bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple Myeloma
Authors: Yakoub-Agha Ibrahim , Einsele Hermann 
Published: February 2022

AbstractTo date, over 100 clinical trials investigating the use of CAR-T cells in MM have been registered at clinicaltrials.gov. Although several CD19-directed CAR-T cell products have been approved (Ghobadi 2018; Yassine et al. 2020), CD19 surface expression on plasma cells is limited or absent, leading to uncertain efficacy in clinical trials that used anti-CD19 alone in patients with MM (Garfall et al. 2015, 2019). Using superresolution microscopy, CD19 can be detected on a large proportion of myeloma cells, which could explain the successful targeting and lysis of myeloma cells by CD19-detecting CAR-T cells (Nerreter et al. 2019). Of note, some ongoing studies in which CD19 is targeted in combination with other antigens, especially BCMA, are being conducted (Beauvais et al. 2020).
Developments in Other Haematological Malignancies: Other Lymphoid Malignancies
Authors: Corradini Paolo , Trümper Lorenz 
Published: February 2022

AbstractPeripheral T cell lymphomas comprise a heterogeneous group of rare diseases, representing 10–15% of all non-Hodgkin lymphomas (NHLs). Upfront treatment for peripheral T cell lymphoma (pTNHL) includes CHOP-like (cyclophosphamide, adriamycin, vincristine, prednisone) multiagent chemotherapy with or without etoposide, followed by stem cell transplantation as consolidation in responsive fit patients. This approach induces durable long-term remission in approximately 40% of cases; early refractoriness during induction occurs in approximately 25% of patients, with the remaining patients typically relapsing within 24 months. With the exception of patients with anaplastic large cell lymphomas who are eligible to receive brentuximab vedotin, there is no standard of care in the relapse setting. In patients not eligible to receive high-dose chemotherapy followed by allogeneic stem cell transplantation, the prognosis is dismal.
Myeloid Malignancies
Authors: Ferrand Christophe , Rambaldi Alessandro 
Published: February 2022

AbstractIn addition to chemotherapy, which remains the basic treatment, the treatment panel for acute myeloid leukaemia (AML) has expanded considerably in recent years. Clinicians now have a large choice of therapies: targeted therapies (anti-IDH1/2, anti-FLT3, and anti-BCL2 therapies, among others), drugs targeting epigenetic mechanisms, kinase inhibitors (FLT3, MAPK, and JAK2, etc.), immunotherapies (monoclonal antibodies linked or not to a toxin, dual/bispecific), and cellular immunotherapies. Moreover, despite its toxicities, allogeneic transplantation often remains an effective final therapeutic alternative. However, most patients are refractory or relapsed (R/R) after several lines of therapy. Thus, there is a clinical need in AML R/R patients, and CAR-T cells may be an option and can find a place in the treatment to reduce tumour burden and clinical evolution of the disease (Fig. 18.1, modified from Roussel et al. (2020)).
Genetic Engineering of Autologous or Allogeneic Immune Effector Cells
Authors: Benabdellah Karim , Thomas Simone , Abken Hinrich 
Published: February 2022

AbstractManufacturing immune effector cells (T or NK cells) with CAR-encoding DNA sequences requires efficient and safe genetic engineering procedures. For this purpose, an appropriate genetic vector is chosen according to numerous factors, including the vector genome packaging capacity, cellular tropism, genomic integration, immune toxicity, and other factors. In clinical trials, genomes integrating viral vectors, in particular vectors based on members of the Retroviridae family, such as retroviruses and lentiviruses, have been successfully used for more than 20 years. These vectors contain an RNA genome that when transcribed into double-stranded DNA by reverse transcriptase integrates into the genome of the transduced cell.
Bridging Chemotherapy: Relapsed/Refractory Aggressive B-Cell Lymphoma
Authors: Thieblemont Catherine , Borchmann Peter 
Published: February 2022

AbstractThe time interval between leukapheresis and CAR-T cell infusion is critical for many patients with R/R B-cell lymphoma and symptomatic disease that could be fatal if left untreated during the cell manufacturing period. Often, oncologists address this dilemma with bridging therapy (BT), which may include steroids, chemotherapy, targeted therapy, or radiation therapy.
Management of Cytokine Release Syndrome (CRS) and HLH
Authors: Ayuketang Francis Ayuk , Jäger Ulrich 
Published: February 2022

AbstractCytokine release syndrome (CRS) is caused by a rapid and mild to massive release of cytokines from immune cells involved in immune reactions, particularly after immunotherapy. The frequency and severity of CRS after CAR-T cell therapy varies between products (any grade: 37–93%, G3/4: 1–23%) (Neelapu et al. 2017; Schuster et al. 2019; Abramson et al. 2020).
Management of Myelotoxicity (Aplasia) and Infectious Complications
Authors: Subklewe Marion , Benjamin Reuben 
Published: February 2022

AbstractHaematologic toxicity is the most common adverse event after CAR-T cell therapy, with a cumulative 1-year incidence of 58% (CTCAE grade ≥ 3) in the real-world setting (Wudhikarn et al., Blood Advances 2020). It is characterized by a biphasic temporal course and is often prolonged (Fried et al., Bone Marrow Transplant 2019, Rejeski et al., Blood et al. 2021a, b, Fig. 29.1). In a report of Axi-Cel-treated patients, only 30% demonstrated a neutrophil count >1 × 109/L and 50% showed a platelet count >50 × 109/L at 30 days following CAR-T cell treatment (Jain et al., Blood Advances 2020). In a long-term follow-up study of patients with ongoing CR and an absence of MDS, 16% of patients experienced prolonged significant cytopenias that lasted up to 22 months after CAR-T cell treatment (Cordeiro et al., Biol Blood Marrow Transplant 2020). These findings highlight that cytopenia can present long after lymphodepletion and the resolution of acute CRS. Risk factors include severe CRS/ICANS, cytopenia prior to initiation of lymphodepleting chemotherapy, and prior allogeneic stem cell transplantation (Jain et al., Blood Advances 2020, Fried et al., BMT, 2019). Importantly, cytopenia predisposes patients to severe infectious complications, which are the most frequent cause of non-relapse mortality (Nastoupil et al., JCO 2020).
What Defines a Good Tumour Antigen?
Authors: Morris Emma C. , Falkenburg J. H. F. 
Published: February 2022

AbstractCompared to standard anticancer therapies, such as chemotherapy, small molecule inhibitors and radiation, T cell immunotherapies have the advantages of a high degree of specificity and durability of response typically associated with cellular therapies. The functional specificity of a T cell is determined by its antigen recognition receptor and the target antigen (Bjorkman et al. 1987; Garcia et al. 1996).
Immune Monitoring
Authors: Berger Susanna Carolina , Fehse Boris , Rubio Marie-Thérèse 
Published: February 2022

AbstractCAR-T cell expansion and persistence are critical parameters for therapeutic efficacy and toxicity (Locke et al. 2020). However, CAR-T cells are patient-specific ‘living drugs’ with an unpredictable ability to expand in vivo. Thus, close postinfusion monitoring should be a major prerequisite to better manage this therapy. Critical parameters include CAR-T cell expansion kinetics and phenotype immune reconstitution and serum biomarkers (Fig. 35.1; Kalos et al. 2011; Hu and Huang 2020). Additionally, prospective collection and storage of patient specimens should be planned for future hypothesis-driven studies at specialized research centres. To date, despite the rapid expansion of CAR-T cell therapy, no standard recommendations exist for CAR monitoring, and harmonization of efforts across multiple centres is urgently needed.
Role of Pharmacists
Authors: Galassi Margherita , Moreno-Martínez Maria Estela 
Published: February 2022

AbstractThe pharmacist has a key role in the management of CAR-T therapies. Selection, ordering, reception, storage, preparation of the product for infusion, and dispensing of CAR-T therapies are some of the pharmacy service responsibilities (Black 2018; Moreno-Martínez et al. 2020; Booth et al. 2020). The pharmacist requires specific training, ensuring coordination with all the professionals in the multidisciplinary team who are involved in the management of these therapies, as summarized in Table 41.1.
GoCART
Authors: Terwel Sofie R. , Kuball Jürgen , Dreyling Martin , Cerisoli Francesco 
Published: February 2022

AbstractCellular therapies manufactured from cells of haematopoietic origin, such as CAR-T–cell therapies, provide a revolutionary treatment for patients suffering from haematological diseases. Nonetheless, there are considerable challenges in the implementation of these therapies in this rapidly evolving field. These challenges include but are not limited to the complexity of the supply chains for these living drugs and the management of side effects, requiring centre qualification as well as additional and ongoing education of health care professionals; the long-term follow-up of patients treated with therapies with curative intent; the myriad regulatory requirements at the European Union and local level; and reimbursement of the treatments by budget-constrained authorities.
The Value of CAR-T-cell Immunotherapy in Cancer
Authors: Abou-el-Enein Mohamed , Gauthier Jordan 
Published: February 2022

AbstractThe development of genetically modified chimeric antigen receptor (CAR) T-cells to target cancer by conferring tumour antigen recognition has tremendously improved the fight against the disease and broadened treatment options for haematological malignancies (Elsallab et al. 2020b). However, in contrast to conventional drugs that patients can easily access, the implementation of CAR-T-cell therapy in routine clinical practice poses significant challenges. Access to CAR-T-cell products is currently limited to specific certified centres meeting the requirements set up by manufacturers and regulatory agencies. There are also issues regarding insurance coverage, reimbursement, affordability, and pricing, which have critical impacts on broadening patient access to these novel therapies (Abou-El-Enein et al. 2016a, b). Current list pricing ranges between $373,000 and $475,000 per one-time infusion for the four CAR-T-cell therapies currently approved by the FDA (tisagenlecleucel, Kymriah®; axicabtagene ciloleucel, Yescarta®; brexucabtagene autoleucel, Tecartus®; lisocabtagene maraleucel, Breyanzi®). In addition to the cost of the CAR-T-cell product, patient preparation (leukapheresis and/or lymphodepletion), product infusion, pre- and post-infusion patient management, and monitoring for side effects (Wagner et al. 2021) significantly add to the final price tag. There are calls for restructuring the current payment and reimbursement models to allow better access to CAR-T-cell therapies (Abou-El-Enein et al. 2014). However, this would only be possible after examining the strength of clinical evidence generated during product development (Abou-El-Enein and Hey 2019; Elsallab et al. 2020a) and, most importantly, by determining the value of CAR-T-cell therapy.
What do Patients Want? The Importance of Patient-reported Outcomes
Authors: Schoemans Hélène , Bolaños Natacha , Warwick Lorna 
Published: February 2022

AbstractUnderstanding of what it means for patients to receive CAR-T therapy remains insufficient due to the small number of studies with a quality of life (QOL) focus, selection bias of respondents, high risk of attrition due to disease relapse, and limited length of follow-up. CAR-T therapy is often presented as a last option for patients with advanced disease. The primary aim of the treatment is patient survival and hopefully disease elimination. However, understanding other aspects of health, such as functional status, cognitive function, psychosocial concerns, and other health-related (QOL) issues, is key to appreciating the full impact of such therapies at both the individual and societal levels.
Why IT Security Needs Therapy
Authors: Menges Uta , Hielscher Jonas , Buckmann Annalina , Kluge Annette , Sasse M. Angela , Verret Imogen 
Published: February 2022

AbstractOver the past decade, researchers investigating IT security from a socio-technical perspective have identified the importance of trust and collaboration between different stakeholders in an organisation as the basis for successful defence. Yet, when employees do not follow security rules, many security practitioners attribute this to them being “weak” or “careless”; many employees in turn hide current practices or planned development because they see security as “killjoys” who “come and kill our baby”. Negative language and blaming others for problems are indicators of dysfunctional relationships. We collected a small set of statements from security experts’ about employees to gauge how widespread this blaming is. To understand how employees view IT security staff, we performed a prolific survey with 100 employees (n = 92) from the US & UK, asking them about their perceptions of, and emotions towards, IT security staff. Our findings indicate that security relationships are indeed often dysfunctional. Psychology offers frameworks for identifying relationship and communication flows that are dysfunctional, and a range of interventions for transforming them into functional ones. We present common examples of dysfunctionality, show how organisations can apply those interventions to rebuild trust and collaboration, and establish a positive approach to security in organisations that seizes human potential instead of blaming the human element. We propose Transactional Analysis (TA) and the OLaF questionnaire as measurement tools to assess how organisations deal with error, blame and guilt. We continue to consider possible interventions inspired by therapy such as conditions from individual and group therapy which can be implemented, for example, in security dialogues or the use of humour and clowns.
Transferring Update Behavior from Smartphones to Smart Consumer Devices
Authors: Fassl Matthias , Neumayr Michaela , Schedler Oliver , Krombholz Katharina 
Published: February 2022

AbstractAutomatic updates are becoming increasingly common, which minimizes the amount of update decisions that users have to make. Rapidly deployed important updates have a major impact on security. However, automatic updates also reduce the users’ opportunities to build useful mental models which makes decision-making harder on other consumer devices without automatic updates. Users generally transfer their understanding from domains that they know well (i.e. smartphones) to others. We investigate how well this transfer process works with respect to updates and if users with automatic updates fare worse than those with manual updates.We conducted a formative field study ($$N = 52$$

N
=
52

) to observe users’ update settings on smartphones and examine reasons for their (de-)activation. Based on the results, we conducted an online survey ($$N = 91$$

N
=
91

) to compare how users perceive update notifications for smartphones and smart consumer devices. One of our main findings is that update decisions based on expected changes do not apply well to these devices since participants do not expect meaningful and visual changes. We suggest naming updates for such devices ‘maintenance’ to move users’ expectations from ‘new features’ to ‘ensuring future functionality’.
A Semantic Model for Embracing Privacy as Contextual Integrity in the Internet of Things (Short Paper)
Authors: Ezennaya-Gomez Salatiel , Vielhauer Claus , Dittmann Jana 
Published: February 2022

AbstractDue to the increasing number of complaints alleging privacy violations against companies to data protection authorities, the translation of business goals to system design goals and the subsequent consequences for customers’ privacy poses a challenge for many companies. For this reason, there is a need to bridge the economics of privacy and threats to privacy. To this end, our work relies on the concept of privacy as contextual integrity. This framework defines privacy as appropriate information flows subjected to social norms within particular social contexts or spheres. In this paper, we introduce a preliminary version of a semantic model which aims to relate and provide understanding on how well-established business goals may affect their customers’ privacy by designing IoT devices with permission access, data acquired by sensors, among other factors. Finally, we provide a use case application showing how to use the semantic model. The model aims to be an educational tool for professionals in business informatics during the modeling and designing process of a product which may gather sensitive data or may infer sensitive information, giving an understanding of the interaction of the product and its footprint with diverse actors (humans or machines). In the future, a further complete model of the presented may also target other groups, such as law enforcement bodies, as part of their educational training in such systems.
Sampling methods for renewable gases and related gases: challenges and current limitations
Authors: Arrhenius Karine , Francini Lorena , Büker Oliver 
Published: February 2022

Abstract
Renewable gases, hydrogen and biomethane can be used for the same applications as natural gas: to heat homes, power vehicles and generate electricity. They have the potential to contribute to the decarbonisation of the gas grid. Hydrogen blending with existing natural gas pipelines is also proposed as a means to increase the performance of renewable energy systems. Carbon capture and storage (CCS) and carbon capture and utilisation (CCU) technologies can be an answer to the global challenge of significantly reducing greenhouse gas emissions. Due to production methods, these gases typically contain species in trace amounts that can negatively impact the equipment they come into contact with or pipelines when injected into the gas grid. It is therefore necessary to ensure proper (and stable) gas quality that meets the requirements set out in the relevant standards. The gas quality standards require the collection and transport of a representative gas sample from the point of use to the analytical laboratory; i.e., no compounds may be added to or removed from the gas during sampling and transport. To obtain a representative sample, many challenges must be overcome. The biggest challenge is material compatibility and managing adsorption risks in the sampling systems (sampling line and sampling vessels). However, other challenges arise from the need for flow measurement with non-pure gases or from the nature of the matrix. Currently, there are no conclusive results of short-term stability measurements carried out under gas purity conditions (suitable pressure, matrix, appropriate concentrations, simultaneous presence of several species).
Repeated drying and rewetting cycles accelerate bacterial growth recovery after rewetting
Authors: Leizeaga Ainara , Meisner Annelein , Rousk Johannes , Bååth Erland 
Published: February 2022

AbstractTwo patterns of bacterial growth response upon drying and rewetting (DRW) of soils have previously been identified. Bacterial growth can either start increasing immediately after rewetting in a linear fashion (“type 1” response) or start increasing exponentially after a lag period (“type 2” response). The effect of repeated DRW cycles was studied in three soils with different response patterns after a single DRW cycle (“type 1”, “type 2” with a short lag period and “type 2” with a long lag period). The soils were exposed to seven DRW cycles, and respiration and bacterial growth were monitored after 1, 2, 3, 5, and 7 cycles. Exposure to repeated DRW shifted the bacterial growth response from a “type 2” to a “type 1” pattern, resulting in an accelerated growth recovery to a pre-disturbance growth rate. Bacterial growth in soils that initially had a “type 1” response also tended to recover faster after each subsequent DRW cycle. The respiration patterns after DRW also indicated the same transition from a “type 2” to a “type 1” pattern. Our results show that exposure to repeated DRW cycles will shape the bacterial response to future DRW cycles, which might be mediated by a shift in species composition, a physiological adjustment, evolutionary changes, or a combination of the three.
Converted laparoscopic distal pancreatectomy: is there an impact on patient outcome and total cost?
Authors: Casadei Riccardo , Ingaldi Carlo , Ricci Claudio , De Raffele Emilio , Alberici Laura , Minni Francesco 
Published: February 2022

Abstract
Purpose
Recent studies have reported worse outcomes of converted laparoscopic distal pancreatectomy (CLDP) with respect to total laparoscopic (TLDP) and open (ODP). The aim of the study was to evaluate the impact of conversion on patient outcome and on total cost.

Methods
Patients requiring a conversion (CLDP) were compared with both TLDP and ODP patients. The relevant patient- and tumour-related variables were collected for each patient. Both intra and postoperative data were extracted. Propensity score matching (PSM) analysis was carried out to equate the groups compared.

Results
Two hundred and five patients underwent DP, 105 (51.2%) ODPs, 81 (39.5%) TLDPs, and 19 (9.3%) CLDPs. After PSM, 19 CLDPs, 38 TLDPs, and 38 ODPs were compared. Patients who underwent CLDP showed a significantly longer operative time (P < 0.001), and an increase in blood loss (P = 0.032) and total cost (P = 0.034) with respect to TLDP, and a significantly longer operative time (P < 0.001), less frequent postoperative morbidity (P = 0.050), and a higher readmission rate (P = 0.035) with respect to ODP.

Conclusion
Total laparoscopic pancreatectomy was superior regarding operative findings and total costs with respect to CLDP; ODP showed a higher postoperative morbidity rate and a lower readmission rate with respect to CLDP. However, the reasons for the readmission of patients who underwent CLDP were mainly related to postoperative pancreatic fistula (POPF) grade B which is usually due to pancreas texture. Thus, the majority of distal pancreatectomies can be started using a minimally invasive approach, performing an early conversion if necessary.
Polynomisches Kontaktmodell zur Abbildung pastösen Materialverhaltens in DEM-Simulationen
Authors: Platzer Felix , Fimbinger Eric 
Published: February 2022

ZusammenfassungZur Simulation pastöser Materialien in der DEM wird ein Kontaktmodell vorgestellt, welches beim Kontaktverlust zweiter ursprünglich in Kontakt befindlicher Partikel (diskrete Elemente) eine anziehende Kraft (Kohäsionskraft) basierend auf einem polynomischen Ansatz bildet. Dieses folglich kapillare Kontaktmodell ist somit in der Lage, pastöse Materialien für Industrie orientierte DEM-Simulationen nachzubilden.Zum Abgleich der hierbei modellierten Materialien wird der Slump-Test als standardisierte und weit verbreitete Methode vorgestellt, wobei über Parametervariation ein Abgleich des im Labor festgestellten Verhaltens des pastösen Materials mit jenem Verhalten des digitalen Modells, aufgebaut als Partikelansammlung in der DEM-Simulation, durchgeführt wird.