tbuckley/cabot-search huggingface dataset:
Combining the effects of increased atmospheric carbon dioxide on protein, iron, and zinc availability and projected climate change on global diets: a modelling study
Authors: Robert H Beach, Timothy B Sulser, Allison Crimmins, Nicola Cenacchi, Jefferson Cole, Naomi K Fukagawa, Daniel Mason-D'Croz, Samuel Myers, Marcus C Sarofim, Matthew Smith, Lewis H Ziska
Journal: The Lancet Planetary Health (2019)

BackgroundIncreasing atmospheric concentrations of carbon dioxide (CO2) affect global nutrition via effects on agricultural productivity and nutrient content of food crops. We combined these effects with economic projections to estimate net changes in nutrient availability between 2010 and 2050.MethodsIn this modelling study, we used the International Model for Policy Analysis of Agricultural Commodities and Trade to project per capita availability of protein, iron, and zinc in 2050. We used estimated changes in productivity of individual agricultural commodities to model effects on production, trade, prices, and consumption under moderate and high greenhouse gas emission scenarios. Two independent sources of data, which used different methodologies to determine the effect of increased atmospheric CO2 on different key crops, were combined with the modelled food supply results to estimate future nutrient availability.FindingsAlthough technological change, market responses, and the effects of CO2 fertilisation on yield are projected to increase global availability of dietary protein, iron, and zinc, these increases are moderated by negative effects of climate change affecting productivity and carbon penalties on nutrient content. The carbon nutrient penalty results in decreases in the global availability of dietary protein of 4·1%, iron of 2·8%, and zinc of 2·5% as calculated using one dataset, and decreases in global availability of dietary protein of 2·9%, iron of 3·6%, and zinc of 3·4% using the other dataset. The combined effects of projected increases in atmospheric CO2 (ie, carbon nutrient penalty, CO2 fertilisation, and climate effects on productivity) will decrease growth in the global availability of nutrients by 19·5% for protein, 13·6% for iron, and 14·6% for zinc relative to expected technology and market gains by 2050. The many countries that currently have high levels of nutrient deficiency would continue to be disproportionately affected.InterpretationThis approach is an improvement in estimating future global food security by simultaneously projecting climate change effects on crop productivity and changes in nutrient content under increased concentrations of CO2, which accounts for a much larger effect on nutrient availability than CO2 fertilisation. Regardless of the scenario used to project future consumption patterns, the net effect of increasing concentrations of atmospheric CO2 will slow progress in decreasing global nutrient deficiencies.FundingUS Environmental Protection Agency, Consultative Group on International Agricultural Research (CIGAR) Research Program on Policies, Institutions and Markets (PIM), and the CGIAR Research Program on Climate Change and Food Security (CCAFS).
Intrinsically Distinct Role of Neutrophil Extracellular Trap Formation in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis Compared to Systemic Lupus Erythematosus
Authors: Laura S. van Dam, Tineke Kraaij, Sylvia W. A. Kamerling, Jaap A. Bakker, Uli H. Scherer, Ton J. Rabelink, Cees van Kooten, Y. K. Onno Teng
Journal: Arthritis & Rheumatology (2019)

Objective Different studies have demonstrated that neutrophil extracellular traps ( NET s) may be involved in the pathophysiology of both antineutrophil cytoplasmic antibody ( ANCA )–associated vasculitis ( AAV ) and systemic lupus erythematosus ( SLE ). AAV and SLE are clinically and pathologically divergent autoimmune diseases with different autoantibodies. However, the respective autoantigens recognized in AAV and SLE have been shown to be an intricate part of NET s. This study aimed to examine whether the mechanisms of NET formation and the composition of NET s are distinct between AAV and SLE . Methods To investigate this hypothesis, healthy neutrophils were stimulated with serum from patients with AAV (n = 80) and patients with SLE (n = 59), and the mechanisms of NET formation and NET composition were compared. Results Both patients with AAV and patients with SLE had excessive NET formation, which correlated with the extent of disease activity (in AAV r = 0.5, P &lt; 0.0001; in SLE r = 0.35, P &lt; 0.01). Lytic NET formation over several hours was observed in patients with AAV , as compared to rapid (within minutes), non‐lytic NET formation coinciding with clustering of neutrophils in patients with SLE . AAV ‐induced NET formation was triggered independent of IgG ANCA s, whereas SLE immune complexes ( IC x) induced NET formation through Fcγ receptor signaling. AAV ‐induced NET formation was dependent on reactive oxygen species and peptidyl arginine deaminases, and AAV ‐induced NET s were enriched for citrullinated histones (mean ± SEM 23 ± 2%). In contrast, SLE ‐induced NET s had immunogenic properties, including binding with high mobility group box chromosomal protein 1 (mean ± SEM 30 ± 3%) and enrichment for oxidized mitochondrial DNA , and were involved in IC x formation. Conclusion The morphologic features, kinetics, induction pathways, and composition of excessive NET formation are all intrinsically distinct in AAV compared to SLE . Recognizing the diversity of NET formation between AAV and SLE provides a better understanding of the pathophysiologic role of NET s in these different autoimmune diseases.
Treatment with Humanized Selective CD19CAR-T Cells Shows Efficacy in Highly Treated B-ALL Patients Who Have Relapsed after Receiving Murine-Based CD19CAR-T Therapies
Authors: Yu Zhao, Zhongfeng Liu, Xuan Wang, Huantong Wu, Jianping Zhang, Junfang Yang, Fayou Zhang, Lining Liu, Jiafu Long, Peihua Lu, Zhiguo Chen
Journal: Clinical Cancer Research (2019)

CD19 chimeric antigen receptor (CAR)-T therapy has shown impactful results in treatment of B-cell malignancies. However, immune recognition of the murine scFv may render subsequent infusion(s) ineffective. Also, nonselective expansion of both CAR-transduced and nontransduced T cells during the production stage affects the yield and purity of final products. Here, we aim to develop a humanized selective (hs) CD19 CAR to solve the above problems.Experimental Design: A CD19 hsCAR was designed, which incorporated a short selective domain between the humanized heavy chain and light chain. The CAR was examined for its property, and then trialed in 5 highly treated B-ALL patients.hsCAR possessed around 6-fold higher affinity to CD19 versus murine CAR (mCAR). Incubation with selective domain-specific mAbs (SmAb) selectively expanded CAR-transduced T cells, and led to a higher proportion of central memory T cells in the final products. SmAb-stimulated CD19 hsCAR-T cells exhibited superior antitumor cytotoxic functions in vitro and in vivo. Autologous (n = 2) and allogeneic donor (n = 3, with hematopoietic stem cell transplantation) hsCAR-T cells were infused into 5 patients who had relapsed after receiving mCAR-T treatments. Two patients received mCAR-T treatments twice previously but the second treatments were ineffective. In contrast, subsequent hsCAR-T treatments proved effective in all 5 patients and achieved complete molecular remission in four, including one with extramedullary disease with central nervous system involvement.hsCD19 CAR-T treatment shows efficacy in highly treated B-ALL patients who have relapsed after receiving CD19 mCAR-T therapies.
Coronary Artery Disease and Transcatheter Aortic Valve Replacement
Authors: Laurent Faroux, Leonardo Guimaraes, Jérôme Wintzer-Wehekind, Lucia Junquera, Alfredo Nunes Ferreira-Neto, David del Val, Guillem Muntané-Carol, Siamak Mohammadi, Jean-Michel Paradis, Josep Rodés-Cabau
Journal: Journal of the American College of Cardiology (2019)
Delayed cognitive, behavioral, and radiological changes related to canial irradiation for pediatric brain tumors
Authors: M. M. Abdel Wahab, H. Hussien, K. M. Maher
Journal: Journal of Clinical Oncology (2007)

20023 Purpose: To evaluate the delayed adverse changes in neuro-cognitive functions as well as white matter damage in radiated survivors of pediatric brain tumors. Methods: Forty two children (22 males) with primary brain tumors who were only treated with cranial radiation, were recruited. 28 patients were treated for low risk medulloblastoma, 10 patients for low grade astrocytoma, 3 patients for low grade ependymoma, and 1 patient for craniopharyngioma. Their ages ranged from 3 to 18 years (mean 10.3±3.98 years).They were subjected, initially just before radiotherapy and at follow-up 1–2 year after completion of cranial radiation, to serial clinical and neuropsychological assessments including Wechseler Intelligence Scale for Children, Vineland social maturity test, Benton Visual Memory Test, and Revised Behavior Problem Checklist. Magnetic resonance scans were also performed to detect the presence of white matter damage before radiotherapy and at follow up. Results: Initially, after surgery and before radiation, intelligence test scores were below normal scores for age and this was of high statistical significance (Total IQ: t= -3.02, P= 0.006). Visual memory test showed evidence of organicity in all cases. Social maturity showed a statistically significant decline as well (t= -2.11, P= 0.04). Follow-up after radiotherapy showed further decline with high statistical significance (Total IQ t= 3.228, P=0.003; visual memory t= 4.08, P= 0.001); An attentional problem has emerged (t= -6.12, P= 0.00). Both radiation dose and volume of radiation showed negative and statistically significant correlation with IQ. Age at diagnosis correlated positively and significantly with IQ ( r= 0.601, P=0.001). Multiple linear regression showed impaired neurocognitive function which was correlated with the degree of white matter damage. (standardized B= -0.577, P= 0.001) and young age at diagnosis (standardized B= -0.427, P= 0.014). Conclusions: Cranial radiation in pediatric brain tumors is associated with a decline in multiple neurocognitive functions including total IQ, visual memory, and attention; which are related to the toxic effect of cranial radiation on white matter of the brain especially in young age of childhood with high dose and whole cranial radiation. No significant financial relationships to disclose.
Evaluation of a dedicated institutional tobacco cessation service for thoracic clinic cancer patients.
Authors: Katharine Ann Dobson Amato, Michael Zevon, Pat Hysert, Robert Hysert, Stephanie Segal, Robert Reed, Gary Giovino, Maansi Bansal-Travers, Heather Ochs-Balcom, Chukwumere E. Nwogu, K. Michael Cummings, Martin Mahoney, Andrew Hyland, Mary E. Reid, Graham Walter Warren
Journal: Journal of Clinical Oncology (2013)

1603 Background: Tobacco use by cancer patients is associated with poor therapeutic outcomes including increased toxicity, decreased quality of life, and decreased survival. Though recommendations provide for tobacco assessment and cessation for cancer patients, few oncologists provide cessation support. Presented are data from universal tobacco assessment and cessation program for patients presenting at a thoracic oncology clinic in a NCI Designated Comprehensive Cancer Center. Methods: A standard set of evidence based tobacco assessment questions were incorporated into an automated electronic medical record based system delivered by nursing at initial consult and at follow-up. Patients eligible for tobacco cessation support (i.e. patients self-reporting tobacco use within 30 days) were automatically referred to a dedicated tobacco cessation service. All referred patients are sent a standardized packet of cessation materials with telephone-based follow-up by trained cessation counselors. Results: A total of 980 new thoracic clinic patients were referred to the cessation service from January 2011 and October 2012. Two-thirds of the patients referred (n=728) referred into the system were current smokers and the remainder had quit in the 30 days prior to assessment. Among the 788 patients with contact attempts by the cessation service, 81.2% (n=640) were successfully contacted and only 2.5% (n=20) refused the offer of cessation support. At first contact, 75.6% (n=484) of patients reported continued current tobacco use. Follow-up calls were placed for 53.1% (n=340) of those who participated in the first contact an average of 39 days after the first successful contact. The follow-up had a 93.2% (n=317) participation rate which revealed that 33.3% (n=106) reported not smoking, an 8.9% increase since the first cessation service telephone call. Conclusions: Data demonstrate that an automated tobacco assessment and cessation service for thoracic oncology patients can effectively generate a large mandatory referral base with high patient interest in cessation, and that cessation support can be implemented and maintained in high risk cancer patients.
RRx-001 is a phase III aerospace-derived small molecule that immunonormalizes the tumor microenvironment.
Authors: Pedro Cabrales
Journal: Journal of Clinical Oncology (2019)

156 Background: Tumor associated macrophages (TAMs) with M2-like phenotypes produce angiogenic factors and cytokines which lead to vascular immaturity. M2 cytokines also impair immune cell activity. CD47 and SIRP⍺ are innate immune checkpoints which inhibit macrophage phagocytosis and enhance M2 polarization. Disruption of the CD47/SIRP⍺ axis polarize TAMs away from an M2-like phenotype to normalize tumor vessels and stimulate antitumor immunity. Normalized vessels facilitate delivery of drugs and immune cells and also sensitizes tumors to therapy and promotes M1-like TAM phenotype. RRx-001 modulates TAM infiltration and phenotype via CD47/SIRP⍺ downregulation, which normalizes both the tumor vasculature, and the immune cell milieu. Methods: The effect of RRx-001 on intratumoral blood flow was evaluated both preclinically and clinically with dynamic contrast MRI. An in vitro phagocytotic assay was used to determine whether RRx-001 promoted engulfment of A549 tumor cells by macrophages. Transcriptional mRNA profiling in murine tumor associated macrophages (TAMs) was performed to analyze the cytokine profile of TAMs in the presence or absence of RRx-001. Athymic mice with intracranial GBM43 were administered RRx-001 (10 mg/kg) followed 4 hours later by 0.4 mg of irinotecan by tail vein on days 12, 18, 24 and 30 after implantation of tumor cells. Mice were euthanized 24 hours after last irinotecan administration, with brains immediately resected and tumor tissue dissected prior to snap-freezing by immersion in liquid nitrogen. Results: RRx-001 was shown to induce: vascular normalization with increased intratumoral perfusion, dual downregulation of CD47 and SIRP⍺, increased phagocytosis, improved delivery of chemotherapy and increased T cell infiltration. Conclusions: RRx-001 leads to vascular normalization and enhanced delivery of chemotherapy and immune cell infiltration. The increase in tumor perfusion diminishes hypoxia and also serves to polarize TAMs away from an M2-like state. These results also suggest and are borne out by clinical biopsies that the effect of RRx-001 depends on the number of TAMs present in the tumor microenvironment with higher numbers leading to better activity.
18F-Fluorocholine PET/CT in the Prediction of Molecular Subtypes and Prognosis for Gliomas
Authors: Ana María García Vicente, Julian Pérez-Beteta, Mariano Amo-Salas, Francisco José Pena Pardo, Maikal Villena Martín, Hernán Sandoval Valencia, Manuela Mollejo Villanueva, Rosa Barbella, Christoph José Klein Zampaña, José María Borrás Moreno, Ángel María Soriano Castrejón, Víctor Manuel Pérez-García
Journal: Clinical Nuclear Medicine (2019)

Aim To study the association of metabolic features of 18 F-fluorocholine in gliomas with histopathological and molecular parameters, progression-free survival (PFS) and overall survival (OS). Methods Prospective multicenter and nonrandomized study (Functional and Metabolic Glioma Analysis). Patients underwent a basal 18 F-fluorocholine PET/CT and were included after histological confirmation of glioma. Histological and molecular profile was assessed: grade, Ki-67, isocitrate dehydrogenase status and 1p/19q codeletion. Patients underwent standard treatment after surgery or biopsy, depending on their clinical situation. Overall survival and PFS were obtained after follow-up. After tumor segmentation of PET images, SUV and volume-based variables, sphericity, surface, coefficient of variation, and multilesionality were obtained. Relations of metabolic variables with histological, molecular profile and prognosis were evaluated using Pearson χ 2 and t test. Receiver operator caracteristic curves were used to obtain the cutoff of PET variables. Survival analysis was performed using Kaplan-Meier and Cox regression analysis. Results Forty-five patients were assessed; 38 were diagnosed as having high-grade gliomas. Significant differences of SUV-based variables with isocitrate dehydrogenase status, tumor grade, and Ki-67 were found. Tumor grade, Ki-67, SUVmax, and SUVmean were related to progression. Kaplan-Meier analysis revealed significant associations of SUVmax, SUVmean, and multilesionaly with OS and PFS. SUVmean, sphericity, and multilesionality were independent predictors of OS and PFS in Cox regression analysis. Conclusions Metabolic information obtained from 18 F-fluorocholine PET of patients with glioma may be useful in the prediction of tumor biology and patient prognosis.
Association of Immune Marker Changes With Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma
Authors: Ola Landgren, Jonathan N. Hofmann, Charlene M. McShane, Loredana Santo, Malin Hultcrantz, Neha Korde, Sham Mailankody, Dickran Kazandjian, Kazunori Murata, Katie Thoren, Lakshmi Ramanathan, Ahmet Dogan, Even Rustad, Sydney X. Lu, Theresia Akhlaghi, Sigurdur Y. Kristinsson, Magnus Björkholm, Sean Devlin, Mark P. Purdue, Ruth M. Pfeiffer, Ingemar Turesson
Journal: JAMA Oncology (2019)

Multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Risk models that estimate the risk of progression from MGUS to multiple myeloma use data from a single time point, usually the initial workup.
A Systematic Review and Meta-Analysis of the Diagnostic Performance of BRAF V600E Immunohistochemistry in Thyroid Histopathology
Authors: Ranjit Singarayer, Ozgur Mete, Laure Perrier, Lehana Thabane, Sylvia L. Asa, Stan Van Uum, Shereen Ezzat, David P. Goldstein, Anna M. Sawka
Journal: Endocrine Pathology (2019)
Randomized controlled trial demonstrating the benefits of delta inulin adjuvanted immunotherapy in patients with bee venom allergy
Authors: Robert Heddle, Anthony Smith, Richard Woodman, Pravin Hissaria, Nikolai Petrovsky
Journal: Journal of Allergy and Clinical Immunology (2019)

Allergic reactions to Hymenoptera insect stings remain a major global clinical problem. Although effective, parenteral desensitization regimens require use of costly venom extracts and require frequent visits over extended periods of time.Adjuvants are commonly used to enhance the efficacy of infectious disease vaccines, and this study asked whether Advax (Vaxine Pty Ltd, Adelaide, Australia), a novel noninflammatory polysaccharide adjuvant, might provide similar benefits for allergy desensitization.A randomized, controlled phase 1/2 trial was undertaken in 27 adults with a history of rapid-onset systemic allergic reactions to honeybee stings and positive specific IgE levels to evaluate the safety and efficacy of honeybee venom immunotherapy (HBVIT) combined with Advax adjuvant. Venom immunotherapy (VIT) was administered monthly for 30 months after achievement of maintenance doses.Advax-adjuvanted HBVIT was well tolerated. Around week 14 of VIT, specific IgG4 responses peaked in both groups but increased earlier, peaked higher, and were better maintained through the end of the study in the Advax-adjuvanted arm. Several different patterns of serologic response to VIT were seen; some subjects had a dominant IgG4 response, some had a combined IgG4 and IgG1 response, and some had an exclusively IgG1 response. In some subjects specific IgE levels increased during the induction phase and then decreased, whereas in others specific IgE levels progressively decreased from the start of VIT.Advax adjuvant favorably enhanced the immunogenicity of HBVIT, with an early and prolonged switch to specific IgG4 production. The ability of Advax adjuvant to enhance VIT efficacy warrants further study.
Adult Pancreatoblastoma With Liver Metastasis Diagnosed by 18F-FDG PET/CT and 2 Years’ Postoperative Follow-up
Authors: En-Tao Liu, Chao Liu, Hui-Ling Wang, Tao-Tao Sun, Shu-Xia Wang
Journal: Clinical Nuclear Medicine (2019)

Abstract Pancreatoblastoma is an extremely rare malignant tumor of the pancreas. Most patients are infants and children; however, a few cases have been reported in adults. Herein, we present the case of a 49-year-old man with pancreatoblastoma and liver metastasis who underwent preoperative multimodal imaging, in which 18 F-FDG PET/CT showed a markedly increased 18 F-FDG uptake in the metastatic lesion and a slightly increased uptake in the primary lesion. Subsequently, the patient underwent complete resection of the primary and metastatic lesions. No recurrences or metastases were found in 2 years of follow-up.
A 44-Year-Old Woman With Dilated Cardiomyopathy
Authors: Joseph M. Lightsey, Takeki Suzuki, Tanyanan Tanawuttiwat
Journal: JAMA Cardiology (2019)

A 44-year-old woman presents with dilated cardiomyopathy after ventricular fibrillation arrest and receives several shocks from an impanted subcutaneous cardioverter defibrillator. What would you do next?
Diabetic foot ulcers
Authors: Michael E Edmonds, A V M Foster
Journal: BMJ (2006)

<h3>Abstract</h3> It remains to be understood how biological motion is hierarchically computed, from discrimination of local "life motion" animacy to global dynamic body perception. Here, we addressed this functional separation of the correlates of the perception of life motion, defined as characteristic for the local motion of parts of living beings, from perception of global motion of a body. We hypothesized that life motion processing can be isolated, by using a single dot motion perceptual decision paradigm featuring the biomechanical details of local realistic motion of a single joint. To ensure that we were indeed tackling processing of biological motion properties we used a discrimination instead of detection task. We discovered using representation similarity analysis that two key early dorsal and two ventral stream regions (visual motion selective hMT+ and V3A, extrastriate body area EBA and a region within fusiform gyrus FFG) showed robust and separable signals related to encoding of life motion and global motion. These signals reflected two independent processing stages, as revealed by representation dissimilarity analysis and deconvolution of fMRI responses to each motion pattern. This study showed that higher level pSTS encodes both classes of biological motion in a similar way, revealing a higher-level integrative stage, reflecting scale independent biological motion perception. Our results reveal a two-stage framework for neural computation of biological motion, with an independent contribution of dorsal and ventral regions for the initial stage.