bluuebunny/crossref_metadata_2025_split huggingface dataset:
CORA Project: Vitrification of Intermediate Level Liquid Radioactive Wastes in Saluggia ENEA Research Centre
Authors: Calle Carlos A. , Luce Alfredo 
Published: April 2020

Abstract
The EUREX reprocessing pilot plant, at ENEA Research Centre, Saluggia (VC - Italy), stores 113 m3 of intermediate level liquid waste and 110 m3 of low level liquid waste, originating from the past reprocessing campaigns.
Conditioning of the above wastes, for the purpose of final disposal, has been planned in a new installation for the solidification of both intermediate and low level wastes at Saluggia site. The installation, under design, has been named CORA Plant (COnditioning of RAdioactive wastes).
Direct Vitrification process using cold crucible melter (CCM) developed by CEA of Marcoule, has been chosen as conditioning technology for a mix of most active wastes and cementation for secondary low level waste produced during vitrification.
A boro-silicate glass matrix has been selected with a specific nominal chemical composition adapted to liquid waste matrix. Characterisation work of this specific glass is under progress.
CORA has been presented to regulatory authority has a modification of a pilot reprocessing Eurex plant.
Vitrification equipment and glass canister interim storage facility of CORA Plant will be housed inside the existing building of Eurex facility properly modified. Cementation unit inside a new building located in a near external yard.
A description of the waste management scheme, as well as a brief description of adopted technologies, chemical glass composition and updated schedule of CORA project is presented in this paper.
Canister Sealing for High Level Waste Encapsulation
Authors: Andrews Richard E. 
Published: April 2020

Abstract
Sweden has chosen to manage spent fuel rods by direct encapsulation and storage in a deep level repository. Two welding processes are being investigated for the sealing of copper vessels that form the outer barrier of the disposal canisters.
TWI Ltd in the UK has developed Reduced Pressure Electron Beam Welding and Friction Stir Welding for 50mm thick copper. This paper describes some of the investigations and compares the techniques. Over the past 3 years a full-size canister welding machine has been designed and built. Specialised tools have been developed for the welding of thick sections in copper with very encouraging results.
Clinical and neuropsychological profile of patients with dementia and chronic traumatic encephalopathy
Authors: LoBue Christian , Schaffert Jeff , Cullum C Munro , Peters Matthew E , Didehbani Nyaz , Hart John , White Charles L 
Published: April 2020

ObjectiveTo determine whether subjects with chronic traumatic encephalopathy (CTE) and dementia have distinct clinical features compared to subjects with pathologically confirmed Alzheimer’s disease (AD).MethodsAmong 339 subjects assessed for CTE in the National Alzheimer’s Coordinating Center dataset, 6 subjects with CTE and 25 subjects with AD neuropathologic change matched for age (±5 years) and sex were identified. All subjects had a clinical diagnosis of dementia. Neurological examination, neuropsychological testing and emotional/behavioural data were compared between CTE and AD subjects at the time of dementia diagnosis and last clinical visit near death.ResultsA history of traumatic brain injury with loss of consciousness (LOC) was reported in one CTE and one AD subject; information about injuries without LOC or multiple injuries was unavailable. CTE and AD subjects did not differ significantly at the time of diagnosis or last visit on the Unified Parkinson’s Disease Rating Scale—Motor Exam, global measures of cognitive functioning (Mini-Mental State Exam and Clinical Dementia Rating Scale), emotional/behaviour symptoms as assessed with the Neuropsychiatric Inventory questionnaire or across neuropsychological measures. All CTE participants had co-occurring neuropathologic processes, including AD and most had TAR DNA-binding protein 43 (TDP-43) neuropathology.ConclusionsCTE pathology was rare in a large multicentre national dataset, and when present, was accompanied by AD and TDP-43 pathologies. CTE was not associated with a different clinical presentation from AD or with greater cognitive impairment or neurobehavioral symptoms. These findings suggest that CTE may not have a distinct clinical profile when other neuropathologic processes are coexistent with CTE pathology.
Elevation of inflammatory S100A8/S100A9 complexes in intracranial aneurysms
Authors: de Korte Antonius Mattheus , Aquarius René , Vogl Thomas , Roth Johannes , Bartels Ronald H M A , Boogaarts Hieronymus D , van Lent Peter L E M , De Vries Joost 
Published: April 2020

BackgroundInflammation-related factors might give further insight into the pathophysiology of vessel wall inflammation and intracranial aneurysm (IA) rupture. One of these factors is the protein complex S100A8/A9, which is released by neutrophils, monocytes, and activated macrophages and is known for its role in cardiovascular disease.ObjectiveTo determine if venous S100A8/A9 levels in patients with a ruptured IA (rIA) or unruptured IA (uIA) are elevated compared with a control group. Second, to assess differences between venous and intra-aneurysmal S100A8/A9 levels of rIA and uIA patients.MethodsA prospective case study was performed between June 2016 and May 2017 in patients harboring a ruptured or unruptured saccular IA. Primary outcome measures were individual S100A8/A9 serum concentrations as measured in venous and intra-aneurysmal blood samples during endovascular treatment. Venous serum S100A8/A9 concentrations from a healthy control group served as a reference.ResultsWe included 16 patients with either a rIA or uIA and 47 healthy controls. Venous S100A8/A9 concentrations were higher in aneurysm patients (rIA and uIA) than those of healthy controls (P≤0.001). S100A8/A9 concentrations were higher in intra-aneurysmal samples than in venous samples of rIA patients (P=0.011). This difference was not found in uIA patients (P=0.054). Intra-aneurysmal S100A8/A9 levels were higher in rIAs than in uIAs (P=0.04).ConclusionsVenous S100A8/A9 levels are elevated in patients with both rIAs and uIAs compared with healthy controls and likely represents aneurysm wall inflammation. S100A8/A9 causes macrophage-induced inflammation and degeneration of the vessel wall which might explain higher intra-aneurysmal S100A8/A9 levels found in rIAs than in uIAs.
Analysis of Bose–Einstein correlation at 7 TeV by LHCb collaboration based on stochastic approach
Authors: Mizoguchi Takuya , Biyajima Minoru 
Published: April 2020

The Bose–Einstein correlation (BEC) in forward region [Formula: see text] measured at 7 TeV in the Large Hadron Collider (LHC) by the LHCb collaboration is analyzed using two conventional formulas of different types named CF[Formula: see text] and CF[Formula: see text]. The first formula is well known and contains the degree of coherence [Formula: see text] and the exchange function [Formula: see text] from the BE statistics. The second formula is an extended formula (CF[Formula: see text]) that contains the second degree of coherence [Formula: see text] and the second exchange function [Formula: see text] in addition to CF[Formula: see text]. To examine the physical meaning of the parameters estimated by CF[Formula: see text], we analyze the LHCb BEC data by using a stochastic approach of the three-negative binomial distribution and the three-generalized Glauber–Lachs formula. Our results reveal that the BEC at 7 TeV consisted of three activity intervals defined by the multiplicity [Formula: see text] ([8, 18], [19, 35], and [36, 96]) can be well explained by CF[Formula: see text].
Cancer Incidence Projections in Northern Ireland to 2040
Authors: Donnelly David W. , Anderson Lesley A. , Gavin Anna 
Published: April 2020

Abstract

Background:
Data on historic trends and estimates of future cancer incidence are essential if cancer services are to be adequately resourced in future years.

Methods:
Age-standardized incidence rates (ASIR) for all cancers combined and 19 common cancers diagnosed during 1993–2017 were determined by sex, year of diagnosis, and age. Data were fitted using an age–period–cohort model, which was used to predict rates in future years up to 2040. These were combined with population projections to provide estimates of the future case number.

Results:
Compared with the annual average in 2013–2017, for all cancers (excluding nonmelanoma skin) ASIRs are expected by 2040 to fall 9% among males and rise 12% among females, while the number of cases diagnosed is projected to increase by 45% for males and 58% for females. Case volume is projected to rise for all cancer types except for cervical and stomach cancer, with the annual number of cases diagnosed projected to more than double among males for melanoma, liver, and kidney cancers, and among females for liver, pancreatic, and lung cancers.

Conclusions:
Increased numbers of cancer cases is projected, due primarily to projected increases in the number of people aged 60 years and over.

Impact:
Projected increases will significantly impact the health services which diagnose and treat cancer. However, while population growth is primarily responsible, reduction of exposure to cancer risk factors, especially tobacco use, obesity, alcohol consumption, and UV radiation, could attenuate the predicted increase in cancer cases.
Modeling the Balance of Benefits and Harms of Cervical Cancer Screening with Cytology and Human Papillomavirus Testing
Authors: Malagón Talía , Mayrand Marie-Hélène , Ogilvie Gina , Gotlieb Walter H. , Blake Jennifer , Bouchard Céline , Franco Eduardo L. , Kulasingam Shalini 
Published: April 2020

Abstract

Background:
Benefits of screening should outweigh its potential harms. We compared various metrics to assess the balance of benefits and harms of cervical cancer screening.

Methods:
We used a cervical cancer natural history Markov model calibrated to the Canadian context to simulate 100,000 unvaccinated women over a lifetime of screening with either cytology every 3 years or human papillomavirus (HPV) testing every 5 years. We estimated the balance of benefits and harms attributable to screening using various metrics, including colposcopies/life-year gained, and net lifetime quality-adjusted life-years (QALY) gained, a measure integrating women's health preferences. We present the average (minimum–maximum) model predictions.

Results:
Cytology-based screening led to 1,319,854 screening tests, 30,395 colposcopies, 13,504 life-years gained over a lifetime, 98 screening tests/life-year gained, 2.3 (1.6–3.3) colposcopies/life-year gained, and a net lifetime gain of 10,735 QALY (5,040–17,797). HPV-based screening with cytology triage in the same population would lead to 698,250 screening tests, 73,296 colposcopies, 15,066 life-years gained over a lifetime, 46 screening tests/life-year gained, 4.9 colposcopies/life-year gained (2.9–11.1), and a net lifetime gain of 11,690 QALY (4,409–18,742). HPV-based screening was predicted to prevent more cancers, but also incur more screening harms than cytology-based screening.

Conclusions:
Metrics using colposcopies as the main harm outcome favored cytology-based screening, whereas metrics based on screening tests and health preferences tended to favor HPV-based screening strategies.

Impact:
Whether HPV-based screening will improve the balance between benefits and harms of cervical cancer screening depends on how the balance between benefits and harms is assessed.
Dendritic Cells, the T-cell-inflamed Tumor Microenvironment, and Immunotherapy Treatment Response
Authors: Garris Christopher S. , Luke Jason J. 
Published: April 2020

AbstractThe development of the most successful cancer immunotherapies in solid tumors, immune-checkpoint blockade, has focused on factors regulating T-cell activation. Until recently, the field has maintained a predominately T-cell centric view of immunotherapy, leaving aside the impact of innate immunity and especially myeloid cells. Dendritic cells (DC) are dominant partners of T cells, necessary for initiation of adaptive immune responses. Emerging evidence supports a broader role for DCs in tumors including the maintenance and support of effector functions during T-cell responses. This relationship is evidenced by the association of activated DCs with immune-checkpoint blockade responses and transcriptional analysis of responding tumors demonstrating the presence of type I IFN transcripts and DC relevant chemokines. T-cell-inflamed tumors preferentially respond to immunotherapies compared with non–T-cell-inflamed tumors and this model suggests a potentially modifiable spectrum of tumor microenvironmental immunity. Although host and commensal factors may limit the T-cell-inflamed phenotype, tumor cell intrinsic factors are gaining prominence as therapeutic targets. For example, tumor WNT/β-catenin signaling inhibits production of chemokine gradients and blocking DC recruitment to tumors. Conversely, mechanisms of innate immune nucleic acid sensing, normally operative during pathogen response, may enhance DC accumulation and make tumors more susceptible to cancer immunotherapy. Elucidating mechanisms whereby DCs infiltrate and become activated within tumors may provide new opportunities for therapeutic intervention. Conceptually, this would facilitate conversion of non–T-cell-inflamed to T-cell-inflamed states or overcome secondary resistance mechanisms in T-cell-inflamed tumors, expanding the proportion of patients who benefit from cancer immunotherapy.
The Immunosuppressive Niche of Soft-Tissue Sarcomas is Sustained by Tumor-Associated Macrophages and Characterized by Intratumoral Tertiary Lymphoid Structures
Authors: Chen Lingling , Oke Teniola , Siegel Nicholas , Cojocaru Gady , Tam Ada J. , Blosser Richard L. , Swailes Jessica , Ligon John A. , Lebid Andriana , Morris Carol , Levin Adam , Rhee Daniel S. , Johnston Fabian M. , Greer Jonathan B. , Meyer Christian F. , Ladle Brian H. , Thompson Elizabeth D. , Montgomery Elizabeth A. , Choi Woonyoung , McConkey David J. , Anders Robert A. , Pardoll Drew M. , Llosa Nicolas J. 
Published: April 2020

Abstract

Purpose:
Clinical trials with immune checkpoint inhibition in sarcomas have demonstrated minimal response. Here, we interrogated the tumor microenvironment (TME) of two contrasting soft-tissue sarcomas (STS), rhabdomyosarcomas and undifferentiated pleomorphic sarcomas (UPS), with differing genetic underpinnings and responses to immune checkpoint inhibition to understand the mechanisms that lead to response.

Experimental Design:
Utilizing fresh and formalin-fixed, paraffin-embedded tissue from patients diagnosed with UPS and rhabdomyosarcomas, we dissected the TME by using IHC, flow cytometry, and comparative transcriptomic studies.

Results:
Our results demonstrated both STS subtypes to be dominated by tumor-associated macrophages and infiltrated with immune cells that localized near the tumor vasculature. Both subtypes had similar T-cell densities, however, their in situ distribution diverged. UPS specimens demonstrated diffuse intratumoral infiltration of T cells, while rhabdomyosarcomas samples revealed intratumoral T cells that clustered with B cells near perivascular beds, forming tertiary lymphoid structures (TLS). T cells in UPS specimens were comprised of abundant CD8+ T cells exhibiting high PD-1 expression, which might represent the tumor reactive repertoire. In rhabdomyosarcomas, T cells were limited to TLS, but expressed immune checkpoints and immunomodulatory molecules which, if appropriately targeted, could help unleash T cells into the rest of the tumor tissue.

Conclusions:
Our work in STS revealed an immunosuppressive TME dominated by myeloid cells, which may be overcome with activation of T cells that traffic into the tumor. In rhabdomyosarcomas, targeting T cells found within TLS may be key to achieve antitumor response.
Impact of DNA Damage Response and Repair (DDR) Gene Mutations on Efficacy of PD-(L)1 Immune Checkpoint Inhibition in Non–Small Cell Lung Cancer
Authors: Ricciuti Biagio , Recondo Gonzalo , Spurr Liam F. , Li Yvonne Y. , Lamberti Giuseppe , Venkatraman Deepti , Umeton Renato , Cherniack Andrew D. , Nishino Mizuki , Sholl Lynette M. , Shapiro Geoffrey I. , Awad Mark M. , Cheng Michael L. 
Published: April 2020

Abstract

Purpose:
DNA damage response and repair (DDR) gene alterations are associated with increased tumor-infiltrating lymphocytes, higher genomic instability, and higher tumor mutational burden (TMB) in cancer. Whether DDR alterations are associated with clinical outcomes to programmed death ligand 1 [PD-(L)1] blockade in non–small cell lung cancer (NSCLC) is unknown.

Experimental Design:
Tumors from patients treated with PD-(L)1 inhibitors were analyzed using targeted next-generation sequencing (NGS). Cancers were categorized on the basis of the presence or absence of deleterious mutations across a panel of 53 DDR genes. Clinical outcomes to PD-(L)1 inhibitors were evaluated according to DDR mutation status.

Results:
Of 266 patients with successful NGS who received PD-(L)1 inhibitors, 132 (49.6%) were identified as having deleterious DDR mutations (DDR-positive). DDR-positive and DDR-negative groups were similar in terms of baseline clinicopathologic characteristics. The median TMB was significantly higher in the DDR-positive group compared with the DDR-negative group (12.1 vs. 7.6 mutations/megabase; P &lt; 0.001). Compared with DDR-negative patients (N = 134), DDR-positive patients had a significantly higher objective response rate (30.3% vs. 17.2%; P = 0.01), longer median progression-free survival [PFS; 5.4 vs. 2.2 months; HR, 0.58 (95% confidence interval (CI), 0.45–0.76); P &lt; 0.001], and longer median overall survival [OS; 18.8 vs. 9.9 months; HR, 0.57 (95% CI, 0.42–0.77); P &lt; 0.001] with PD-(L)1 therapy. After adjusting for PD-L1, TMB, performance status, tobacco use, and line of therapy, DDR-positive status was associated with a significantly longer PFS [HR, 0.68 (95% CI, 0.51–0.92); P = 0.01] and OS [HR, 0.60 (95% CI, 0.43–0.85); P = 0.004] in multivariate analysis.

Conclusions:
Deleterious DDR mutations are frequent in NSCLC and are associated with improved clinical outcomes in patients with NSCLC treated with PD-(L)1 blockade.
Therapeutic Efficacy of Immune Stimulatory Thymidine Kinase and fms-like Tyrosine Kinase 3 Ligand (TK/Flt3L) Gene Therapy in a Mouse Model of High-Grade Brainstem Glioma
Authors: Mendez Flor , Kadiyala Padma , Nunez Felipe J. , Carney Stephen , Nunez Fernando M. , Gauss Jessica C. , Ravindran Ramya , Pawar Sheeba , Edwards Marta , Garcia-Fabiani Maria Belen , Haase Santiago , Lowenstein Pedro R. , Castro Maria G. 
Published: April 2020

Abstract

Purpose:
Diffuse intrinsic pontine glioma (DIPG) bears a dismal prognosis. A genetically engineered brainstem glioma model harboring the recurrent DIPG mutation, Activin A receptor type I (ACVR1)-G328V (mACVR1), was developed for testing an immune-stimulatory gene therapy.

Experimental Design:
We utilized the Sleeping Beauty transposase system to generate an endogenous mouse model of mACVR1 brainstem glioma. Histology was used to characterize and validate the model. We performed RNA-sequencing analysis on neurospheres harboring mACVR1. mACVR1 neurospheres were implanted into the pons of immune-competent mice to test the therapeutic efficacy and toxicity of immune-stimulatory gene therapy using adenoviruses expressing thymidine kinase (TK) and fms-like tyrosine kinase 3 ligand (Flt3L). mACVR1 neurospheres expressing the surrogate tumor antigen ovalbumin were generated to investigate whether TK/Flt3L treatment induces the recruitment of tumor antigen–specific T cells.

Results:
Histologic analysis of mACVR1 tumors indicates that they are localized in the brainstem and have increased downstream signaling of bone morphogenetic pathway as demonstrated by increased phospho-smad1/5 and Id1 levels. Transcriptome analysis of mACVR1 neurosphere identified an increase in the TGFβ signaling pathway and the regulation of cell differentiation. Adenoviral delivery of TK/Flt3L in mice bearing brainstem gliomas resulted in antitumor immunity, recruitment of antitumor-specific T cells, and increased median survival (MS).

Conclusions:
This study provides insights into the phenotype and function of the tumor immune microenvironment in a mouse model of brainstem glioma harboring mACVR1. Immune-stimulatory gene therapy targeting the hosts' antitumor immune response inhibits tumor progression and increases MS of mice bearing mACVR1 tumors.
A New Role for the Aldosterone/Mineralocorticoid Receptor Pathway in the Development of Mitral Valve Prolapse
Authors: Ibarrola Jaime , Garcia-Peña Amaia , Matilla Lara , Bonnard Benjamin , Sádaba Rafael , Arrieta Vanessa , Alvarez Virginia , Fernández-Celis Amaya , Gainza Alicia , Navarro Adela , Alvarez de la Rosa Diego , Rossignol Patrick , Jaisser Frederic , López-Andrés Natalia 
Published: April 2020

Rationale:
Mitral valve prolapse (MVP) is one of the most common valvular disorders. However, the molecular and cellular mechanisms involved in fibromyxomatous changes in the mitral leaflet tissue have not been elucidated. Aldosterone (Aldo) promotes fibrosis in myocardium, and MR (mineralocorticoid receptor) antagonists (MRAs) improve cardiac function by decreasing cardiac fibrosis.

Objective:
We investigated the role of the Aldo/MR in the fibromyxomatous modifications associated with MVP.

Methods and Results:
Aldo enhanced valvular interstitial cell activation markers and induced endothelial-mesenchymal transition in valvular endothelial cells, resulting in increased proteoglycan secretion. MRA blocked all the above effects. Cytokine arrays showed CT-1 (cardiotrophin-1) to be a mediator of Aldo-induced valvular interstitial cell activation and proteoglycan secretion and CD (cluster of differentiation) 14 to be a mediator of Aldo-induced endothelial-mesenchymal transition and proteoglycan secretion in valvular endothelial cells. In an experimental mouse model of MVP generated by nordexfenfluramine administration, MRA treatment reduced mitral valve thickness and proteoglycan content. Endothelial-specific MR deletion prevented fibromyxomatous changes induced by nordexfenfluramine administration. Moreover, proteoglycan expression was slightly lower in the mitral valves of MVP patients treated with MRA.

Conclusions:
These findings demonstrate, for the first time, that the Aldo/MR pathway regulates the phenotypic, molecular, and histological changes of valvular interstitial cells and valvular endothelial cells associated with MVP development. MRA treatment appears to be a promising option to reduce fibromyxomatous alterations in MVP.