tbuckley/cabot-search huggingface dataset:
Conditional reprogramming culture conditions facilitate growth of lower-grade glioma models
Authors: Ming Yuan, David White, Linda Resar, Eli Bar, Mari Groves, Alan Cohen, Eric Jackson, Jennifer Bynum, Jeffrey Rubens, Jeff Mumm, Liam Chen, Liqun Jiang, Eric Raabe, Fausto J Rodriguez, Charles G Eberhart
Journal: Neuro-Oncology (2020)

Abstract Background The conditional reprogramming cell culture method was developed to facilitate growth of senescence-prone normal and neoplastic epithelial cells, and involves co-culture with irradiated fibroblasts and the addition of a small molecule Rho kinase (ROCK) inhibitor. The aim of this study was to determine whether this approach would facilitate the culture of compact low-grade gliomas. Methods We attempted to culture 4 pilocytic astrocytomas, 2 gangliogliomas, 2 myxopapillary ependymomas, 2 anaplastic gliomas, 2 difficult-to-classify low-grade neuroepithelial tumors, a desmoplastic infantile ganglioglioma, and an anaplastic pleomorphic xanthoastrocytoma using a modified conditional reprogramming cell culture approach. Results Conditional reprogramming resulted in robust increases in growth for a majority of these tumors, with fibroblast conditioned media and ROCK inhibition both required. Switching cultures to standard serum containing media, or serum-free neurosphere conditions, with or without ROCK inhibition, resulted in decreased proliferation and induction of senescence markers. Rho kinase inhibition and conditioned media both promoted Akt and Erk1/2 activation. Several cultures, including one derived from a NF1-associated pilocytic astrocytoma (JHH-NF1-PA1) and one from a BRAF p.V600E mutant anaplastic pleomorphic xanthoastrocytoma (JHH-PXA1), exhibited growth sufficient for preclinical testing in vitro. In addition, JHH-NF1-PA1 cells survived and migrated in larval zebrafish orthotopic xenografts, while JHH-PXA1 formed orthotopic xenografts in mice histopathologically similar to the tumor from which it was derived. Conclusions These studies highlight the potential for the conditional reprogramming cell culture method to promote the growth of glial and glioneuronal tumors in vitro, in some cases enabling the establishment of long-term culture and in vivo models.
17570 Secukinumab demonstrated high efficacy in clearing nail psoriasis: Results from posthoc analyses from the phase III programs
Authors: Kristian Reich, Peter Nash, Bruce Kirkham, Weibin Bao, Maher Aassi, Jennifer A. Frueh, Corine Gaillez, Boni Elewski
Journal: Journal of the American Academy of Dermatology (2020)
MSC Differentiation: Osteogenic and Adipogenic Differentiation of Mesenchymal Stem Cells in Gelatin Solutions of Different Viscosities (Adv. Healthcare Mater. 23/2020)
Authors: Kyubae Lee, Yazhou Chen, Toru Yoshitomi, Naoki Kawazoe, Yingnan Yang, Guoping Chen
Journal: Advanced Healthcare Materials (2020)

In article number 2000617 by Guoping Chen and co-workers, a 3D biphasic gelatin solution/hydrogel system is used to investigate the influence of solution viscosity on balancing osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs). The differentiation of MSCs in gelatin solutions is dependent on their viscosities. High viscosity is beneficial for osteogenic differentiation while low viscosity for adipogenic differentiation.
Abstract 18182: Intra-Aortic Balloon Pump Improves Right Ventricular Function in Patients with End-Stage Congestive Heart Failure
Authors: Chris Kapelios, Ioannis Terrovitis, Argyrios Ntalianis, Elisabeth Kaldara, Evaggelos Repasos, Panagiotis Siskas, Chris Kontogiannis, Vassilis Sousonis, Titika Sfakianaki, Chris Charitos, George Alexopoulos, John Nanas
Journal: Circulation (2013)

Objective: Right ventricular dysfunction is a major contraindication for implantation of left ventricular assist device (LVAD) in patients with end stage heart failure (HF). The objective of the study was to investigate the effect of prolonged IABP support on anatomy and function of right ventricle (RV) in patients with idiopathic dilated cardiomyopathy (IDM) and end-stage HF. Methods: We recorded the baseline characteristics and the course of the echocardiography indices of right ventricular function in patients with IDM and HF ineligible for LVAD implantation who underwent support with IABP as bridge to candidacy in our hospital between May 2009 and Nov 2012. Results: During this period, 15 patients (mean age 49.3 ± 14.2 years) underwent support with IABP for a mean period of 91.1 ± 55.1 days [range 21-215 days]. All patients suffered from IDM and were severely symptomatic (New York Heart Association class IV). Nine patients (60%) were in INTERMACS level II while the other six were in INTERMACS level 1. Mean left ventricular ejection fraction, pulmonary capillary wedge pressure, cardiac index, BNP, and daily furosemide dose were 21.6 ± 7.3%, 24.8 ± 6.0 mmHg, 1.43 ± 0.33 L/min/m 2 , 2468 ± 1201 pg/ml και 801 ± 608 mg. The support with IABP led to reduction of right ventricular dimensions (RV base from 42.4 ± 2.3 to 37.7 ± 7.9 mm, p=0.24, mid RV from 33.7 ± 5.7 to 27.4 ± 7.2 mm, p=0,001) and to amelioration of systolic function (max velocity of the tricuspid annulus [Sm] from 9.1 ± 1.9 cm/s to 11.3 ± 2.1 cm/s, p=0.006). Right ventricular stroke work index (RVSWI), a valuable marker of intra-operative mortality demonstrated significant increase (from 352.6 ± 217.3 to 557.5 ± 136.2 mmHg x ml/m 2 , p=0.022). Even IVA, an indice which reflects RV myocardial contractility , largely independent of loading conditions also increased with IABP support (from 0.76 ± 0.35 m/s 2 to 1.43 ± 0.69 m/s 2 , p=0.043, [Normal values: 1.4 ± 0.5 m/s 2 ]). Conclusion: Support with IABP of end stage HF patients with dilated cardiomyopathy improves RV function, potentially rendering patients previously ineligible for LVAD to candidates for this life saving treatment.
SURG-39. 5-AMINOLEVULINIC ACID FLUORESCENCE (5-ALA) GUIDED RESECTION OF GLIOBLASTOMA, LESSON LEARNED FROM 26 CASES
Authors: Jinmo Cho
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION 5-ALA is known as useful tool for high grade glioma resection and the accumulation extent of 5-ALA is known as far beyond gadolinium enhancement. Extent of resection is key factor for favorable outcome and long-term survival for high grade glioma patients and 5-ALA might increase extent of resection. We present our experience of 5-ALA guided glioma surgeries. MATERIALS AND METHODS Total 26 patients were performed 5-ALA guided surgery. They ingested 20mg/kg, four hours before craniotomy. We tried to perform supra-total resection rather than gross total resection according to the tumor consistency and if the tumor located relatively non-eloquent area, we tried to perform lobectomy rather than lesionectomy. After tumor resection, we inspect the tumor bed under 5-ALA fluorescence, and we confirmed the complete loss of fluorescence on the tumor resected bed. We check the MRI within 48 hour after operation and assess the extent of resection. RESULTS Among the 26 patients, 22 patients were confirmed glioblastoma and 3 anaplastic astrocytoma and 1 anaplastic oligoastrocytoma. We confirmed all enhancing lesion was completely removed, however, 4 patients show residual non-enhancing lesion in post-operative MRI. Two patients suffered temporary hemiparesis and 2 patients show permanent visual field defect. CONCLUSION 5-ALA is useful tool for glioma surgery. Resection extent could be increased, however, non-enhancing lesion in the high grade gliomas, might be missed under 5-ALA guidance.
Definition of a genetic relatedness cutoff to exclude recent transmission of meticillin-resistant Staphylococcus aureus: a genomic epidemiology analysis
Authors: Francesc Coll, Kathy E Raven, Gwenan M Knight, Beth Blane, Ewan M Harrison, Danielle Leek, David A Enoch, Nicholas M Brown, Julian Parkhill, Sharon J Peacock
Journal: The Lancet Microbe (2020)

Whole-genome sequencing (WGS) can be used in genomic epidemiology investigations to confirm or refute outbreaks of bacterial pathogens, and to support targeted and efficient infection control interventions. We aimed to define a genetic relatedness cutoff, quantified as a number of single-nucleotide polymorphisms (SNP), for meticillin-resistant Staphylococcus aureus (MRSA), above which recent (ie, within 6 months) patient-to-patient transmission could be ruled out.We did a retrospective genomic and epidemiological analysis of MRSA data from two prospective observational cohort studies in the UK to establish SNP cutoffs for genetic relatedness, above which recent transmission was unlikely. We used three separate approaches to calculate these thresholds. First, we applied a linear mixed model to estimate the S aureus substitution rate and 95th percentile within-host diversity in a cohort in which multiple isolates were sequenced per individual. Second, we applied a simulated transmission model to this same genomic dataset. Finally, in a second cohort, we determined the genetic distance (ie, the number of SNPs) that would capture 95% of epidemiologically linked cases. We applied the three approaches to both whole-genome and core-genome sequences.In the linear mixed model, the estimated substitution rate was roughly 5 whole-genome SNPs (wgSNPs) or 3 core-genome SNPs (cgSNPs) per genome per year, and the 95th percentile within-host diversity was 19 wgSNPs or 10 cgSNPs. The combined SNP cutoffs for detection of MRSA transmission within 6 months per this model were thus 24 wgSNPs or 13 cgSNPs. The simulated transmission model suggested that cutoffs of 17 wgSNPs or 12 cgSNPs would detect 95% of MRSA transmission events within the same timeframe. Finally, in the second cohort, cutoffs of 22 wgSNPs or 11 cgSNPs captured 95% of epidemiologically linked cases within 6 months.On the basis of our results, we propose conservative cutoffs of 25 wgSNPs or 15 cgSNPS above which transmission of MRSA within the previous 6 months can be ruled out. These cutoffs could potentially be used as part of a genomic sequencing approach to the management of outbreaks of MRSA in conjunction with traditional epidemiological techniques.UK Department of Health, Wellcome Trust, UK National Institute for Health Research.
Endoscopic ultrasound-guided therapy of gastric varices with coils plus cyanoacrylate injection versus coiling alone: getting evidence-based data but are they comparable?
Authors: Rafael Romero-Castro, Mark Ellrichmann, Victoria A. Jimenez-Garcia
Journal: Endoscopy (2020)

See also:Endoscopic ultrasonography-guided deployment of embolization coils and cyanoacrylate injection in gastric varices versus coiling alone: a randomized trialEndoscopy 2020; 52(04): 268-275DOI: 10.1055/a-1123-9054See also:Reply to Romero-Castro et al.Endoscopy 2021; 53(01): 102-102DOI: 10.1055/a-1243-0569
p38 Mitogen-Activated Protein Kinase: A Future Target for Heart Failure Therapy?⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Risto Kerkela, Thomas Force
Journal: Journal of the American College of Cardiology (2006)
Trends and determinants of newborn mortality in Kyrgyzstan: a Countdown country case study
Authors: Mahdis Kamali, James E Wright, Nadia Akseer, Hana Tasic, Kaitlin Conway, Saman Brar, Cholpon Imanalieva, Gerrit Maritz, Arjumand Rizvi, Baktyiar Stanbekov, Sagynbu Abduvalieva, Elvira Toialieva, Zulfiqar A Bhutta
Journal: The Lancet Global Health (2020)

Kyrgyzstan has made considerable progress in reducing child mortality compared with other countries in the region, despite a comparatively low economic standing. However, maternal mortality is still high. Given the availability of an established birth registration system, we aimed to comprehensively assess the trends and determinants of reproductive, maternal, newborn, and child health in Kyrgyzstan.
THU0198 Lumbar spine involvement in rheumatoid arthritis
Authors: B Moura, D Mauget, M Dougados
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Lumbar spine is considered as rarely involved in rheumatoid arthritis (RA). At variance, low back pain is commonly observed and is usually thought to be related to osteoporotic vertebral fractures. <h3>Objectives</h3> To evaluate the prevalence of both vertebral fractures and lumbar discopathy in patients with RA and low back pain. <h3>Methods</h3> <h3>Patients-Methods</h3> Study design: Trans-sectionnal, case control radiological study. Patients: Two groups of patients were evaluated (RA and controls), all of them were suffering from low back pain defined as any back pain of the lumbar area which had occurred during the past 10 years. RA patients (ACR criteria) were in- or out- consecutive patients. Controls were consecutive patients without inflammatory rheumatic disorders for whom lumbar spine X-rays was indicated. Outcome measures: a) vertebral fractures, b) discopathy defined as a disc space narrowing using a 4 grade scale (Kappa statistics = 0.93 and 0.9 for intra- and inter-reproducibility, respectively). Marked discopathy was arbitrarily and a priori defined as a disc space narrowing of at least 66%. Analysis: All the films were blinded for patient’s identity and were allocated a number after randomization permitting an analysis by two trained observers unaware of the group of patients (i.e., RA or controls). <h3>Results</h3> Of the 123 recruited patients, 53 were suffering for RA (57 ± 13 years old, 79% females) and 70 defined the control group (55 ± 13 years old, 81% females). An osteoporotic vertebral fracture was observed in 8 RA patients and never in the control group (p = 0.002). A marked discopathy was observed in 20 (38%) and in 13 (19%) patients in the RA and control group respectively (p = 0.017). <h3>Conclusion</h3> This study confirms the higher prevalence of osteoporotic vertebral fracture in RA but also suggests that lumbar discopathy might be involved in the occurrence and severity of low back pain in RA.
Polyphosphate: A Novel Modulator of Hemostasis and Thrombosis
Authors: James Morrissey
Journal: Circulation (2013)

Although inorganic polyphosphate is widespread in biology and plays diverse roles in many organisms, most of our knowledge of its functions comes from studies of microorganisms. In 2004, Docampo and colleagues showed that polyphosphate is a major component of the dense granules in human platelets, and furthermore that platelets secrete polyphosphate upon activation. Studies from my laboratory and others have now demonstrated that polyphosphate is a novel and potentially important modulator of the human blood clotting system. Many infectious microorganisms contain long-chain polyphosphate, which is a highly potent, pathophysiologic activator of the contact pathway of blood clotting and may help explain the role of this limb of the clotting pathway in inflammation and host responses to pathogens. Shorter-chain polyphosphate—of the size range secreted by activated platelets—has multiple downstream effects on clotting, including accelerating factor V activation, abrogating the function of tissue factor pathway inhibitor (TFPI), and enhancing fibrin clot structure. Interestingly, platelet polyphosphate also greatly accelerates the back-activation of factor XI by thrombin, which may help explain the otherwise perplexing contribution of factor XI to normal hemostasis. Polyphosphate is an interesting therapeutic and diagnostic target, including the use of polyphosphates in novel hemostatic agents, as well as the use of inhibitors of polyphosphate function as a novel approach to antithrombotic/anti-inflammatory therapy. Many more contributions of polyphosphate to hemostasis, thrombosis and inflammation are doubtless waiting to be discovered.
A novel 3D vascular assay for evaluating angiogenesis across porous membranes
Authors: Jing Bai, Kristina Haase, Justine J. Roberts, Joseph Hoffmann, Huu Tuan Nguyen, Zhengpeng Wan, Shun Zhang, Bapi Sarker, Nathan Friedman, Čedomila Ristić-Lehmann, Roger D. Kamm
Journal: Biomaterials (2020)
Abstract 10198: Benzodiazepine is Associated With Adverse Prognosis in Heart Failure Patients With Insomnia
Authors: Yu Sato, Akiomi Yoshihisa, Yu Hotsuki, Koichiro Watanabe, Yusuke Kimishima, Takatoyo Kiko, Yuki Kanno, Tetsuro Yokokawa, Satoshi Abe, Tomofumi Misaka, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2019)

Introduction: The inappropriate use of benzodiazepine (BZ) has being a world-wide health problem. However, it has been unclear whether BZ deteriorates the prognosis of patients with heart failure (...
18F-FDG PET/CT Imaging of Pancreatic and Adrenal Metastases in a Patient With Mesenchymal Chondrosarcoma
Authors: Jiangming Sun, Wenjie Zhang, Tao He, Hui Wang, Rong Tian
Journal: Clinical Nuclear Medicine (2020)

Metastases of mesenchymal chondrosarcoma to either the pancreas or the adrenal glands are rare. We hereby presented the 18F-FDG PET/CT images of a 21-year-old man initially diagnosed with chondrosarcoma of the right 11th rib. His 18F-FDG PET/CT scan after radiotherapy demonstrated 2 hypermetabolic lesions in the right adrenal gland and the pancreas, respectively. These 2 lesions were later confirmed by biopsy to be metastatic mesenchymal chondrosarcoma.
GCT-42. CLINICAL CHARACTERISTICS OF LOCALIZED CENTRAL NERVOUS SYSTEM NON-GERMINOMATOUS GERM CELL TUMORS (NGGCT) PATIENTS ENROLLED ON ACNS1123 WITH RELAPSE: A CHILDREN’S ONCOLOGY GROUP (COG) STUDY
Authors: Girish Dhall, Shengjie Wu, Arzu Onar-Thomas, Dennis Shaw, Shannon MacDonald, Erin Murphy, Soumen Khatua, Ute Bartels, Jason Fangusaro
Journal: Neuro-Oncology (2020)

Abstract ACNS1123 was a Children’s Oncology Group Phase 2 study that was undertaken to determine whether irradiation could be safely reduced without impacting survival in a subgroup of NGGCT patients. Between May 2012-Jan 2017, 107 eligible patients were accrued to Stratum 1 (NGGCT stratum). Sixty-six (61.7%) patients achieved a complete/partial response (CR/PR) to induction chemotherapy and received 30.6Gy whole ventricular field irradiation followed by 54Gy tumor-bed boost achieving a 2-year progression-free survival rate of 89% (95% CI:81%-97%) and overall survival rate of 92% (95% CI:86%- 99%). Eight patients progressed; 6 had a spinal relapse and 2 patients had a local plus spinal relapse. Seven of eight patients had marker elevation at relapse and data was not available in one patient. At diagnosis, location was pineal in six cases, suprasellar in one, and bifocal in one case. Four patients had beta HCGβ and AFP elevation and two each had HCGβ and AFP elevation alone at diagnosis. Only two patients had HCGβ or AFP &amp;gt;1000 (HCGβ 3550 in one patient and AFP of 1340 in another). All eight patients were CR by markers; four had radiographic CR and four had a PR. Five patients had surgery at diagnosis: two had embryonal carcinoma, one germinoma, and two mixed germ cell tumor with malignant elements on histology. A consistent significant risk factor could not be identified to explain excess of spinal failures seen in our cohort.
RARE-44. CLINICAL CHARACTERIZATION AND OUTCOME; OUR EXPERIENCE OF CHORDOMAS IN PEDIATRIC AND YOUNG ADULTS
Authors: Amber Gibson, Muhammad Baig, Shaan Raza, David Grosshans, Wafik Zaky
Journal: Neuro-Oncology (2020)

Abstract Pediatric chordomas are exceedingly rare and there are limited data to guide treatment decisions. We report a retrospective analysis of 19 patients with chordomas who received treatment at our institution from 2001–2020. Of the 19 patients, 15 had clival (79%), 3 cervical and 1 sacral chordoma. There were 9 males (47%). Median age at diagnosis of 10.6 years. Eight patients had gross total (42%) and 11 (58%) had sub-total resection. As front line therapy 15 patients (79%) underwent surgery followed by radiation (1 photon and 14 proton), 3 patients (16%) received surgery and chemotherapy (anaplastic histology) and 1 patient received only surgery. For patients treated with radiation therapy the average prescribed dose was 70 Gy (range: 52–74). Post-surgery and radiation, 14 of 15 patients remained in remission. Five (26%) patients had progressive disease (PD) with median time to progression of 13 months of whom 3 died of disease at median of 18 months. Treatment of PD consisted of chemotherapy and radiation for 3, re-resection with radiation for 1 and chemotherapy alone for 1 patient. The patients with metastatic and anaplastic disease mean survival is 21 month versus 45 for the rest of the cohort. In summary, post-operative adjuvant radiation provided an overall good outcome in majority of patients. Patients with anaplastic pathology and metastasis at diagnosis had worse outcome. Those who relapsed, subsequent treatment was palliative at best with short survival. Molecular analysis is warranted in future for better disease stratification.
BIOM-16. IMMUNOMIC ANALYSIS OF GLIOBLASTOMA (GBM) USING GENE EXPRESSION PROFILING
Authors: Michael Castro, Nilofar Badra-Azar, Thomas Kessler, Moritz Schütte, Bodo Lange, Marie-Laure Yaspo
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Despite the success of immunotherapy across the spectrum of human cancer, a successful strategy has not emerged for GBM. While PD-L1 IHC and TMB have demonstrated some utility as predictors of immunotherapy benefit, responsiveness is complexly determined by factors affecting T cell trafficking, antigen presentation, other immune checkpoints, and mediators of immune exhaustion. Thus, we set out to to characterize mediators of immune resistance and their diversity in a population of GBM patients utilizing quantitative gene expression. METHODS A set of 54 immunotherapy and checkpoint relevant genes and seven genes related to immune failure were selected from the literature. RNA gene counts for TCGA glioblastoma multiforme samples (N=163) were downloaded from https://portal.gdc.cancer.gov/. Annotation on subtypes and PFS values were obtained from PMID: 24120142. Gene expression normalization as FPKM, hierarchical clustering and box-plots were performed using R-3.6.0. Statistical differences of gene expression between subtypes were quantified using a TurkeyHSD test. RESULTS A heatmap with hierarchical clustering for immune related genes for the TCGA GBM cohort was generated including colored annotation for the subtype and progression free survival. The graph shows a rough separation into two groups, where one group of the genes is tentatively associated with mesenchymal subtype and shorter survival and showing higher expression for most immune evasion genes. However, a heterogeneity of immune evasion signatures was identified within and across subtypes. Transcripts related to antigen presentation, EZH2, and LDHA varied significantly between GBM subtypes (p &amp;lt; 0.05). CONCLUSION Gene expression analysis has utility to identify specific mediators of immune evasion and to inform the selection of combination therapies for discrete subsets of patients. A Bayesian approach to patient selection for specific immunotherapy strategies may enhance the likelihood of successful implementation of immunotherapy in the clinic.
46P [18F]2-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18FDG-PET/CT) in patients treated with immune checkpoint inhibitors (ICI) for microsatellite instability-high metastatic colorectal cancer (MSI mCRC)
Authors: T. Pudlarz, F. Montravers, M-L. Garcia-Larnicol, E. Kempf, J. Bennouna, C. de la Fouchardière, D. Tougeron, C. Borg, T. Mazard, B. Chibaudel, Y. Parc, M. Svrcek, Y.M. Menu, R. Cohen, T. Andre
Journal: Annals of Oncology (2020)