tbuckley/cabot-search huggingface dataset:
LTBK-12. EORTC 26951, RANDOMIZED STUDY OF ADJUVANT PCV AFTER 59.4 GY RADIOTHERAPY: VERY LONG TERM FOLLOW-UP
Authors: Martin van den Bent, Khe Hoang-Xuan, Alba Brandes, Johan Kros, M C M Kouwenhoven, Martin Taphoorn, Jean-Yves Delattre, Hans Bernsen, Marc Frenay, Nathalie Synhaeve, Michael Weller, Roelien Enting, Pim French, Winand Dinjens, Vassilis Golfinopoulos, Thierry Gorlia
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Between 1995 and 2002 the EORTC Brain Tumor Group conducted a prospective phase III study on adjuvant procarbazine, CCNU and vincristine (PCV) chemotherapy in anaplastic oligodendroglioma (AOD). A mature follow-up presented in 2012 showed survival benefit of the addition of PCV, in particular in 1p/19q co-deleted tumors and tumors with MGMT promoter methylation. We now present very long term follow-up. MATERIALS AND METHODS Patients were eligible if locally diagnosed with a newly diagnosed AOD. They were randomized between radiotherapy (RT, 33 x 1.8 Gy) and the same RT followed by 6 cycles PCV (RT/PCV). Primary endpoints were overall survival (OS) and progression free survival (PFS). 1p/19q status (FISH) was determined in 300 patient. Kaplan- Meier technique and Cox modeling were used for long term survival analysis. Primary analyses were adjusted for known prognostic factors. For other analyses no adjustment was performed. RESULTS With 368 patients included, a median follow-up of 18.4 years and 307 (83%) survival events, median and 20-year survival after RT/PCV versus RT alone were 42.3 mo and 16.8% vs 30.6 months and 10.1% (HR 0.78; 95% CI (0.63, 0.98), adjusted p=0.06). Eighty patients were 1p/19q codel of which 26 (33%) were still alive, in this subgroup median and 20-year survival after RT/PCV versus RT alone were 14 years and 37.1% versus 9.3 years and 13.6% (HR 0.60, 95% CI (0.35, 1.03), unadjusted p=0.06). Twenty year PFS in 1p/19q codel was 31.3% in RT/PCV treated patients and 10.8% in RT only treated patients (HR 0.49, 95% CI (0.29, 0.83), unadjusted p=0.007). In the 1p/19q codel subgroup age, WHO PS and necrosis at pathology were identified to be of independent prognostic value for OS. CONCLUSION This long term analysis confirms the earlier conclusions and provides data on long term survival in this patient group. In 1p/19q codel patients treated with RT/PCV, the 20-year PFS and OS rates are 31% and 37% respectively.
Manufacturing Scale-up and Preclinical Development of ET-01, Autologous CD34+ Cells with the BCL11A Erythroid Enhancer Edited By CRISPR/Cas9, for Patients with β-Thalassemia Major
Authors: Riguo Fang, Pengfei Yuan, Lingling Yu, Huihui Yang, Jie Liu, Jia Shi, Yongjian Zhang, Wei Zhang, Yiding Zhao, Zhiyong Peng, Chunfu Li, Yun Li, Dong Wei
Journal: Blood (2019)
Correction: Corrigendum: EGFR and MET receptor tyrosine kinase–altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers
Authors: Michela Garofalo, Giulia Romano, Gianpiero Di Leva, Gerard Nuovo, Young-Jun Jeon, Apollinaire Ngankeu, Jin Sun, Francesca Lovat, Hansjuerg Alder, Gerolama Condorelli, Jeffrey A Engelman, Mayumi Ono, Jin Kyung Rho, Luciano Cascione, Stefano Volinia, Kenneth P Nephew, Carlo M Croce
Journal: Nature Medicine (2014)
A Novel HCK and BTK Dual Inhibitor Kin-8194 Shows Superior Activity over Ibrutinib and Overcomes BTKC481S Mediated Ibrutinib Resistance in Vitro and In Vivo in MYD88 Mutated B-Cell Lymphomas
Authors: Guang Yang, Jinhua Wang, Xia Liu, Manit Munshi, Jiaji G Chen, Amanda Kofides, Lian Xu, Nicholas Tsakmaklis, Maria Demos, Maria Luisa Guerrera, Gloria G Chan, Cristina Jimenez, Zachary R Hunter, Christopher Patterson, Jorge J. Castillo, Sara J Buhrlage, Nathanael Gray, Steven P Treon
Journal: Blood (2019)
Shiga toxin–producing Escherichia coli–associated hemolytic uremic syndrome in solid organ transplant recipients
Authors: Simon Ville, Amandine Ydee, Claire Garandeau, Emmanuel Canet, Adrien Tissot, Diego Cantarovich, Véronique Frémeaux-Bacchi, Patricia Mariani-Kurkdjian, François Provôt, Fadi Fakhouri
Journal: Kidney International (2019)
A Molecular Mechanism Underlying Genotype‐Specific Intrahepatic Cholestasis Resulting From MYO5B Mutations
Authors: Arend W. Overeem, Qinghong Li, Yi‐Ling Qiu, Fernando Cartón‐García, Changsen Leng, Karin Klappe, Just Dronkers, Nai‐Hua Hsiao, Jian‐She Wang, Diego Arango, Sven C.D. van Ijzendoorn
Journal: Hepatology (2019)

Background and Aims Progressive familial intrahepatic cholestasis (PFIC) 6 has been associated with missense but not biallelic nonsense or frameshift mutations in MYO5B , encoding the motor protein myosin Vb (myoVb). This genotype‐phenotype correlation and the mechanism through which MYO5B mutations give rise to PFIC are not understood. The aim of this study was to determine whether the loss of myoVb or expression of patient‐specific myoVb mutants can be causally related to defects in canalicular protein localization and, if so, through which mechanism. Approach and Results We demonstrate that the cholestasis‐associated substitution of the proline at amino acid position 600 in the myoVb protein to a leucine (P660L) caused the intracellular accumulation of bile canalicular proteins in vesicular compartments. Remarkably, the knockout of MYO5B in vitro and in vivo produced no canalicular localization defects. In contrast, the expression of myoVb mutants consisting of only the tail domain phenocopied the effects of the Myo5b‐P660L mutation. Using additional myoVb and rab11a mutants, we demonstrate that motor domain‐deficient myoVb inhibited the formation of specialized apical recycling endosomes and that its disrupting effect on the localization of canalicular proteins was dependent on its interaction with active rab11a and occurred at the trans ‐Golgi Network/recycling endosome interface. Conclusions Our results reveal a mechanism through which MYO5B motor domain mutations can cause the mislocalization of canalicular proteins in hepatocytes which, unexpectedly, does not involve myoVb loss‐of‐function but, as we propose, a rab11a‐mediated gain‐of‐toxic function. The results explain why biallelic MYO5B mutations that affect the motor domain but not those that eliminate myoVb expression are associated with PFIC6.
Does Addition of Rituximab (R) to BEAM Conditioning Improve Outcomes of Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Undergoing Autologous Hematopoietic Cell Transplantation (auto-HCT)?
Authors: Deepa Jagadeesh, Navneet S. Majhail, He Yizeng, Kwang Woo Ahn, Carlos Litovich, Timothy S. Fenske, Anna Sureda, Mohamed A Kharfan-Dabaja, Mehdi Hamadani
Journal: Blood (2019)
Ibrutinib for Relapsed Mantle Cell Lymphoma after Standard First Line Therapy and ASCT Is Efficacious but Does Not Overcome the Impact of POD24 - a Retrospective Study from the LWP-EBMT
Authors: Claire Burney, Stephen Robinson, Ariane Boumendil, Hervé Finel, Irma Khvedelidze, Hannah Hunter, Xavier Poire, Bruno Lioure, Karl S Peggs, Robin Foà, Srinivas Pillai, Tom Van Meerten, Juan Jose Bargay, Christoph Schmid, Vergote Vibeke, Arnold Ganser, Luca Castagna, Ghulam J. Mufti, Silvia Montoto
Journal: Blood (2019)
Alveolar Macrophage Immunometabolism and Lung Function Impairment in Smoking and Chronic Obstructive Pulmonary Disease
Authors: Sarah L. O’Beirne, Sarah Ann Kikkers, Clara Oromendia, Jacqueline Salit, Mahboubeh R. Rostmai, Karla V. Ballman, Robert J. Kaner, Ronald G. Crystal, Suzanne M. Cloonan
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
Vaccine-elicited cross-neutralizing HIV antibodies directed to multiple sites of Env vulnerability following heterologous NFL trimer-liposome prime:boosting
Authors: V. Dubrovskaya, K. Tran, G. Ozorowski, J. Guenaga, R. Wilson, S. Bale, C. Cottrell, G. Seabright, S. O'Dell, J.L. Torres, L. Yang, Y. Feng, D. Leaman, N.V. Bernat, H. Turner, A. Movsesyan, T. Liban, M. Pancera, N. Doria-Rose, G.B.K. Hedestam, M. Zwick, M. Crispin, J.R. Mascola, A.B. Ward, R.T. Wyatt
Journal: Immunity (2019)
Outcomes after Stem Cell Transplant in Older Patients with Acute Myeloid Leukemia Treated with Venetoclax-Based Therapies
Authors: Keith W. Pratz, Courtney D. DiNardo, Martha L. Arellano, Anthony G. Letai, Michael Thirman, Vinod A. Pullarkat, Gail J. Roboz, Pamela S. Becker, Wan-Jen Hong, Qi Jiang, John Hayslip, Jalaja Potluri, Daniel A Pollyea
Journal: Blood (2019)
The Effect of CpG Sequences on Capsid-Specific CD8+ T Cell Responses to AAV Vector Gene Transfer
Authors: ZhiQuan Xiang, Raj K. Kurupati, Yan Li, Klaudia Kuranda, Xiangyang Zhou, Federico Mingozzi, Katherine A. High, Hildegund C.J. Ertl
Journal: Molecular Therapy (2019)

Transfer of genes by adeno-associated virus (AAV) vectors is benefiting patients with particular genetic defects. Challenges remain by rejection of AAV-transduced cells, which may be caused by CD8+ T lymphocytes directed to AAV capsid antigens. Reducing the number of CpG motifs from the genome of AAV vectors reduces expansion of naive T cells directed against an epitope within the capsid. In contrast, AAV capsid-specific memory CD8+ T cells respond more vigorously to AAV vectors lacking CpG motifs than to those with CpG motifs presumably reflecting dampening of T cell expansion by cytokines from the innate immune system. Depending on the purification method, AAV vector preparations can contain substantial amounts of empty AAV particles that failed to package the genome. Others have used empty particles as decoys to AAV-neutralizing antibodies. We tested if empty AAV vectors given alone or mixed with genome-containing AAV vectors induce proliferation of naive or memory CD8+ T cells directed to an antigen within an AAV capsid. Naive CD8+ T cells failed to respond to empty AAV vectors, which in contrast induced expansion of AAV-specific memory CD8+ T cells.
Dysfunctional missense variant of<i>OAT10/SLC22A13</i>decreases gout risk and serum uric acid levels
Authors: Toshihide Higashino, Keito Morimoto, Hirofumi Nakaoka, Yu Toyoda, Yusuke Kawamura, Seiko Shimizu, Takahiro Nakamura, Kazuyoshi Hosomichi, Akiyoshi Nakayama, Keiko Ooyama, Hiroshi Ooyama, Toru Shimizu, Miki Ueno, Toshimitsu Ito, Takashi Tamura, Mariko Naito, Hiroshi Nakashima, Makoto Kawaguchi, Mikiya Takao, Yosuke Kawai, Naoki Osada, Kimiyoshi Ichida, Ken Yamamoto, Hiroshi Suzuki, Nariyoshi Shinomiya, Ituro Inoue, Tappei Takada, Hirotaka Matsuo
Journal: Annals of the Rheumatic Diseases (2019)

Organic anion transporter 10 (OAT10), also known as SLC22A13, has hitherto been identified as a urate transporter by in vitro analyses.1 Despite the reported expression of OAT10 on the apical membrane of the renal proximal tubular cells,1 the physiological impact of OAT10 on urate handling in humans remains to be elucidated. Accumulating evidence suggests that functional variants of already-characterised, physiologically important urate transporters—URAT1/SLC22A12, GLUT9/SLC2A9, BCRP/ABCG2 and NPT1/SLC17A1—affect serum uric acid (SUA) levels and susceptibility of gout,2–6 the most common form of inflammatory arthritis. However, there are no reports on the association between OAT10 gene and either hyperuricaemia or gout. Here, for the first time, we reveal that a dysfunctional variant of OAT10 decreases both gout risk and SUA levels, suggesting OAT10 to be physiologically involved in urate reabsorption in the human kidney, as described below.

To explore exonic variants in OAT10 potentially associated with gout susceptibility, we sequenced all exons of OAT10 in 480 gout cases and 480 controls of Japanese male6 and conducted an association analysis (see online supplementary tables S1 and S2), followed by a replication study on 924 gout cases and 2113 controls (see online supplementary figure S1). In two identified OAT10 variants with minor allele frequency (MAF) >0.5%, only rs117371763 (c.1129C>T; p.Arg377Cys [R377C]) was significantly associated with gout susceptibility after Bonferroni correction (p=0.014). The significant association between rs117371763 and gout susceptibility was replicated, and our meta-analysis showed a significant protective effect of rs117371763 on gout susceptibility (OR=0.67; 95% CI 0.53 to 0.85; pmeta …
DEAF-1 is a transcription factor and potential tumor suppressor from 11p15.5 with reduced expression in prostate cancer
Authors: Michael W. Collard, Philip J. Jensik, Saira Khan, Ramya Raghaven, Kounosuke Watabe, Jodi I. Huggenvik
Journal: Cancer Research (2005)

830  DEAF-1 is a transcriptional regulator that maps to human chromosomal region 11p15.5, a region that undergoes loss of heterozygosity (LOH) in many types of human cancers including breast, ovarian, Wilms’, and prostate tumors. The high frequency with which LOH of 11p15.5 occurs in these cancers indicates a shared molecular mechanism in their initiation and/or progression. Immunohistochemistry was used to examine 81 prostate tumors and decreased DEAF-1 levels were observed in 41 of the tumors. Decreased DEAF-1 staining was statistically correlated with increased Gleason and nuclear grades and decreased patient survival. Decreased DEAF-1 staining was also correlated with decreased staining for the tumor suppressor PTEN. The human transcriptional promoter for PTEN was fused to a CAT reporter gene and in transient transfections of HEK293 cells, DEAF-1 produced transcriptional activation of the reporter gene. Thus, loss of DEAF-1 expression may contribute to decreased PTEN expression in prostate tumors. Cell extracts from the prostate cancer cell line PC3 contain DEAF-1 interacting proteins identified by mass spectrometry as components of DNA protein kinase. DEAF-1 was found to increase Bax-mediated apoptosis in transiently transfected cells by a transcription-independent mechanism. The rhabdomyosarcoma cell line RD was stably transfected using a tetracycline-inducible DEAF-1 gene, and the proapoptotic affects of DEAF-1 on UV-induced apoptosis was confirmed. PC3 cells stably transfected with DEAF-1 showed increased DEAF-1 levels following treatment with agents that produce DNA damage and genotoxic stress. These data suggest that DEAF-1 may be a potential tumor suppressor from 11p15.5 that normally functions as a proapoptotic factor in response to cellular stress and that is eliminated in prostate and perhaps other cancers.
Current Practices in Hernia Screening—Evidence Based or Profit Driven?
Authors: Ryan Howard, Justin B. Dimick, Dana A. Telem
Journal: JAMA Surgery (2019)

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Parenting experiences of cancer patients with minor children and their conversations about the possibility of death: A cross-sectional web-based survey for the online cancer community
Authors: Y. Usui, K. Kosugi, Y. Nishiguchi, T. Miura, D. Fujisawa, Y. Uehara, T. Kawaguchi, K. Izumi, J. Takehana, Y. Matsumoto
Journal: Annals of Oncology (2019)
Accuracy of in-utero MRI to detect fetal brain abnormalities and prognosticate developmental outcome: postnatal follow-up of the MERIDIAN cohort
Authors: Anthony R Hart, Nicholas D Embleton, Michael Bradburn, Daniel J A Connolly, Laura Mandefield, Cara Mooney, Paul D Griffiths
Journal: The Lancet Child & Adolescent Health (2019)

BackgroundIn utero MRI (iuMRI) detects fetal brain abnormalities more accurately than ultrasonography and provides additional clinical information in around half of pregnancies. We aimed to study whether postnatal neuroimaging after age 6 months changes the diagnostic accuracy of iuMRI and its ability to predict developmental outcome.MethodsFamilies enrolled in the MERIDIAN study whose child survived to age 3 years were invited to have a case note review and assessment of developmental outcome with the Bayley Scales of Infant and Toddler Development, the Ages and Stages Questionnaire, or both. A paediatric neuroradiologist, masked to the iuMRI results, reviewed the postnatal neuroimaging if the clinical report differed from iuMRI findings. Diagnostic accuracy was recalculated. A paediatric neurologist and neonatologist categorised participants' development as normal, at risk, or abnormal, and the ability of iuMRI and ultrasonography to predict developmental outcome were assessed.Findings210 participants had case note review, of whom 81 (39%) had additional investigations after age 6 months. The diagnostic accuracy of iuMRI remained higher than ultrasonography (proportion of correct cases was 529 [92%] of 574 vs 387 [67%] of 574; absolute difference 25%, 95% CI 21 to 29; p<0·0001). Developmental outcome data were analysed in 156 participants, and 111 (71%) were categorised as normal or at risk. Of these 111 participants, prognosis was normal or favourable for 56 (51%) using ultrasonography and for 76 (69%) using iuMRI (difference in specificity 18%, 95% CI 7 to 29; p=0·0008). No statistically significant difference was seen in infants with abnormal outcome (difference in sensitivity 4%, 95% CI −10 to 19; p=0·73).InterpretationiuMRI remains the optimal tool to identify fetal brain abnormalities. It is less accurate when used to predict developmental outcome, although better than ultrasonography for identifying children with normal outcome. Further work is needed to determine how the prognostic abilities of iuMRI can be improved.FundingNational Institute for Health Research Health Technology Assessment programme.
Impaired ATM activation in B cells is associated with bone resorption in rheumatoid arthritis
Authors: Kofi A. Mensah, Jeff W. Chen, Jean-Nicolas Schickel, Isabelle Isnardi, Natsuko Yamakawa, Andrea Vega-Loza, Jennifer H. Anolik, Richard A. Gatti, Erwin W. Gelfand, Ruth R. Montgomery, Mark C. Horowitz, Joe E. Craft, Eric Meffre
Journal: Science Translational Medicine (2019)

Defective ATM activation skews the B cell repertoire and increases RANKL production, promoting joint erosion in patients with rheumatoid arthritis.
A Knowledge-Based Approach for Clinical Annotation of Oncogenic Variants to Support Patient-Tailored Diagnosis in Myeloid Disease
Authors: Elsa Bernard, Kenichi Yoshida, Gunes Gundem, Jacob Grinfeld, Jyoti Nangalia, Daniel Leongamornlert, Noushin Farnoud, Juan Medina, Matahi Moarii, Charlie Massie, Yasunobu Nagata, Yusuke Okuno, Torsten Haferlach, Seishi Ogawa, Amanda Gilkes, Oliver G. Ottmann, Robert K. Hills, Nigel H. Russell, Brian J.P Huntly, Anthony R Green, Alan K. Burnett, Peter Campbell, Elli Papaemmanuil
Journal: Blood (2017)
Frequency of burn-out among palliative care physicians participating in continuing medical education.
Authors: Suresh Reddy, Sriram Yennu, Kimberson Cochien Tanco, Aimee Elizabeth Anderson, Diana Guzman, Janet L. Williams, Diane D. Liu, Eduardo Bruera
Journal: Journal of Clinical Oncology (2019)

77 Background: There is a growing concern about high frequency of burn out (BO) among physicians, and higher among palliative care providers, reported to be in the range of 62%. There are very limited studies done among Palliative Care (PC) physicians. Objective: The main objective of our study was to determine the frequency of burnout among PC physicians participating in PC Continuing Medical Education (CME). Secondary objectives included determining characteristics of physicians who expressed higher BO and also to determine overall attitudes towards PC practice. Methods: During 2018 Annual Hospice &amp; Palliative Medicine Board Review Course, we conducted a survey of 41 questions to determine the frequency of BO among physicians. This included Maslach Burn Inventory ( MBI )–General. The survey was given to both the in house and webinar participants. Results: Of 110 physicians who were given the surveys, 91/110 (83%) completed surveys. The median age was 48 years with 59 (65%) being females, 74 (81%) married. Majority, 41 (46%) were in community practice. 24 (38%) were in practice for more than 6 years, and 52 (57%) were board certified. 56 (62%) practiced PC for more than 50 % of time. Majority, 69 (76%) were doing clinical work. The median number of physician in the group practice was 3. 35 (38 %) of participants reported at least one symptom burnout based on MBI criteria. Only being single/separated correlated significantly with burn-out (p = 0.056). PC work is appreciated at their place of work by 73 (80%), 58 (64%) reported insurance was a burden, electronic medical record as a burden by 58 (64%), and 82 (90%) of physicians felt optimistic about continuing PC in future. Conclusions: BO among palliative care physicians who attended a board review course tends to be high, but lower than previously reported. Physicians who choose to attend CME may have unique motivating characteristics to cope better with stress and BO. More research is needed to better characterize BO among PC physicians.
Development of Injectable Amniotic Membrane Matrix for Postmyocardial Infarction Tissue Repair
Authors: Jeffrey J. D. Henry, Lawrence Delrosario, Jun Fang, Sze Yue Wong, Qizhi Fang, Richard Sievers, Surya Kotha, Aijun Wang, Diana Farmer, Praneeth Janaswamy, Randall J. Lee, Song Li
Journal: Advanced Healthcare Materials (2019)

Ischemic heart disease represents the leading cause of death worldwide. Heart failure following myocardial infarction (MI) is associated with severe fibrosis formation and cardiac remodeling. Recently, injectable hydrogels have emerged as a promising approach to repair the infarcted heart and improve heart function through minimally invasive administration. Here, a novel injectable human amniotic membrane (hAM) matrix is developed to enhance cardiac regeneration following MI. Human amniotic membrane is isolated from human placenta and engineered to be a thermoresponsive, injectable gel around body temperature. Ultrasound-guided injection of hAM matrix into rat MI hearts significantly improves cardiac contractility, as measured by ejection fraction (EF), and decrease fibrosis. The results of this study demonstrate the feasibility of engineering as an injectable hAM matrix and its efficacy in attenuating degenerative changes in cardiac function following MI, which may have broad applications in tissue regeneration.
Deep Profiling of Genetic Aberrations and Clonal Evolution in Follicular Lymphoma
Authors: Baoyan Bai, Daniel Vodák, Sigve Nakken, Jillian F. Wise, Yngvild Nuvin Blaker, Ole Christian Lingjærde, Marianne Brodtkorb, Vera Hilden, Gunhild Trøen, Suzanne Lorenz, Michael S. Lawrence, Ola Myklebost, Leonardo Meza-Zepeda, Klaus Beiske, Eivind Hovig, Erlend B. Smeland, Harald Holte, June Helen Myklebust
Journal: Blood (2019)
Overall survival (OS) from the AURA3 phase III study: Osimertinib vs platinum-pemetrexed (plt-pem) in patients (pts) with EGFR T790M advanced non-small cell lung cancer (NSCLC) and progression on a prior EGFR-tyrosine kinase inhibitor (TKI)
Authors: Y.-L. Wu, T.S.K. Mok, J.-Y. Han, M.-J. Ahn, A. Delmonte, S.S. Ramalingam, S.-W. Kim, F.A. Shepherd, J. Laskin, Y. He, H. Akamatsu, W.S.M.E. Theelen, W.-C. Su, T. John, M. Sebastian, H. Mann, M. Miranda, G. Laus, Y. Rukazenkov, V. Papadimitrakopoulou
Journal: Annals of Oncology (2019)