tbuckley/cabot-search huggingface dataset:
ABO incompatibility in mismatched unrelated donor allogeneic hematopoietic cell transplantation for acute myeloid leukemia: A report from the acute leukemia working party of the EBMT
Authors: Jonathan Canaani, Bipin N. Savani, Myriam Labopin, Mauricette Michallet, Charles Craddock, Gerard Socié, Lisa Volin, Johan A. Maertens, Charles Crawley, Didier Blaise, Per T. Ljungman, Jan Cornelissen, Nigel Russell, Frédéric Baron, Norbert Gorin, Jordi Esteve, Fabio Ciceri, Christoph Schmid, Sebastian Giebel, Mohamad Mohty, Arnon Nagler
Journal: American Journal of Hematology (2017)

ABO incompatibility is commonly observed in stem cell transplantation and its impact in this setting has been extensively investigated. HLA-mismatched unrelated donors (MMURD) are often used as an alternative stem cell source but are associated with increased transplant related complications. Whether ABO incompatibility affects outcome in MMURD transplantation for acute myeloid leukemia (AML) patients is unknown. We evaluated 1,013 AML patients who underwent MMURD transplantation between 2005 and 2014. Engraftment rates were comparable between ABO matched and mismatched patients, as were relapse incidence [34%; 95% confidence interval (CI), 28-39; for ABO matched vs. 36%; 95% CI, 32-40; for ABO mismatched; P = .32], and nonrelapse mortality (28%; 95% CI, 23-33; for ABO matched vs. 25%; 95% CI, 21-29; for ABO mismatched; P = .2). Three year survival was 40% for ABO matched and 43% for ABO mismatched patients (P = .35), Leukemia free survival rates were also comparable between groups (37%; 95% CI, 32-43; for ABO matched vs. 38%; 95% CI, 33-42; for ABO mismatched; P = .87). Incidence of grade II-IV acute graft versus host disease was marginally lower in patients with major ABO mismatching (Hazard ratio of 0.7, 95% CI, 0.5-1; P = .049]. ABO incompatibility probably has no significant clinical implications in MMURD transplantation.
Bay 94-9027, a Site-Specifically Pegylated Recombinant Factor VIII: Preliminary Results from an International Comparative Laboratory Field Study
Authors: Nikki Church, Lilley Leong, Yvonne Katterle, Yadagiri Rao Danda, Hannes-Friedrich Ulbrich, Iris Noerenberg, Stefan Bruns, Lisa A. Michaels
Journal: Blood (2016)
Emergency Department Query for Patient-Centered Approaches to Sexual Orientation and Gender Identity
Authors: Adil H. Haider, Eric B. Schneider, Lisa M. Kodadek, Rachel R. Adler, Anju Ranjit, Maya Torain, Ryan Y. Shields, Claire Snyder, Jeremiah D. Schuur, Laura Vail, Danielle German, Susan Peterson, Brandyn D. Lau
Journal: JAMA Internal Medicine (2017)

The Institute of Medicine and The Joint Commission recommend routine documentation of patients' sexual orientation in health care settings. Currently, very few health care systems collect these data since patient preferences and health care professionals' support regarding collection of data about patient sexual orientation are unknown.
P08.54 Targeting brain tumor with mesenchymal stem cells in the experimental model of the orthotopic glioblastoma
Authors: G. Timin, Y. Marchenko, L. Yakovleva, B. Nikolaev, V. Ryzhov, E. Tolkunova, M. Shevtsov
Journal: Neuro-Oncology (2017)

Introduction: Tumor tracking properties of mesenchymal stem cells (MSCs) provide an attractive opportunity for targeted suicide gene therapy of brain tumors. However, intravenously injected MSCs can accumulate in other organs, thereby contributing to plausible side effects. Therefore, in vivo MSCs biodistribution studies are of high importance. Materials and Methods: Tumor-targeting and organ biodistribution of the intravenously administered rat MSCs were assessed in the intracranial C6 rat glioma model. Cells were labeled with superparamagnetic iron oxide nanoparticles (SPIONs) that enable the visualization of MSCs using high-resolution (11T) magnetic resonance imaging (MRI). Biodistribution studies were performed using nonlinear-longitudinal-response-M2 (NLR-M2) measurements with subsequent histological analyses. Results: MSCs isolated from bone marrow of adult rats were efficiently labeled by SPIONs as was demonstrated by confocal and transmission electron microscopies. Cytotoxicity studies (i.e., MTT assay) clearly demonstrated that intracellular inclusion of nanoparticles did not affect the cell survival as well as the in vitro adipogenic, osteogenic and hondrogenic differentiation capacity. In vivo studies showed that following intravenous injection of the SPIONs-labeled MSCs in the glioma bearing animals the cells accumulated in the tumor site. On the T2-weighted MR images the cells presented as ´dark zones´ in the glioma tissue. Subsequent biodistribution analyses with the help of NLR-M2 method indicated retention of MSCs in the tumor that was further confirmed by histological assessment. Conclusions: Taken together, the presented study suggests that MSCs could be applied for noninvasive targeting and imaging of malignant brain tumors.
Abstract 332: Nanostructure-Templated Alignment of Cardiomyocytes for 3-Dimensional Cardiac Tissue Engineering
Authors: Eduard Sleep, Jason Mantei, Mark McClendon, Eneda Hoxha, Raj Kishore, Samuel I Stupp
Journal: Circulation Research (2012)

Introduction: Heart muscle shows a significant amount of alignment and strategies for cardiac tissue engineering should aim at mimicking such topology. So far, conditions to align cardiomyocytes in three-dimensional (3D) engineered cardiac constructs include static and active mechanical stress and the application of a directional electric field. However, the question of how topological cues from the matrix in which cardiomyocytes are embedded affect their alignment has not been addressed yet. Here, we investigated how cardiomyocytes align and mature in novel 3D gels made out of peptide amphiphiles (PAs) that can be aligned at the nanostructure level. Methods: We seeded HL-1 cardiomyocytes, mouse ES cell-derived cardiomyocytes and human iPS cell-derived cardiomyocytes into PA solutions that were either or not aligned upon gellation. We assessed the alignment of the cardiomyocytes along with their maturation status by observing their structural proteins and the formation of functional syncitiums by connexin 43 expression and the propagation of calcium fluxes. We also tested whether the stiffness of the gel affected the above-mentioned parameters by changing the chemical structure of the PAs. Results: We found that cardiomyocytes aligned along the direction of the alignment of the nanostructures in the gel and that the alignment of the matrix contributed to the functional maturation of the construct. Moreover, we observed a relationship between the stiffness of the gels and the alignment of the cardiomyocytes. Conclusions: This study shows for the first time that the nanostructural features of 3D scaffolds can be exploited to create aligned cardiac constructs.
Identification of Super-Enhancer-Associated Cancer Genes Provides Novel Therapeutic Targets in Adult T-Cell Leukemia/Lymphoma
Authors: Regina Wan Ju Wong, Phuong Thi Ngoc Cao, Wei Zhong Leong, Alice Wei Yee Yam, Tinghu Zhang, Shinsuke Iida, Takashi Okamoto, Ryuzo Ueda, Nathanael S. Grey, Takashi Ishida, Takaomi Sanda
Journal: Blood (2016)
What is the physiological time to recovery after concussion? A systematic review
Authors: Joshua Kamins, Erin Bigler, Tracey Covassin, Luke Henry, Simon Kemp, John J Leddy, Andrew Mayer, Michael McCrea, Mayumi Prins, Kathryn J Schneider, Tamara C Valovich McLeod, Roger Zemek, Christopher C Giza
Journal: British Journal of Sports Medicine (2017)

<h3>Aim or objective</h3> The aim of this study is to consolidate studies of physiological measures following sport-related concussion (SRC) to determine if a time course of postinjury altered neurobiology can be outlined. This biological time course was considered with respect to clinically relevant outcomes such as vulnerability to repeat injury and safe timing of return to physical contact risk. <h3>Design</h3> Systematic review. <h3>Data sources</h3> PubMed, CINAHL, Cochrane Central, PsychINFO. <h3>Eligibility criteria for selecting studies</h3> Studies were included if they reported original research on physiological or neurobiological changes after SRC. Excluded were cases series &lt;5 subjects, reviews, meta-analyses, editorials, animal research and research not pertaining to SRC. <h3>Results</h3> A total of 5834 articles were identified, of which 80 were included for full-text data extraction and review. Relatively few longitudinal studies exist that follow both physiological dysfunction and clinical measures to recovery. <h3>Summary/conclusions</h3> Modalities of measuring physiological change after SRC were categorised into the following: functional MRI, diffusion tensor imaging, magnetic resonance spectroscopy, cerebral blood flow, electrophysiology, heart rate, exercise, fluid biomarkers and transcranial magnetic stimulation. Due to differences in modalities, time course, study design and outcomes, it is not possible to define a single ‘physiological time window’ for SRC recovery. Multiple studies suggest physiological dysfunction may outlast current clinical measures of recovery, supporting a buffer zone of gradually increasing activity before full contact risk. Future studies need to use generalisable populations, longitudinal designs following to physiological and clinical recovery and careful correlation of neurobiological modalities with clinical measures.
P16.30 4th ventricle glioblastoma
Authors: E. Unal, S. Isik, M. Gurbuz, K. Kilic
Journal: Neuro-Oncology (2017)

Introduction: We present the 2nd case ever known in English literature describing a glioblastoma of the fourth ventricle originating from cerebellar peduncle. CASE DESCIPTION: A 66 years old woman was admitted to hospital with dizziness and nausea for four months. An MRI scan showed fourth ventricle mass. First impression was an ependymoma due to MRI scan characteristics. Results: A surgery was performed and histopathology revealed Grade IV glial tumor. Radiotherapy was done. CONCLUSION: This report suggests that GBM can mimic every tumor in the CNS. Surgery is the best option for these tumors not only for aggressive behaviour of glioblastoma but also to prevent hydrocephalus and associated symptoms.
A Middle-aged Man With Progressive Ophthalmoparesis, Ataxia, and Spastic Paraparesis
Authors: Nathan H. Kung, Gregory P. Van Stavern, Robert C. Bucelli
Journal: JAMA Neurology (2017)

A 50-year old man presented for evaluation of progressive gait ataxia with a superimposed spastic paraparesis. During his clinic visit, he was also observed to have slow and limited eye movements. In this article, we discuss the clinical approach to this triad of symptoms and guide the reader to discover the patient's ultimate genetic diagnosis.
P17.09 Lipid alteration following proton beam irradiation in mouse brain of radiation necrosis model
Authors: N. Kondo, K. Nakayama, Y. Sakurai, T. Takata, K. Kume, S. Miyatake, T. Inoue, O. Ogawa, M. Suzuki
Journal: Neuro-Oncology (2017)

Introduction: Brain radiation necrosis (RN) is irreversible severe adverse effect after radiation therapy for brain tumors over 60 Gy. Effective treatment for this irreversible event has not been established. The lying mechanism of RN is to be elucidated in order to establish a new therapy. We have established brain RN mouse model using proton beam at the Wakasa Wan Energy research Center. In this model, RN was induced 8 months after irradiation and the histology of the necrosis recapitulated the human RN patients [Kondo N.2015]. So far, some researchers investigated the mechanism of RN based on protein level. However, with the advanced mass spectrometry technology, lipid mediator response to ionizing radiation was reported [Laiakis EC, 2014]. Therefore, in this study, lipid alteration after proton beam irradiation was investigated in mouse brain RN model using high-resolution matrix- assisted laser desorption/ionizing imaging mass spectrometry (HR-MALDI-IMS). Materials and Methods: Generation of mouse brain RN model: C57BL/6J mice were irradiated in the restricted area of right brain at 60 Gy using proton beam. Tissue preparation: After 4 months later mouse was sacrificed by transcardial perfusion with cold PBS. The brain was extracted and immediately frozen in liquid nitrogen and kept in -80°C. The brain was sliced to a thickness of 4 μm with a cryostat and placed onto an indium tin oxide coated glass slide and stored at -20 °C until matrix application and subsequent HR-MALDI-IMS analysis. Each slide was anchored in vacuum deposition equipment and coated with 9-aminoacridine hemihydrates (9-AA) matrix layer obtained by sublimation at 220°C. The sequential sections were mounted onto glass slides for hematoxylin and eosin (H&E) staining. HR-MALDI-IMS analysis: HR-MALDI-IMS analysis was performed on a high-resolution microscopic imaging mass spectrometer (iMScope; Shimadzu, Kyoto, Japan). Mass spectrometry data were acquired in negative and positive mode in the mass range of m/z 700-1000. Statistical Analysis: Hierarchical Cluster Analysis was performed by Imaging MS Solution (ver 1, 12, 26; Shimadzu, Kyoto, Japan). Results: Compared to non-irradiated area, in the irradiated right hemisphere, i) elevation of phosphatidylcholine (PC) (34:1, 36:4, 36:1, 38:6, 40:6) and ii) decline of phosphatidylinositol (PI) (36:4, 38:4) were detected. Conclusion: The data indicated the phospholipid alterations after irradiation in mouse brain RN model in the chronic phase before establishment of RN. Further analysis for component of these phospholipids may include the precursor of lipid mediator, arachidonic acid (AA) or other fatty acids. We will investigate time-dependent change of phospholipids using mouse brain RN model and HR-MALDI-IMS analysis then finally find the responsible lipid mediators which induce brain RN.Grant: Kyoto University Research Development Program
OS09.9 Identification of IDH1R132H-specific T cell receptors from glioma patients and from MHC-humanized mice
Authors: L. Bunse, T. Bunse, K. Sanghvi, E. Green, F. Sahm, T. Omokoko, U. Sahin, M. Schmitt, W. Wick, M. Platten
Journal: Neuro-Oncology (2017)

Introduction: Central to an effective immunotherapy for gliomas are the discovery of tumor-specific antigens and the development of therapeutic strategies that effectively exploit them. One such example is the mutation in the gene encoding for isocitrate dehydrogenase 1 (IDH1). IDH1R132H is present in 80 % of grade II and grade III gliomas and secondary glioblastomas. We have previously shown that an IDH1R132H-peptide vaccine evokes an MHC class II-restricted T-helper cell response and is therapeutic in an MHC-humanized mouse sarcoma model. Materials and Methods: To identify IDH1R132H-specific T-cell receptors (TCRs), a T-cell line was generated from splenocytes of vaccinated MHC-humanized mice by re-stimulations with autologous IDH1R132Hp132-142-loaded splenocytes. Subsequently, T-cells were sorted for IDH1R132H-specificity exploiting IDH1R132H-specific HLA-DR1-tetramers. In addition, we analyzed IDH1R132H-reactive T-cells from an HLA-DR13+ and HLA-DR16+ patient with progressive IDH1R132H+ astrocytoma and IDH1R132H-specific immune response. Results: Sequencing analyses of the V-J or V-D-J regions of the TRA and TRB genes, respectively, revealed three dominant TRA and TRB sequences in the established murine T-cell line. Full length murine TCRs were constructed by pairing the two most dominant TRA and TRB sequences and cloned into expression vectors for functional validation. T-cells from the glioma patient were expanded in vitro and subjected to single-cell-sorting and subsequent TCR sequencing. 11 different TCR sequences have been identified. Conclusions: Identification of IDH1R132H-specific TCRs may expand the immunotherapeutic spectrum, e.g. enable adoptive T-cell transfer, for IDH1R132H-mutated gliomas.
Concurrent Isolation of 3 Distinct Cardiac Stem Cell Populations From a Single Human Heart Biopsy
Authors: Megan M. Monsanto, Kevin S. White, Taeyong Kim, Bingyan J. Wang, Kristina Fisher, Kelli Ilves, Farid G. Khalafalla, Alexandria Casillas, Kathleen Broughton, Sadia Mohsin, Walter P. Dembitsky, Mark A. Sussman
Journal: Circulation Research (2017)

The relative actions and synergism between distinct myocardial-derived stem cell populations remain obscure. Ongoing debates on optimal cell population(s) for treatment of heart failure prompted implementation of a protocol for isolation of multiple stem cell populations from a single myocardial tissue sample to develop new insights for achieving myocardial regeneration.Establish a robust cardiac stem cell isolation and culture protocol to consistently generate 3 distinct stem cell populations from a single human heart biopsy.Isolation of 3 endogenous cardiac stem cell populations was performed from human heart samples routinely discarded during implantation of a left ventricular assist device. Tissue explants were mechanically minced into 1 mm3 pieces to minimize time exposure to collagenase digestion and preserve cell viability. Centrifugation removes large cardiomyocytes and tissue debris producing a single cell suspension that is sorted using magnetic-activated cell sorting technology. Initial sorting is based on tyrosine-protein kinase Kit (c-Kit) expression that enriches for 2 c-Kit+ cell populations yielding a mixture of cardiac progenitor cells and endothelial progenitor cells. Flowthrough c-Kit- mesenchymal stem cells are positively selected by surface expression of markers CD90 and CD105. After 1 week of culture, the c-Kit+ population is further enriched by selection for a CD133+ endothelial progenitor cell population. Persistence of respective cell surface markers in vitro is confirmed both by flow cytometry and immunocytochemistry.Three distinct cardiac cell populations with individualized phenotypic properties consistent with cardiac progenitor cells, endothelial progenitor cells, and mesenchymal stem cells can be successfully concurrently isolated and expanded from a single tissue sample derived from human heart failure patients.
P03.14 Validation of microscopy with ultraviolet surface excitation - MUSE - imaging of human primary and metastatic brain tumors
Authors: M. Lechpammer, M. Tian, K. Shahlaie, F. Fereidouni, Z. T. Harmany, A. D. Borowsky, D. Zagzag, R. M. Levenson
Journal: Neuro-Oncology (2017)

Introduction: Small tissue specimens, like brain tissue core-needle biopsies, can be consumed during the primary morphological diagnostics, leaving little or no tumor sample available for molecular analyses. The consequence is either that the patient receives no molecular data, or may be subjected to additional, uncomfortable, and occasionally dangerous, brain tissue-harvesting procedures. Development of tissue-sparing, slide-free methods for rapid tissue histological analysis may eliminate a need for frozen section and ensure tissue availability for molecular testing in addition to morphological diagnosis. Materials and Methods: In this pilot study we have validated diagnostic reliability of MUSE (microscopy using ultraviolet surface excitation) imaging – a novel, tissue-sparing microscopy technique that obviates conventional histology processing, formalin-fixation and paraffin-embedding (FFPE) – in the pathologic analysis of primary and metastatic brain and spinal cord tumors. A panel of board-certified pathologists conducted blinded analysis to compare diagnostic accuracy of MUSE images vs. standard FFPE, microtome-sectioned and H&E-stained slides of the same brain tumor specimens. Any differences in diagnosis (either between MUSE and conventional methodology or within the panel of observers) were graded on a scale of (0) equivalent (1) minor difference probably not clinically significant (2) intermediate difference such as differences in size measurements or grade (3) major difference (falsely positive or negative). Results: 24 adult patients (14 male, 10 female), mean age 54 years (range 19 – 83 years), who underwent surgical resection for newly diagnosed brain and spinal cord tumors were included into the study. 7/24 (29%) were diagnosed with diffuse astrocytic or oligodendroglial tumors; 8/24 (33.5%) with meningioma’s; 3/24 (12.5%) with ependymal and choroid plexus tumors; 3/24 (12.5%) with tumors of the cranial or paraspinal nerves and 3/24 (12.5%) with metastatic tumors by the conventional methodology. We have found 97% concordance between MUSE and light microscopy diagnostics across all examined brain tumors, with 94% overall concordance (87% based on tumor grade) within the pathologists panel. In addition, MUSE topographical information from portions of samples below the plane of the cut surface provided novel 2.5-dimensional insights, especially valuable for analyzing complex neuroanatomical structures. Conclusions: Diagnostic validation of MUSE imaging reported here serves as a proof-of-concept showing that this new optical microscopy technique may rapidly generate diagnostic-quality histological images of brain and spinal cord tumors, with high resolution and enhanced content, from fresh or fixed tissue. More extensive studies are thus warranted to fully evaluate potential of using MUSE in routine neuropathology practice.
Sexual Dimorphism of Parental Care: From Genes to Behavior
Authors: Noga Zilkha, Niv Scott, Tali Kimchi
Journal: Annual Review of Neuroscience (2017)

Parental care is found in species across the animal kingdom, from small insects to large mammals, with a conserved purpose of increasing offspring survival. Yet enormous variability exists between different species and between the sexes in the pattern and level of parental investment. Here, we review the literature on the neurobiological mechanisms underlying maternal and paternal care, especially in rodents, and discuss the relationship between sex differences in behavior and sexual dimorphism in the brain. We argue that although several brain regions and circuits regulating parental care are shared by both sexes, some of the fundamental components comprising the maternal brain are innate and sex specific. Moreover, we suggest that a more comprehensive understanding of the underlying mechanisms can be achieved by expanding the methodological toolbox, applying ethologically relevant approaches such as nontraditional wild-derived animal models and complex seminatural experimental set-ups.