healthy control [HC] subjects, 16 T1DM individuals with hypoglycemia awareness [T1DM-Aware], and 13 T1DM individuals with hypoglycemia unawareness [T1DM-Unaware]) underwent blood oxygen level-dependent functional MRI brain imaging during a 2-step hyperinsulinemic euglycemic (90 mg/dl)-hypoglycemic (60 mg/dl) clamp for assessment of neural responses to mild hypoglycemia.Mild hypoglycemia in HC subjects altered activity in the caudate, insula, prefrontal cortex, and angular gyrus, whereas T1DM-Aware subjects showed no caudate and insula changes, but showed altered activation patterns in the prefrontal cortex and angular gyrus. Most strikingly, in direct contrast to HC and T1DM-Aware subjects, T1DM-Unaware subjects failed to show any hypoglycemia-induced changes in brain activity. These findings were also associated with blunted hormonal counterregulatory responses and hypoglycemia symptom scores during mild hypoglycemia.In T1DM, and in particular T1DM-Unaware patients, there is a progressive blunting of brain responses in cortico-striatal and fronto-parietal neurocircuits in response to mild-moderate hypoglycemia. These findings have implications for understanding why individuals with impaired hypoglycemia awareness fail to respond appropriately to falling blood glucose levels.This study was supported in part by NIH grants R01DK020495, P30 DK045735, K23DK109284, K08AA023545. The Yale Center for Clinical Investigation is supported by an NIH Clinical Translational Science Award (UL1 RR024139).
The atypical chemokine receptor 2 limits renal inflammation and fibrosis in murine progressive immune complex glomerulonephritis
Authors: Andrei Bideak, Alexander Blaut, John M. Hoppe, Martin B. Müller, Giuseppina Federico, Nuru Eltrich, Hermann-Josef Gröne, Massimo Locati, Volker Vielhauer
Journal: Kidney International (2018)
Quality of Life Outcomes for Cabozantinib Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma: METEOR Phase III Randomized Trial
Authors: David Cella, Bernard Escudier, Nizar M. Tannir, Thomas Powles, Frede Donskov, Katriina Peltola, Manuela Schmidinger, Daniel Y.C. Heng, Paul N. Mainwaring, Hans J. Hammers, Jae Lyun Lee, Bruce J. Roth, Florence Marteau, Paul Williams, John Baer, Milan Mangeshkar, Christian Scheffold, Thomas E. Hutson, Sumanta Pal, Robert J. Motzer, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2018)

Purpose In the phase III METEOR trial ( ClinicalTrials.gov identifier: NCT01865747), 658 previously treated patients with advanced renal cell carcinoma were randomly assigned 1:1 to receive cabozantinib or everolimus. The cabozantinib arm had improved progression-free survival, overall survival, and objective response rate compared with everolimus. Changes in quality of life (QoL), an exploratory end point, are reported here. Patients and Methods Patients completed the 19-item Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI-19) and the five-level EuroQol (EQ-5D-5L) questionnaires at baseline and throughout the study. The nine-item FKSI-Disease-Related Symptoms (FKSI-DRS), a subset of FKSI-19, was also investigated. Data were summarized descriptively and by repeated-measures analysis (for which a clinically relevant difference was an effect size ≥ 0.3). Time to deterioration (TTD) was defined as the earlier of date of death, radiographic progressive disease, or ≥ 4-point decrease from baseline in FKSI-DRS. Results The QoL questionnaire completion rates remained ≥ 75% through week 48 in each arm. There was no difference over time for FKSI-19 Total, FKSI-DRS, or EQ-5D data between the cabozantinib and everolimus arms. Among the individual FKSI-19 items, cabozantinib was associated with worse diarrhea and nausea; everolimus was associated with worse shortness of breath. These differences are consistent with the adverse event profile of each drug. Cabozantinib improved TTD overall, with a marked improvement in patients with bone metastases at baseline. Conclusion In patients with advanced renal cell carcinoma, relative to everolimus, cabozantinib generally maintained QoL to a similar extent. Compared with everolimus, cabozantinib extended TTD overall and markedly improved TTD in patients with bone metastases.
Comparison of reporting phase III randomized controlled trials of antibiotic treatment for common bacterial infections in ClinicalTrials.gov and matched publications
Authors: D. Shepshelovich, D. Yelin, A. Gafter-Gvili, S. Goldman, T. Avni, D. Yahav
Journal: Clinical Microbiology and Infection (2018)

Discrepancies between ClinicalTrials.gov entries and matching publications were previously described in general medicine. We aimed to evaluate the consistency of reporting in trials addressing systemic antibiotic therapy.We searched ClinicalTrials.gov for completed phase III trials comparing antibiotic regimens until May 2017. Matched publications were identified in PubMed. Two independent reviewers extracted data and identified inconsistencies. Reporting was assessed among studies started before and after 1 July 2005, when the International Committee of Medical Journal Editors (ICMJE) required mandatory registration as a prerequisite for considering a trial for publication.Matching publications were identified for 75 (70%) of 107 ClinicalTrials.gov entries. Median time from study completion to publication was 26 months (interquartile range 19-42). Primary outcome definition was inconsistent between ClinicalTrials.gov and publications in seven trials (7/72, 10%) and reporting of the primary outcome timeframe was inconsistent in 14 (14/71, 20%). Secondary outcomes definitions were inconsistent in 36 trials (36/66, 55%). Reporting of inclusion criteria and study timeline were inconsistent in 17% (13/65) and 3% (2/65), respectively. Trials started after July 2005 were significantly less likely to have reporting inconsistencies and were published in higher impact factor journals.We found a lower inconsistency rate of outcome reporting compared with other medical disciplines. Reporting completeness and consistency were significantly better after July 2005. The ICMJE requirement for mandatory registration was associated with significant improvement in reporting quality in infectious diseases trials. Prolonged time lag to publication and missing data from unpublished trials should raise a discussion on current reporting and publishing procedures.
Poverty and reductions in fitness levels in children and adolescents in upper middle-income countries
Authors: Angela Donkin, Michael Marmot
Journal: British Journal of Sports Medicine (2018)

Increasingly it is recognised that what happens in childhood has a significant impact on health in adulthood. As we and others have shown—social, emotional, cognitive and physical development in childhood and adolescence tracks through to later life.1 2 The paper by Tomkinson and colleagues3 examined trends in cardiorespiratory fitness (CRF) levels in childhood and adolescence. It is an important piece of work because poor fitness levels in adolescence are significantly linked with higher all-cause mortality rates later in life4 and because, as the authors illustrate in their comprehensive study, CRF fitness levels in children and adolescents in high-income and high-middle-income countries have significantly declined since the 1980s.

There is some relief in the fact that since 2000 the rate of decline has slowed significantly. A question to ask is whether the reason for a slower decline to do with the fact that there is not much more ‘fitness’ to cut back on. We are also interested in the sex differences between base levels of fitness but the paper does not extend that far, and there is also no mention of the technological revolution seen in terms of children’s modern ‘toys’, and …
Elimination of Cost Sharing for Screening Mammography in Medicare Advantage Plans
Authors: Amal N. Trivedi, Bryan Leyva, Yoojin Lee, Orestis A. Panagiotou, Issa J. Dahabreh
Journal: New England Journal of Medicine (2018)

The Affordable Care Act (ACA) required most insurers and the Medicare program to eliminate cost sharing for screening mammography.
Immunological Synapse Predicts Effectiveness of Chimeric Antigen Receptor Cells
Authors: Wei Xiong, Yuhui Chen, Xi Kang, Zhiying Chen, Peilin Zheng, Yi-Hsin Hsu, Joon Hee Jang, Lidong Qin, Hao Liu, Gianpietro Dotti, Dongfang Liu
Journal: Molecular Therapy (2018)

Chimeric antigen receptor (CAR)-modified T cell therapy has the potential to improve the overall survival of patients with malignancies by enhancing the effectiveness of CAR T cells. Precisely predicting the effectiveness of various CAR T cells represents one of today's key unsolved problems in immunotherapy. Here, we predict the effectiveness of CAR-modified cells by evaluating the quality of the CAR-mediated immunological synapse (IS) by quantitation of F-actin, clustering of tumor antigen, polarization of lytic granules (LGs), and distribution of key signaling molecules within the IS. Long-term killing capability, but not secretion of conventional cytokines or standard 4-hr cytotoxicity, correlates positively with the quality of the IS in two different CAR T cells that share identical antigen specificity. Xenograft model data confirm that the quality of the IS in vitro correlates positively with performance of CAR-modified immune cells in vivo. Therefore, we propose that the quality of the IS predicts the effectiveness of CAR-modified immune cells, which provides a novel strategy to guide CAR therapy.Graphical abstract
Prefrontal-Periaqueductal Gray-Projecting Neurons Mediate Context Fear Discrimination
Authors: Robert R. Rozeske, Daniel Jercog, Nikolaos Karalis, Fabrice Chaudun, Suzana Khoder, Delphine Girard, Nânci Winke, Cyril Herry
Journal: Neuron (2018)

Survival critically depends on selecting appropriate defensive or exploratory behaviors and is strongly influenced by the surrounding environment. Contextual discrimination is a fundamental process that is thought to depend on the prefrontal cortex to integrate sensory information from the environment and regulate adaptive responses to threat during uncertainty. However, the precise prefrontal circuits necessary for discriminating a previously threatening context from a neutral context remain unknown. Using a combination of single-unit recordings and optogenetic manipulations, we identified a neuronal subpopulation in the dorsal medial prefrontal cortex (dmPFC) that projects to the lateral and ventrolateral periaqueductal gray (l/vlPAG) and is selectively activated during contextual fear discrimination. Moreover, optogenetic activation and inhibition of this neuronal population promoted contextual fear discrimination and generalization, respectively. Our results identify a subpopulation of dmPFC-l/vlPAG-projecting neurons that control switching between different emotional states during contextual discrimination.
The Coronary Artery Disease–Reporting and Data System (CAD-RADS)
Authors: Joe X. Xie, Ricardo C. Cury, Jonathon Leipsic, Matthew T. Crim, Daniel S. Berman, Heidi Gransar, Matthew J. Budoff, Stephan Achenbach, Bríain Ó Hartaigh, Tracy Q. Callister, Hugo Marques, Ronen Rubinshtein, Mouaz H. Al-Mallah, Daniele Andreini, Gianluca Pontone, Filippo Cademartiri, Erica Maffei, Kavitha Chinnaiyan, Gilbert Raff, Martin Hadamitzky, Joerg Hausleiter, Gudrun Feuchtner, Allison Dunning, Augustin DeLago, Yong-Jin Kim, Philipp A. Kaufmann, Todd C. Villines, Benjamin J.W. Chow, Niree Hindoyan, Millie Gomez, Fay Y. Lin, Erica Jones, James K. Min, Leslee J. Shaw
Journal: JACC. Cardiovascular imaging (2018)
Vaginal mesh procedures need compulsory register, says royal college
Authors: Abi Rimmer
Journal: BMJ (2018)

A mandatory register to record outcomes in all women treated with vaginal mesh is essential to properly monitor the adverse effects of these implants, the Royal College of Obstetricians and Gynaecologists (RCOG) has said.

The college was responding to government plans announced last month1 for an audit of problems caused by vaginal mesh. The audit, which aims to better understand complications related to mesh implants used for incontinence and prolapse, is expected to be completed by April.

Tim Hillard, RCOG clinical lead for patient safety, said that, while he supported the audit, he would like to see more done. …
Clinical Pharmacology of CTL019 in Patients with Relapsed/Refractory (r/r) Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Rakesh Awasthi, Constantine S. Tam, Ulrich Jaeger, Samantha Jaglowski, Stephen Ronan Foley, Koen Van Besien, Nina D. Wagner-Johnston, Marie Jose Kersten, Stephen J. Schuster, Gilles Andre Salles, Richard Thomas Maziarz, Oezlem Anak, Lida Bubuteishvili Pacaud, Lucien Gazi, Edward Waldron, Jason Hamilton, Iulian Pruteanu, Feng Tai, Karen Thudium Mueller, Edmund K. Waller
Journal: Blood (2017)
Autonomous role of Wiskott-Aldrich syndrome platelet deficiency in inducing autoimmunity and inflammation
Authors: Lucia Sereni, Maria Carmina Castiello, Francesco Marangoni, Achille Anselmo, Dario di Silvestre, Sara Motta, Elena Draghici, Stefano Mantero, Adrian J. Thrasher, Silvia Giliani, Alessandro Aiuti, Pierluigi Mauri, Luigi D. Notarangelo, Marita Bosticardo, Anna Villa
Journal: Journal of Allergy and Clinical Immunology (2018)
Meta-analysis of randomized controlled trials challenging the usefulness of purgative preparation before small-bowel video capsule endoscopy
Authors: Paraskevas Gkolfakis, Georgios Tziatzios, George Dimitriadis, Konstantinos Triantafyllou
Journal: Endoscopy (2018)

Abstract Background The usefulness of purgative preparation before small-bowel video capsule endoscopy is controversial. We aimed to examine the effect of purgative preparation on small-bowel video capsule endoscopy outcomes. Methods We performed literature searches in MEDLINE and the Cochrane library for randomized controlled trials evaluating the effect of purgative preparation (polyethylene glycol, sodium phosphate, others) vs. clear-liquid diet/fasting in patients undergoing small-bowel capsule endoscopy. Meta-analysis outcomes included the examination’s diagnostic yield, small-bowel mucosal visualization quality, the examination’s completion rate, and gastric and small-bowel transit times. The effect size on study outcomes was calculated using a fixed- or random-effect model, as appropriate, and is shown as the risk ratio (RR) with 95 % confidence interval (CI). Results We identified 12 eligible trials with 17 sets of data including 1221 subjects. Significant heterogeneity was detected with no evidence of publication bias. As compared with clear-liquid diet, purgative bowel preparation did not increase capsule endoscopy diagnostic yield (RR 1.17 [95 %CI 0.97 to 1.40]; P = 0.11). Neither the small-bowel mucosal visualization quality (RR 1.14 [95 %CI 0.96 to 1.35]; P = 0.15) nor completion rate for the examination (RR 0.99 [95 %CI 0.95 to 1.04]; P = 0.76) significantly improved after purgative preparation. Purgatives also had no effect on video capsule endoscopy gastric and small-bowel transit times. Conclusions Our analysis challenges the usefulness of purgative preparation for improving the diagnostic yield of small-bowel video capsule endoscopy and the quality of small-bowel mucosal visualization.