tbuckley/cabot-search huggingface dataset:
SURG-20. IDENTIFICATION OF INFILTRATIVE CANCER CELLS AT THE GLIOMA RESECTION CAVITY MARGIN USING STIMULATED RAMAN SCATTERING MICROSCOPY
Authors: Ramin Morshed, Melike Pekmezci, Jacob Young, Manish Aghi, Mike McDermott, Philip Theodosopoulos, Mitchel Berger, Shawn Hervey-Jumper
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Microscopic residual disease at the tumor margin is the primary barrier to complete resection which impacts outcome. Stimulated Raman scattering microscopy (SRM) has proven effective to classify CNS tumor tissue and detect tumor cells within grossly normal post mortem glioma specimens. In this study, we use SRM for detection of residual glioma cells within the resection cavity margins. METHODS Patients with gliomas undergoing surgical resection were included. Margin samples were taken after the primary surgeon determined the resection cavity wall to be grossly normal and were analyzed using (1) true H&amp;E, (2) SRM pseudo H&amp;E, (3) immunohistochemical stains (IHC) for IDH1-R132H or p53. The sections were scored on a scale of 0–3 by a neuropathologist blinded to the corresponding results from each modality (0=no definite tumor cells; 1=rare tumor cells; 2=moderate tumor cells with preserved neuropil; 3 = abundant tumor cells). Positive and negative predictive values and Spearman correlation coefficients were calculated. RESULTS Ninety-one margin samples from 19 patients were included. Tumors were WHO grade II (29.7%), III (38.5%), and IV (31.8%). There was a strong correlation between SRM and H&amp;E (Spearman correlation (r) = 0.76), SRM and IHC (r=0.81), and H&amp;E and IHC scores (r=0.91). PPV of SRM score of 3 was 100%. The presence of tumor cells on SRM (scores 1–3) strongly correlated with the presence of tumor cells on H&amp;E (PPV = 95%) and IHC (PPV = 91%). The absence of tumor cells on SRM correlated with absence of tumor on H&amp;E and IHC only 10% and 50% (NPV) of the time, respectively. CONCLUSIONS The PPV of utilizing SRM to detect residual glioma cells in grossly normal resection cavity margins is high however the NPV is low. SRM may have utility as a rapid point-of-care intraoperative tool for identification of infiltrative glioma within resection cavity margins.
Mutational Profile of Leukemic Stem Cells in FLT3-ITD Mutated AML
Authors: Tiziana Ottone, Serena Travaglini, Valentina Alfonso, Daniela Angelini, Gisella Guerrera, Serena Lavorgna, Mariadomenica Divona, Anna Maria Nardozza, Antonio Cristiano, Maria irno Consalvo, Marco de Bardi, Benedetta Neri, Francesco Marchesi, Carmelo Gurnari, Giovangiacinto Paterno, Vincenza Martini, Luca Battistini, Adriano Venditti, Francesco Buccisano, William Arcese, Francesco Lo-Coco, Maria Teresa Voso
Journal: Blood (2019)
NIMG-40. ROBUST MODALITY-AGNOSTIC SKULL-STRIPPING IN PRESENCE OF DIFFUSE GLIOMA: A MULTI-INSTITUTIONAL STUDY
Authors: Siddhesh Thakur, Jimit Doshi, Sung Min Ha, Gaurav Shukla, Aikaterini Kotrotsou, Sanjay Talbar, Uday Kulkarni, Daniel Marcus, Rivka Colen, Christos Davatzikos, Guray Erus, Spyridon Bakas
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Skull-stripping describes essential pre-processing in neuro-imaging, directly impacting subsequent analyses. Existing skull-stripping algorithms are typically developed and validated only on T1-weighted MRI scans without apparent gliomas, hence may fail when applied on neuro-oncology scans. Furthermore, most algorithms have large computational footprint and lack generalization to different acquisition protocols, limiting their clinical use. We sought to identify a practical, generalizable, robust, and accurate solution to address all these limitations. METHODS We identified multi-institutional retrospective cohorts, describing pre-operative multi-parametric MRI modalities (T1,T1Gd,T2,T2-FLAIR) with distinct acquisition protocols (e.g., slice thickness, magnet strength), varying pre-applied image-based defacing techniques, and corresponding manually-delineated ground-truth brain masks. We developed a 3D fully convolutional deep learning architecture (3D-ResUNet). Following modality co-registration to a common anatomical template, the 3D-ResUNet was trained on 314 subjects from the University of Pennsylvania (UPenn), and evaluated on 91, 152, 25, and 29 unseen subjects from UPenn, Thomas Jefferson University (TJU), Washington University (WashU), and MD Anderson (MDACC), respectively. To achieve robustness against scanner/resolution variability and utilize all modalities, we introduced a novel “modality-agnostic” training approach, which allows application of the trained model on any single modality, without requiring a pre-determined modality as input. We calculate the final brain mask for any test subject by applying our trained modality-agnostic 3D-ResUNet model on the modality with the highest resolution. RESULTS The average(±stdDev) dice similarity coefficients achieved for our novel modality-agnostic model were equal to 97.81%+0.8, 95.59%+2.0, 91.61%+1.9, and 96.05%+1.4 for the unseen data from UPenn, TJU, WashU, and MDACC, respectively. CONCLUSIONS Our novel modality-agnostic skull-stripping approach produces robust near-human performance, generalizes across acquisition protocols, image-based defacing techniques, without requiring pre-determined input modalities or depending on the availability of a specific modality. Such an approach can facilitate tool standardization for harmonized pre-processing of neuro-oncology scans for multi-institutional collaborations, enabling further data sharing and computational analyses.
Biochemical Findings in Suprarenal Adenoma
Authors: R. W. Logan
Journal: BMJ (1965)

Mml C" 303 said that she had swallowed her dental plate at about 2 p.m. the same day.She could feel it in her throat X-ray pictures were reported by a consultant radiologist " no foreign body is seen."On clinical examination it was obvious that the denture was impacted in the upper oesophagus.At oesophagoscopy at 5 p.m. the dental plate ._
The Biological Inferences from the Ranking of SF3B1 Mutations in the Clonal Hierarchy of Myeloid Neoplasia
Authors: Hassan Awada, Jibran Durrani, Ashwin Kishtagari, Vera Adema, Cassandra M Kerr, Sunisa Kongkiatkamon, Bartlomiej Przychodzen, Jack Khouri, Heesun J. Rogers, Manja Meggendorfer, Anjali S. Advani, Aziz Nazha, Torsten Haferlach, Hetty E. Carraway, Mikkael A. Sekeres, Jaroslaw P. Maciejewski, Valeria Visconte
Journal: Blood (2019)
Chronic Myelomonocytic leukemia: 2020 update on diagnosis, risk stratification and management
Authors: Mrinal M. Patnaik, Ayalew Tefferi
Journal: American Journal of Hematology (2019)

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, with an inherent risk for leukemic transformation (~15% over 3-5 years).Diagnosis is based on the presence of sustained (>3 months) peripheral blood monocytosis (≥1 × 109 /L; monocytes ≥10%), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ~ 30% of patients, while >90% have gene mutations. Mutations involving TET2 (~60%), SRSF2 (~50%), ASXL1 (~40%) and the oncogenic RAS pathway (~30%) are frequent; while the presence of ASXL1 and DNMT3A mutations and the absence of TET2 mutations negatively impact over-all survival.Molecularly integrated prognostic models include; the Groupe Français des Myélodysplasies (GFM), Mayo Molecular Model (MMM) and the CMML specific prognostic model (CPSS-Mol). Risk factors incorporated into the MMM include presence of nonsense or frameshift ASXL1 mutations, absolute monocyte count>10 × 109 /L, hemoglobin <10 g/dL, platelet count <100 × 109 /L and the presence of circulating immature myeloid cells. The MMM stratifies CMML patients into four groups; high (≥3 risk factors), intermediate-2 (2 risk factors), intermediate-1 (1 risk factor) and low (no risk factors), with median survivals of 16, 31, 59 and 97 months, respectively.Hypomethylating agents such as 5-azacitidine and decitabine are commonly used, with overall response rates of ~40%-50% and complete remission rates of ~7%-17%; with no impact on mutational allele burdens. Allogeneic stem cell transplant is the only potentially curative option, but is associated with significant morbidity and mortality.
The Landscape of Genome Wide Somatic Alterations Identifies a Good-Risk Group in Newly Diagnosed Multiple Myeloma
Authors: Mehmet Kemal Samur, Anil Aktas Samur, Tessa Han, Marco Roncador, Mariateresa Fulciniti, Raphael Szalat, Masood A. Shammas, Jill Corre, Paul G. Richardson, Florence Magrangeas, Stephane Minvielle, Philippe Moreau, Michel Attal, Anjan Thakurta, Kenneth C. Anderson, Giovanni Parmigiani, Herve Avet-Loiseau, Nikhil C. Munshi
Journal: Blood (2019)
Capecitabine-Related Eruption Mimicking Dermatomyositis in 2 Patients With Metastatic Breast Cancer
Authors: Gabriela A. Cobos, Caroline A. Nelson, Abeer Alsarheed, Avery LaChance, Alvaro C. Laga, Nicole LeBoeuf, Ruth Ann Vleugels
Journal: JAMA Dermatology (2019)

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 Dermatology 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 Dermatology journal
DNA Methyltransferase Inhibitors Promote Homologous Recombination Deficiency through Induction of Immune Signaling, Sensitizing Acute Myeloid Leukemia Cells to PARP Inhibitors
Authors: Aksinija A Kogan, Lena J Mclaughlin, Maria R. Baer, Stephen Baylin, Michael Topper, Feyruz V. Rassool
Journal: Blood (2019)
BRAFV600E-Positive Precursors As Molecular Markers of Bone Marrow Involvement in Pediatric Langerhans Cell Histiocytosis
Authors: Ko Kudo, Rika Kanezaki, Akie Kobayashi, Tomohiko Sato, Takuya Kamio, Shinya Sasaki, Imamura Masaru, Chihaya Imai, Masahiro Irie, Yoji Sasahara, Kumiko Ando, Harumi Kakuda, Takehiko Doi, Hiroshi Kawaguchi, Kazuko Kudo, Hirokazu Kanegane, Kiminori Terui, Tsutomu Toki, Etsuro Ito
Journal: Blood (2019)
Human Olfaction without Apparent Olfactory Bulbs
Authors: Tali Weiss, Timna Soroka, Lior Gorodisky, Sagit Shushan, Kobi Snitz, Reut Weissgross, Edna Furman-Haran, Thijs Dhollander, Noam Sobel
Journal: Neuron (2019)

(Neuron 105, https://doi.org/10.1016/j.neuron.2019.10.006; January 8, 2020) In one analysis and related figure, the authors reported on publicly available data from the Human Connectome Project (HCP). The authors applied a reporting format that was inconsistent with HCP policies. In the corrected version, which now appears online, the authors have amended the report to conform with HCP guidelines. The authors regret this oversight. Human Olfaction without Apparent Olfactory BulbsWeiss et al.NeuronNovember 6, 2019In BriefThe olfactory bulbs are the sole known relay station of odor information from nose to brain. Using MRI, Weiss et al. discover that ∼4% of left-handed women have normal olfaction without apparent olfactory bulbs. How these women can smell remains unknown. Full-Text PDF Open Access
Novel Biomarkers for Change in Renal Function in People With Dysglycemia
Authors: Hertzel C. Gerstein, Guillaume Paré, Matthew J. McQueen, Shun Fu Lee, Shrikant I. Bangdiwala, Aimo Kannt, Sibylle Hess
Journal: Diabetes Care (2019)

OBJECTIVE Diabetes is a major risk factor for renal function decline and failure. The availability of multiplex panels of biochemical markers provides the opportunity to identify novel biomarkers that can better predict changes in renal function than routinely available clinical markers. RESEARCH DESIGN AND METHODS The concentration of 239 biochemical markers was measured in stored serum from participants in the biomarker substudy of Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial. Repeated-measures mixed-effects models were used to compute the annual change in eGFR (measured as mL/min/1.73 m2/year) for the 7,482 participants with a recorded baseline and follow-up eGFR. Linear regression models using forward selection were used to identify the independent biomarker determinants of the annual change in eGFR after accounting for baseline HbA1c, baseline eGFR, and routinely measured clinical risk factors. The incidence of the composite renal outcome (i.e., renal replacement therapy, renal death, renal failure, albuminuria progression, doubling of serum creatinine) and death within each fourth of change in eGFR predicted from these models was also estimated. RESULTS During 6.2 years of median follow-up, the median annual change in eGFR was −0.18 mL/min/1.73 m2/year. Fifteen biomarkers independently predicted eGFR decline after accounting for cardiovascular risk factors, as did 12 of these plus 1 additional biomarker after accounting for renal risk factors. Every 0.1 mL/min/1.73 m2 predicted annual fall in eGFR predicted a 13% (95% CI 12, 14%) higher mortality. CONCLUSIONS Adding up to 16 biomarkers to routinely measured clinical risk factors improves the prediction of annual change in eGFR in people with dysglycemia.
INNV-06. TREATMENT RESPONSE TO BEVACIZUMAB OVER TWO YEARS IN A PATIENT WITH GENETICALLY PROVEN SOMATIC NEUROFIBROMATOSIS TYPE 2 MOSAICISM
Authors: Elena Basenach, Alisa Förster, Peter Raab, Samer Alzein, Gunnar Schmidt, Joachim Krauss, Fedor Heidenreich, Christian Hartmann, Bernd Auber, Bettina Wiese, Ruthild Weber
Journal: Neuro-Oncology (2019)

Abstract Neurofibromatosis type 2 (NF2) is a tumor predisposition syndrome characterized by the development of schwannomas, especially bilateral vestibular schwannomas (VS), and meningiomas. Heterozygous pathogenic variants in the NF2 gene are known to cause NF2, whereby somatic mosaicism is present in ~25% of simplex patients. In schwannomatosis, a disorder phenotypically similar to NF2, heterozygous SMARCB1 or LZTR1 variants may be causative. Recently, bevacizumab has shown efficiency as therapy for VS in some NF2 patients. We report on a thirty-three-year-old patient with bilateral VS, fourteen additional schwannomas and one intracranial meningioma. Next generation sequencing using a cancer gene panel and Sanger sequencing of LZTR1 on blood and oral mucosa DNA revealed no pathogenic variants in NF2, SMARCB1 or LZTR1. Sanger sequencing on DNA from three schwannomas identified the known NF2 nonsense variant c.784C &gt;T;p.(R262*) (NM_000268.3, GRCh37/hg19) in all tumors, leading to the diagnosis of somatic NF2 mosaicism. Because of hearing impairment and tumor progression the patient underwent an off-label therapy with 5mg/kg bevacizumab. To determine treatment response, we evaluated MRI scans from five pre-therapeutic and two therapeutic years as well as pure-tone audiometry. After 25 months of treatment, (i) the pure-tone average improved by 11.2 dB indicating a hearing benefit, (ii) four of seven non-vestibular schwannomas showed a volume reduction of ≥ 20%, (iii) the volume of three of seven schwannomas stabilized, and (iv) the growth rate of the meningioma decreased. In conclusion, in a patient with somatic NF2 mosaicism, an off-label therapy with bevacizumab was efficient with respect to hearing improvement and tumor shrinkage in over half of non-vestibular schwannomas over a period of two years.
Malignant T-Cells and Normal Intratumoral T-Cells Have Similar Expression of Immune Checkpoint Molecules in Angioimmunoblastic T-Cell Lymphoma
Authors: Joshua C Pritchett, Zhi-Zhang Yang, Hyojin Kim, Jose C Villasboas, Andrew L. Feldman, James R. Cerhan, Stephen M Ansell
Journal: Blood (2019)
Pevonedistat, a Nedd-8 Activating Enzyme Inhibitor, Upregulates NOXA to Increase Effectiveness of Azacitidine and Venetoclax in Preclinical Models of Acute Myelogenous Leukemia
Authors: Brianna N Smith, Dan Cojocari, Julie J Purkal, Maria Arrate, Haley E. Ramsey, Joel D. Leverson, Erwin Boghaert, Darren C. Phillips, Michael R. Savona
Journal: Blood (2019)
Maternal Deaths from Aspiration Asphyxia
Authors: R. Jamieson
Journal: BMJ (1963)

BRDISH 1129 enough to keep him awake at night.He had some frequency of micturition but no dysuria, and his pain was aggravated by coughing and deep breathing.On examination his temperature was 101.8°F. (38.8°C.), pulse 96, respiration 20.The W.B.C. count was 11,200 (90% neutro- phils).The E.S.R. was 22 mm. in the first hour.The urine was acid in reaction and contained neither protein nor pus cells and yielded no significant bacterial growth on culture.A nose swab grew Staph.pyogenes.An x-ray of chest and left ribs showed no abnormality.A blood culture also grew Staph.pyogenes.The only abnormal physi- cal signs were tenderness in the left loin, renal angle, and over the left lower ribs, posteriorly with obvious swelling in the same regions.The temperature remained around 104°F.
SDR9C7 catalyzes critical dehydrogenation of acylceramides for skin barrier formation
Authors: Takuya Takeichi, Tetsuya Hirabayashi, Yuki Miyasaka, Akane Kawamoto, Yusuke Okuno, Shijima Taguchi, Kana Tanahashi, Chiaki Murase, Hiroyuki Takama, Kosei Tanaka, William E. Boeglin, M. Wade Calcutt, Daisuke Watanabe, Michihiro Kono, Yoshinao Muro, Junko Ishikawa, Tamio Ohno, Alan R. Brash, Masashi Akiyama
Journal: Journal of Clinical Investigation (2019)

The corneocyte lipid envelope, composed of covalently bound ceramides and fatty acids, is important to the integrity of the permeability barrier in the stratum corneum, and its absence is a prime structural defect in various skin diseases associated with defective skin barrier function. SDR9C7 encodes a short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7) recently found mutated in ichthyosis. In a patient with SDR9C7 mutation and a mouse Sdr9c7-KO model, we show loss of covalent binding of epidermal ceramides to protein, a structural fault in the barrier. For reasons unresolved, protein binding requires lipoxygenase-catalyzed transformations of linoleic acid (18:2) esterified in ω-O-acylceramides. In Sdr9c7-/- epidermis, quantitative liquid chromatography-mass spectometry (LC-MS) assays revealed almost complete loss of a species of ω-O-acylceramide esterified with linoleate-9,10-trans-epoxy-11E-13-ketone; other acylceramides related to the lipoxygenase pathway were in higher abundance. Recombinant SDR9C7 catalyzed NAD+-dependent dehydrogenation of linoleate 9,10-trans-epoxy-11E-13-alcohol to the corresponding 13-ketone, while ichthyosis mutants were inactive. We propose, therefore, that the critical requirement for lipoxygenases and SDR9C7 is in producing acylceramide containing the 9,10-epoxy-11E-13-ketone, a reactive moiety known for its nonenzymatic coupling to protein. This suggests a mechanism for coupling of ceramide to protein and provides important insights into skin barrier formation and pathogenesis.
Isolated Trisomy 11 in Patients with Myeloid Malignancies - Is the Prognosis Not As Grim As Previously Thought?
Authors: Jan Philipp Bewersdorf, Rory M Shallis, Autumn Diadamo, Lohith Gowda, Nikolai A. Podoltsev, Steven D. Gore, Thomas Prebet, Stephanie Halene, Iris Isufi, Francine M. Foss, Scott F. Huntington, Tae Kon Kim, Manoj M Pillai, Terri L Parker, Natalia Neparidze, Noffar Bar, Stuart Seropian, Alexa J. Siddon, Amer M. Zeidan
Journal: Blood (2019)
EZH2 negatively regulates PD-L1 expression in hepatocellular carcinoma
Authors: Gang Xiao, Li-Lian Jin, Chao-Qun Liu, Yong-Chun Wang, Ya-Ming Meng, Zhong-Guo Zhou, Jing Chen, Xing-Juan Yu, Yao-Jun Zhang, Jing Xu, Limin Zheng
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Accumulating studies suggest that targeting epigenetic modifications could improve the efficacy of tumor immunotherapy; however, the mechanisms underlying this phenomenon remain largely unknown. Here, we investigated the ability of the epigenetic modifier, enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), to regulate the expression of immune checkpoint inhibitor, programmed death-1 ligand 1 (PD-L1) in hepatocellular carcinoma (HCC). <h3>Methods</h3> Immunohistochemistry and multiplex immunofluorescence staining were performed to analyze the expression and correlation of EZH2 and PD-L1 in HCC tissues. Immunoblotting, quantitative real-time PCR, flow cytometry, chromatin immunoprecipitation, and dual-luciferase reporter gene assays were performed to evaluate the regulatory roles of EZH2 on PD-L1 expression. <h3>Results</h3> In vitro cell experiments revealed that EZH2 negatively regulated the PD-L1 expression of hepatoma cell lines in IFNγ-dependent manner. Mechanistic studies demonstrated that EZH2 could suppress PD-L1 expression by upregulating the H3K27me3 levels on the promoters of <i>CD274</i> (encoding PD-L1) and interferon regulatory factor 1 (<i>IRF1</i>), an essential transcription factor for PD-L1 expression, without affecting the activation of the IFNγ-signal transducer and activator of transcription 1 (STAT1) pathway. Clinical samples from HCC patients with immune-activated microenvironments showed negative correlations between EZH2 and PD-L1 expression in hepatoma cells. Multivariate Cox analysis demonstrated that the combination of EZH2 and PD-L1 was an independent prognostic factor for both OS and RFS for patients with HCC. <h3>Conclusions</h3> The epigenetic modificator EZH2 can suppress the expression of immune checkpoint inhibitor PD-L1 by directly upregulating the promoter H3K27me3 levels of <i>CD274</i> and <i>IRF1</i> in hepatoma cells, and might serve as a potential therapeutic target for combination of immunotherapy for immune-activated HCC.