bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mass Imbalance Diagnostics in Wind Turbines Using Deep Learning With Data Augmentation
Authors: Dabetwar Shweta , Ekwaro-Osire Stephen , Dias João Paulo , Hübner Guilherme R. , Franchi Claiton M. , Pinheiro Humberto 
Published: April 2022

Abstract
Wind turbines suffer from mass imbalance due to manufacturing, installation, and severe climatic conditions. Condition monitoring systems are essential to reduce costs in the wind energy sector. Many attempts were made to improve the detection of faults at an early stage to plan predictive maintenance strategies, but effective methods have not yet been developed. Artificial intelligence has a huge potential in the wind turbine industry. However, several shortcomings related to the datasets still need to be overcome. Thus, the research question developed for this paper was “Can data augmentation and fusion techniques enhance the mass imbalance diagnostics methods applied to wind turbines using deep learning algorithms?” The specific aims developed were: (i) to perform sensitivity analysis on classification based on how many samples/sample frequencies are required for stabilized results; (ii) to classify the imbalance levels using Gramian angular summation field and Gramian angular difference field and compare against data fusion; and (iii) to classify the imbalance levels using data fusion for augmented data. Convolutional neural network (CNN) techniques were employed to detect rotor mass imbalance for a multiclass problem using the estimated rotor speed as an input variable. A 1.5-MW turbine model was considered and a database was built using the software turbsim, fast, and simulink. The model was tested under different wind speeds and turbulence intensities. The data augmentation and fusion techniques used along with CNN techniques showed improvement in the classification and hence the diagnostics of wind turbines.
Head Impact Kinematics and Brain Deformation in Paired Opposing Youth Football Players
Authors: Milef Gabriella M. , Miller Logan E. , DiGuglielmo Daniella M. , Payne Tanner D. , Filben Tanner M. , Urban Jillian E. , Stitzel Joel D. 
Published: April 2022

Head impact exposure is often quantified using peak resultant kinematics. While kinematics describes the inertial response of the brain to impact, they do not fully capture the dynamic brain response. Strain, a measure of the tissue-level response of the brain, may be a better predictor of injury. In this study, kinematic and strain metrics were compared to contact characteristics in youth football. Players on 2 opposing teams were instrumented with head impact sensors to record impact kinematics. Video was collected to identify contact scenarios involving opposing instrumented players (ie, paired contact scenarios) and code contact characteristics (eg, player role, impact location). A previously validated, high-resolution brain finite element model, the atlas-based brain model, was used to simulate head impacts and calculate strain metrics. Fifty-two paired contact scenarios (n = 105 impacts) were evaluated. Lighter players tended to have greater biomechanical metrics compared to heavier players. Impacts to the top of the helmet were associated with lower strain metrics. Overall, strain was better correlated with rotational kinematics, suggesting these metrics may be better predictors of the tissue-level brain response than linear kinematics. Understanding the effect of contact characteristics on brain strain will inform future efforts to improve sport safety.
Activation of innate-adaptive immune machinery by poly(I:C) exposes a therapeutic vulnerability to prevent relapse in stroma-rich colon cancer
Authors: Corry Shania M , McCorry Amy MB , Lannagan Tamsin RM , Leonard Niamh A , Fisher Natalie C , Byrne Ryan M , Tsantoulis Petros , Cortes-Lavaud Xabier , Amirkhah Raheleh , Redmond Keara L , McCooey Aoife J , Malla Sudhir B , Rogan Emily , Sakhnevych Svetlana , Gillespie Michael A , White Mark , Richman Susan D , Jackstadt Rene-Filip , Campbell Andrew D , Maguire Sarah ,   S:CORT and ACRCelerate consortia, McDade Simon S , Longley Daniel B , Loughrey Maurice B , Coleman Helen G , Kerr Emma M , Tejpar Sabine , Maughan Timothy , Leedham Simon J , Small Donna M , Ryan Aideen E , Sansom Owen J , Lawler Mark , Dunne Philip D 
Published: April 2022

ObjectiveStroma-rich tumours represent a poor prognostic subtype in stage II/III colon cancer (CC), with high relapse rates and limited response to standard adjuvant chemotherapy.DesignTo address the lack of efficacious therapeutic options for patients with stroma-rich CC, we stratified our human tumour cohorts according to stromal content, enabling identification of the biology underpinning relapse and potential therapeutic vulnerabilities specifically within stroma-rich tumours that could be exploited clinically. Following human tumour-based discovery and independent clinical validation, we use a series ofin vitroand stroma-richin vivomodels to test and validate the therapeutic potential of elevating the biology associated with reduced relapse in human tumours.ResultsBy performing our analyses specifically within the stroma-rich/high-fibroblast (HiFi) subtype of CC, we identify and validate the clinical value of a HiFi-specific prognostic signature (HPS), which stratifies tumours based on STAT1-related signalling (High-HPS v Low-HPS=HR 0.093, CI 0.019 to 0.466). Usingin silico, in vitroandin vivomodels, we demonstrate that the HPS is associated with antigen processing and presentation within discrete immune lineages in stroma-rich CC, downstream of double-stranded RNA and viral response signalling. Treatment with the TLR3 agonist poly(I:C) elevated the HPS signalling and antigen processing phenotype acrossin vitroandin vivomodels. In anin vivomodel of stroma-rich CC, poly(I:C) treatment significantly increased systemic cytotoxic T cell activity (p<0.05) and reduced liver metastases (p<0.0002).ConclusionThis study reveals new biological insight that offers a novel therapeutic option to reduce relapse rates in patients with the worst prognosis CC.
Joint British Societies’ guideline on management of cardiac arrest in the cardiac catheter laboratory
Authors: Dunning Joel , Archbold Andrew , de Bono Joseph Paul , Butterfield Liz , Curzen Nick , Deakin Charles D , Gudde Ellie , Keeble Thomas R , Keys Alan , Lewis Mike , O'Keeffe Niall , Sarma Jaydeep , Stout Martin , Swindell Paul , Ray Simon 
Published: April 2022

More than 300 000 procedures are performed in cardiac catheter laboratories in the UK each year. The variety and complexity of percutaneous cardiovascular procedures have both increased substantially since the early days of invasive cardiology, when it was largely focused on elective coronary angiography and single chamber (right ventricular) permanent pacemaker implantation. Modern-day invasive cardiology encompasses primary percutaneous coronary intervention, cardiac resynchronisation therapy, complex arrhythmia ablation and structural heart interventions. These procedures all carry the risk of cardiac arrest.We have developed evidence-based guidelines for the management of cardiac arrest in adult patients in the catheter laboratory. The guidelines include recommendations which were developed by collaboration between nine professional and patient societies that are involved in promoting high-quality care for patients with cardiovascular conditions. We present a set of protocols which use the skills of the whole catheter laboratory team and which are aimed at achieving the best possible outcomes for patients who suffer a cardiac arrest in this setting. We identified six roles and developed a treatment algorithm which should be adopted during cardiac arrest in the catheter laboratory. We recommend that all catheter laboratory staff undergo regular training for these emergency situations which they will inevitably face.
Sex difference in atrial fibrillation recurrence after catheter ablation and antiarrhythmic drugs
Authors: Park Yoon Jung , Park Je-Wook , Yu Hee Tae , Kim Tae-Hoon , Uhm Jae-Sun , Joung Boyoung , Lee Moon-Hyoung , Pak Hui-Nam 
Published: April 2022

ObjectiveThe risk of recurrence after atrial fibrillation (AF) catheter ablation (AFCA) is higher in women than in men. However, it is unknown whether a sex difference exists in antiarrhythmic drug (AAD) responsiveness among patients with recurrence.MethodsAmong 2999 consecutive patients (26.5% women, 58.3±10.9 years old, 68.1% paroxysmal AF) who underwent de novo AFCA, we compared and evaluated the sex differences in rhythm outcome in 1094 patients with recurrence and in 788 patients who subsequently underwent rhythm control with AAD.ResultsDuring a follow-up of 48.2±34.9 months, 1094 patients (36.5%) had AF recurrence after AFCA, and 508 of 788 patients (64.5%) had AF recurrence under AAD. Although the rhythm outcome of a de novo AFCA was worse (log-rank p=0.041, HR 1.28, 95% CI 1.02 to 1.59), p=0.031) in women, AAD response after postprocedural recurrences was better in women than in men (log-rank p=0.003, HR 0.75, 95% CI 0.59 to 0.95, p=0.022), especially in women older than 60 years old (log-rank p=0.003). In 249 patients who underwent repeat procedure after AAD use, the pulmonary vein (PV) reconnection rate (62.7% vs 76.8%, p=0.048) was lower in women than in men but not the existence of extra-PV trigger (37.8% vs 25.4%, p=0.169).ConclusionsAlthough women showed worse rhythm outcomes than men after AFCA, the post-AFCA AAD response was better in elderly women than in men.Trial registration numberNCT02138695.
Direct targeting of FOXP3 in Tregs with AZD8701, a novel antisense oligonucleotide to relieve immunosuppression in cancer
Authors: Revenko Alexey , Carnevalli Larissa S , Sinclair Charles , Johnson Ben , Peter Alison , Taylor Molly , Hettrick Lisa , Chapman Melissa , Klein Stephanie , Solanki Anisha , Gattis Danielle , Watt Andrew , Hughes Adina M , Magiera Lukasz , Kar Gozde , Ireland Lucy , Mele Deanna A , Sah Vasu , Singh Maneesh , Walton Josephine , Mairesse Maelle , King Matthew , Edbrooke Mark , Lyne Paul , Barry Simon T , Fawell Stephen , Goldberg Frederick W , MacLeod A Robert 
Published: April 2022

BackgroundThe Regulatory T cell (Treg) lineage is defined by the transcription factor FOXP3, which controls immune-suppressive gene expression profiles. Tregs are often recruited in high frequencies to the tumor microenvironment where they can suppress antitumor immunity. We hypothesized that pharmacological inhibition of FOXP3 by systemically delivered, unformulated constrained ethyl-modified antisense oligonucleotides could modulate the activity of Tregs and augment antitumor immunity providing therapeutic benefit in cancer models and potentially in man.MethodsWe have identified murine Foxp3 antisense oligonucleotides (ASOs) and clinical candidate human FOXP3 ASO AZD8701. Pharmacology and biological effects of FOXP3 inhibitors on Treg function and antitumor immunity were tested in cultured Tregs and mouse syngeneic tumor models. Experiments were controlled by vehicle and non-targeting control ASO groups as well as by use of multiple independent FOXP3 ASOs. Statistical significance of biological effects was evaluated by one or two-way analysis of variance with multiple comparisons.ResultsAZD8701 demonstrated a dose-dependent knockdown of FOXP3 in primary Tregs, reduction of suppressive function and efficient target downregulation in humanized mice at clinically relevant doses. Surrogate murine FOXP3 ASO, which efficiently downregulated Foxp3 messenger RNA and protein levels in primary Tregs, reduced Treg suppressive function in immune suppression assays in vitro. FOXP3 ASO promoted more than 70% reduction in FOXP3 levels in Tregs in vitro and in vivo, strongly modulated Treg effector molecules (eg, ICOS, CTLA-4, CD25 and 4-1BB), and augmented CD8+ T cell activation and produced antitumor activity in syngeneic tumor models. The combination of FOXP3 ASOs with immune checkpoint blockade further enhanced antitumor efficacy.ConclusionsAntisense inhibitors of FOXP3 offer a promising novel cancer immunotherapy approach. AZD8701 is being developed clinically as a first-in-class FOXP3 inhibitor for the treatment of cancer currently in Ph1a/b clinical trial (NCT04504669).
High levels of chromosomal aberrations negatively associate with benefit to checkpoint inhibition in NSCLC
Authors: Frigola Joan , Carbonell Caterina , Iranzo Patricia , Pardo Nuria , Callejo Ana , Cedres Susana , Martinez-Marti Alex , Navarro Alejandro , Soleda Mireia , Jimenez Jose , Hernandez-Losa Javier , Vivancos Ana , Felip Enriqueta , Amat Ramon 
Published: April 2022

BackgroundImmune checkpoint inhibitors (ICIs) targeting the programmed cell death 1/programmed death-ligand 1 axis have transformed the management of advanced non-small cell lung cancer (NSCLC). However, many patients do not benefit from this type of treatment, and thus several molecular biomarkers of benefit have been explored. The value of somatic copy number alterations (SCNAs) burden remains elusive.Patients and methodsWe assembled a cohort of 109 patients with NSCLC treated with ICIs and available tumor samples. We performed shallow whole-genome sequencing on 89 patients to determine genome-wide SCNAs and targeted gene expression analysis on 63 patients to study immune infiltration. We analyzed SCNAs burden in different ways (ie, the fraction of the genome altered or number of events) and studied their association with ICIs benefit based on survival analysis. We correlated SCNAs burden and immune infiltration on 35 patients of our cohort and on patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA).ResultsHigh SCNAs burden, computed in diverse ways, is negatively associated with ICIs progression-free survival (PFS), with the fraction of the genome altered (FGA) by arm and chromosome events showing the strongest association with PFS (p=0.002) (n=77). Nevertheless, we found differences in SCNAs across some clinicopathological features (sample site origin). A multivariate analysis adjusted for relevant characteristics showed that the FGA of arm and chromosome alterations was strongly associated with PFS (HR=2.21, p=3.3 x 10−5). Finally, we confirmed that SCNAs burden negatively correlates with tumor immune infiltration (n=35), although this correlation was not found for the males studied. Similar results were observed in the TCGA cohort.ConclusionsSCNAs burden is a potential biomarker of benefit to ICIs in patients with NSCLC, although there appear to be some nuances worth consideration. Further studies will be needed to establish its role as a biomarker of benefit to ICIs.
Combining bempegaldesleukin (CD122-preferential IL-2 pathway agonist) and NKTR-262 (TLR7/8 agonist) improves systemic antitumor CD8+T cell cytotoxicity over BEMPEG+RT
Authors: Rolig Annah S , Rose Daniel C , McGee Grace Helen , Rubas Werner , Kivimäe Saul , Redmond William L 
Published: April 2022

BackgroundTumor cell death caused by radiation therapy (RT) triggers antitumor immunity in part because dying cells release adjuvant factors that amplify and sustain dendritic cell and T cell responses. We previously demonstrated that bempegaldesleukin (BEMPEG: NKTR-214, an immunostimulatory IL-2 cytokine prodrug) significantly enhanced the antitumor efficacy of RT through a T cell-dependent mechanism. Because RT can induce either immunogenic or tolerogenic cell death, depending on various factors (radiation dose, cell cycle phase), we hypothesized that providing a specific immunogenic adjuvant, like intratumoral therapy with a novel toll-like receptor (TLR) 7/8 agonist, NKTR-262, would improve systemic tumor-specific responses through the activation of local innate immunity. Therefore, we evaluated whether intratumoral NKTR-262 combined with systemic BEMPEG treatment would elicit improved tumor-specific immunity and survival compared with RT combined with BEMPEG.MethodsTumor-bearing mice (CT26; EMT6) received BEMPEG (0.8 mg/kg; intravenously), RT (12 Gy × 1), and/or intratumoral NKTR-262 (0.5 mg/kg). Flow cytometry was used to evaluate CD4+and CD8+T cell responses in the blood and tumor 7 days post-treatment. The contribution of specific immune subsets was determined by depletion of CD4+, CD8+, or NK cells. CD8+T cell cytolytic activity was determined by an in vitro CTL assay. Data are representative of 1–2 independent experiments (n=5–14/group) and statistical significance was determined by 1-way analysis of variance (ANOVA) or repeated measures ANOVA (p value cut-off of 0.05).ResultsBEMPEG+NKTR-262 significantly improved survival compared with BEMPEG+RT in a CD8+T cell-dependent manner. Response to BEMPEG+NKTR-262 was characterized by a significant expansion of activated CD8+T cells (GzmA+; Ki-67+; ICOS+; PD-1+) in the blood, which correlated with reduced tumor size (p<0.05). In the tumor, BEMPEG+NKTR-262 induced higher frequencies of GzmA+CD8+T cells exhibiting reduced expression of suppressive molecules (PD-1+), compared with BEMPEG+RT (p<0.05). Further, BEMPEG+NKTR-262 treatment induced greater tumor-specific CD8+T cell cytolytic function than BEMPEG+RT.ConclusionsBEMPEG+NKTR-262 therapy elicited more robust expansion of activated CD8+T cells compared with BEMPEG+RT, suggesting that intratumoral TLR stimulation provides superior antigen presentation and costimulatory activity compared with RT. A clinical trial of BEMPEG+NKTR-262 for patients with metastatic solid tumors is in progress (NCT03435640).
Albumin and interferon-β fusion protein serves as an effective vaccine adjuvant to enhance antigen-specific CD8+ T cell-mediated antitumor immunity
Authors: Tseng Ssu-Hsueh , Cheng Max A , Farmer Emily , Ferrall Louise , Kung Yu Jui , Lam Brandon , Lim Ling , Wu T-C , Hung Chien-Fu 
Published: April 2022

BackgroundType I interferons (IFN) promote dendritic cells maturation and subsequently enhance generation of antigen-specific CD8 +T cell for the control of tumor. Using type I interferons as an adjuvant to vaccination could prove to be a potent strategy. However, type I interferons have a short half-life. Albumin linked to a protein will prolong the half-life of the linked protein.MethodsIn this study, we explored the fusion of albumin to IFNβ (Alb-IFNβ) for its functional activity both in vitro and in vivo. We determined the half-life of Alb-IFNβ following treatment in the serum, tumor, and tumor draining lymph nodes in both wild type and FcRn knockout mice. We characterized the ability of Alb-IFNβ to enhance antigen-specific CD8+ T cells using ovalbumin (OVA) or human papillomavirus (HPV) E7 long peptides. Next, we evaluated the therapeutic antitumor effect of coadministration of AlbIFNβ with antigenic peptides against HPVE7 expressing tumor and the treatment’s ability to generate HPVE7 antigen specific CD8+ T cells. The contribution of the antitumor effect by lymphocytes was also examined by an antibody depletion experiment. The ability of Alb-IFNβ to serve as an adjuvant was tested using clinical grade therapeutic protein-based HPV vaccine, TACIN.ResultsAlb-IFNβ retains biological function and does not alter the biological activity of IFNβ. In addition, Alb-IFNβ extends half-life of IFNβ in serum, lymph nodes and tumor. The coadministration of Alb-IFNβ with OVA or HPVE7 antigenic peptides enhances antigen-specific CD8 +T cell immunity, and in a TC-1 tumor model results in a significant therapeutic antitumor effect. We found that CD8 +T cells and dendritic cells, but not CD4 +T cells, are important for the observed antitumor therapeutic effect mediated by Alb-IFNβ. Finally, Alb-IFNβ served as a potent adjuvant for TA-CIN for the treatment of HPV antigen expressing tumors.ConclusionsOverall, Alb-IFNβ serves as a potent adjuvant for enhancement of strong antigen-specific CD8 +T cell antitumor immunity, reduction of tumor burden, and increase in overall survival. Alb-IFNβ potentially can serve as an innovative adjuvant for the development of vaccines for the control of infectious disease and cancer.
Identifying urban features for vulnerable road user safety in Europe
Authors: Klanjčić Marina , Gauvin Laetitia , Tizzoni Michele , Szell Michael 
Published: April 2022

AbstractOne of the targets of the UN Sustainable Development Goals is to substantially reduce the number of global deaths and injuries from road traffic collisions. To this aim, European cities adopted various urban mobility policies, which has led to a heterogeneous number of injuries across Europe. Monitoring the discrepancies in injuries and understanding the most efficient policies are keys to achieve the objectives of Vision Zero, a multi-national road traffic safety project that aims at zero fatalities or serious injuries linked to road traffic. Here, we identify urban features that are determinants of vulnerable road user safety through the analysis of inter-mode collision data across European cities. We first build up a data set of urban road crashes and their participants from 24 cities in 5 European countries, using the widely recommended KSI indicator (killed or seriously injured individuals) as a safety performance metric. Modelling the casualty matrices including road infrastructure characteristics and modal share distribution of the different cities, we observe that cities with the highest rates of walking and cycling modal shares are the safest for the most vulnerable users. Instead, a higher presence of low-speed limited roads seems to only significantly reduce the number of injuries of car occupants. Our results suggest that policies aimed at increasing the modal share of walking and cycling are key to improve road safety for all road users.
On the uniform bound of reducibility index of parameter ideals of idealizations
Authors: Nam Pham Hong 
Published: April 2022

Let [Formula: see text] be a Noetherian local ring and [Formula: see text] a finitely generated [Formula: see text]-module. In this paper, we study the polynomial type and the sequential polynomial type of the idealization [Formula: see text] of [Formula: see text] and [Formula: see text] introduced by Cuong [On the least degree of polynomials bounding above the differences between lengths and multiplicities of certain systems of parameters in local rings, Nagoya Math. J. 125 (1992) 105–114] and Nhan-Dung-Chau [A measure for non-sequential Cohen Macaulayness of finitely generated modules, J. Algebra 468 (2016) 275–295], respectively. In addition, we give a uniform bound for the reducibility index of parameter ideals of idealizations whose polynomial type and sequential polynomial type are at most one.
Managing R&D and Innovation Projects: An Integrated Conceptual Model for Technology Transfer
Authors: Rocha António , Lima Rui M. , Amorim Marlene , Romero Fernando , Cruz-Cunha Manuela 
Published: April 2022

Projects start with an idea, which is deployed into a set of actions to deliver expected or foreseen outcomes, and they should be carried out in a cohesive and unified context. In this paper, contributions are devised to integrate project management and technology transfer practices to drive the transformation of knowledge into innovation within the scope of research and development projects at universities and research laboratories or centers. These contributions are presented in the form of a conceptual model that includes three interrelated groups. The first group is focused on project ideas’ definition and selection, the second group on project management, and the third group on knowledge and technology transfer, these groups are supported by improvement, innovation and project management guidelines and standards. To obtain insights to define the model, quantitative and qualitative methods have been used and the data was processed using content analysis and descriptive and inferential techniques meant to ensure the complementarity of the data to obtain a holistic understanding of the practices under analysis. The approach was exploratory and descriptive, but also analytical in the sense that it states the issues at stake to support project management and technology transfer.