tbuckley/cabot-search huggingface dataset:
Clinical, laboratory, and temporal predictors of neutralizing antibodies against SARS-CoV-2 among COVID-19 convalescent plasma donor candidates
Authors: Jim Boonyaratanakornkit, Chihiro Morishima, Stacy Selke, Danniel Zamora, Sarah McGuffin, Adrienne E. Shapiro, Victoria L. Campbell, Christopher L. McClurkan, Lichen Jing, Robin Gross, Janie Liang, Elena Postnikova, Steven Mazur, Vladimir V. Lukin, Anu Chaudhary, Marie K. Das, Susan L. Fink, Andrew Bryan, Alex L. Greninger, Keith R. Jerome, Michael R. Holbrook, Terry B. Gernsheimer, Mark H. Wener, Anna Wald, David M. Koelle
Journal: Journal of Clinical Investigation (2020)

BACKGROUND. SARS-CoV-2–specific antibodies may protect from reinfection and disease, providing rationale for administration of plasma containing SARS-CoV-2–neutralizing antibodies (nAbs) as a treatment for COVID-19. Clinical factors and laboratory assays to streamline plasma donor selection, and the durability of nAb responses, are incompletely understood.
ZFP36L1, a Novel Potential Tumor Supressor Gene in Myelofibrosis, Epigenetically Deregulated By Methylation of the Enhancer Region
Authors: Nicolas Martinez-Calle, Marien Pascual, Raquel Ordoñez, Edurne San Jose Eneriz, Victor Segura, Giancarlo Castellano, Jose J. Rifon, Maria Jose Calasanz, José I. Martin-Subero, Xabier Agirre, Felipe Prosper
Journal: Blood (2017)
14P High CMTM6 and PD-L1 co-expression predict metastasis and poor prognosis in oesophageal squamous cell carcinoma
Authors: Y. Luo, C. Zhang, Z. Zhang, G. Zhang, L. Xue, Q. Zeng, Q. Xue, S. Gao, N. Sun, J. He
Journal: Annals of Oncology (2020)
MBRS-48. IDENTIFICATION OF NOVEL THERAPEUTIC APPROACHES FOR MYC-DRIVEN MEDULLOBLASTOMA
Authors: Kübra Taban, David Pauck, Mara Maue, Viktoria Marquardt, Hua Yu, Olivier Ayrault, Daniel Picard, Jasmin Bartl, Nan Qin, Arndt Borkhardt, Guido Reifenberger, Marc Remke
Journal: Neuro-Oncology (2020)

Abstract Medulloblastoma (MB) is the most common malignant brain tumor in children and is frequently metastatic at diagnosis. Treatment with surgery, radiation and multi-agent chemotherapy may leave survivors of these brain tumors with long-term deficits as a consequence. One of the four consensus molecular subgroups of MB is the MYC-driven group 3 MB, which is the most malignant type and has a poor prognosis under current therapy. Thus, it is important to discover more effective targeted therapeutic approaches. We conducted a high-throughput drug screening to identify novel compounds showing efficiency in group 3 MB using both clinically established inhibitors (n=196) and clinically-applicable compounds (n=464). More than 20 compounds demonstrated a significantly higher anti-tumoral effect in MYChigh (n=7) compared to MYClow (n=4) MB cell models. Among these compounds, Navitoclax and Clofarabine showed the strongest effect in inducing cell cycle arrest and apoptosis in MYChigh MB models. Furthermore, we show that Navitoclax, an orally bioavailable and blood-brain barrier passing anti-cancer drug, inhibits specifically Bcl-xL proteins. In line, we found a significant correlation between BCL-xL and MYC mRNA levels in 763 primary MB patient samples (Data source: “R2 https://hgserver1.amc.nl”). In addition, Navitoclax and Clofarabine have been tested in cells obtained from MB patient-derived-xenografts, which confirmed their specific efficacy in MYChigh versus MYClow MB. In summary, our approach has identified promising new drugs that significantly reduce cell viability in MYChigh compared to MYClow MB cell models. Our findings point to novel therapeutic vulnerabilities for MB that need to be further validated in vitro and in vivo.
ADRB1 Variants in Atrial Fibrillation: Small Steps and Giant Leaps Toward Personalized Therapy in Cardiovascular Disease⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Sharon Cresci
Journal: Journal of the American College of Cardiology (2012)
SURG-23. REOPERATION IN MOLECULAR SUBTYPES OF RECURRENT GLIOBLASTOMA
Authors: Antonio Dono, Ping Zhu, Emma Holmes, Takeshi Takayasu, Angel Blanco, Sigmund Hsu, Meenakshi Bhattacharjee, Jay-Jiguang Zhu, Leomar Y Ballester, Yoshua Esquenazi, Nitin Tandon
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Recurrent glioblastoma (rGBM) treatment is not well defined and multiple therapeutic approaches have been proposed, none of which has shown to prolong survival in randomized trials. The role of reoperation for rGBM is still unclear. While most studies demonstrate improve overall survival (OS) and post-progression survival (PPS), recent studies employing time-dependent analysis appear to undermine the OS benefit in reoperated patients. Moreover, the relevance of rGBM molecular subtypes that benefit from reoperation is an important question that may guide clinical decision-making. METHODS A retrospective review of rGBM demographics, clinical, molecular, and outcome characteristics was performed for all cases managed by us between 01/2005 to 10/2019 at our institution. IDH1/IDH2 status was determined by immunohistochemistry and/or next-generation sequencing (NGS). A genetic subanalysis was conducted for most rGBM IDH-wildtype (IDH-WT) by NGS. The primary outcome was PPS. Kaplan-Meier method, multivariable Cox proportional-hazards model, and accelerated failure time model were performed in survival analysis. Random survival forest was applied to identify variable importance. RESULTS 284 rGBM patients fulfill inclusion criteria, 145 (51.1%) had reoperation at their 1st recurrence. Reoperated patients were significantly younger, had better performance status, and had a higher extent of resection at initial surgery; meanwhile, they were less likely to receive bevacizumab. Patients undergoing reoperation experienced superior PPS (11.5 vs. 7.4, months, log-rank test: p= 0.002), which kept consistent in multivariable Cox model (HR: 0.62, p= 0.001). Moreover, reoperated rGBM IDH-WT (N= 238) had 37% reduced risk of post-progression death compared to non-reoperated patients. A subanalysis of rGBM IDH-WT molecular subtypes identified that EGFR mutant, NF1 wildtype, and TP53 wildtype subgroups could benefit from reoperation (all p&amp;lt; 0.008). CONCLUSIONS Maximal safe re-resection improved the PPS of rGBM regardless of their IDH status. Reoperation for 1st recurrence was especially beneficial for GBM IDH-WT harboring EGFR alteration, TP53 WT, and NF1-WT.
In acute ischemic stroke or TIA, adding ticagrelor to aspirin reduced stroke or death and increased severe bleeding
Authors: Michael D. Hill
Journal: Annals of Internal Medicine (2020)

ACP Journal Club15 December 2020In acute ischemic stroke or TIA, adding ticagrelor to aspirin reduced stroke or death and increased severe bleedingMichael D. Hill, MD, MScMichael D. Hill, MD, MScUniversity of Calgary, Calgary, Alberta, Canada (M.D.H.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ202012150-063 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationJohnston SC, Amarenco P, Denison H, et al. Ticagrelor and aspirin or aspirin alone in acute ischemic stroke or TIA. N Engl J Med. 2020;383:207-17. https://pubmed.ncbi.nlm.nih.gov/32668111Clinical Impact RatingsEmergency Med: Hospitalists: Neurology: References1 Wu CM, McLaughlin K, Lorenzetti DL, et al. Early risk of stroke after transient ischemic attack: a systematic review and meta-analysis. Arch Intern Med. 2007;167:2417-22. [PMID: 18071162] Google Scholar2 Kennedy J, Hill MD, Ryckborst KJ, et al. Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial. Lancet Neurol. 2007;6:961-9. [PMID: 17931979] Google Scholar3 Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369:11-9. [PMID: 23803136] Google Scholar4 Johnston SC, Easton JD, Farrant M, et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med. 2018;379:215-25. [PMID: 29766750] Google Scholar5 Pan Y, Chen W, Wang Y, et al. Association between ABCB1 polymorphisms and outcomes of clopidogrel treatment in patients with minor stroke or transient ischemic attack: secondary analysis of a randomized clinical trial. JAMA Neurol. 2019;76:552-60. [PMID: 30742211] Google Scholar6 Pereira NL, Farkouh ME, So D, et al. Effect of genotype-guided oral P2Y12 inhibitor selection vs conventional clopidogrel therapy on ischemic outcomes after percutaneous coronary intervention: the TAILOR-PCI randomized clinical trial. JAMA. 2020;324:761-71. [PMID: 32840598] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Calgary, Calgary, Alberta, Canada (M.D.H.)Disclosures: The commentator has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-3050. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 December 2020Volume 173, Issue 12Page: JC63KeywordsAntiplatelet therapyAspirinDisabilitiesHazard ratioHemorrhageIschemic strokeSafetyStenosisStrokeTransient ischemic attacks ePublished: 15 December 2020 Issue Published: 15 December 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
RONC-22. SECOND TUMORS IN PEDIATRIC PATIENTS TREATED WITH PROTON THERAPY TO THE CENTRAL NERVOUS SYSTEM
Authors: Daniel J Indelicato, James Bates, Raymond Mailhot-Vega, Christopher Morris, Eric Sandler, Phillip Aldana, Julie Bradley
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Previous institutional data suggests the 10-year cumulative incidence of second tumors is 3% in children treated with photon radiation for central nervous system (CNS) malignancy, with 90% of these tumors occurring in areas receiving ≤36 Gy. Comparative figures for children treated with proton therapy (PT) does not exist. METHODS 1056 consecutive pediatric patients with a median follow-up of 5.0 years were treated between 2006–2019 with double-scattered PT to a site within the craniospinal axis. 230 patients were ≤3 years old and 14 had neurofibromatosis. A second tumor was defined as any solid neoplasm with histologic features different from the original tumor that had arisen within the irradiated volume. RESULTS Five patients developed second tumors resulting in a 5- and 10-year cumulative incidence of 0.2% (95% CI: 0–1.2%) and 1.6% (95% CI: 0.6%-3.9%), respectively. Of those who developed second tumors, median age at radiation was 4.3 years old (range, 2.1 to 5.1 years old) and diagnoses consisted of medulloblastoma (n=2), ependymoma (n=2), and craniopharyngioma (n=1). The second tumors included high grade gliomas (n=3) and high grade sarcoma (n=1) that occurred in regions receiving at least 54 Gy. One patient with neurofibromatosis developed both a low-grade glioma and choroidal melanoma in craniospinal irradiation regions receiving 36 Gy. Four of five patients with second tumors are alive. CONCLUSION The reduction in moderate-to-low dose radiation exposure from proton therapy may be associated with a decreased incidence of second tumors in children treated for CNS neoplasms. More follow-up is needed to confirm these findings.
Role of yes‐associated protein in interleukin‐13 induced nasal remodeling of chronic rhinosinusitis with nasal polyps
Authors: Tian Yuan, Rui Zheng, Jing Liu, Kai Sen Tan, Zhi‐qun Huang, Xiang‐Min Zhou, Xiao‐xue Zi, Hui‐jun Qiu, Xin‐yue Wang, Wei‐hao Wang, Hui‐yi Deng, Yu‐bin Chen, Wei‐feng Kong, Qing‐wu Wu, Ying Huang, Hsiao Hui Ong, Xue‐kun Huang, Zhuang‐gui Chen, De‐Yun Wang, Qin‐Tai Yang
Journal: Allergy (2020)

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LINC-42. EPIDEMIOLOGICAL OVERVIEW OF CHILDHOOD CNS TUMORS IN THE NEUROSURGICAL UNIT IN YEREVAN, ARMENIA
Authors: Nune Karapetyan, Samvel Danielyan, Gevorg Tamamyan, Armen Tananyan, Liana Safaryan, Margar Martirosyan, Tatul Saghatelyan, Samvel Bardakhchyan, Ruzanna Papyan, Jemma Arakelyan, Karen Bedirian, Martin Harutyunyan, Vahagn Matevosyan, Nara Lalazaryan, Eduard Asatryan
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Central nervous system (CNS) tumors are the second most common malignant neoplasms among children worldwide. The current paper aims to analyze the situation in pediatric neuro-oncology in Armenia from the neurosurgical perspective. METHODS We have collected data of pediatric patients with CNS tumors treated in the Neurosurgery department of “Surb Astvasamayr” Medical Center from 01.01.2010 till 01.12.2019. Incidence by gender, age at diagnosis, and histopathology results were calculated. Survival rates were calculated based on the follow-up results performed until 30.12.2019. RESULTS Hospital-based data showed that during the previous 10 years 47 patients with CNS tumors received neurosurgical treatment in the unit, among them 66% were females. 38.3%, 31.9% and 29.8% of diagnosed patients were aged 0–4, 5–9, and 10–18 respectively. In 41 cases, the disease was not disseminated at diagnosis. The most common observed malignancies were low-grade gliomas (21.3%) and embryonal tumors (19.1%), followed by high-grade gliomas (14.9%) and ependymal tumors (8.5%). Follow-up information only for 33 patients is available. From them, 14 are dead and 19 alive. Survival rates in most common groups were 62.5%, 80%, 50%, and 50% respectively. The median follow-up time was 18 months (range 1–113 months). CONCLUSION Similar to the data reported in the literature, low-grade gliomas, and embryonal tumors are the most frequent pediatric CNS tumors in Armenia. On the other hand, the pediatric CNS tumor survival rates are lower compared to those reported in developed countries.
1O Clinical outcomes in post-operative ctDNA-positive muscle-invasive urothelial carcinoma (MIUC) patients after atezolizumab adjuvant therapy
Authors: T.B. Powles, Z.J. Assaf, N. Davarpanah, M. Hussain, S. Oudard, J.E. Gschwend, P. Albers, D. Castellano, H. Nishiyama, S. Daneshmand, P. Grivas, S. Sharma, H. Sethi, A. Aleshin, J. Zhang, V. Degaonkar, C. Bais, C.A. Carter, J. Bellmunt, S. Mariathasan
Journal: Annals of Oncology (2020)
DIPG-66. FEASIBILITY AND APPLICABILITY OF MOLECULAR GUIDED THERAPY IN HIGH GRADE GLIOMA/DIFFUSE MIDLINE GLIOMA: RESULTS FROM BEAT CHILDHOOD CANCER NMTRC-009 MOLECULAR GUIDED THERAPY STUDY
Authors: Virginia Harrod, Abhinav Nagulapally, Elizabeth Lewis, Giselle Sholler
Journal: Neuro-Oncology (2020)

Abstract High grade gliomas/diffuse midline gliomas (HGG/DMG) historically have a poor prognosis with an overall survival of less than 20% at 5 years. The pathophysiology is under close investigation across the world in efforts to understand this tumor type with aims of increasing effective treatment options. We present our results on the feasibility and outcomes of patients treated on our Molecular Guided Therapy study. Tumor samples were analyzed with whole exome (DNA) and RNA sequencing. Three drug matching algorithms were utilized to generate a report that was reviewed at a multi-institutional tumor board meeting, culminating in a proposed treatment protocol. Eleven patients enrolled, but one did not complete cycle 1 of therapy due to progression of disease, thus ten patients (6-HGG, 4-DMG) were evaluable and received at least 2 cycles of therapy. Time to reports generated and tumor board assembly was (median) 18 and 24 days, respectively. Secondary goals included evaluation of efficacy. Responses showed 50% of patients with stable disease or better at 2 cycles of therapy, but these were temporary with median time to progression of 81 days. In conclusion, we determined that it is feasible to collect individual biological DNA and RNA sequencing information to offer patients individualized treatment plans for this devastating group of diseases. Though data is not statistically significant, we show that there is a suggestion of efficacy in this approach to treatment for patients, indicating a need to expand on this treatment approach with individualized medicine.
EXTH-39. HEXON SWAPPING MITIGATES ANTI-VIRAL IMMUNE RESPONSE DURING BRAIN TUMOR VIROTHERAPY
Authors: Dong Ho Shin, Teresa Nguyen, Hong Jiang, Sagar Sohoni, Sumit Gupta, Ashley Ossimetha, Marta M Alonso, Candelaria Gomez-Manzano, Juan Fueyo
Journal: Neuro-Oncology (2020)

Abstract Cancer virotherapy is a paradigm-shifting treatment modality based on the capabilities of virus-mediated oncolysis to elicit an anti-tumor immune response. Phase 1 and 2 clinical trials have demonstrated the safety and efficacy of our oncolytic adenovirus DNX-2401 (Delta-24-RGD) for patients with recurrent malignant gliomas. While a subset of the patients showed significant benefits, our goal is to improve the response rate. Clearance of the therapeutic virus by dominant anti-viral immune responses may contribute to the observed limits of the virotherapy. Adenovirus serotype 5 that provides the backbone of most oncolytic adenoviruses is highly prevalent in the human population and neutralizing antibodies against the capsid protein hexon may inhibit viral infection and replication. In this study, we showed using immunofluorescence that in mice bearing orthotopic syngeneic glioblastoma GSC005 treated with Delta-24-RGD, IgG antibodies crossed the disrupted blood-brain barrier and infiltrated the brain tumor parenchyma to colocalize with the viral hexon, suggesting that the systemic immune response may eradicate the virus within the infected tumor. To overcome this obstacle, we generated a chimeric virus called Delta-24-RGD-H43m with hexon hypervariable regions replaced with those from a lesser prevalent serotype 43 to avoid recognition by antibodies generated against serotype 5. The molecular swapping of the hexon did not significantly interfere with virion assembly nor attenuate its anti-glioma effect. Thus, the two viruses showed comparable efficacy in vitro (P= 0.568) and in vivo for animals without prior virus exposures (P= 0.228). Importantly, Delta-24-RGD-H43m evaded neutralizing antibodies generated against Delta-24-RGD and maintained its oncolytic ability (P&amp;lt; 0.0001). We conclude that hexon swapping strategies may improve virotherapy by alleviating the dominant immune response against the virus. Despite limited understanding of the interaction between oncolytic viruses and the host immune system, further research on strategies to circumvent virus-specific immune responses should aid the development of enhanced, glioma-targeted virotherapies.
EPID-06. QUANTIFYING THE POTENTIAL PUBLIC HEALTH IMPACT OF VARICELLA ZOSTER VIRUS (VZV) VACCINATION ON GLIOMA INCIDENCE
Authors: Erica Shen, Alexander Wallace, Chenan Zhang, Callie Shannon, David Ashley, Kyle Walsh
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Varicella zoster virus (VZV) is a neurotropic a-herpesvirus that causes chickenpox and establishes latency in the dorsal root ganglion. Live attenuated VZV vaccine was approved for use in 1995, with the CDC estimating 95% of teens had been vaccinated in 2014. Prior epidemiological literature suggests an association between VZV infection and glioma risk. METHODS We conducted a systematic review and meta-analysis of prior studies on the association between VZV infection and glioma risk. We also identified genetic instruments for VZV infection from prior GWAS and tested these for association with glioma risk in TCGA and GliomaScan (2244 cases, 4914 controls). RESULTS In six previous studies, individuals with positive chickenpox history or anti-VZV IgG seropositivity had 1.8-fold lower odds of glioma (ORmeta=0.55, 95%Cl=0.39–0.77), with similar effects by grade. GWAS hits for personal history of chickenpox (HLA-A Gly107 and rs9266089) and shingles (HLA-AArg97, HLA-DRB1 PheSerHis13, rs2523591, rs41316748 and rs7047299) were not associated with glioma risk, nor were polygenic scores (P &amp;gt;0.05). DISCUSSION Prior VZV infection is associated with reduced glioma risk and, based on analysis of genetic instruments, this appears to be an acquired protection caused by VZV infection rather than innate immunologic differences. VZV infection in known to elicit a broader antibody response than vaccination, but it is unknown whether VZV vaccination provides comparable protection against glioma. Because 89% of U.S. adults have had chickenpox, the “prevented fraction” of glioma due to chickenpox is ~29% of annual incidence. If VZV vaccination confers an equivalent 1.8-fold reduction in glioma risk, this prevented fraction could increase to 32%. However, if VZV vaccination is less protective, it could decrease to just 2%. This potentially drastic increase in glioma incidence in coming decades merits mechanistic studies comparing the neuro-immunologic consequences of VZV vaccination versus chickenpox infection and warrants early public health attention.
RONC-27. PROTON THERAPY REDUCES DOSE TO CRITICAL CENTRAL NERVOUS SYSTEM STRUCTURES IN MEDULLOBLASTOMA: A DOSIMETRIC ANALYSIS OF CHILDREN’S ONCOLOGY GROUP (COG) ACNS0331
Authors: Matthew Deek, Matthew Ladra, Lan Lin, Yimei Li, Yuanyuan Han, Kristina Hardy, Jeff Michalski
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Recently published data demonstrated proton therapy (PRT) significantly reduced cognitive decline relative to photons for pediatric medulloblastoma. These findings imply that reductions in dose to critical CNS structures during the boost phase may account for better outcomes over time. Here, we examine differences in dosimetric data for medulloblastoma patients treated on ACNS0331 with photon (Intensity Modulated Radiation Therapy, 3D-Conformal Radiation Therapy) vs PRT to identify potential structures responsible for cognitive benefit. METHODS COG ACNS0331 was a randomized trial examining the impact of reduced craniospinal irradiation (CSI) dose (standard vs low dose, in patients aged 3–7) and volume (whole posterior fossa vs involved field) in pediatric medulloblastoma patients. We identified 136 patients (IMRT=95, 3DCRT=28, Proton=13) enrolled on ACNS0331 with complete radiation and imaging data and re-contoured 10 critical brain structures to calculate dose. RESULTS Proton therapy significantly reduced the dose to critical structures. For example, temporal lobe mean dose and V30 were 30Gy/38% (PRT), 40Gy/89% (IMRT), 41Gy/84% (3DCRT)), hippocampi mean dose were 51 Gy (IMRT), 52 Gy (3DCRT), and 44Gy (PRT) and cochlear mean dose were 43 Gy (IMRT), 49 Gy (3DCRT), and 31Gy (PRT). Dose to several other critical structures were also significantly reduced including the whole brain, supratentorium, cerebellum, and pituitary. CONCLUSIONS Proton therapy greatly reduces dose to critical CNS structures when compared to IMRT or 3DCRT. Further studies are needed to correlate dose reductions in these structures with improved cognitive outcomes.