bluuebunny/crossref_metadata_2025_split huggingface dataset:
Collaborative Decision-Making Processes for Local Innovation: The CoULL Methodology in Living Labs Approach
Authors: Cerreta Maria , Panaro Simona 
Published: February 2022

AbstractThe concept of the Living Lab is closely connected to the priorities of the Europe 2020 strategy and of the Digital Agenda for Europe and is the subject of numerous user-centric open innovation programs and European projects supported by the European ENoLL Network. The chapter presents a new methodology, called Collaborative Urban Living Lab (CoULL), to support the Collaborative Decision-Making Processes to activate local innovation processes at the neighbourhood, city or landscape scale. Starting from the Quintuple Helix framework and the literature review on the Living Lab concept, its extension to the city and territorial context, and the related people-centred approaches have been discussed. The potentials to using them for putting open innovation into practice and developing innovative solutions for the cities have been shown. Nowadays, the built environments need to accelerate the transition to sustainable, climate-neutral, inclusive, resilient, healthy and smart prosperous. In the last few years, the Living Lab approaches have been promoted and used by local and international research and innovation agencies in collaboration with enterprises, NGOs and local governments to find solutions to the new issues. However, the Living Lab methodologies to guide the urban scale’s co-development solutions are few and need more accurate research and experimentations. In that direction, the CoULL methodology, tested in four different research projects (including the REPAiR project), has defined a suitable process for supporting the co-design, co-production and co-decision cycles of urban innovative and sustainable solutions.
Manufactured in the Peri-Urban: Regenerative Strategies for Critical Lands
Authors: Guida Giuseppe 
Published: February 2022

AbstractPeri-urban is an intermediate land. On the one hand, its hybrid nature makes it particularly vulnerable to speculation, indiscriminate use of soil resources, erosion of agricultural residues, and so on; on the other hand, it is difficult to control through planning instruments and policies. Starting from this background, the chapter will investigate the territories of the large Campania Plain, in the South of Italy, between Naples and Caserta. Until the middle of twentieth century, this territory was known as Campania Felix due to its agricultural vocation. Subsequently, a series of development policies and a misinterpreted concept of valorization and modernization of the territory have changed its characteristics and identity, giving many parts of it to disorder: industrial settlements, plants, logistics, landfills, and large infrastructures that clash with the residential, agricultural, or residual areas and in-between natural ones. In this context, the chapter summarizes the first results of a research project that aims to rethink the role of the large Industrial Development Areas, established in the peri-urban contexts of the plain in the province of Caserta, in Italy.
Urban Manufacturing for Circularity: Three Pathways to Move from Linear to Circular Cities
Authors: Hausleitner Birgit , Hill Adrian , Domenech Teresa , Muñoz Sanz Victor 
Published: February 2022

AbstractUrban manufacturing and manufacturers play a vital role in delivering circular economy ambitions through processing materials, providing skills and technology for repair or reconditioning goods and the capacity to deliver innovative technology. The transdisciplinary approach of Cities of Making (CoM) puts forward three ways of addressing manufacturing, and by extension, circularity, within urban areas. Central to triangulate the facilitation of urban manufacturing are the perspectives of (1) material flows and technology, (2) spatial design (3) people and networks. The integration of the three pathways requires convergence while retaining the richness of the three perspectives. The challenge is to find a common language that provides a comparable, operative framework for exploring possible solutions. The CoM framework of integration followed three main principles: (1) reducing the complexity of information, (2) reducing the complexity of combinations of possible solutions, and (3), applying an accessible, applicable instrument for the solutions. The resulting pattern language is co-created in a transdisciplinary setting and is also an instrument for the transdisciplinary application. The low threshold accessible system of solutions allows actors from different disciplines to access patterns developed in the context of another discipline and laypeople who are affected or interested to co-create.
Indolent Lymphomas
Authors: Morschhauser Franck , Zinzani Pier Luigi 
Published: February 2022

AbstractIndolent non-Hodgkin lymphoma (iNHL), including follicular (FL) and marginal zone (MZL) lymphoma, now enjoy durable disease control with first-line immunochemotherapy, with a median overall survival (OS) of over 15 years in most series (Kahl and Yang 2016). However, iNHL is still widely considered incurable in most cases, and disease history remains characterized by a relapsing and remitting course, with each remission period shorter than the previous one, and OS and progression-free survival (PFS) decrease with each subsequent line of conventional therapy (Batlevi et al. 2020). Patients with unmet needs include approximately 20% of FL patients who experience disease progression within 24 months (POD24) after initial chemoimmunotherapy (with a 5-year OS of 48% (Casulo et al. 2015)—although it remains unclear how much this worse outcome is driven by misdiagnosed transformed follicular lymphoma (Freeman et al. 2019)) and those who fail multiple regimens (5-year PFS of 23%) (Rivas-Delgado et al. 2019) have double refractory disease (Gopal et al. 2017) or experience relapse after autologous stem cell transplantation (ASCT) (Sesques et al. 2020). Although promising results were obtained with an immunomodulatory regimen combining anti-C20 Moab and lenalidomide (Leonard et al. 2019; Morschhauser et al. 2019), most current approved therapies do not overcome incremental disease resistance, resulting in multiple lines of treatment with cumulative toxicity over a patient’s lifetime. The autologous anti-CD19 chimeric antigen receptor T cell (CAR-T) therapies tisa-cel and axi-cel, which are now approved for patients with relapsed/refractory (r/r) large B cell lymphoma (LBCL), have also been tested in iNHL, with promising results.
Bridging Chemotherapy: Adult Acute Lymphoblastic Leukaemia
Authors: Boissel Nicolas , Ciceri Fabio 
Published: February 2022

AbstractBridging therapy can be given after leukapheresis and before lymphodepletion during CAR-T cell manufacturing. The primary goal of bridging therapies is to prevent uncontrolled progression of the underlying disease during the manufacturing period before CAR-T cell infusion. Several studies indicate that a high tumour burden is associated with an increased risk of complications after CAR-T cell infusion (Cohen et al. 2019). Therefore, controlling the disease and even possibly decreasing the tumour burden is critical during the manufacturing period. The choice of bridging therapies is essential for the success of the procedure.
Bridging Chemotherapy: Follicular Lymphoma, Mantle Cell Lymphoma, and CLL
Authors: Gagelmann Nico , Gribben John , Kröger Nicolaus 
Published: February 2022

AbstractWhile lisocabtagene maraleucel (liso-cel) is the only product that is specifically approved to treat grade 3B follicular lymphoma (FL), specifically in aggressive lymphoma indications, to date, axi-cel is the first and only approved CAR-T product for indolent NHL.
Management of Hypogammaglobulinaemia and B-Cell Aplasia
Authors: Topp Max , Feuchtinger Tobias 
Published: February 2022

AbstractThe development and regulatory approval of CAR-T cell therapies targeting B-lineage surface antigens (Maude et al. 2018), such as CD19 or CD22, represents a major milestone in cancer immunotherapy. This treatment results in the depletion of malignant and normal B cells and is associated with hypogammaglobulinaemia. These on-target, off-tumour toxicities may result in an increased risk of infection. Careful long-term follow-up assessment of patients receiving CAR-T cell therapy is important. Management of these on-target, off-tumour effects should be well coordinated between treatment and referring centres if the patient returns to local providers following therapy. Aims of this toxicity management:
ICU
Authors: Holtick Udo , Azoulay Elie 
Published: February 2022

AbstractCAR-T cell treatment comes with significant side effects that challenge the structure and capacity of haematology wards and will regularly necessitate intermittent patient transfer to the ICU. Life-threatening adverse events include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, which can occur within hours or days after administration. Sepsis might also require ICU admission within the days that follow CAR-T infusion in these high-risk immunocompromised patients.
Educational Needs for Physicians
Authors: Kröger Nicolaus , Gribben John , Sánchez-Ortega Isabel 
Published: February 2022

AbstractCAR-T cells are novel therapies associated with promising and potentially curative outcomes in patients with high-risk relapsed disease. In Europe, there are currently three approved products (tisagenlecleucel, axicabtagene ciloleucel, and brexucabtagene autoleucel) for patients with acute lymphoblastic leukaemia, aggressive B-cell lymphoma, and mantle cell lymphoma, although expanded haematologic and nonhaematologic indications are expected soon.
Tumour Escape from CAR-T Cells
Authors: Rasche Leo , Vago Luca , Mutis Tuna 
Published: February 2022

AbstractOver the past decade, CAR-T cells have emerged as one of the most powerful cellular immune therapy approaches in the battle against haematological malignancies. Nonetheless, similar to other immunotherapeutic approaches, tumour cells develop strategies to evade CAR-T cell therapy, often with the support of a highly immunosuppressive and protective tumour microenvironment. To date, antigen loss, immune dysfunction, exhaustion and (microenvironment-mediated) upregulation of antiapoptotic pathways have been identified as major modes of tumour escape from CAR-T cell therapy. This chapter will focus on our current understanding of these modes of immune escape from CAR-T cells.
Education Needs for Nurses in Adult and Paediatric Units
Authors: Kenyon Michelle , Murray John , Ellard Rose , Hutt Daphna 
Published: February 2022

AbstractComplex nursing care for patients on the CAR-T cell therapy pathway involves many different nursing roles that have important functions at different stages in the pathway. Within the multiprofessional team, nurse education is critical to safe and competent care and to the patient’s treatment experience. As we consider the education needs of the nursing workforce throughout the entire patient pathway, including the supply chain, chain of custody, and clinical care delivery, we recognize the important roles of expert nurses, practice educators, and the wider multiprofessional team in sharing their knowledge and experience. Nurse education strategies should include referring nursing teams to facilitate seamless patient care throughout referral, treatment, and follow-up to optimize communication and appropriately meet patient and caregiver information needs.
CART Initiatives in Europe
Authors: Urbano-Ispizua Alvaro , Hudecek Michael 
Published: February 2022

AbstractThe efficacy of chimeric antigen receptor T cells (CARTs) in B cell neoplasms, ALL, large B cell lymphoma, and now multiple myeloma has been one of the great achievements in the fight against cancer in recent decades (Porter et al. 2011). However, there is still a need to increase the proportion of responses (especially in NHL) (Locke et al. 2019) and to decrease the proportion of relapse (especially in ALL) (Grupp et al. 2013). More importantly, currently, commercial CAR-T products are not available for T cell neoplasms, myeloid malignant haemopathies, or solid tumours. As a reflection of the necessary efforts to expand the efficacy of CARTs, more than 500 clinical trials are currently underway worldwide, mostly led by American or Chinese groups. Unfortunately, European institutions are underrepresented in these initiatives. It is our duty to push and harmonize European academic clinical trials. We identified 35 early clinical trials promoted by European groups in Eudract and ClinTrialsGov (20 February 2021). Among them, 20 are initiatives from academic institutions, and 15 are initiatives from European companies allied with European academic institutions. In this summary, CART clinical trials promoted by European academic centres or by small to medium European companies are listed. The aim is to inform European groups treating haemato-oncology diseases of the current situation in this field, facilitating the inclusion of patients in these clinical trials. We aim to support the groups promoting these studies to increase collaboration.
Point-of-Care Production of CAR-T Cells
Authors: Delgado Julio , Roddie Claire , Schmitt Michael 
Published: February 2022

AbstractCAR-T cells for clinical application are classified as advanced therapy medicinal products (ATMPs), and their manufacture is subject to laws and regulations governed by the European Medicines Agency (EMA) and by federal and regional authorities. CAR-T cells must be manufactured to achieve good manufacturing practice (GMP) compliance and are defined as potent products manufactured safely according to standardized methods under closely controlled, reproducible, and auditable conditions. BioPharma supplies the vast majority of CAR-T products for patients, but some academic centres have developed point-of-care cGMP CAR-T manufacturing capability, striving to uphold the same stringency of product quality while improving patient access to CAR-T cells and streamlining the costs of therapy. Point-of-care CAR-T manufacturing can only be performed in facilities with the appropriate regulatory approvals in place.
Off-the-Shelf Allogeneic CAR-T Cells or Other Immune Effector Cells
Authors: Depil Stephane , Qasim Waseem 
Published: February 2022

Abstract“Off-the-shelf” allogeneic CAR TCRab T cells and other immune effector cells, such as natural killer (NK) or gamma delta (gd) T cells, can be premanufactured from healthy donors and may offer alternatives to autologous strategies. However, major barriers, namely HLA disparity resulting in graft versus host disease (GvHD) and host-mediated rejection, must be addressed.
Organisational Contexts of Energy Cybersecurity
Authors: Wallis Tania , Paul Greig , Irvine James 
Published: February 2022

AbstractThe energy system is going through huge transformation to integrate distributed renewable generation and to achieve the goals of net-zero carbon emissions. This involves a significant adjustment to how the system is controlled and managed, with increasing digitalisation of technology and growing complexities across interconnected systems. Traditionally electricity networks adjusted their supply of energy in response to changes in demand. The future energy system will require more flexible demand to be able to use or store energy when renewables are generating. This change is exacerbated by additional demand for electricity for heat and transport uses.Utility organisations hold responsibility for securing their networks and assuring the supply of electricity. This paper describes a full investigation of cybersecurity issues and concerns for utilities. This industry review was carried out to create a clear organisational context for the ongoing design of cybersecurity improvements. The assessment of potential impact and consequences of cyber-attack is recommended to direct necessary preparations towards protecting essential functions and processes. Improving resilience across interdependent actors is discussed and resilience measures suggested to guide the contributions of different actors towards whole system resilience.
The top quark electro-weak couplings after LHC Run 2
Authors: Miralles Víctor , López Marcos Miralles , Llácer María Moreno , Peñuelas Ana , Perelló Martin , Vos Marcel 
Published: February 2022

Abstract
Recent measurements at the Large Hadron Collider allow for a robust and precise characterisation of the electro-weak interactions of the top quark. We present the results of a global analysis at next-to-leading order precision including LHC, LEP/SLD and Tevatron data in the framework of the Standard Model Effective Field Theory. We include a careful analysis of the impact of correlations among measurements, as well as of the uncertainties in the Effective Field Theory setup itself. We find remarkably robust global fit results, with central values in good agreement with the Standard Model prediction, and 95% probability bounds on Wilson coefficients that range from ±0.35 to ±8 TeV−2. This result represents a considerable improvement over previous studies, thanks to the addition of differential cross-section measurements in associated production processes of top quarks and neutral gauge bosons.
Abfall von Sauerstoffsättigung und Blutdruck sowie Anstieg des zentralen Venendrucks im Rahmen eines Mitralklappenclippings bei einer 81-Jährigen
Authors: Volz Martin J. , Aurich Matthias , Konstandin Mathias , Katus Hugo A. , Frey Norbert , Kreusser Michael M. , Raake Philip W. 
Published: February 2022

Zusammenfassung
Hintergrund
Atriumseptumdefekte (ASD) im Rahmen eines endovaskulären Mitralklappenclippings sind potenziell hämodynamisch relevante Komplikationen. Ein sofortiger Verschluss mittels Okkluder kann eine sichere und effektive Therapie darstellen.

Fallzusammenfassung
Eine 81-jährige Patientin mit schwerer Dyspnoe bei vorbekannter hochgradiger Mitralklappeninsuffizienz wurde zum elektiven Mitralklappenclipping vorgestellt. Die Clipimplantation verlief komplikationslos. Nach Entfernung der transseptalen Schleuse kam es zu einem plötzlichen Abfall der Sauerstoffsättigung und des Blutdrucks sowie zu einem sofortigen Anstieg des zentralen Venendrucks. Es zeigte sich ein iatrogener Links-rechts-Shunt auf Vorhofebene mit relevantem Shuntvolumen. Daraufhin erfolgte der sofortige Verschluss mittels Vorhofseptumokkluder, was zu einer unmittelbaren Besserung der Kreislaufparameter und der Sauerstoffsättigung führte.

Schlussfolgerung
Ein Anstieg des zentralen Venendrucks, ein Blutdruckabfall oder Sättigungsabfall nach Rückzug der transseptalen steuerbaren Schleuse im Rahmen des Mitralklappenclippings sollte bezüglich eines möglichen ASD abgeklärt werden.
Early Cambrian highly metalliferous black shale in South China: Cu and Zn isotopes and a short review of other non-traditional stable isotopes
Authors: Lehmann Bernd , Pašava Jan , Šebek Ondřej , Andronikov Alexandre , Frei Robert , Xu Lingang , Mao Jingwen 
Published: February 2022

AbstractEarly Cambrian black shales on the Yangtze Platform host a regionally distributed highly metalliferous sulfide-rich carbonaceous unit which has been the subject of extensive debate. This marker unit, with a few centimeters or tens of centimeters in thickness, displays extreme enrichment in Mo and Ni (wt% range), and in a broad spectrum of other metals such as As, Au, PGE, Re, Cu, Zn, Cd, Ag, Sb, Se, Tl, and Hg, and occurs discontinuously along the western passive margin of the Yangtze Platform. It grades laterally in stratigraphically equivalent meter-thick vanadium-rich shale and tens-of-meter-thick sapropelite (combustible shale). New Cu and Zn isotope data, combined with existing Cd, Cr, Ni, Mo, Hg, and Se isotope and other chemical data, allow to attempt an integrated view on the formation of this intriguing unit of hyper-enriched metalliferous black shale. The authigenic Cu enrichment in the 1000-ppm range has produced no or little Cu isotope fractionation (0.03 ± 0.26 ‰ δ65Cu) beyond the lithogenic background. Heavy zinc and cadmium isotope enrichment in the sulfidic samples (1.11 ± 0.18 ‰ δ66Zn, 0.31 ± 0.10 ‰ δ114Cd) is controlled by sulfide fractionation and contrasts with V-rich and barren shale (0.60 ± 0.18 ‰ δ66Zn, 0.00 ± 0.14 ‰ δ114Cd). The distinctly negative Ni isotope composition of the metalliferous unit (−0.84 ± 0.05 ‰ δ60Ni) with Ni in the percent range has been interpreted as due to hydrothermal activity related to the leaching of mafic rocks and their sulfides. Sorption processes (Fe-oxyhydroxides) and redox cycling in the water column and the bottom sediment with microbial activity could be an alternative interpretation. The extreme metal enrichment can be understood as due to a process chain, from high biological productivity in the oxic photic zone to sulfate reduction in the deeper sulfidic water column and upper sediment layer. Key to the metal enrichment seems to be extremely low clastic sedimentation and advanced carbon destruction by anaerobic oxidation. Hydrothermal input of basinal brines along the rifted margin of the Yangtze Platform was likely a part of this scenario.
Nonlinear nexus between corruption and tourism arrivals: a global analysis
Authors: Maria Krambia-Kapardis , Ioanna Stylianou , Salomi Demetriou 
Published: February 2022

AbstractThe relationship between corruption and tourism has been sporadically examined over the years. According to the existing theory, there is an inverted U relationship which implies that tourism demand initially increases as corruption increases (greasing the wheels) and after a certain threshold level of corruption, tourism demand decreases (sanding the wheels). Empirical studies so far concentrated on capturing the nonlinear relationship, by applying a simple linear model and by including corruption as a quadratic term. In the current paper, the authors revisit the “greasing and sanding the wheels” hypothesis by applying an advanced econometric technique, the threshold regression model, which deals with a key element of model uncertainty, namely parameter heterogeneity. In particular, using a sample of 83 countries from 2001 to 2018, the authors firstly examine if there is a nonlinear relationship between corruption and tourism, and then, they estimate the threshold value of corruption. According to the results, the null hypothesis of a linear model against the alternative of a threshold model with two regimes is strongly rejected. Furthermore, while the effect of corruption on tourism is positive in the low corruption regime and negative in the high corruption regime, a heterogeneous relationship is also found between other politico-socio-economic variables and tourism demand in the low and high corruption regimes.