tbuckley/cabot-search huggingface dataset:
First external validation of sensitivity and specificity of the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for idiopathic inflammatory myopathies with a Japanese cohort
Authors: Masatoshi Jinnin, Akiko Ohta, Shoichiro Ishihara, Hirofumi Amano, Tatsuya Atsumi, Manabu Fujimoto, Takashi Kanda, Yasushi Kawaguchi, Atsushi Kawakami, Akio Mimori, Tsuneyo Mimori, Toshihide Mimura, Yoshinao Muro, Hajime Sano, Jun Shimizu, Tsutomu Takeuchi, Yoshiya Tanaka, Kazuhiko Yamamoto, Takayuki Sumida, Hitoshi Kohsaka
Journal: Annals of the Rheumatic Diseases (2019)

Objective To externally validate the performance of the new European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria set for idiopathic inflammatory myopathies (IIM) with a Japanese cohort. Methods This study included 420 IIM and 402 non-IIM cases. Probability of having IIM in each patient was calculated using the collected data set. The cut-off probability was set at 55%, as recommended by EULAR/ACR. Patients classified as IIM by the criteria were further subclassified with classification trees. Results When the probability cut-off was set at 55%, the sensitivity/specificity of the new criteria to diagnose IIM were 89.3%/91.0% in the total cohort, 88.1%/95.1% without muscle biopsy data and 90.4%/65.5% with biopsy data. The cohort included 12 overlap syndrome patients with biopsy data, who were included as non-IIM cases in accordance with traditional Japanese methods. When they were included in the IIM cases, the specificity in patients with biopsy increased to 74.4%. The sensitivity/specificity of the new criteria to diagnose polymyositis/dermatomyositis (PM/DM) plus juvenile and amyopathic DM in the Japanese cohort was 87.4%/92.4%, which were greater than those of the Tanimoto’s criteria revised to enable classification of amyopathic DM (ADM) (71.2%/87.8%) and were comparable with those of Bohan &amp; Peter’s criteria to diagnose those diseases except for ADM (88.4%/88.3%). Conclusions Our study externally validated high specificity of the new criteria for the first time, although with several limitations, including low percentage of child patients. The new criteria have higher sensitivity and/or specificity in classification of PM/DM than the previously reported criteria, demonstrating its usefulness for interethnic patients.
Regulatory T Cells (Treg) Are Depressed in Patients with Relapsed/Refractory Multiple Myeloma (MM) and Increases towards Normal Range in Responding Patients Treated with Lenalidomide (LEN).
Authors: Hang Quach, David Ritchie, Paul Neeson, Simon Harrison, Tsin Tai, Kellie Tainton, Kevin Lynch, Miles Prince
Journal: Blood (2008)
ATIM-40. CIRCULATING MYELOID-DERIVED SUPPRESSOR CELLS PREDICT FAVORABLE RESPONSE TO IMMUNE CHECKPOINT THERAPY IN A RANDOMIZED TRIAL OF NIVOLUMAB AND BEVACIZUMAB IN RECURRENT GBM
Authors: Manmeet Ahluwalia, Matthew Grabowski, Tyler Alban, Balint Otvos, Defne Bayik, Anas Saeed Bamashmos, Patricia Rayman, Marcela Diaz-Montero, David Reardon, Patrick Wen, David Peereboom, Justin Lathia
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM) creates an immunosuppressive environment that presents a challenge to efficacy of immunotherapeutic approaches. Results from the CheckMate-143 trial demonstrated responses in 8% of patients with nivolumab, underscoring the need for further insight into the mechanisms and markers of immune suppression and response. Given a limited set of biomarkers predictive of immunotherapy response in GBM, we explored the changes in immune cell populations in nivolumab and bevacizumab-treated GBM patients pre and post-treatment in order to help predict response. In these studies, we utilized traditional and newly developed approaches, including mass cytometry time-of-flight (CyTOF), single-cell RNA sequencing, and 10X Genomics simultaneous cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq). We analyzed patients’ samples in a randomized, phase 2 study of nivolumab and bevacizumab at GBM first recurrence (NCT03452579). Nine patients were identified as responders or non-responders at 8 weeks after therapy initiation. Utilizing peripheral blood samples, we observed a 6.4-fold decrease in immunosuppressive myeloid-derived suppressor cells (MDSCs) between baseline and first imaging follow-up in responders compared to non-responders, with a 4.9-fold decrease in the granulocytic MDSC (G-MDSC) subtype in responders over non-responders. While no significant changes in overall T-cell numbers were noted, expression of PD-1 on CD4+ T cells was significantly elevated at baseline and follow-up in responders as compared to non-responders – signatures which were confirmed by CyTOF. Given these immunophenotypic changes, preliminary results of a detailed investigation of this cohort by CITE-seq indicate that responders had increased IL7R-positive T cells post-treatment, which was not observed in non-responders. These results are currently being validated in an additional 40 patients that have been enrolled. Altogether, differences in immunophenotypes that were specific to responders and non-responders were observed, and characterization of these immune populations may be helpful in identifying GBM patients likely to benefit from immunotherapy.
Variant Pcgf-PRC1 Regulates Susceptibility of PRC2 Mediated H3K27me3 to Safeguard B Cell Fate of Hematopoietic Stem/Progenitor Cells
Authors: Junichiro Takano, Yaeko Nakajima-Takagi, Shinsuke Ito, Haruhiko Koseki, Atsushi Iwama, Tomokatsu Ikawa
Journal: Blood (2019)
Comparative study of RT-qPCR- and NGS- based platforms for circulating human microRNA biomarker detection
Authors: C. Gargiuli, M. Dugo, L. De Cecco, M.F. Iannò, A. Mariancini, E. Marchesi, E. Mancinelli, A. Micali, M. Boeri, G. Sozzi, M. Sensi
Journal: Annals of Oncology (2019)
Phase II Study of the Hyper-CVAD Regimen in Combination with Ofatumumab (HCVAD-O) As Frontline Therapy for Adult Patients (pts) with CD20-Positive B-Cell Acute Lymphoblastic Leukemia (B-ALL)
Authors: Guillaume Richard-Carpentier, Hagop M. Kantarjian, Marina Y Konopleva, Keyur P. Patel, Kathryn G. Roberts, Zhaohui Gu, Farhad Ravandi, Nitin Jain, Nicholas J. Short, Guillermo Garcia-Manero, Heather M Schroeder, Monica Kwari, Rebecca Garris, Rita Khouri, Mike Jones, Christopher Loiselle, Jorge E. Cortes, Koji Sasaki, Ghayas C. Issa, Tapan M. Kadia, Courtney D. DiNardo, Srdan Verstovsek, Naval G. Daver, Charles G. Mullighan, Susan M. O'Brien, Elias Jabbour
Journal: Blood (2019)
A Core Proliferative Program Induced By B-Cell Receptor Stimulation in Chronic Lymphocytic Leukemia Cells
Authors: Cédric Schleiss, Raphael Carapito, Luc Mathieu Fornecker, Leslie Muller, Paul Nicodeme, Ouria Tahar, Angélique Pichot, Laurent Mauvieux, Raoul Herbrecht, Myriam Maumy-Bertrand, Jean-Noel Freund, Christine Carapito, Seiamak Bahram, Frederic Bertrand, Laurent Vallat
Journal: Blood (2019)
CMET-18. IMPACT OF KRAS MUTATION STATUS ON THE EFFICACY OF IMMUNOTHERAPY IN LUNG CANCER BRAIN METASTASES
Authors: Adam Lauko, Assad Ali, Soumya Sagar, Addison Barnett, Hong Li, Samuel Chao, Glen Stevens, Nathan Pennell, David Peereboom, Jennifer Yu, Erin Murphy, Lilyana Angelov, Pauline Funchain, Alireza Mohammadi, John Suh, Gene Barnett, Manmeet Ahluwalia
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Immunotherapy is increasingly used in patients with non-small cell lung cancer brain metastases (NSCLCBM). KRAS mutations are associated with worse prognosis and there is no FDA approved targeted therapy. KRAS mutations are associated with increased expression of PD-L1. We evaluated the outcomes of NSCLCBM with KRAS mutations treated with immune checkpoint inhibitors (ICI). METHODS We reviewed 800 patients with NSCLCBM treated at our tertiary care center. 226 had known KRAS mutational status, 121 of which received immunotherapy. Overall survival (OS) was calculated from either the start of immunotherapy (when both groups received immunotherapy) or from the date of diagnosis of brain metastasis. Kaplan-Meier method and Cox Proportional hazard model were utilized to determine differences in OS and the Chi-square test was utilized to determine differences in PD-L1 expression. RESULTS In 109 patients where both KRAS and PD-L1 status were known, KRAS mutations had greater PD-L1 expression (80.1% vs 61.9% positive, p=0.04). There was no difference in OS between KRAS mutant vs KRAS wild-type patients treated with immunotherapy. Median survival from the start of immunotherapy was 15.6 vs 15.5 months respectively (p=0.7), after adjusting for age, KPS, lesion number and extra-cranial metastasis (HR = .91, p=.7). Patients with KRAS mutations treated with immunotherapy versus those who received chemotherapy had a 1-year OS from the diagnosis of brain metastasis of 60.9% vs 38.7% respectively (trending towards significance, p=0.05). KRAS wild-type patients treated with immunotherapy versus those who did not receive immunotherapy had a 1-year OS from the diagnosis of brain metastasis of 61.9% vs 62.5% (p=0.85), respectively. DISCUSSION KRAS mutations are associated with increased PD-L1 expression. Use of immunotherapy negates the poor outcomes seen traditionally in patients with NSCLCBM and KRAS mutations and it improves survival compared to use of chemotherapy. Our experience supports the use of immunotherapy in these patients.
Invasive Fungal Diseases Caused By Rare Pathogens in Large Cohort of Pediatric and Adult Patients after Hematopoietic Stem Cell Transplantation and Chemotherapy
Authors: Marina O Popova, Yuliya Rogacheva, Alisa G Volkova, Anastasia S Frolova, Inna V Markova, Aleksandr N Shvetcov, Ilya Y Nikolaev, Svetlana M Ignatyeva, Tatyana S Bogomolova, Asmic G Gevorgian, Olesia V Paina, Tatiana A Bykova, Elena I Darskaya, Oleg V Goloshchapov, Elena V Morozova, Maria D Vladovskaya, Ivan S Moiseev, Ludmila S Zubarovskaya, Nikolay N Klimko, Boris V Afanasyev
Journal: Blood (2019)
Evaluating Machine Learning Articles
Authors: Finale Doshi-Velez, Roy H. Perlis
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Efficient Correction of ELANE mutations in Primary HSPCs of Severe Congenital Neutropenia Patients Using CRISPR/Cas9 and rAVV6 HDR Repair Templates
Authors: Malte U Ritter, Benjamin Secker, Maksim Klimiankou, Masoud Nasri, Narges Aghaallaei, Benjamin Dannenmann, Regine Bernhard, Ingeborg Steiert, Karin Haehnel, Baubak Bajoghli, Cornelia Zeidler, Karl Welte, Julia Skokowa
Journal: Blood (2019)
Pitting breastfeeding against formula is simplistic and unhelpful
Authors: Catherine M Pennington
Journal: BMJ (2019)

Joffe and colleagues discuss the environmental benefits of breastfeeding over formula milk.1

As a doctor and recent breastfeeding mother, I would like to emphasise that breastfeeding is not an automatic bodily function, nor is it free or resource neutral. I was unable to breastfeed exclusively, …
Prognostic Impact of a Composite Genetic Profile Defined By Cytogenetics and Next Generation Sequencing at Diagnosis on Treatment Outcomes Following Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia
Authors: Georgina S. Daher-Reyes, TaeHyung Kim, Kyoung Ha Kim, Jae-Sook Ahn, Tracy L. Stockley, Jose Mario Capo-Chichi, Zeyad Al-Shaibani, Arjun Law, Wilson Lam, Fotios V. Michelis, Auro Viswabandya, Jeffrey H. Lipton, Rajat Kumar, Jonas Mattsson, Aaron D Schimmer, Caroline J McNamara, Tracy Murphy, Dawn Maze, Vikas Gupta, Hassan Sibai, Steven M Chan, Karen W.L. Yee, Mark D. Minden, Zhaolei Zhang, Andre C. Schuh, Dennis Dong Hwan Kim
Journal: Blood (2019)
A Computational Based Approach for Identification and Validation of Gene Mutations As Surrogate Markers of Gene Essentiality in Acute Myeloid Leukemia
Authors: Fernando Carazo, Edurne San Jose, Leire Garate, Estibaliz Miranda, Ana Alfonso Pierola, Sara Villar, Jose J. Rifon Roca, Bruno Paiva, Jesús San-Miguel, Xabier Agirre, Felipe Prósper, Angel Rubio
Journal: Blood (2019)
A Phase II Clinical Trial of Cpi-613 (devimistat) in Patients with Relapsed or Refractory Burkitt Lymphoma/Leukemia or High-Grade B-Cell Lymphoma with Rearrangements of MYC and BCL2and/or BCL6
Authors: Ariela Noy, Timothy S. Pardee, Liana Nikolaenko, Raphael Eric Steiner, Jeremy S. Abramson, Kieron Dunleavy, Sanjeev Luther
Journal: Blood (2019)
Predictors of Disease Progression and Survival in Patients with Myelodysplastic Syndrome Secondary to Inherited Bone Marrow Failure Syndromes
Authors: Reena Pabari, Elisa Cohen, Geoffrey Cuvelier, Robert J Klaassen, Conrad Fernandez, Josee Brossard, Sharon Abish, MacGregor Steele, Yves D. Pastore, Jeffrey H. Lipton, Meera Rayar, Vicky R. Breakey, Mariana Silva, Lawrence Jardine, Roona Sinha, Lisa Goodyear, Bruno Michon, Catherine Corriveau-Bourque, Lillian Sung, Yeon Jung Lim, Bozana Zlateska, Yigal Dror, Michaela Cada
Journal: Blood (2019)
TMOD-26. MODELING GLIOBLASTOMA BY IMPLANTATION OF INTACT PATIENT-DERIVED ORGANOIDS INTO RODENT BRAINS
Authors: Phuong Nguyen, Fadi Jacob, Ryan Salinas, Daniel Zhang, Hongjun Song, Guo-li Ming
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma multiforme (GBM) is the most common primary and aggressive brain tumors in adults with extremely poor prognosis and limited treatment options. A major hallmark of GBM is the rapid and diffused infiltration of tumor cells into the surrounding healthy tissue that contribute to tumor recurrence and therapeutic resistance. However, existing in vitro cell culture or in vivo xenograft models inadequately recapitulate the inter-tumoral and intra-tumoral heterogeneity which are key features of GBM. For example, common oncogenic drivers of GBM such as epidermal growth factor receptor (EGFR) amplification and EGFRvIII mutation do not persist in traditional in vitro models due to selection pressures, thus requires exogenous overexpression. Alternatively, EGFR statuses can be maintained in xenografted mice, but implantation of the primary GBM cells into the flank is required to first establish the tumor prior to secondary injection into the brains. Recently, we have established a novel protocol for culturing GBM tissue as organoids (GBOs) directly from patient tumor resection that retain many distinct cell populations in vitro with high fidelity evidenced by histological, whole-exome, bulk and single cell RNA analyses. Compared to prolonged generation time of previously established in vitro and xenograft models, our methodology is robust for generating GBOs within 1–2 weeks from initial resection. In addition, these GBOs can be readily xenografted into the adult mouse brains as an intact organoid, exhibit rapid and aggressive infiltration phenotypes, and maintains driver mutation EGFRviii within as little as one month. Consequently, they can be used to test in vivo treatment efficacies in a timely fashion. The presence of diverse cell types in this GBO model offers a promising platform for not only understanding of tumor biology, but also more strategic development of new therapies.
Diagnostic Classification of Bronchopulmonary Dysplasia: A Compromise between Defining Lung Disease versus Long-Term Outcome Prediction
Authors: Eduardo Bancalari, Nelson Claure, Deepak Jain
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Walter and Reyfman that because our bulk approach did not capture the relative contributions that specific AM subtypes made to the overall transcriptional signal, our ability to detect differentially expressed genes may have been weakened.Despite this limitation, our bulk transcriptomic approach has advanced our understanding of AM function in ARDS by identifying AM-specific genetic programs that were associated with good versus poor outcomes.Future work is needed to identify the AM subtypes that might be responsible for the bulk transcriptional signatures we identified in our clinical cohort.We believe that "lumping" and "splitting" approaches are complementary in furthering our understanding of the pathobiology of syndromes such as ARDS and sepsis.Analytical approaches such as cellular deconvolution ( 7) may be able to bridge bulk transcriptomic datasets and clinical cohorts like ours with highly granular single-cell datasets to fully leverage the strengths of both lumping and splitting approaches to understand the mechanisms of complex human syndromes.
Molecular Characterization of Bone Marrow and Peripheral Blood Compartments from Patients with Plasma Cell Leukemia in the Mmrf Commpass Study
Authors: Sheri Skerget, Austin Christofferson, Sara Nasser, Christophe Legendre, The MMRF CoMMpass Network, Jennifer Yesil, Daniel Auclair, Sagar Lonial, Jonathan J Keats
Journal: Blood (2019)
Transgender and gender non-conforming adult preparedness for aging: Concerns for aging, and familiarity with and engagement in planning behaviors
Authors: Richard S. Henry, Paul B. Perrin, Bethany M. Coston, Tarynn M. Witten
Journal: International Journal of Transgender Health (2019)

Background: Research on transgender and gender-nonconforming (TGNC) aging is limited. To date, most of the literature about TGNC aging has focused on discrimination (particularly in healthcare), violence and abuse, caregiving and family relations, and religiosity.Aims: The purposes of this study were to: (a) document concerns about aging among TGNC adults, including concerns that are identity-specific; (b) examine preparation for aging and end of life (i.e., familiarity and planning) among TGNC adults; and (c) examine potential differences in familiarity and planning based on gender identity.Methods: One hundred fifty-four individuals who currently or have ever identified as TGNC completed a national online survey assessing these constructs.Results: TGNC individuals reported many concerns about aging, both gender identity-specific and not. The most common aging concern was losing the ability to care for themselves followed by having to go into a nursing home or assisted living facility. The age preparatory behaviors individuals were most commonly aware of included: life insurance, wills, organ donation, regular medical checkups, living wills, durable power of attorney for healthcare, and trusts. Gender-nonconforming individuals had significantly more familiarity with age preparatory behaviors than trans feminine individuals, but had lower levels of planning to engage in age preparatory behaviors than both trans masculine and trans feminine individuals.Conclusion: The current findings highlight the need for providers to address age preparatory behaviors with TGNC individuals or provide referrals to support individuals in this planning.
Maternal embryonic leucine zipper kinase is a novel target for diffuse large B cell lymphoma and mantle cell lymphoma
Authors: Anke Maes, Ken Maes, Philip Vlummens, Hendrik De Raeve, Julie Devin, Vanessa Szablewski, Kim De Veirman, Eline Menu, Jerome Moreaux, Karin Vanderkerken, Elke De Bruyne
Journal: Blood Cancer Journal (2019)

Abstract Diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) are among the most aggressive B cell non-Hodgkin lymphomas. Maternal embryonic leucine zipper kinase (MELK) plays a role in cancer cell cycle progression and is associated with poor prognosis in several cancer cell types. In this study, the role of MELK in DLBCL and MCL and the therapeutic potential of MELK targeting is evaluated. MELK is highly expressed in DLBCL and MCL patient samples, correlating with a worse clinical outcome in DLBCL. Targeting MELK, using the small molecule OTSSP167, impaired cell growth and survival and induced caspase-mediated apoptosis in the lymphoma cells. Western blot analysis revealed that MELK targeting decreased the phosphorylation of FOXM1 and the protein levels of EZH2 and several mitotic regulators, such as Cdc25B, cyclin B1, Plk-1, and Aurora kinases. In addition, OTSSP167 also sensitized the lymphoma cells to the clinically relevant Bcl-2 inhibitor venetoclax by strongly reducing Mcl1 levels. Finally, OTSSP167 treatment of A20-inoculated mice resulted in a significant prolonged survival. In conclusion, targeting MELK with OTSSP167 induced strong anti-lymphoma activity both in vitro and in vivo. These findings suggest that MELK could be a potential new target in these aggressive B cell malignancies.
PTPN11 Mutated Acute Myeloid Leukemia (AML) Features an Abundant Epichaperome Network and Is Sensitive to the Epichaperome Inhibitor PU-H71
Authors: Justin D. Kaner, Montreh Tavakkoli, Lisa Toudic, Brett M. Stevens, Craig T Jordan, Tony Taldone, Gabriela Chiosis, Ellen K. Ritchie, Pinkal Desai, Michael B. Samuel, Sangmin Lee, Gail J. Roboz, Monica L. Guzman
Journal: Blood (2019)
NCMP-10. OUTCOMES WITH ACYCLOVIR TREATMENT IN HERPES SIMPLEX ENCEPHALITIS AFTER SURGERY FOR SOLID CNS TUMORS: A CASE REPORT AND SYSTEMATIC REVIEW OF THE LITERATURE
Authors: Solomon Ambe, Niloofar Yari, Ekokobe Fonkem, Ethan Benardete, Wencong Chen
Journal: Neuro-Oncology (2019)

Abstract OBJECTIVE To characterize the incidence, diagnostic and therapeutic trends and raise awareness of cases of Herpes Simplex Encephalitis occurring within 30 days after neurosurgery for CNS tumors. METHOD Literature search for cases meeting above criteria and meta-analysis of data. RESULTS 18 cases were studied. The most common tumor was meningitis. Encephalopathy, fever and seizure were the most common presenting symptoms (94%, 83% and 50 % respectively). 50% of cases had HSV-1, 22% had HSV-2, while 28% were unspecified. A majority of the patients (78%) received in acyclovir, with a 79% survival rate with treatment. Mortality rate was 100% without acyclovir treatment. Median time of starting acyclovir was 17 days. Most patients received steroids (78%) but steroids was not associated with a specific outcome. CONCLUSION Herpes simplex Encephalitis should be suspected after neurosurgery for tumors in patients with fever, encephalopathy or seizures and should be promptly treated with iv acyclovir. A delay in recognition and failure to treat could result in severe morbidity and mortality. In our study steroid use was not associated with improved outcome but larger studies are needed.
Differential Neutralization of Apixaban, Betrixaban, Edoxaban, and Rivaroxaban By Andexanet Alfa As Measured By Whole Blood Thromboelastographic Analysis
Authors: Siddharth Mehrotra, Debra Hoppensteadt, Walter Jeske, Omer Iqbal, Alfonso J Tafur, Bruce Lewis, Jawed Fareed
Journal: Blood (2019)