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Introduction: The phase 2 RAMONA study demonstrated that second-line nivolumab ± ipilimumab immunotherapy was feasible and effective in older patients with advanced esophageal squamous cell cancer (ESCC). Here, we presented results from functional status (FS) and quality-of-life (QoL) analyses., Materials and Methods: Patients aged ≥65 years with advanced ESCC and disease progression following first-line therapy were enrolled for study treatment with nivolumab ± ipilimumab. Geriatric assessments (GA) consisting of G8 and GoGo/SlowGo evaluation, and quality of life (QoL) assessments with EORTC QLQ-C30 questionnaires were conducted at baseline and during the treatment. A post hoc analysis was performed to compare therapy efficacy, toxicity, and QoL between age groups (≥70 years vs. <70 years) and functionality groups (G8 > 14 vs. ≤14 and GoGo vs. SlowGo)., Results: In 66 treated patients with a median age of 70.5 years, older patients had non-inferior overall survival and tumor response compared to younger patients, with no increased treatment-related adverse events. Fitter patients (G8 > 14, GoGo) had a clinically, yet not statistically significant, survival advantage than less fit patients (G8 ≤ 14, SlowGo) patients. Moreover, FS by G8 and GoGo/SlowGo significantly correlated with QoL. Overall, QoL was impaired at baseline but remained stable in all scales over the course of immunotherapy., Discussion: The administration of nivolumab ± ipilimumab second-line immunotherapy in older patients with ESCC did not show age-dependent effects and maintained QoL. GA could identify functional deficits and limitations of QoL and should be implemented in the context of immunotherapy., Clinicaltrials: gov: NCT03416244., Competing Interests: Declaration of Competing Interest NMB reports research funding and receipt of equipment from Deutsche Forschungsgemeinschaft. RDH reports advisory for Amgen, Astra Zeneca, Bristol Myers Squibb, Boehringer, Daichi, Lilly, Merck, MSD, Pierre Fabre, Roche, and Servier; honoraria for lectures and presentations from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer, Daichi, Lilly, medac, Merck, MSD, Pierre Fabre, Roche, Saladax, Sanofi, and Servier; and consulting fees from Amgen, Astra Zeneca, Bayer, BMS, Boehringer, Daichi, Lilly, medac, Merck, MSD, Pierre Fabre, Roche, Saladax, Sanofi, and Servier. AV reports consultancy and advisory role for AstraZeneca, Amgen, BeiGene, Böhringer Mannheim, BMS, BTG, Daichi-Sankyo, EISAI, Incyte, Ipsen, MSD, PierreFabre, Roche, Servier, Sirtex, Tahio and Terumo. MdW reports research funding from Pfizer, Abbvie, Novartis, Astellas, Bristol Myers Squibb, AstraZeneca and MorphoSys; speaker's honoraria from AstraZeneca and Janssen; travel or accommodation expenses from Astellas and Janssen. RJ reports consulting fees from Roche and Bayer; payments for lectures and presentations from Dr. Falk Pharma and Bristol Myers Squibb; for writing of manuscripts from Boston Scientific and Springer Nature; advisory for Heidelberg University Hospital; and leading the Endoscopy section of the German Society of Gastroenterology. GS reports consulting fees from Servier, Pharmacosmos, Bristol Myers Squibb, Amgen and travel support from Daichi-Sankyo. PTP reports consulting fees from Bristol Myers Squibb, AstraZeneca, and MSD. TL is Scientific Head at CROLLL GmbH. HB is an employee of a commercial provider of clinical statistics and programming services (Staburo GmbH, Munich). MPE reports funding for conducting the trial from AIO-Studien-gGmbH which is the regulatory sponsor of the trial, and advisory for Bristol Myers Squibb. NH reports advisory for Bristol Myers Squibb. All remaining authors declare no conflicts of interests., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The overall survival of patients with advanced and refractory oesophageal squamous cell carcinoma, mostly aged 65 years and older, is poor. Treatment with PD-1 antibodies showed improved progression-free survival and overall survival. We assessed the safety and efficacy of combined nivolumab and ipilimumab therapy in this population., Methods: This multicentre, open-label, phase 2 trial done in 32 sites in Germany included patients aged 65 years and older with oesophageal squamous cell carcinoma and disease progression or recurrence following first-line therapy. Patients were treated with nivolumab (240 mg fixed dose once every 2 weeks, intravenously) in the safety run-in phase and continued with nivolumab and ipilimumab (nivolumab 240 mg fixed dose once every 2 weeks and ipilimumab 1 mg/kg once every 6 weeks, intravenously). The primary endpoint was overall survival, which was compared with a historical cohort receiving standard chemotherapy in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03416244., Findings: Between March 2, 2018, and Aug 20, 2020, we screened 75 patients with advanced oesophageal squamous cell carcinoma. We enrolled 66 patients (50 [76%] men and 16 [24%] women; median age 70·5 years [IQR 67·0-76·0]), 44 (67%) of whom received combined nivolumab and ipilimumab therapy and 22 (33%) received nivolumab alone. Median overall survival time at the prespecified data cutoff was 7·2 months (95% CI 5·7-12·4) and significantly higher than in a historical cohort receiving standard chemotherapy (p=0·0063). The most common treatment-related adverse events were fatigue (12 [29%] of 42), nausea (11 [26%]), and diarrhoea (ten [24%]). Grade 3-5 treatment-related adverse events occurred in 13 (20%) of 66 patients. Treatment-related death occurred in one patient with bronchiolitis obliterans while on nivolumab and ipilimumab treatment., Interpretation: Patients aged at least 65 years, with advanced oesophageal squamous cell carcinoma might benefit from combined nivolumab and ipilimumab therapy in second-line treatment., Funding: Bristol Myers Squibb., Competing Interests: Declaration of interests MPE reports receiving funding to conduct the trial from AIO Studien, the regulatory sponsor of the trial, and serving as an advisor with Bristol Myers Squibb. NMB reports receiving research funding and receipt of equipment from Deutsche Forschungsgemeinschaft. RH reports serving as an advisor with Amgen, Astra Zeneca, Bristol Myers Squibb, Boehringer, Daichi, Lilly, Merck, MSD, Pierre Fabre, Roche, and Servier; honoraria for lectures and presentations from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer, Daichi, Lilly, medac, Merck, MSD, Pierre Fabre, Roche, Saladax, Sanofi, and Servier; and consulting fees from Amgen, Astra Zeneca, Bayer, BMS, Boehringer, Daichi, Lilly, medac, Merck, MSD, Pierre Fabre, Roche, Saladax, Sanofi, and Servier. AV reports serving as an advisor with Roche, Bayer, Bristol Myers Squibb, Lilly, Eisai, AstraZeneca, IPSEN, MSD, Sirtex, BTG, Servier, Terumo, and Imaging Equipment; and consulting fees and honoraria for lectures from Roche, Bayer, Bristol Myers Squibb, Lilly, Eisai, Astra Zeneca, IPSEN, MSD, Sirtex, BTG, Servier, Terumo, and Imaging Equipment. RJ reports receiving consulting fees from Roche and Bayer; payments for lectures and presentations from Dr Falk Pharma and Bristol Myers Squibb; for writing of manuscripts from Boston Scientific and Springer Nature; serving as an advisor with Heidelberg University Hospital; and leading the Endoscopy section of the German Society of Gastroenterology. PTP reports receiving consulting fees from Bristol Myers Squibb, AstraZeneca, and MSD. TGa reports receiving honoraria from Bristol Myers Squibb, MSD, and Roche for presentations and advisory functions. JNK reports receiving consulting fees from Owkin and Panakeia as well as honoraria for lectures from MSD and Eisai. MM reports employment with AIO Studien, who was the regulatory sponsor of the trial. NH reports serving as an advisor with Bristol Myers Squibb. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The aim of the present study was to assess the feasibility of a 3D tumor cell culture model, that is, multicellular tumor spheroids (MCTSs) as an adequate model for micrometastases and therefore as a pharmacological model for efficacy testing of trifunctional therapeutic antibodies. Unlike conventional monolayer cultures, spheroids allow researchers to study parameters, such as 3D cell shape, 3D cell arrangement and microenvironment, and penetration efficiency of defense cells that may largely influence the efficacy of antibody treatment in vivo. The authors established a long-term coculture of human MCTSs with peripheral blood mononuclear cells (PBMCs) to test the anticancer effect of the trifunctional, bispecific antibody catumaxomab (anti-EpCAM x anti-CD3) or similar therapeutic molecules. The test system is accessible to various analytical methods and thus allows for characterizing multiple parameters, which can help elucidate the mode of action of immunotherapeutic anticancer treatment. For example, the novel approach enables precise, reproducible volume growth analysis of MCTSs under immunotherapeutic treatments. For evaluation of changes within individual spheroids, cryosections can be stained (e.g., for proliferating or apoptotic cells as well as infiltrating PBMCs). Molecular PCR-based assays or flow cytometric analyses allow for discrimination between different cell types, particularly leukocyte subtypes. Furthermore, MCTSs can be disaggregated to form standard monolayers for cell viability or plating efficiency experiments. For these reasons, the MCTS model is a powerful tool to analyze drug efficacy with various endpoints under highly reproducible, standardized conditions.

Understanding the mechanisms that regulate T cell immunity is critical for the development of effective therapies for diseases associated with T cell dysfunction, including autoimmune diseases, chronic infections, and cancer. Co-inhibitory "checkpoint molecules," such as programmed cell death protein-1, balance excessive or prolonged immune activation by T cell–intrinsic signaling. Here, by screening for mediators of natural killer (NK) cell recognition on T cells, we identified the immunoglobulin superfamily ligand B7H6 to be highly expressed by activated T cells, including patient-infused CD19-targeting chimeric antigen receptor (CAR) T cells. Unlike other checkpoint molecules, B7H6 mediated NKp30-dependent recognition and subsequent cytolysis of activated T cells by NK cells. B7H6+ T cells were prevalent in the tissue and blood of several diseases, and their abundance in tumor tissue positively correlated with clinical response in a cohort of patients with immune checkpoint inhibitor–treated esophageal cancer. In humanized mouse models, NK cell surveillance via B7H6 limited the persistence and antitumor activity of CAR T cells, and its genetic deletion enhanced T cell proliferation and persistence. Together, we provide evidence of B7H6 protein expression by activated T cells and suggest the B7H6-NKp30 axis as a therapeutically actionable NK cell–dependent immune checkpoint that regulates human T cell function. Editor's summary: Natural killer (NK) cells can eliminate infected or malignant cells, but they are also believed to be capable of killing host immune cells. By screening NK cell ligands on human T cells, Kilian et al. found that the immunoglobulin superfamily ligand B7H6 promotes cytolysis of activated T cells by NK cells. In leukemia-bearing humanized mice, NK cells restricted the antitumor activity of chimeric antigen receptor (CAR) T cells in a B7H6-dependent manner. A higher ratio of intratumoral NK to T cells was associated with poor response to immune checkpoint inhibition in a cohort of patients with esophageal cancer. These findings demonstrate that B7H6 recognition by NK cells can restrict human antitumor T cell responses. —Claire Olingy [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Erziehungswissenschaft is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zeitschrift für Pädagogische Psychologie is the property of Hogrefe AG and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The rapid growth of online education provides massive behavioral data for classroom behavior research. To analyse the empirical research of classroom behavior, this article retrieved 124 empirical researches of classroom behavior from Web of Science, EBSCO, and CNKI. After statistical analysis, the results were as follows: (1) The empirical research on classroom behavior has increased rapidly. (2) The topics focused on the research of classroom behavior influencing factors and classroom behavior characteristics. (3) The research mostly used manual acquisition for data collection and were mainly quantitative researches. (4) Most of the researches centered on primary and secondary school subjects with incomplete overviews of school divisions and disciplines. (5) Empirical research of classroom behavior provided reference for mining the law of classroom behavior and improving classroom teaching. Therefore, the article called for a more sophisticated approach to empirical research which combines online education and complex classroom behaviors. [ABSTRACT FROM AUTHOR]

Background: The development of morality is vital for fostering prosocial behavior and enhancing both individual and societal well-being. Clarifying what contextual and individual factors play a role in moral processes during childhood can contribute to our understanding of the development of morality. Given the previous acknowledgment of importance, yet lack of existing empirical findings, the study focused on the significance of callous-unemotional traits (i.e., an affective-interpersonal personality trait, related to psychopathy in adulthood) and emotion regulation (i.e., an essential part of socio-emotional competence, and a transdiagnostic factor in the development of psychopathology) for moral emotions and cognitions during middle childhood. The concrete aim was to examine direct and indirect effects of callous-unemotional trait dimensions (callousness, uncaring, unemotionality) onto immoral emotional attribution (i.e., feeling good after immoral decisions) and admissibility of immoral actions (i.e., evaluating immoral actions as being okay) via emotion regulation skills. Methods: A cross-sectional study was conducted with 194 children attending Grades 1 to 4, and their primary caregivers. The children completed the Inventory of Callous-Unemotional Traits and caregivers completed the Emotion Regulation Checklist. The children were also presented with a set of moral dilemma vignettes, and asked about the emotions of protagonists who acted immoral, and the admissibility of their actions. Results: Path-model analysis revealed (1) negative direct effects of emotion regulation skills onto immoral emotional attribution and admissibility of immoral actions, (2) positive direct effects of the dimensions callousness and uncaring onto immoral emotional attribution and admissibility of immoral actions, and (3) negative direct effects of dimensions callousness and uncaring onto emotion regulation skills. Indirect effects, indicating that emotion regulation skills mediate the association between the callous-unemotional trait dimensions and morality, were also found. Conclusion: The findings address a knowledge gap and indicate that emotion regulation skills, callousness, and uncaring play an important role in morality in middle childhood and should be included in frameworks of moral decision-making and development. [ABSTRACT FROM AUTHOR]

Simple Summary: The extensive array of applications in 3D culture models closely mimics the precise physiological conditions of in vivo settings, enabling the investigation of anticancer drug resistance, which suggests that, in addition to genes, cell structure significantly impacts toxicity outcomes. Commercial 3D culture systems offer a valuable platform to explore various facets of oral cancer research. These models present an ethical and reproducible alternative to animal studies, facilitating the examination of oral microbial population dynamics, cellular interactions between cancer cells and immune cells, and the role of macrophage cells in oral cancer. The onset and progression of oral cancer are accompanied by a dynamic interaction with the host immune system, and the immune cells within the tumor microenvironment play a pivotal role in the development of the tumor. By exploring the cellular immunity of oral cancer, we can gain insight into the contribution of both tumor cells and immune cells to tumorigenesis. This understanding is crucial for developing effective immunotherapeutic strategies to combat oral cancer. Studies of cancer immunology present unique challenges in terms of modeling due to the extraordinary complexity of the immune system. With its multitude of cellular components, each with distinct subtypes and various activation states, the immune system interacts with cancer cells and other components of the tumor, ultimately shaping the course of the disease. Conventional two-dimensional (2D) culture methods fall short of capturing these intricate cellular interactions. Mouse models enable us to learn about tumor biology in complicated and dynamic physiological systems but have limitations as the murine immune system differs significantly from that of humans. In light of these challenges, three-dimensional (3D) culture systems offer an alternative approach to studying cancer immunology and filling the existing gaps in available models. These 3D culture models provide a means to investigate complex cellular interactions that are difficult to replicate in 2D cultures. The direct study of the interaction between immune cells and cancer cells of human origin offers a more relevant and representative platform compared to mouse models, enabling advancements in our understanding of cancer immunology. This review explores commonly used 3D culture models and highlights their significant contributions to expanding our knowledge of cancer immunology. By harnessing the power of 3D culture systems, we can unlock new insights that pave the way for improved strategies in the battle against oral cancer. [ABSTRACT FROM AUTHOR]

In this paper the initialization of the city is considered, which consists of several steps, including the creation of city objects with their locations, creation of residents with their attributes and own daily schedules, etc. A description of the model is provided as a tuple of attributes. The adequacy of the simulation model is checked based on the statistical data from the city of Lviv, Ukraine. Generated locations of city ecosystem objects are presented. The daily schedule of residents is simulated. A possible work schedule for each specialty is given, and separate schedules are created for working days and holidays. A unique schedule is predicted for the resident, which depends on their age and work specialty. The dynamics of visits to facilities by residents on weekdays and at weekends are analyzed. Based on the conducted experiments, the adequacy of the model and its realistic reflection of the functioning of the city's ecosystem during the day are proven. It means that by using this model, researchers can assess the impact of different behavioral scenarios on the residents within the city ecosystem more reliably. This enables a better understanding of how certain actions or changes in behavior can affect the spread and control of diseases in a specific geographic area. This model has the potential to serve as a foundation for future modeling of systems at the medium and macro scales. [ABSTRACT FROM AUTHOR]

The moral self is increasingly being debated in research, i.e., what causes children to internalise and evaluate the importance of certain moral values. The aim of the present study is to analyse associations between parental warmth and harsh parenting, temperamental self-regulation (inhibitory control and impulsivity), and the moral self in middle childhood. A total of 194 (n = 52 children with special educational needs in emotional–social development) six- to eleven-year-old children (Mage = 8.53, SDage = 1.40) and their primary caregivers (Mage = 40.41, SDage = 5.94) participated in this cross-sectional questionnaire study. Parental warmth and impulsivity were associated with the moral self. Impulsivity mediated the relationship between harsh parenting as well as parental warmth and the moral self. Results are discussed in terms of their relevance to social information processing theory. The importance of parenting and temperamental self-regulation is discussed as implications that may in turn strengthen children's moral selves. [ABSTRACT FROM AUTHOR]

The aim of the current investigation was to compare the association between attachment and behaviour problems in children attending regular schools and children attending special education schools with a focus on emotional and social development. We draw upon data collected from 169 children attending regular schools (Mage = 9.66), and 91 children attending special education schools (Mage= 10.52). The children completed the Experiences in Close Relationships Scale-Revised (ECR-RC), which assess their maternal attachment-related anxiety and avoidance. Parents completed the Child Behaviour Checklist (CBCL/6-18 R) which captures their child's internalising and externalising problems. Special education children showed higher levels of attachment-related anxiety and avoidance, than regular education children. Furthermore, regular and special education children showed different associations between attachment and internalising and externalising problems. Our results have implications for the transferability of previous research findings from children without to children with special needs and highlight the importance of considering maternal attachment for children attending special education schools. [ABSTRACT FROM AUTHOR]

The manufacturing of viable and functional β‐cell spheroids is required for diabetes cell therapy and drug testing. Mesenchymal stromal/stem cells (MSCs) are known to improve β‐cell viability and functionality. We therefore investigated the aggregation behavior of three different β‐cell lines (rat insulinoma‐1 cell line [INS‐1], mouse insulinoma‐6 cell line [MIN6], and a cell line formed by the electrofusion of primary human pancreatic islets and PANC‐1 cells [1.1B4]), two MSC types, and mixtures of β‐cells and MSCs under different conditions. We screened several static systems to produce uniform β‐cell and MSC spheroids, finding cell‐repellent plates the most suitable. The three different β‐cell lines differed in their aggregation behavior, spheroid size, and growth in the same static environment. We found no major differences in spheroid formation between primary MSCs and an immortalized MSC line, although both differed with regard to the aggregation behavior of the β‐cell lines. All spheroids showed a reduced viability due to mass transfer limitations under static conditions. We therefore investigated three dynamic systems (shaking multi‐well plates, spinner flasks, and shaking flasks). In shaking flasks, there were no β‐cell‐line‐dependent differences in aggregation behavior, resulting in uniform and highly viable spheroids. We found that the aggregation behavior of the β‐cell lines changed in a static coculture with MSCs. The β‐cell/MSC coculture conditions must be refined to avoid a rapid segregation into distinct populations under dynamic conditions. [ABSTRACT FROM AUTHOR]

Cancer is a multifactorial disease that is responsible for 10 million deaths per year. The intra- and inter-heterogeneity of malignant tumors make it difficult to develop single targeted approaches. Similarly, their diversity requires various models to investigate the mechanisms involved in cancer initiation, progression, drug resistance and recurrence. Of the in vitro cell-based models, monolayer adherent (also known as 2D culture) cell cultures have been used for the longest time. However, it appears that they are often less appropriate than the three-dimensional (3D) cell culture approach for mimicking the biological behavior of tumor cells, in particular the mechanisms leading to therapeutic escape and drug resistance. Multicellular tumor spheroids are widely used to study cancers in 3D, and can be generated by a multiplicity of techniques, such as liquid-based and scaffold-based 3D cultures, microfluidics and bioprinting. Organoids are more complex 3D models than multicellular tumor spheroids because they are generated from stem cells isolated from patients and are considered as powerful tools to reproduce the disease development in vitro. The present review provides an overview of the various 3D culture models that have been set up to study cancer development and drug response. The advantages of 3D models compared to 2D cell cultures, the limitations, and the fields of application of these models and their techniques of production are also discussed. [ABSTRACT FROM AUTHOR]

Cloud computing has become the most popular concept for on-demand delivery of Cloud computing services. Due to its high flexibility, many Cloud computing services are designed and implemented to meet the users' needs and expectations. As a result, new challenges have emerged in the search for relevant Cloud services. In fact, the description, discovery, and recommendation of Cloud services are the main challenges of Cloud computing. It stems from the lack of standardization for the Cloud services description and publication, as well as the exponential growth in the number and functionality of Cloud services. Our objective in this paper is to present a comparative study of the different approaches that address the Cloud services description, discovery, and recommendation issues. This comparison study's findings are separated into three parts. First, the approaches to Cloud service description have several flaws, such as the lack of a unified description that encompasses all types of Cloud services, the lack of a definition for several properties (such as Cloud characteristics, actors, and pricing model), and the failure to consider several critical SLA elements (for example, QoS guarantee, compensation, monitoring, notification, and termination). Second, we determined that web-based approaches, also known as crawling approaches, are the most likely to be adopted in the field of Cloud service discovery, in order to keep up with the ever-changing nature of Cloud computing. Hence, the crawling approach's main purpose is to update the Cloud service registry with new services that are available on the internet. Existing crawling methods, on the other hand, have a set of shortcomings, including the types and categories of discovered Cloud services, the constant increase in web-published Cloud services, and the automatic updating of Cloud vocabulary. Finally, major Cloud service recommendation issues such as cold start, data sparsity, attack resistance, and diversity remain unaddressed. [ABSTRACT FROM AUTHOR]

The present study sought to refine knowledge about the structure underlying externalizing dimensions. From a "top-down" ICD/DSM-based perspective, externalizing symptoms can be categorized into attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD). From a "bottom-up" developmental theory-based perspective, disruptive behaviors can be meaningfully described as aggressive (AGG) and rule-breaking (RB) behaviors. We analyzed five large data sets comprising externalizing symptom ratings obtained with a screening instrument using different sources (parents, teachers, self-ratings) from different samples. Using confirmatory factor analyses, we evaluated several factor models (unidimensional; correlated factors; bifactor (S-1) models) derived from an ICD/DSM- and theory-based perspective. Our optimally fitting models were assessed for measurement invariance across all sources, sample settings, and sex. Following several model-based criteria (model fit indices; factor loadings; omega statistics; model parsimony), we discarded our models stepwise and concluded that both the ICD/DSM-based model with three correlated factors (ADHD, ODD, CD) and the developmental theory-based model with three correlated factors (ADHD, AGG, RB) displayed a statistically sound factor structure and allowed for straightforward interpretability. Furthermore, these two models demonstrated metric invariance across all five samples and across sample settings (community, clinical), as well as scalar invariance across sources and sex. While the dimensions AGG and RB may depict a more empirically coherent view than the categorical perspective of ODD and CD, at this point we cannot clearly determine whether one perspective really outperforms the other. Implications for model selection according to our model-based criteria and clinical research are discussed. [ABSTRACT FROM AUTHOR]

Cloud computing has emerged as a tremendous opportunity for both industry and academia as it introduces a fundamental shift in Cloud service delivery. This situation has led to more competitive Cloud providers giving end-users greater freedom to choose the best Cloud service. However, each Cloud provider uses its techniques to describe its Cloud services. As a result, it is increasingly difficult for users to find and access Cloud services with similar functionality. The variety of these techniques is due to the lack of Cloud services description standardization. To deal with such issues and due to the vast search space, we propose in this paper a Cloud services description ontology, "CSDO," that assists the Cloud service publication, discovery, and selection processes. The proposed description is based on the Linked-USDL language to describe Cloud services thanks to its expressiveness. [ABSTRACT FROM AUTHOR]

Previous studies pointed out that dealing with difficult behaviour is perceived by teachers as a major challenge in inclusive settings. However, research on the students' perception of the classroom behavioural climate (CBC) is rare. Therefore, this study aims to examine students' perceptions of CBC and to identify predictors of CBC as well as associated variables. The sample consists of 650 German students from secondary schools (5th‐9th grade) of whom 83 students are diagnosed with special educational needs (SEN). CBC was measured via four subscales ('students' possibilities to study and concentrating on teaching', 'disruptive behaviour', 'physical and psychological safety' and 'caring for the physical environment'). Results show significant differences in students' perceptions of CBC between students from different school tracks. Furthermore, gender (being male) and SEN (having a) predict the perception of 'physical and psychological safety'. Additionally, social inclusion, emotional experience as well as teacher support and care are associated with CBC. Accordingly, a positive CBC is important for the successful implementation of inclusive education: while diversity in classrooms is a challenge for behavioural climate, poor behavioural climate may also pose specific barriers to learning for some students with SEN and thus is a general challenge for equity in inclusive classrooms. [ABSTRACT FROM AUTHOR]

The 2017 National Assessment of Education Progress (NAEP) findings indicate that only 37% of the nation's twelfth graders are at or above proficiency in reading and the average reading score for students with disabilities is under the basic skill level. Consequently, high school teachers are faced with developing targeted interventions to address their limited reading skills. An effective response may be to enhance students' visualization as they read and interact with text, motivating them to make meaning. Students with high incidence disabilities (e.g., attention deficits, learning disabilities) can often be confused by text structure and experience difficulty creating mental images in order to engage with the text. Additionally, it is difficult to motivate reluctant readers to read texts without pictures. Based on the facets of transactional theory and dual coding theory, this descriptive pilot study explored promoting visualization in order to increase reading comprehension in students with disabilities. In a three-week intervention, ten high school students with high incidence disabilities learned to identify seven elements of a screenplay in various movies. They were guided in identifying the visual features in the movies that corresponded with each element. They subsequently practiced using mental imagery, to identify the same elements in literature of increasing complexity using plot diagrams. Findings indicated students visualized more and were able to identify elements within the text structure. Comprehension results were mixed, based on response format. Implications for reading comprehension are discussed. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) is among the ten leading malignancies worldwide, with India solely contributing one-third of global oral cancer cases. The current focus of all cutting-edge strategies against this global malignancy are directed towards the heterogeneous tumor microenvironment that obstructs most treatment blueprints. Subsequent to the portrayal of established information, the review details the application of single cell technology, organoids and spheroid technology in relevance to head and neck cancer and the tumor microenvironment acknowledging the resistance pattern of the heterogeneous cell population in HNC. Bioinformatic tools are used for study of differentially expressed genes and further omics data analysis. However, these tools have several challenges and limitations when analyzing single-cell gene expression data that are discussed briefly. The review further examines the omics of HNC, through comprehensive analyses of genomics, transcriptomics, proteomics, metabolomics, and epigenomics profiles. Patterns of alterations vary between patients, thus heterogeneity and molecular alterations between patients have driven the clinical significance of molecular targeted therapies. The analyses of potential molecular targets in HNC are discussed with connotation to the alteration of key pathways in HNC followed by a comprehensive study of protein kinases as novel drug targets including its ATPase and additional binding pockets, non-catalytic domains and single residues. We herein review, the therapeutic agents targeting the potential biomarkers in light of new molecular targeted therapies. In the final analysis, this review suggests that the development of improved target-specific personalized therapies can combat HNC's global plight. [ABSTRACT FROM AUTHOR]

Summary: The vendor lock‐in is a prominent issue in cloud computing. It is caused by cloud providers who offer proprietary services, which hinders the cloud interoperability. Client‐centric interoperability enables the migration of the data and applications across clouds; it gives the clients control over their workloads and a wider range of service choices. Whereas, provider‐centric interoperability allows the providers to collaborate. Thus, providers, who have spare resources, can lend them to other providers who lack computational or storage capabilities to overcome the limitations of their local resources. In this article, we conduct a survey to differentiate between client‐ and provider‐centric interoperability solutions. We aim to provide an up‐to‐date analysis of the current tendencies and the neglected areas of the cloud interoperability field. Thus, we study the cloud service interoperability evolution through the years. Furthermore, we propose definitions for the intra‐cloud and inter‐cloud interoperability. Moreover, we propose a taxonomy to classify the cloud interoperability approaches into client‐centric and provider‐centric categories. Then, for each category, we classify the approaches based on their interoperability environment into single cloud or interconnected clouds. Finally, we analyze and compare the approaches based on multiple criteria. The study reveals the focus on the client‐centric solutions and the interoperability in interconnected clouds. We notice more interest in the data and application levels interoperability, mainly, in infrastructure as a service model. We also find that client‐centric solutions are, mostly, semantic technologies and brokers. However, provider‐centric solutions are middleware, protocols, and standards. We conclude that a generic cloud service interoperability model is needed. [ABSTRACT FROM AUTHOR]

Copyright of Prävention und Gesundheitsförderung is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

With the increasing processing capability of mobile platforms and advancements in Internet of Things, modern mobile devices have shown a favorable prospect for on-the-go service provisioning. However, there is much to be done to realize this. A detailed, dynamic, and lightweight service description is an important requirement for automatic and efficient discovery, selection, and subsequent provisioning of services over mobile devices. Traditional approaches for service description are usually not directly adaptable to mobile environments owing to the latter’s dynamic and distinct nature. In this paper, we propose a dynamic, lightweight, extensible, and detailed service description especially designed for mobile environments, considering crucial aspects such as isolated data source, collaborator partners, and hardware aspects along with the functional, non-functional, business, and contextual aspects. The description has been partitioned along these lines and various parts of the description are distributed between service registries and the mobile service providers. An up-to-date and light weight description has been achieved by this, without compromising on the overall consistency of the description. A prototype of the proposed system has been implemented with the intent of validating the feasibility of the approach. Further, the proposed approach is suitable for a heterogeneous environment comprising both wired and wireless systems. [ABSTRACT FROM AUTHOR]

Bispecific antibodies capable of simultaneously binding two targets have been studied for many years with a view to their implementation in clinical practice. Unique biological and pharmacological properties, as well as the diversity of their formats, make it possible to consider bispecific antibodies as promising agents for use in various procedures: from visualization of intracellular processes to targeted anticancer therapy. Bispecific antibodies help to determine more precisely the therapeutic target, thereby increasing the efficiency of therapy and reducing the probability of side effects. The present review describes the main formats of bispecific antibodies, methods for their generation, and possibilities for practical application. [ABSTRACT FROM AUTHOR]

Recent advances in next-generation sequencing and other omics technologies capable to map cell fate provide increasing evidence on the crucial role of intra-tumor heterogeneity (ITH) for cancer progression. The different facets of ITH, from genomic to microenvironmental heterogeneity and the hierarchical cellular architecture originating from the cancer stem cell compartment, contribute to the range of tumor phenotypes. Decoding these complex data resulting from the analysis of tumor tissue complexity poses a challenge for developing novel therapeutic strategies that can counteract tumor evolution and cellular plasticity. To achieve this aim, the development of in vitro and in vivo cancer models that resemble the complexity of ITH is crucial in understanding the interplay of cells and their (micro)environment and, consequently, in testing the efficacy of new targeted treatments and novel strategies of tailoring combinations of treatments to the individual composition of the tumor. This challenging approach may be an important cornerstone in overcoming the development of pharmaco-resistances during multiple lines of treatment. In this paper, we report the latest advances in patient-derived 3D (PD3D) cell cultures and patient-derived tumor xenografts (PDX) as in vitro and in vivo models that can retain the genetic and phenotypic heterogeneity of the tumor tissue. [ABSTRACT FROM AUTHOR]

An area that has come to be of tremendous interest in tumor research in the last decade is the role of the microenvironment in the biology of neoplastic diseases. The tumor microenvironment (TME) comprises various cells that are collectively important for normal tissue homeostasis as well as tumor progression or regression. Seminal studies have demonstrated the role of the dialogue between cancer cells (at many sites) and the cellular component of the microenvironment in tumor progression, metastasis, and resistance to treatment. Using an appropriate system of microenvironment and tumor culture is the first step towards a better understanding of the complex interaction between cancer cells and their surroundings. Three-dimensional (3D) models have been widely described recently. However, while it is claimed that they can bridge the gap between in vitro and in vivo, it is sometimes hard to decipher their advantage or limitation compared to classical two-dimensional (2D) cultures, especially given the broad number of techniques used. We present here a comprehensive review of the different 3D methods developed recently, and, secondly, we discuss the pros and cons of 3D culture compared to 2D when studying interactions between cancer cells and their microenvironment. [ABSTRACT FROM AUTHOR]

We argue that cloud service brokerage (CSB) mechanisms can strengthen the resilience of services in cloud-based VEs. In this respect, we present the Service Completeness-Compliance Checker (SC $$^3$$ ), a mechanism which offers capabilities with respect to the quality assurance dimension of CSB. More specifically, the SC $$^3$$ strengthens the resilience of cloud services by evaluating their conformance with pre-specified policies concerning the business aspects of their delivery, as well as by managing the evolution of their lifecycle in a controlled and policy-based manner. By relying on an ontology-based representation of policies and services, the SC $$^3$$ achieves a proper separation of concerns between policy definition and policy enforcement. This effectively enables the SC $$^3$$ to operate in a manner generic and agnostic to any underlying cloud delivery platform, as well as to reason about the well-formedness of the pre-specified policies. [ABSTRACT FROM AUTHOR]

In the present study, we applied the Particle Swarming Optimization (PSO) procedure to parametrize two Local Maxima (LM) algorithms and a pattern recognition model based on raster and point-cloud datasets in order to extract treetops of coniferous forests from high resolution LiDAR-data of different forest structures (monoplane, biplane and multi-layer) in the Alps region. The approach based on the pattern recognition model uses the geomorphon algorithm applied to the DSM to detect the treetops. The geomorphon model gave good results in terms of matching rates (Rmat: 0.8) with intermediate values of commission and omission rates (Rcom: 0.22, Rom: 0.2). Therefore, it could be a valid alternative to the LM-algorithms when only raster products (DSM - CHM) are available. The geomorphon pattern recognition model has been proved to be a powerful method in order to properly detect treetops of coniferous stands with complex forest structures. This model allows to obtain high detection rates and estimation accuracy of forest volume, also in comparison to the most recent available literature data. The models are developed in Java under Free and Open Source license and are integrated in the JGrassTools library, which is now available as SpatialToolbox of the GIS gvSIG. [ABSTRACT FROM AUTHOR]

Service-oriented computing and cloud computing offer many opportunities for developing and deploying applications. In this paper, we propose and describe a component-oriented method for automated provisioning of cloud business applications. The method covers the whole application's lifecycle and is based on cloud orchestration tools that manage the deployment and dependencies of supplied components. We aim to reduce the necessary technical knowledge for provisioning component-oriented cloud applications. To this end, we extend Linked Unified Service Description Language to describe services for matching user's requirements. We adopt a real case study to show the feasibility of the method. [ABSTRACT FROM AUTHOR]