tbuckley/cabot-search huggingface dataset:
INNV-31. ACCELERATING NEURO-ONCOLOGY RESEARCH AND IMPROVING PATIENT CARE THROUGH A ROBUST DATA FOUNDATION
Authors: Kristin Alfaro-Munoz, Gemma Hallatt, Vinod ravi, Andrew Futreal, Jamie Sookprasong, Emily Yu, Bryan Lari, Jeff Jin, John DeGroot
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND MD Anderson (MDA) strives to maximize learning from the &gt; 44,000 patients seen annually. This has historically been challenging due to the diverse, often unstructured, and siloed nature of patient data. In 2018, MDA partnered with Palantir Technologies to integrate disparate clinical and research data sources into a single cloud-based platform enabling both technical and non-technical users to directly access and analyze data. METHODS IT experts, Palantir engineers and end users collaborated to integrate 150 deidentified datasets from the existing data warehouse, Natural Language Processing pipelines, molecular reports, public data and manually curated data, representing data from &gt; 1.5 million patients. Data integration was tested by answering 12 retrospective queries, of which 5 were specific to neuro-oncology cohorts. RESULTS All 12 queries were resolved and within the neuro-oncology department we found the cohort identification process to be accelerated with users able to create reports backed by live data, with clear visibility into inputs, analysis and history. In addition, templates were created of common statistical workflows, empowering non-technical users to perform analyses (e.g. KM curve; Volcano plot). Secure access controls enabled increased collaboration between neuro-oncology and other departments. CONCLUSIONS This work highlights the value of a data foundation and unlocks the potential for new studies, fueling scientific discovery within neuro-oncology and across the institution. To extend the impact we are piloting a combination of (1) Purposeful structured data capture at the time of care, (2) Use of logic to suggest commonly uncaptured but critical patient events such as progression, and (3) Auditing functionality to allow users to manually fill in gaps and correct data in a transparent manner. Upon completion, we anticipate the ability to increase our research throughput and scope.
Long noncoding RNA PiHL regulates p53 protein stability through GRWD1/RPL11/MDM2 axis in colorectal cancer
Authors: Xuan Deng, Sihan Li, Fanyang Kong, Haoyu Ruan, Xiao Xu, Xinju Zhang, Zhiyuan Wu, Lin Zhang, Ying Xu, Hong Yuan, Haixia Peng, Da Yang, Ming Guan
Journal: Theranostics (2019)

We identified a novel long noncoding RNA (lncRNA) upregulated in colorectal cancer (CRC). We elucidated its role and clinical significance in CRC carcinogenesis. Methods: LncRNA candidates were identified using TCGA database. LncRNA expression profiles were studied by qRT-PCR and microarray in paired tumor and normal tissues. The independence of the signature in survival prediction was evaluated by multivariable Cox regression analysis. The mechanisms of lncRNA function and regulation in CRC were examined using molecular biological methods. Results: We identified a novel long noncoding gene (PiHL, P53 inHibiting LncRNA) from 8q24.21 as a p53 negative regulator. PiHL is drastically upregulated in CRC and is an independent predictor of CRC poor prognosis. Further in vitro and in vivo models demonstrated that PiHL was crucial in maintaining cell proliferation and inducing 5-FU chemoresistance through a p53-dependent manner. Mechanistically, PiHL acts to promote p53 ubiquitination by sequestering RPL11 from MDM2, through enhancing GRWD1 and RPL11 complex formation. We further show that p53 can directly bind to PiHL promoter and regulating its expression. Conclusion: Our study illustrates how cancer cells hijack the PiHL-p53 axis to promote CRC progression and chemoresistance. PiHL plays an oncogenic role in CRC carcinogenesis and is an independent prognostic factor as well as a potential therapeutic target for CRC patients.
A Burst of Genetic Innovation in Drosophila Actin-Related Proteins for Testis-Specific Function
Authors: Courtney M Schroeder, John R Valenzuela, Isabel Mejia Natividad, Glen M Hocky, Harmit S Malik
Journal: Molecular Biology and Evolution (2019)

Many cytoskeletal proteins perform fundamental biological processes and are evolutionarily ancient. For example, the superfamily of actin-related proteins (Arps) specialized early in eukaryotic evolution for diverse cellular roles in the cytoplasm and the nucleus. Despite its strict conservation across eukaryotes, we find that the Arp superfamily has undergone dramatic lineage-specific diversification in Drosophila. Our phylogenomic analyses reveal four independent Arp gene duplications that occurred in the common ancestor of the obscura group of Drosophila and have been mostly preserved in this lineage. All four obscura-specific Arp paralogs are predominantly expressed in the male germline and have evolved under positive selection. We focus our analyses on the divergent Arp2D paralog, which arose via a retroduplication event from Arp2, a component of the Arp2/3 complex that polymerizes branched actin networks. Computational modeling analyses suggest that Arp2D can replace Arp2 in the Arp2/3 complex and bind actin monomers. Together with the signature of positive selection, our findings suggest that Arp2D may augment Arp2's functions in the male germline. Indeed, we find that Arp2D is expressed during and following male meiosis, where it localizes to distinct locations such as actin cones-specialized cytoskeletal structures that separate bundled spermatids into individual mature sperm. We hypothesize that this unprecedented burst of genetic innovation in cytoskeletal proteins may have been driven by the evolution of sperm heteromorphism in the obscura group of Drosophila.
Antenatal Preparation for Labour
Authors: W. Lynch
Journal: BMJ (1964)

Your most recent article on " Analgesia in Labour " (13 June, p. 1555) suggests that except in dire emergency manual removal of an adherent placenta should not be carried out at home, but again that the woman should be sent to hospital.Surely this is against all current teaching.It is much better to get on and perform this operation as soon as it appears indicated.This I have done in the home a number of times, frequently with only gas and air or " trilene " (trichloroethylene) from a cyprane inhaler, aided by local anaes- thetic, and without causing the patient any distress.To move a shocked patient to hos- pital is surely most dangerous.-Iam, etc., Norwich.
Age-Related Bias in Total Step Count Recorded by Wearable Devices
Authors: Pei-Lun Kuo, Jacek K. Urbanek, Jennifer A. Schrack
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
A Phase II Non-Randomized Study to Evaluate the Efficacy of Single Dose Rasburicase (1.5mg) in Adult Acute Leukemia and High Grade Lymphomas with Established Tumor Lysis Syndrome
Authors: Jayshree Thorat, Swaratika Majumdar, Hasmukh Jain, Avinash Bonda, Lingaraj Nayak, Bhausaheb Bagal, Manju Sengar
Journal: Blood (2019)
Daratumumab, Carfilzomib, Lenalidomide and Dexamethasone (Dara-KRd) Induction, Autologous Transplantation and Post-Transplant, Response-Adapted, Measurable Residual Disease (MRD)-Based Dara-Krd Consolidation in Patients with Newly Diagnosed Multiple Myeloma (NDMM)
Authors: Luciano J. Costa, Saurabh Chhabra, Kelly N. Godby, Eva Medvedova, Robert F. Cornell, Aric C. Hall, Rebecca W. Silbermann, Racquel Innis-Shelton, Binod Dhakal, Diego DeIdiaquez, Pamela Hardwick, Yelak Biru, James L. Omel, Parameswaran Hari, Natalie Scott Callander
Journal: Blood (2019)
Synergistic Effect of Carfilzomib and Metformin in Vascular Plasticity; The Emerging Role of Autophagy
Authors: Panagiotis Efentakis, Ioanna Andreadou, Panagiota-Efstathia Nikolaou, Claudius Witzler, Svenja Siemer, Eftathios Kastritis, Philip Wenzel, Meletios A. Dimopoulos, Evangelos Terpos
Journal: Blood (2019)
Protein Arginine Methyltransferase 1 Is Required for Maintenance of Normal Adult Hematopoiesis
Authors: Lei Zhu, Xin He, Haojie Dong, Jie Sun, Hanying Wang, Yinghui Zhu, Feiteng Huang, Jingying Zou, Xiaoying Zhao, Ling Li
Journal: Blood (2019)
Use of Lenalidomide Plus Rituximab in TP53-Mutated Mantle Cell Lymphoma (MCL) Outside of Clinic Trial: The Moffitt Experience
Authors: Nikesh Shah, Franco Castillo-Tokumori, Julio C. Chavez, Leidy Isenalumhe, Hayder Saeed, Celeste Bello, Lubomir Sokol, Javier Pinilla Ibarz, Bijal Shah
Journal: Blood (2019)
Academic, Phase I/II Trial on T Cells Expressing a Second Generation, CD19-Specific Chimeric Antigen Receptor (CAR) and Inducible Caspase 9 Safety Switch for the Treatment of B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) and B-Cell Non-Hodgkin Lymphoma (B-NHL) in Children
Authors: Francesca Del Bufalo, Concetta Quintarelli, Biagio De Angelis, Ignazio Caruana, Matilde Sinibaldi, Luciana Vinti, Pietro Merli, Mattia Algeri, Annalisa Ruggeri, Federica Galaverna, Valentina Cirillo, Maria Giuseppina Cefalo, Giuseppina Li Pira, Giovanna Leone, Valentina Bertaina, Franca Fassio, Monica Gunetti, Stefano Iacovelli, Franco Locatelli
Journal: Blood (2019)
Development of a Pathway-Directed Drug Screen Platform for Cutaneous T Cell Lymphoma Using Patient-Derived Xenograft Models
Authors: CHI-HENG WU, Chen-Yen Yang, Linlin Wang, Hua-Xin Gao, Rakhshandehroo Taha, Shervin Afghani, Laura Pincus, Ronald Balassanian, James Rubenstein, Ryan Gill, Sourav Bandyopadhyay, Frank McCormick, Mark Moasser, Weiyun Z. Ai
Journal: Blood (2019)
GENE-28. LONGITUDINAL MOLECULAR TRAJECTORIES OF DIFFUSE GLIOMA IN ADULTS
Authors: Floris Barthel, Kevin C Johnson, Frederick Varn, Anzhela Moskalik, Georgette Tanner, Emre Kocakavuk, Kevin Anderson, Olajide Abiola, Jason Huse, John DeGroot, Lucy F Stead, Roel Verhaak
Journal: Neuro-Oncology (2019)

Abstract Treatment options for adult patients with glioma has remained largely unchanged over the past three decades. Targeted inhibitors and immunotherapies have improved outcomes for many cancer types but their relevance in glioma is unclear. The inevitability of glioma disease recurrence demands an understanding of mechanisms driving therapy resistance. The Glioma Longitudinal Analysis (GLASS) Consortium was initiated to establish a definitive portrait of the recurrence process and to discover vulnerabilities that render the tumor sensitive to therapeutic intervention. GLASS is a community-driven effort that seeks to overcome the logistical challenges in constructing adequately powered longitudinal genomic glioma datasets by pooling data from patients treated at institutions worldwide. Currently, the GLASS Data Resource comprises DNA sequencing data (exome and/or whole-genome) from 288 patients of whom high-quality data in at least two time points are present from 222 patients (n = 134 IDHwt, n = 63 IDHmutant-noncodel, n = 25 IDHmutant-codel). We inferred longitudinal mutation, copy number, clonal frequency, and neoantigen profiles and demonstrated that driver genes found at initial disease persisted into recurrence. Treatment with alkylating-agents resulted in a hypermutator phenotype at different rates across glioma subtypes, most frequently among IDHmutant-noncodels, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent IDHmutant-noncodel gliomas and further converged with acquired cell cycle pathway alterations and poor outcomes. We showed that the clonal architecture of each tumor remains largely intact over time and that genetic drift was associated with increased survival. Finally, we found that neoantigens were exposed to stable selective pressures throughout a tumor’s progression. Our results collectively suggest that the strongest selective pressures occur early during glioma development and that current therapies shape this evolution in a largely stochastic manner. The GLASS Data Resource provides a genomic reference to study the patterns of glioma evolution.
SP0047 NEW IMAGING TECHNOLOGIES IN OA: WHERE ARE THE ADDED VALUES?
Authors: Philip G Conaghan
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> The exact role for new imaging technologies in osteoarthritis (OA) depends in part on the setting (clinical trials or routine care) and also on the tissues we decide are important to be studied. In clinical practice, modern imaging such as ultrasound provides a useful adjunct for patients where there is diagnostic uncertainty - the EULAR recommendations for the use of imaging in the clinical management of peripheral joint OA provide an evidence-based background to this use of imaging. The impact of imaging is minimal in guiding choice of therapy as our therapeutic options (outside of surgery) are very limited. In clinical studies and trials, there are a number of imaging modalities that provide insights into a range of OA tissues, for both quantification and characterisation. Most techniques have been based on MRI because of its soft-tissue advantages. In OA trials, MRI-based quantification methods provide improved responsiveness advantages over semi-quantitative scores, which have served an important role in highlighting the multi-tissue nature of OA and frequency of pathology. Using appropriate sequences, manual segmentation of cartilage or contrast-enhancing synovitis can be quantified, and dynamic-contrast enhanced images can also be used to provide volumetric and pharmacokinetic assessments of the synovium. Using such information, we now know how to power studies for cartilage thickness endpoints. A number of MRI techniques have been developed to study cartilage composition, such as T2mapping and T1rho. They have provided insights into structural deterioration, but are limited by technical aspects which make them difficult to apply in multicentre clinical trials. Artificial intelligence and supervised machine learning have promised much in medicine, but in MSK imaging there has been some useful applications. Early technology applied 2D statistical shape models (SSMs) to X-rays, usually of the hip, providing novel information on bone shape. However the advent of 3D MRI or CT-based SSM technology has provided the ability to do automated quantification of large OA datasets. One of the most interesting tissues studied to date has been 3D bone shape. Studies have shown changes in bone shape are more responsive than radiographic joint space narrowing or even MRI quantitative cartilage thickness, predict incident radiographic OA, and that bone shape is associated with subsequent joint replacement. Recent work has shown a relationship between bone shape and bone marrow lesions, though these likely represent different elements of subchondral bone pathology. Work is just beginning on other relevant tissues such as the meniscus, and on other OA joints. <h3>Disclosure of Interests:</h3> Philip G Conaghan Consultant for: Flexion Therapeutics, AbbVie, Medivir, Merck Serono, Novartis, GlaxoSmithKline
STEM-28. TARGETING KIF11 TO RADIOSENSITIZE GLIOBLASTOMA
Authors: Abigail Zalenski, Miranda Montgomery, Kuntal De, Treg Grubb, Monica Venere
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM) is the most common primary brain tumor, and is incredibly lethal, with less than 10% of patients surviving more than 5 years after diagnosis. These tumors are routinely treated with radiotherapy, although we and others have shown that there is a subpopulation of GBM cells, called cancer stem-like cells (CSCs), that are radio-resistant, and do not respond to this standard therapy. We aim to overcome the radio-resistance of GBM CSCs by using radiotherapy in combination with a KIF11 inhibitor. We previously reported that the mitotic kinesin KIF11, required for bipolar spindle formation during mitosis, is elevated in GBM and portends poor prognosis. We also demonstrated that invasiveness and self-renewal of CSCs could be targeted with ispinesib, a small molecule inhibitor to KIF11. Furthermore, survival of mice bearing orthotopic glioblastoma was prolonged with KIF11 inhibition, although tumor burden increased with cessation of treatment. To combat tumor recurrence after treatment cessation, we proposed to use a KIF11 inhibitor with radiotherapy. KIF11 inhibitors will arrest cells in G2/M, where they are most sensitive to radiotherapy. By enriching CSCs in G2/M, we hypothesized that we would overcome CSC radio-resistance to decrease CSC viability and improve survival. We first tested the efficacy of combining a KIF11 inhibitor and irradiation in vitro. We found that using combination therapy to treat CSCs significantly decreased CSC survival over vehicle or either treatment used as a monotherapy. We then investigated the effects of combination therapy in vivo. Using a KIF11 inhibitor combined with irradiation increased survival of mice bearing orthotopic glioblastoma. Our results suggest that targeting KIF11 in combination with radiotherapy is a promising technique to overcome the radio-resistance of CSCs, and holds potential to significantly improve treatment outcomes and extend survival of patients with GBM.
Suspected heroin-related overdoses incidents in Cincinnati, Ohio: A spatiotemporal analysis
Authors: Zehang Richard Li, Evaline Xie, Forrest W. Crawford, Joshua L. Warren, Kathryn McConnell, J. Tyler Copple, Tyler Johnson, Gregg S. Gonsalves
Journal: PLoS Medicine (2019)

Background Opioid misuse and deaths are increasing in the United States. In 2017, Ohio had the second highest overdose rates in the US, with the city of Cincinnati experiencing a 50% rise in opioid overdoses since 2015. Understanding the temporal and geographic variation in overdose emergencies may help guide public policy responses to the opioid epidemic. Methods and findings We used a publicly available data set of suspected heroin-related emergency calls (n = 6,246) to map overdose incidents to 280 census block groups in Cincinnati between August 1, 2015, and January 30, 2019. We used a Bayesian space-time Poisson regression model to examine the relationship between demographic and environmental characteristics and the number of calls within block groups. Higher numbers of heroin-related incidents were found to be associated with features of the built environment, including the proportion of parks (relative risk [RR] = 2.233; 95% credible interval [CI]: [1.075–4.643]), commercial (RR = 13.200; 95% CI: [4.584–38.169]), manufacturing (RR = 4.775; 95% CI: [1.958–11.683]), and downtown development zones (RR = 11.362; 95% CI: [3.796–34.015]). The number of suspected heroin-related emergency calls was also positively associated with the proportion of male population, the population aged 35–49 years, and distance to pharmacies and was negatively associated with the proportion aged 18–24 years, the proportion of the population with a bachelor's degree or higher, median household income, the number of fast food restaurants, distance to hospitals, and distance to opioid treatment programs. Significant spatial and temporal heterogeneity in the risks of incidents remained after adjusting for covariates. Limitations of this study include lack of information about the nature of incidents after dispatch, which may differ from the initial classification of being related to heroin, and lack of information on local policy changes and interventions. Conclusions We identified areas with high numbers of reported heroin-related incidents and features of the built environment and demographic characteristics that are associated with these events in the city of Cincinnati. Publicly available information about opiate overdoses, combined with data on spatiotemporal risk factors, may help municipalities plan, implement, and target harm-reduction measures. In the US, more work is necessary to improve data availability in other cities and states and the compatibility of data from different sources in order to adequately measure and monitor the risk of overdose and inform health policies.
PATH-43. DIAGNOSIS OF GLIOMAS USING CIRCULATING GLIAL CELLS
Authors: Darshana Patil, Dadasaheb Akolkar, Stefan Schuster, H B Govardhan, Vineet Datta, Jatinder Bhatia, Revati Patil, Sneha Puranik, Sachin Apurwa, Ajay Srinivasan, Pooja Fulmali, Rajan Datar
Journal: Neuro-Oncology (2019)

Abstract Invasive procedures for diagnosis of CNS malignancies carry inherent risks of high morbidity and mortality. Although circulating biomarkers such as cell free DNA (cfDNA) and microvesicle (MV) borne nucleic acids have been proposed as potential diagnostic aids, their stand-alone utility has inherent limitations. However, Circulating Glial Cells (CGCs) combined with cfDNA could offer a viable alternative to invasive biopsies for diagnosis of CNS malignancies; yet the technological challenge in the detection of CGCs in glioma patients presents a formidable challenge. In this study, we evaluated the feasibility of harvesting CGCs from suspected cases of Glioma. From a cohort of 23 suspected cases of CNS malignancies, we used 15ml of peripheral blood and used the CellWizard™ process and related protocol for isolation of CGCs. CellWizard™ is an epigenetically active media with paradoxical chemo-toxicity that selectively induces lethality in normal cells which have a functionally responsive cell death (apoptosis) mechanism, while simultaneously conferring survival privilege on apoptosis resistant cells typically released from a malignant tumor. This paradoxical cytotoxicity of the medium leads to selective elimination of most leukocytes thus facilitating a label free negative enrichment of CGCs, which can be harvested and further characterized. Patients included 11 Glioblastoma, 3 Anaplastic astrocytoma, 2 Medulloblastoma, 5 Oligodendroglioma, 1 Gliosarcoma and 1 meningioma patient. Characterization of CGCs was performed using GFAP, S100 and CD45 markers. CGCs were detected in 16 out of 23 (69.6 %) patients and could be stained positively for both GFAP and S100 and negatively for CD45. Detection of viable CGCs in cases of CNS malignancies can be used for characterization of markers related to the diagnosis.