tbuckley/cabot-search huggingface dataset:
Quantification and Localization of Protein–RNA Interactions in Patient-Derived Archival Tumor Tissue
Authors: Emmeline L. Blanchard, Danae Argyropoulou, Chiara Zurla, Sushma M. Bhosle, Daryll Vanover, Philip J. Santangelo
Journal: Cancer Research (2019)

Abstract Abnormal post-transcriptional regulation induced by alterations of mRNA–protein interactions is critical during tumorigenesis and cancer progression and is a hallmark of cancer cells. A more thorough understanding is needed to develop treatments and foresee outcomes. Cellular and mouse tumor models are insufficient for vigorous investigation as they lack consistency and translatability to humans. Moreover, to date, studies in human tumor tissue are predominately limited to expression analysis of proteins and mRNA, which do not necessarily provide information about the frequency of mRNA–protein interactions. Here, we demonstrate novel optimization of a method that is based on FISH and proximity ligation techniques to quantify mRNA interactions with RNA-binding proteins relevant for tumorigenesis and cancer progression in archival patient-derived tumor tissue. This method was validated for multiple mRNA-protein pairs in several cellular models and in multiple types of archival human tumor samples. Furthermore, this approach allowed high-throughput analysis of mRNA–protein interactions across a wide range of tumor types and stages through tumor microarrays. This method is quantitative, specific, and sensitive for detecting interactions and their localization at both the individual cell and whole-tissue scales with single interaction sensitivity. This work presents an important tool in investigating post-transcriptional regulation in cancer on a high-throughput scale, with great potential for translatability into any applications where mRNA–protein interactions are of interest. Significance: This work presents an approach to sensitively, specifically, and quantitatively detect and localize native mRNA and protein interactions for analysis of abnormal post-transcriptional regulation in patient-derived archival tumor samples.
Clinical, molecular, and radiomic profile of gliomas with FGFR3-TACC3 fusions
Authors: Anna Luisa Di Stefano, Alberto Picca, Edouard Saragoussi, Franck Bielle, Francois Ducray, Chiara Villa, Marica Eoli, Rosina Paterra, Luisa Bellu, Bertrand Mathon, Laurent Capelle, Véronique Bourg, Arnaud Gloaguen, Cathy Philippe, Vincent Frouin, Yohann Schmitt, Julie Lerond, Julie Leclerc, Anna Lasorella, Antonio Iavarone, Karima Mokhtari, Julien Savatovsky, Agusti Alentorn, Marc Sanson
Journal: Neuro-Oncology (2020)

Actionable fibroblast growth factor receptor 3 (FGFR3)-transforming acidic coiled-coil protein 3 fusions (F3T3) are found in approximately 3% of gliomas, but their characteristics and prognostic significance are still poorly defined. Our goal was to characterize the clinical, radiological, and molecular profile of F3T3 positive diffuse gliomas.We screened F3T3 fusion by real-time (RT)-PCR and FGFR3 immunohistochemistry in a large series of gliomas, characterized for main genetic alterations, histology, and clinical evolution. We performed a radiological and radiomic case control study, using an exploratory and a validation cohort.We screened 1162 diffuse gliomas (951 unselected cases and 211 preselected for FGFR3 protein immunopositivity), identifying 80 F3T3 positive gliomas. F3T3 was mutually exclusive with IDH mutation (P < 0.001) and EGFR amplification (P = 0.01), defining a distinct molecular cluster associated with CDK4 (P = 0.04) and MDM2 amplification (P = 0.03). F3T3 fusion was associated with longer survival for the whole series and for glioblastomas (median overall survival was 31.1 vs 19.9 mo, P = 0.02) and was an independent predictor of better outcome on multivariate analysis.F3T3 positive gliomas had specific MRI features, affecting preferentially insula and temporal lobe, and with poorly defined tumor margins. F3T3 fusion was correctly predicted by radiomics analysis on both the exploratory (area under the curve [AUC] = 0.87) and the validation MRI (AUC = 0.75) cohort. Using Cox proportional hazards models, radiomics predicted survival with a high C-index (0.75, SD 0.04), while the model combining clinical, genetic, and radiomic data showed the highest C-index (0.81, SD 0.04).F3T3 positive gliomas have distinct molecular and radiological features, and better outcome.
Abstract 21027: Prognostic Evaluation and Risk Assessment in Scleroderma Patients With Newly Diagnosed Pulmonary Arterial Hypertension
Authors: Valentina Mercurio, Nermin Diab, Rachel L Damico, Todd M Kolb, Stephen Mathai, Paul M Hassoun
Journal: Circulation (2017)

Introduction: Systemic sclerosis related pulmonary arterial hypertension (SScPAH) is characterized by a worse prognosis in comparison to idiopathic pulmonary arterial hypertension (IPAH). The estimated mortality risk reported in the current European guidelines for pulmonary hypertension has been evaluated mostly in IPAH patients. The aim of this study was to explore the ability of the risk assessment proposed in the guidelines to predict long-term mortality in SScPAH patients. Methods: The study population constituted patients diagnosed with SScPAH and prospectively enrolled in the Johns Hopkins Pulmonary Hypertension Program from 2000-2016. Patients with assessment of WHO functional class, 6-minute walking distance (6MWD), and right heart catheterization measurements at diagnosis were included in the analysis. A Cox proportional hazards model was used to examine the adjusted hazard ratio (HR) of mortality for each of the following four low-risk criteria: WHO functional class I-II, 6MWD &gt;440m, right atrial pressure &lt;8mmHg, and cardiac index ≥2.5L/min/m 2 . A Kaplan-Meier curve was plotted to describe overall survival at 5 years. Results: 151 patients (mean age 61.2, 84.8% female) were included in the analysis. Over a mean follow-up period of 4.9 years, 87 patients (57.6%) died. In Cox proportional hazards multivariate analysis, the HR (95%CI) of mortality compared to the presence of no low-risk criteria was 0.65 for one criterion (0.37-1.15), 0.34 for two (0.17-0.68), 0.16 for three (0.06-0.44), and 0.10 for four (0.01-0.78). Figure 1 describes the 5-year survival according to the number of criteria. Conclusion: Our study highlights that only a small proportion of SScPAH patients are diagnosed at an early stage of PAH disease, suggesting the need of more intense PAH screening programs for this population. Current guidelines for risk assessment in IPAH patients can also be helpful in SScPAH patients, particularly in identifying patients at higher risk of mortality.
P14.92 Study of Glutaminergic and Glutamatergic Metabolism in 1H-MRS Monovoxel in the Most Aggressive Part of 62 Glioblastoma Before and After 18 months Treatment
Authors: A Heintz, J Chombar, S Boussida, Z Saidak, M Lefranc, N Deleval, A Coutte, B Chauffert, M Boone, J Constans
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND To study the relationships between glutaminergic metabolism (Glx/tCr), tumor proliferation (tCho/tCr) and other metabolic activities in patients with glioblastoma (GBM). MATERIAL AND METHODS Patients: 62 patients with glioblastoma, all having a STUPP Protocol (radiotherapy and concomitant chemotherapy), were selected and separated into 2 groups: Biopsies (30) and resections (32). In total, 269 NMR spectra (PRESS at GE 1.5T and 3T; multi-TEs TE=35ms and TE=144ms) were acquired. Processing: MRS data were processed with jMRUI software and quantitated using HLSVD and QUEST algorithms. Statistical analysis of longitudinal MRS data (every 3 months) RESULTS Glx/tCr and Lac/tCr ratios are correlated with the tumoral proliferation (tCho/tCr) before the beginning of treatment. This correlations decreases over time in biopsied and resected patients. In biopsied patients, the evolution of lactate (Lac/tCr) and Glx (Glx/tCr) ratios is similar along the follow-up with a progressive decrease in tumor proliferation (tCho/tCr). However, in resected patients, the evolution of lactate (Lac/tCr) and Glx (Glx/tCr) ratios is similar until 6 months and differ above: a progressive decrease of Lac/tCr and Glx/tCr until 18 months with a higher level of Glx/tCr. CONCLUSION Despite the difficulties to separate glutamine from glutamate (post-processing improvement is ongoing), spectroscopic measurements of Glx changes before clinical deterioration. The increase of Glx is longer (in time) than the Lactate increase after 6 months of treatment in the resected patients could be predictive of the observed increase of tumor proliferation at 12 months of treatment.The study of glutaminergic metabolism in the GBM could be used to evaluate the response to treatment. Being able to predict the increase of tumor proliferation in resected patients could allow a faster treatment adaptation.
A Crucial Role for Diet in the Relationship Between Gut Microbiota and Cardiometabolic Disease
Authors: Ilias Attaye, Sara-Joan Pinto-Sietsma, Hilde Herrema, Max Nieuwdorp
Journal: Annual Review of Medicine (2019)

Cardiometabolic disease (CMD), such as type 2 diabetes mellitus and cardiovascular disease, contributes significantly to morbidity and mortality on a global scale. The gut microbiota has emerged as a potential target to beneficially modulate CMD risk, possibly via dietary interventions. Dietary interventions have been shown to considerably alter gut microbiota composition and function. Moreover, several diet-derived microbial metabolites are able to modulate human metabolism and thereby alter CMD risk. Dietary interventions that affect gut microbiota composition and function are therefore a promising, novel, and cost-efficient method to reduce CMD risk. Studies suggest that fermentable carbohydrates can beneficially alter gut microbiota composition and function, whereas high animal protein and high fat intake negatively impact gut microbiota function and composition. This review focuses on the role of macronutrients (i.e., carbohydrate, protein, and fat) and dietary patterns (e.g., vegetarian/vegan and Mediterranean diet) in gut microbiota composition and function in the context of CMD.
Unified Approach Needed to Implement Nutrition Support Services
Authors: Katherine Rediger, D. R. Bailey Miles
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
Potential impacts of climate change on child stunting via income and food price in 2030: a global-level model
Authors: Simon Lloyd, Mook Bangalore, Zaid Chalabi, R Sari Kovats, Stephane Hallegatte, Julie Ronberg, Hugo Valin
Journal: The Lancet Planetary Health (2019)

BackgroundIn 2016, 23% of children younger than 5 years were stunted. Global-level modelling has consistently found that climate change impacts on food production are likely to impair progress on reducing undernutrition. We adopt a new perspective, assessing how climate change may affect child stunting via its impacts on two interacting socioeconomic drivers: incomes of the poorest 20% of populations and food prices.MethodsWe developed a statistical model, driven by upstream poverty and food price models, to project moderate and severe stunting in children younger than 5 years in rural and urban areas in 2030 under low and high climate change scenarios combined with poverty and prosperity scenarios in 44 countries.FindingsWe estimated that, in the absence of climate change, 110 million children younger than 5 years would be stunted in 2030 under the poverty scenario in comparison with 83 million under the prosperity scenario. Estimates of climate change-attributable stunting ranged from 570 000 under the prosperity/low climate change scenario to more than 1 million under the poverty/high climate change scenario. The projected impact of climate change on stunting was greater in rural versus urban areas under both socioeconomic scenarios. Patterns in the results showed that, in countries where incomes remain low and food prices are relatively high (compared with incomes), further price rises tend to increase stunting. In contrast, in countries where incomes rise and food prices are relatively low, slowly rising prices tend to decrease stunting.InterpretationShifting the focus from food production to interactions between incomes and food price has provided new insights. The patterns in the results suggest that food prices that provide decent incomes to farmers alongside high employment with living wages will reduce undernutrition and vulnerability to climate change. Futures that protect health should consider not just availability, accessibility, and quality of food, but also the incomes generated by those producing the food.FundingThe research was partially funded by the Office of the Chief Economist of the Climate Change Group and the Global Facility for Disaster Reduction and Recovery of the World Bank, and the NIHR Health Research Health Protection Research Unit in Environmental Change and Health at the London School of Hygiene & Tropical Medicine in partnership with Public Health England (PHE), and in collaboration with the University of Exeter, University College London, and the Met Office. The views expressed are those of the authors and not necessarily those of the World Bank, NHS, the NIHR, the Department of Health, or Public Health England.
P03.05 Could suspected Glioblastomas be Treated without Hystological Diagnosis?
Authors: K Cortés Mateus, I Valduvieco Ruíz, E Verger Fransoy, E Pineda Losada, L Oleaga Zufiria, T Pujol Farre, J González Sánchez, L Pedrosa Eguílaz, F Graus Ribas, T Barreto Zambrano, D Muñoz Guglielmetti, C Castro Cuevas, E Escudero López, A Lloret Puerto, J Sáez Beltrán, C Camacho López, C Conill Llobet, G Oses González, S Garrido Alcantud, M Mollà Armada
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Probable unresectable Glioblastomas (GB) diagnosed by imaging techniques withouth anatomo-pathological (ap) confirmation could be treated under standard treatment. We reported the outcomes from this strategy in our center after tumor board evaluation. MATERIAL AND METHODS From January/10 to September/16, 303 patients (pt) with GB were assessed by tumor board, during the same period 66 patients were consecutive analyzed with suspected GB by radiological criteria without histological diagnosis. We focus in the last group and analyzed the demographic/radiological data, non-biopsy causes, treatment type (concomitant Radio-Chemotherapy (RT/Ch), exclusive RT or Ch or Best supportive care (BSC)), Karnofsky index (KI) and degree of comorbidity (Charlson index (CI)). RESULTS Sixty six patients, 17.88% of the total GB cases (with/without ap). Average age: 77 years (33–91). Biopsy: non-diagnostic in 4pt. No biopsy: 62pt; due to non medical indication (71%), localization (22.7%), voluntary (4.5%). Treatment Type: Active: 43.93%, without biopsy due to non-medical indication (44.8%) and localization (41.37%). BSC: 53.03%, without biopsy due to non-medical indication 82.85%, localization 8.5%, voluntary 5.7%. Overall survival: 11.65 months in patients with active treatment and 4.8 months in BSC, greater benefit in &lt;70 years and KI≥ 70 with statistical signification. CONCLUSION The diagnosis of GB by radiological criteria with the new imaging techniques has a good diagnostic-therapeutic correlation. In cases where surgical intervention is not possible, standard treatment offers good results. Age and KPS are variables that allow predicting a better evolution course. Although it was not possible to obtain a histological diagnosis, in this type of cases liquid biopsy could contribute to diagnosis this type of lesions inaccessible to biopsy.
P13.11 Metabolomics and molecular profiling in glioma patients: an interactomic approach
Authors: A C Fuentes-Fayos, M L Gandía-González, A Cano-Rojas, C J Blanco, E M Negro-Moral, Á Toledano, M J Ramos, A Cano-Sánchez, R M Luque, R M Ortega-Salas, J M Roda, S Cerdán, M L García-Martín, J Solivera
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND A wider view of the interaction between different omic-domains is needed to identify potential biomarkers of low- and high-grade gliomas. Using an interactomic approach, we analyzed the correlation between radiological data, IDH mutation, gene expression profiling and metabolic signature in glioma samples. MATERIAL AND METHODS Tumor biopsies from 25 patients with clinical diagnosis of glioma were surgically collected during 2017–2019 at the senior author’s institution. Metabolomic data was obtained by high resolution 31P and 1H magnetic resonance spectroscopy (MRS, 19 metabolites quantified with LCModel). Gene expression profiling was performed using real-time qPCR of 19 genes related to energy metabolism. IDH1/2 common mutation (IDH1R132H/IDH2R172H) was verified by immunohistochemistry and amplicon sanger sequencing. All data was integrated using the R package mixOmics, and we built correlation network plot graphs and correlation maps to identify the most significant interactions, that were analyzed thereafter. RESULTS Mean age was 48±10 years and 72% were men. The most frequent clinical presentation was intracranial hypertension and focal deficit. Imaging revealed 88% of single lobar tumors, 96% of contrast enhancement, 52% located near eloquent areas, 48% with augmented perfusion (mean values of 300±130%) and 60% showed restricted diffusion. WHO 2016 diagnosis were glioblastoma IDH mutated (IDHmut, 16%), IDH wildtype (IDHw, 56%); anaplastic astrocytoma IDHmut (4%), IDHw (16%); diffuse astrocytoma IDHmut (4%), SEGA (4%). The genetic and metabolic profiles were normalized per sample using the total sum of all the studied variables per case. This step made the interactomic approach possible. We found no differences between the metabolic or genetic profiles of glioma grade III and IV samples. However, there was a statistical significance or near-threshold correlation between some metabolic patterns and IDH-mutation, where Alanine (4.7±1.3% IDHw vs 2.5±0.7 IDHmut, p=0.046), Glycine (2.7±0.5% vs. 1.6±0.4%, p=0.095), Glycerophosphorylcholine (3.9±0.4% vs. 6.4±0.9%, p=0.013) and Myo-inositol (4.9±1.0% vs 11.9±2.1%, p=0.004) were the most important biomarkers. Overexpression of Lactate Dehydrogenase subunit B (LDHB, 19±3% vs. 31±6%, p=0.039) and Aconitase 1 (ACO1, 0.5±0.1% vs 1.2±0.3%, p=0.08) had also a significant or near-threshold relationship with IDH-mutation. These correlations were shown as hot spots in the correlation graphs and maps. CONCLUSION These preliminary results indicate that metabolic patterns by high resolution 31P and 1H MRS could be a useful tool to improve our knowledge about glioma gene expression profiles and to identify potential biomarkers to tackle this pathology.
Outcome of Autologous Stem Cell Transplantation in Waldenström's Macroglobulinemia
Authors: Romil Patel, Neeraj Y Saini, Ankur Varma, Omar Hasan, Qaiser Bashir, Ruby Delgado, Uday Popat, Chitra Hosing, Akash Mukherjee, Yago Nieto, Partow Kebriaei, Donna M. Weber, Sheeba K. Thomas, Hans C. Lee, Elisabet E. Manasanch, Robert Z Orlowski, Richard E Champlin, Muzaffar H. Qazilbash, Krina K. Patel
Journal: Blood (2018)
P11.34 Bone Morphogenetic Protein 4 can sensitize glioblastoma cells to temozolomide
Authors: I Verploegh, A Conidi, M Lamfers, C Dirven, S Leenstra, D Huylebroeck
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma (GBM) is the most prevalent and lethal primary brain tumor. Its recurrence and resistance to current therapies, i.e. temozolomide (TMZ), is thought to result from a subpopulation of cells exhibiting stem cell properties, called glioblastoma stem-like cells (GSCs). Bone Morphogenetic Protein 4 (BMP4) induces GSCs differentiation, leading to a less resistant phenotype. In this study we show that co-treatment of BMP4 with TMZ has therapeutic benefit in a subset of GBM cell lines. Furthermore, we looked for patients’ molecular signatures that could predict sensitivity to this combination treatment. MATERIAL AND METHODS A panel of 17 primary GBM cultures (passages 5–10) were treated with increasing concentrations of TMZ, BMP4 and TMZ + BMP4 for 5 and 7 days and cell viability has been measured. The Combination Index (CI) of the two drugs was calculated to assess the response of each line to TMZ and BMP4 treatment. DNA was used to determine the MGMT promotor methylation status and for targeted exome sequencing. Expression levels of BMP signaling components and differentiation associated genes were determined by qPCR. RESULTS 12 cultures of primary GBMs and 5 cultures of recurrent GBMs were included. Overall, 71% of the tested cell lines was resistant to TMZ, while 41% was resistant to BMP4. Strikingly, 53% of primary cultures show synergy between TMZ and BMP4 (CI &lt; 1 at a Fraction Affected of 50% (Fa50)). There was no significant difference in synergy between five or seven days of treatment. However, combination treatment of BMP4 and TMZ was more effective than sequential treatment. CONCLUSION Co-treatment of BMP4 and TMZ could be of therapeutic benefit in GBM patients, irrespective of their sensitivity to TMZ. Further research regarding the mechanism behind this synergy is necessary as to identify predictive markers for treatment response.