Search

58 p.-5 fig.-7 box., Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize an abundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease., I. Vitale is and has been supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC, IG 2017 #20417 and IG 2022 #27685) and by a startup grant from the Italian Institute for Genomic Medicine (Candiolo, Turin, Italy) and Compagnia di San Paolo (Torino, Italy). M. Piacentini, G. Melino, S. Melino, G. Ciliberto are supported by the Ministro dell’Università (Italy) progetto Heal Italia PE6. L. Galluzzi is/has been supported (as a PI unless otherwise indicated) by two Breakthrough Level 2 grants from the US DoD BCRP (#BC180476P1; #BC210945), by a Transformative Breast Cancer Consortium Grant from the US DoD BCRP (#W81XWH2120034, PI: Formenti), by a U54 grant from NIH/NCI (#CA274291, PI: Deasy, Formenti, Weichselbaum), by the 2019 Laura Ziskin Prize in Translational Research (#ZP-6177, PI: Formenti) from the Stand Up to Cancer (SU2C), by a Mantle Cell Lymphoma Research Initiative (MCL-RI, PI: Chen-Kiang) grant from the Leukemia and Lymphoma Society (LLS), by a Rapid Response Grant from the Functional Genomics Initiative (New York, US), by startup funds from the Dept. of Radiation Oncology at Weill Cornell Medicine (New York, US), by industrial collaborations with Lytix Biopharma (Oslo, Norway), Promontory (New York, US) and Onxeo (Paris, France), as well as by donations from Promontory (New York, US), the Luke Heller TECPR2 Foundation (Boston, US), Sotio a.s. (Prague, Czech Republic), Lytix Biopharma (Oslo, Norway), Onxeo (Paris, France), Ricerchiamo (Brescia, Italy), and Noxopharm (Chatswood, Australia). G. Kroemer is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; AMMICa US23/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Cancéropôle Ile-de-France; European Research Council Advanced Investigator Grand “ICD-Cancer”, Fondation pour la Recherche Médicale (FRM); a donation by Elior; Equipex Onco-Pheno-Screen; European Joint Programme on Rare Diseases (EJPRD); European Research Council (ICD-Cancer), European Union Horizon 2020 Projects Oncobiome and Crimson; Fondation Carrefour; Institut National du Cancer (INCa); Institut Universitaire de France; LabEx Immuno-Oncology (ANR-18-IDEX-0001); a Cancer Research ASPIRE Award from the Mark Foundation; the RHU Immunolife; Seerave Foundation; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and SIRIC Cancer Research and Personalized Medicine (CARPEM)

BACKGROUND Considering the global burden of cardiovascular disease, we analysed trends in interventional coronary and structural procedures over the past 16 years (2005-2021), using continuous data from the Swiss national registry. METHODS Based on a standardised questionnaire, data on coronary and structural interventions in Switzerland were assessed by the Working Group Interventional Cardiology of the Swiss Society of Cardiology (SSC). Here, we analysed the trend of annually performed interventions from 2005 to 2021 in Switzerland and the impact of the COVID-19 pandemic. RESULTS We observed a constant increase in the total number of cases (including coronary angiographies (CA) and percutaneous coronary interventions (PCI)) from 36,436 cases in 2005 to 56,555 cases in 2021 (+55%). With 18 cases in 2007, TAVI procedures have increased to 2004 cases in 2021. During the early phase of the COVID-19 pandemic in 2020, a slight decrease in CAs and PCIs of 9.15% was observed. In contrast, we did not observe an impact of the COVID-19 pandemic on the number of no TAVI procedures. Most importantly, all cause in-hospital mortality for coronary interventions before and during the peak of the COVID-19 pandemic was comparable (1.4% vs. 1.3%). CONCLUSION Over a 16-year period, we observed an upward trend in diagnostic and therapeutic procedures for coronary as well as structural heart disease, with only a small short-term impact of the COVID-19 pandemic on interventions and a similar procedure-related in-hospital-mortality in Switzerland.

Artificial intelligence (AI) is increasingly permeating all areas of life and not only changing coexistence in society for the better. Unfortunately, there is an increasing number of examples where AI systems show problematic behavior, such as discrimination or insufficient accuracy, missing data privacy or transparency. To counteract this trend, an EU initiative has drafted a legal framework and recommendations on how AI can be more trustworthy and comply with people's fundamental rights. However, fundamental rights are currently not reflected in procedure models for the development and operation of AI systems. Our work contributes to closing this gap so that companies, especially SMEs with small IT departments and limited financial resources, are supported in the development process. Within the framework of a structured literature review, we derive a procedure model for the development and operation of AI systems and subsequently integrate concrete recommendations for achieving trustworthiness.

Solute carrier (SLC) transporters are membrane transport proteins, which catalyse the movement of nutrients, ions, and drugs across cell membranes. Here, I will present our contribution to understanding the mechanism of the sodium/proton exchangers (NHE), belonging to the SLC9 family of membrane transporters. NHEs exchange sodium ions for protons across biological membranes, which is a critical reaction for the fine-tuning of cytoplasmic and organelle pH, sodium levels and volume homeostasis. Dysfunction of NHE members has been linked to a number of diseases and disorders, such as hypertension, heart failure, autism spectrum disorder, epilepsy and the susceptibility of long COVID. Protein structures are important for developing mechanistic models, but due to technical challenges only bacterial homologue structures of NHE proteins were previously available. Accumulating many years of effort, we were able to determine the first structure of a mammalian Na+/H+ exchanger, the endosomal isoform NHE9 by single-particle cryo-EM. The structure of NHE9 demonstrated that NHE proteins are architecturally most similar to bacterial homologues with 13-TM segments and likely operated by a similar elevator mechanism (I). Interestingly, native MS and thermal-shift assays indicted that the NHE9 homodimer is stabilized by the binding of a rare lipid only found in late endosomes, which implies the cell may use this lipid as means to switch-on NHE9 activity once it reaches its correct functional localization. We further provided evidence that the large cytoplasmic tail in NHE proteins likely acts in an auto-inhibitory manner. It is only removed upon the binding of extrinsic proteins (II). Indeed, the first structure of a potassium specific K+/H+ exchanger KefC reveals how its cytoplasmic tail restricts movement of the ion-transporting domain to directly inhibit transport. The structure of KefC is also the first ion-bound state seen for this family and, unlike to the modeled Na+/H+ exchanger sites with a hydrated Na+ ion, coordinates K+ as a dehydrated ion (IV). Lastly, we determining the structure of a bacterial Na+/H+ exchanger NhaA to high-resolution at an active pH of 6.5. With this structure we demonstrated how a cytoplasmic “pH gate” controlled by the pH activated NhaA (III).

Aus dem Inhalt: Track 1: Produktion & Cyber-Physische Systeme Requirements and a Meta Model for Exchanging Additive Manufacturing Capacities Service Systems, Smart Service Systems and Cyber- Physical Systems—What’s the difference? Towards a Unified Terminology Developing an Industrial IoT Platform – Trade-off between Horizontal and Vertical Approaches Machine Learning und Complex Event Processing: Effiziente Echtzeitauswertung am Beispiel Smart Factory Sensor retrofit for a coffee machine as condition monitoring and predictive maintenance use case Stakeholder-Analyse zum Einsatz IIoT-basierter Frischeinformationen in der Lebensmittelindustrie Towards a Framework for Predictive Maintenance Strategies in Mechanical Engineering - A Method-Oriented Literature Analysis Development of a matching platform for the requirement-oriented selection of cyber physical systems for SMEs Track 2: Logistic Analytics An Empirical Study of Customers’ Behavioral Intention to Use Ridepooling Services – An Extension of the Technology Acceptance Model Modeling Delay Propagation and Transmission in Railway Networks What is the impact of company specific adjustments on the acceptance and diffusion of logistic standards? Robust Route Planning in Intermodal Urban Traffic Track 3: Unternehmensmodellierung & Informationssystemgestaltung (Enterprise Modelling & Information Systems Design) Work System Modeling Method with Different Levels of Specificity and Rigor for Different Stakeholder Purposes Resolving Inconsistencies in Declarative Process Models based on Culpability Measurement Strategic Analysis in the Realm of Enterprise Modeling – On the Example of Blockchain-Based Initiatives for the Electricity Sector Zwischenbetriebliche Integration in der Möbelbranche: Konfigurationen und Einflussfaktoren Novices’ Quality Perceptions and the Acceptance of Process Modeling Grammars Entwicklung einer Definition für Social Business Objects (SBO) zur Modellierung von Unternehmensinformationen Designing a Reference Model for Digital Product Configurators Terminology for Evolving Design Artifacts Business Role-Object Specification: A Language for Behavior-aware Structural Modeling of Business Objects Generating Smart Glasses-based Information Systems with BPMN4SGA: A BPMN Extension for Smart Glasses Applications Using Blockchain in Peer-to-Peer Carsharing to Build Trust in the Sharing Economy Testing in Big Data: An Architecture Pattern for a Development Environment for Innovative, Integrated and Robust Applications Track 4: Lern- und Wissensmanagement (e-Learning and Knowledge Management) eGovernment Competences revisited – A Literature Review on necessary Competences in a Digitalized Public Sector Say Hello to Your New Automated Tutor – A Structured Literature Review on Pedagogical Conversational Agents Teaching the Digital Transformation of Business Processes: Design of a Simulation Game for Information Systems Education Conceptualizing Immersion for Individual Learning in Virtual Reality Designing a Flipped Classroom Course – a Process Model The Influence of Risk-Taking on Knowledge Exchange and Combination Gamified Feedback durch Avatare im Mobile Learning Alexa, Can You Help Me Solve That Problem? - Understanding the Value of Smart Personal Assistants as Tutors for Complex Problem Tasks Track 5: Data Science & Business Analytics Matching with Bundle Preferences: Tradeoff between Fairness and Truthfulness Applied image recognition: guidelines for using deep learning models in practice Yield Prognosis for the Agrarian Management of Vineyards using Deep Learning for Object Counting Reading Between the Lines of Qualitative Data – How to Detect Hidden Structure Based on Codes Online Auctions with Dual-Threshold Algorithms: An Experimental Study and Practical Evaluation Design Features of Non-Financial Reward Programs for Online Reviews: Evaluation based on Google Maps Data Topic Embeddings – A New Approach to Classify Very Short Documents Based on Predefined Topics Leveraging Unstructured Image Data for Product Quality Improvement Decision Support for Real Estate Investors: Improving Real Estate Valuation with 3D City Models and Points of Interest Knowledge Discovery from CVs: A Topic Modeling Procedure Online Product Descriptions – Boost for your Sales? Entscheidungsunterstützung durch historienbasierte Dienstreihenfolgeplanung mit Pattern A Semi-Automated Approach for Generating Online Review Templates Machine Learning goes Measure Management: Leveraging Anomaly Detection and Parts Search to Improve Product-Cost Optimization Bedeutung von Predictive Analytics für den theoretischen Erkenntnisgewinn in der IS-Forschung Track 6: Digitale Transformation und Dienstleistungen Heuristic Theorizing in Software Development: Deriving Design Principles for Smart Glasses-based Systems Mirroring E-service for Brick and Mortar Retail: An Assessment and Survey Taxonomy of Digital Platforms: A Platform Architecture Perspective Value of Star Players in the Digital Age Local Shopping Platforms – Harnessing Locational Advantages for the Digital Transformation of Local Retail Outlets: A Content Analysis A Socio-Technical Approach to Manage Analytics-as-a-Service – Results of an Action Design Research Project Characterizing Approaches to Digital Transformation: Development of a Taxonomy of Digital Units Expectations vs. Reality – Benefits of Smart Services in the Field of Tension between Industry and Science Innovation Networks and Digital Innovation: How Organizations Use Innovation Networks in a Digitized Environment Characterising Social Reading Platforms— A Taxonomy-Based Approach to Structure the Field Less Complex than Expected – What Really Drives IT Consulting Value Modularity Canvas – A Framework for Visualizing Potentials of Service Modularity Towards a Conceptualization of Capabilities for Innovating Business Models in the Industrial Internet of Things A Taxonomy of Barriers to Digital Transformation Ambidexterity in Service Innovation Research: A Systematic Literature Review Design and success factors of an online solution for cross-pillar pension information Track 7: IT-Management und -Strategie A Frugal Support Structure for New Software Implementations in SMEs How to Structure a Company-wide Adoption of Big Data Analytics The Changing Roles of Innovation Actors and Organizational Antecedents in the Digital Age Bewertung des Kundennutzens von Chatbots für den Einsatz im Servicedesk Understanding the Benefits of Agile Software Development in Regulated Environments Are Employees Following the Rules? On the Effectiveness of IT Consumerization Policies Agile and Attached: The Impact of Agile Practices on Agile Team Members’ Affective Organisational Commitment The Complexity Trap – Limits of IT Flexibility for Supporting Organizational Agility in Decentralized Organizations Platform Openness: A Systematic Literature Review and Avenues for Future Research Competence, Fashion and the Case of Blockchain The Digital Platform Otto.de: A Case Study of Growth, Complexity, and Generativity Track 8: eHealth & alternde Gesellschaft Security and Privacy of Personal Health Records in Cloud Computing Environments – An Experimental Exploration of the Impact of Storage Solutions and Data Breaches Patientenintegration durch Pfadsysteme Digitalisierung in der Stressprävention – eine qualitative Interviewstudie zu Nutzenpotenzialen User Dynamics in Mental Health Forums – A Sentiment Analysis Perspective Intent and the Use of Wearables in the Workplace – A Model Development Understanding Patient Pathways in the Context of Integrated Health Care Services - Implications from a Scoping Review Understanding the Habitual Use of Wearable Activity Trackers On the Fit in Fitness Apps: Studying the Interaction of Motivational Affordances and Users’ Goal Orientations in Affecting the Benefits Gained Gamification in Health Behavior Change Support Systems - A Synthesis of Unintended Side Effects Investigating the Influence of Information Incongruity on Trust-Relations within Trilateral Healthcare Settings Track 9: Krisen- und Kontinuitätsmanagement Potentiale von IKT beim Ausfall kritischer Infrastrukturen: Erwartungen, Informationsgewinnung und Mediennutzung der Zivilbevölkerung in Deutschland Fake News Perception in Germany: A Representative Study of People’s Attitudes and Approaches to Counteract Disinformation Analyzing the Potential of Graphical Building Information for Fire Emergency Responses: Findings from a Controlled Experiment Track 10: Human-Computer Interaction Towards a Taxonomy of Platforms for Conversational Agent Design Measuring Service Encounter Satisfaction with Customer Service Chatbots using Sentiment Analysis Self-Tracking and Gamification: Analyzing the Interplay of Motivations, Usage and Motivation Fulfillment Erfolgsfaktoren von Augmented-Reality-Applikationen: Analyse von Nutzerrezensionen mit dem Review-Mining-Verfahren Designing Dynamic Decision Support for Electronic Requirements Negotiations Who is Stressed by Using ICTs? A Qualitative Comparison Analysis with the Big Five Personality Traits to Understand Technostress Walking the Middle Path: How Medium Trade-Off Exposure Leads to Higher Consumer Satisfaction in Recommender Agents Theory-Based Affordances of Utilitarian, Hedonic and Dual-Purposed Technologies: A Literature Review Eliciting Customer Preferences for Shopping Companion Apps: A Service Quality Approach The Role of Early User Participation in Discovering Software – A Case Study from the Context of Smart Glasses The Fluidity of the Self-Concept as a Framework to Explain the Motivation to Play Video Games Heart over Heels? An Empirical Analysis of the Relationship between Emotions and Review Helpfulness for Experience and Credence Goods Track 11: Information Security and Information Privacy Unfolding Concerns about Augmented Reality Technologies: A Qualitative Analysis of User Perceptions To (Psychologically) Own Data is to Protect Data: How Psychological Ownership Determines Protective Behavior in a Work and Private Context Understanding Data Protection Regulations from a Data Management Perspective: A Capability-Based Approach to EU-GDPR On the Difficulties of Incentivizing Online Privacy through Transparency: A Qualitative Survey of the German Health Insurance Market What is Your Selfie Worth? A Field Study on Individuals’ Valuation of Personal Data Justification of Mass Surveillance: A Quantitative Study An Exploratory Study of Risk Perception for Data Disclosure to a Network of Firms Track 12: Umweltinformatik und nachhaltiges Wirtschaften Kommunikationsfäden im Nadelöhr – Fachliche Prozessmodellierung der Nachhaltigkeitskommunikation am Kapitalmarkt Potentiale und Herausforderungen der Materialflusskostenrechnung Computing Incentives for User-Based Relocation in Carsharing Sustainability’s Coming Home: Preliminary Design Principles for the Sustainable Smart District Substitution of hazardous chemical substances using Deep Learning and t-SNE A Hierarchy of DSMLs in Support of Product Life-Cycle Assessment A Survey of Smart Energy Services for Private Households Door-to-Door Mobility Integrators as Keystone Organizations of Smart Ecosystems: Resources and Value Co-Creation – A Literature Review Ein Entscheidungsunterstützungssystem zur ökonomischen Bewertung von Mieterstrom auf Basis der Clusteranalyse Discovering Blockchain for Sustainable Product-Service Systems to enhance the Circular Economy Digitale Rückverfolgbarkeit von Lebensmitteln: Eine verbraucherinformatische Studie Umweltbewusstsein durch audiovisuelles Content Marketing? Eine experimentelle Untersuchung zur Konsumentenbewertung nachhaltiger Smartphones Towards Predictive Energy Management in Information Systems: A Research Proposal A Web Browser-Based Application for Processing and Analyzing Material Flow Models using the MFCA Methodology Track 13: Digital Work - Social, mobile, smart On Conversational Agents in Information Systems Research: Analyzing the Past to Guide Future Work The Potential of Augmented Reality for Improving Occupational First Aid Prevent a Vicious Circle! The Role of Organizational IT-Capability in Attracting IT-affine Applicants Good, Bad, or Both? Conceptualization and Measurement of Ambivalent User Attitudes Towards AI A Case Study on Cross-Hierarchical Communication in Digital Work Environments ‘Show Me Your People Skills’ - Employing CEO Branding for Corporate Reputation Management in Social Media A Multiorganisational Study of the Drivers and Barriers of Enterprise Collaboration Systems-Enabled Change The More the Merrier? The Effect of Size of Core Team Subgroups on Success of Open Source Projects The Impact of Anthropomorphic and Functional Chatbot Design Features in Enterprise Collaboration Systems on User Acceptance Digital Feedback for Digital Work? Affordances and Constraints of a Feedback App at InsurCorp The Effect of Marker-less Augmented Reality on Task and Learning Performance Antecedents for Cyberloafing – A Literature Review Internal Crowd Work as a Source of Empowerment - An Empirical Analysis of the Perception of Employees in a Crowdtesting Project Track 14: Geschäftsmodelle und digitales Unternehmertum Dividing the ICO Jungle: Extracting and Evaluating Design Archetypes Capturing Value from Data: Exploring Factors Influencing Revenue Model Design for Data-Driven Services Understanding the Role of Data for Innovating Business Models: A System Dynamics Perspective Business Model Innovation and Stakeholder: Exploring Mechanisms and Outcomes of Value Creation and Destruction Business Models for Internet of Things Platforms: Empirical Development of a Taxonomy and Archetypes Revitalizing established Industrial Companies: State of the Art and Success Principles of Digital Corporate Incubators When 1+1 is Greater than 2: Concurrence of Additional Digital and Established Business Models within Companies Special Track 1: Student Track Investigating Personalized Price Discrimination of Textile-, Electronics- and General Stores in German Online Retail From Facets to a Universal Definition – An Analysis of IoT Usage in Retail Is the Technostress Creators Inventory Still an Up-To-Date Measurement Instrument? Results of a Large-Scale Interview Study Application of Media Synchronicity Theory to Creative Tasks in Virtual Teams Using the Example of Design Thinking TrustyTweet: An Indicator-based Browser-Plugin to Assist Users in Dealing with Fake News on Twitter Application of Process Mining Techniques to Support Maintenance-Related Objectives How Voice Can Change Customer Satisfaction: A Comparative Analysis between E-Commerce and Voice Commerce Business Process Compliance and Blockchain: How Does the Ethereum Blockchain Address Challenges of Business Process Compliance? Improving Business Model Configuration through a Question-based Approach The Influence of Situational Factors and Gamification on Intrinsic Motivation and Learning Evaluation von ITSM-Tools für Integration und Management von Cloud-Diensten am Beispiel von ServiceNow How Software Promotes the Integration of Sustainability in Business Process Management Criteria Catalog for Industrial IoT Platforms from the Perspective of the Machine Tool Industry Special Track 3: Demos & Prototyping Privacy-friendly User Location Tracking with Smart Devices: The BeaT Prototype Application-oriented robotics in nursing homes Augmented Reality for Set-up Processe Mixed Reality for supporting Remote-Meetings Gamification zur Motivationssteigerung von Werkern bei der Betriebsdatenerfassung Automatically Extracting and Analyzing Customer Needs from Twitter: A “Needmining” Prototype GaNEsHA: Opportunities for Sustainable Transportation in Smart Cities TUCANA: A platform for using local processing power of edge devices for building data-driven services Demonstrator zur Beschreibung und Visualisierung einer kritischen Infrastruktur Entwicklung einer alltagsnahen persuasiven App zur Bewegungsmotivation für ältere Nutzerinnen und Nutzer A browser-based modeling tool for studying the learning of conceptual modeling based on a multi-modal data collection approach Exergames & Dementia: An interactive System for People with Dementia and their Care-Network Workshops Workshop Ethics and Morality in Business Informatics (Workshop Ethik und Moral in der Wirtschaftsinformatik – EMoWI’19) Model-Based Compliance in Information Systems - Foundations, Case Description and Data Set of the MobIS-Challenge for Students and Doctoral Candidates Report of the Workshop on Concepts and Methods of Identifying Digital Potentials in Information Management Control of Systemic Risks in Global Networks - A Grand Challenge to Information Systems Research Die Mitarbeiter von morgen - Kompetenzen künftiger Mitarbeiter im Bereich Business Analytics Digitaler Konsum: Herausforderungen und Chancen der Verbraucherinformatik

Das Internet of Everything bietet große Potenziale, die Gesundheitsversorgung zu verbessern und die Grundlage für ein vernetztes Internet of Health (IoH) zu bilden. Während in den letzten Jahren viele digitale Insellösungen entstanden sind, mangelt es im Gesundheitswesen an einer intelligenten Verknüpfung von Personen, Prozessen, Daten und Dingen. Im vorliegenden Beitrag wird elektronische Gesundheitsakte (eGA) als patientenzentriertes Vernetzungsinstrument im IoH vorgestellt. Für eine Analyse des State of the Art werden zunächst aktuelle Anbieter einer eGA in Deutschland vorgestellt und 25 Anwendungsfälle der eGA identifiziert. Anschließend wird das Potenzial der eGA als Vernetzungsinstrument im IoH herausgearbeitet. Im Rahmen von neun Experteninterviews mit Gesundheitsdienstleistern werden Anwendungsfälle der eGA sowie Herausforderungen für den flächendeckenden Einsatz der eGA abgeleitet.

In this century small villages face the great challenge to ensure the local supply with food and essential goods. Urbanisation and demographic change have caused many village stores and supermarkets to close their subsidiaries in rural areas. Thus, new concepts for village stores are needed. Based on a real situation this study presents a participatory research approach to gather the requirements for a multifunctional, digitalised village store. Together with the population in the reference village we conducted workshops, information events and an experimental vignette methodology (EVM) to gather the requirements of most citizens so that the design corresponds to the needs of the majority of the village population. The results show that the digital transformation of the village store has to be evolutionary to ensure a high users’ acceptance. Besides, the use of new digital technologies is essential to contribute for the local long-term supply with food and indispensable goods in rural areas.

Soziale Netzwerke haben in den vergangenen Jahren stark an Bedeutung in der Gesellschaft gewonnen. Vor allem die jungen Generationen sind mehrheitlich in diesen angemeldet. Senioren sind bei der Adaption sozialer Netzwerke hingegen vergleichsweise zurückhaltend. In diesem Beitrag wird ein Competence Developing Game (CDG) entwickelt und evaluiert, welches der Generation 50+ entsprechende Medienkompetenz im sicheren Umgang mit sozialen Netzwerken anhand des Beispiels Facebook vermittelt. Die Evaluation des entwickelten CDG zeigt, dass die Inhalte entsprechend der kognitiven und physischen Fähigkeiten der jeweiligen Altersgruppe aufbereitet und vermittelt werden sollten. Insbesondere die Integration von Videos und „Minispielen“ wurde von den Anwendern des entwickelten CDG als hilfreich hervorgehoben.

Der demografische Wandel und dessen Auswirkungen sind besonders im ländlichen Raum zu spüren. Die Anforderungen und Bedürfnisse der immer älter werdenden Bevölkerung können häufig nicht durch die vorhandene medizinische und soziale Versorgungsinfrastruktur gedeckt werden. Der vorliegende Beitrag adressiert die Konzeption, Entwicklung und Evaluierung eines Smart Home Predictice Analytics Systems bestehend aus dem Patientenortungssystem QuoLoco und der Plattform „opta data one“. In dieser werden unterschiedliche Dienstleistungen nutzerorientiert zusammengeführt und zugänglich gemacht. Durch das Smart Home Predictive Analytics System können ältere Menschen länger selbstständig und selbstbestimmt in den eigenen vier Wänden wohnen bleiben, ohne dabei starke Einschränkungen bezüglich Gesundheits-und Sicherheitsaspekten zu erfahren. Das System wurde mithilfe des MEESTAR-Modells hinsichtlich ethischer Fragen evaluiert und wird aktuell in einer Pflegeeinrichtung getestet.

Summary Tumor necrosis factor (TNF) can drive inflammation, cell survival, and death. While ubiquitylation-, phosphorylation-, and nuclear factor κB (NF-κB)-dependent checkpoints suppress the cytotoxic potential of TNF, it remains unclear whether ubiquitylation can directly repress TNF-induced death. Here, we show that ubiquitylation regulates RIPK1’s cytotoxic potential not only via activation of downstream kinases and NF-kB transcriptional responses, but also by directly repressing RIPK1 kinase activity via ubiquitin-dependent inactivation. We find that the ubiquitin-associated (UBA) domain of cellular inhibitor of apoptosis (cIAP)1 is required for optimal ubiquitin-lysine occupancy and K48 ubiquitylation of RIPK1. Independently of IKK and MK2, cIAP1-mediated and UBA-assisted ubiquitylation suppresses RIPK1 kinase auto-activation and, in addition, marks it for proteasomal degradation. In the absence of a functional UBA domain of cIAP1, more active RIPK1 kinase accumulates in response to TNF, causing RIPK1 kinase-mediated cell death and systemic inflammatory response syndrome. These results reveal a direct role for cIAP-mediated ubiquitylation in controlling RIPK1 kinase activity and preventing TNF-mediated cytotoxicity., Graphical Abstract, Highlights • Ubiquitylation directly controls RIPK1 kinase activity in TNF signaling • UBA-dependent ubiquitylation of RIPK1 represses its kinase activity and cell death • The UBA contributes to optimal occupancy of ubiquitin-acceptor lysines in RIPK1 • UBA-dependent ubiquitylation of RIPK1 also targets it for proteasomal degradation, Annibaldi et al. show that cIAP-mediated ubiquitylation of RIPK1 kinase suppresses its auto-activation and, in addition, marks it for proteasomal degradation. These results reveal a direct role for ubiquitin in controlling RIPK1 kinase activity and suppressing TNF-mediated cytotoxicity.

Caspases provide vital links in non-apoptotic regulatory networks controlling inflammation, compensatory proliferation, morphology and cell migration. How caspases are activated under non-apoptotic conditions and process a selective set of substrates without killing the cell remain enigmatic. Here we find that the Drosophila unconventional myosin CRINKLED (CK) selectively interacts with the initiator caspase DRONC and regulates some of its non-apoptotic functions. Loss of CK in the arista, border cells or proneural clusters of the wing imaginal discs affects DRONC-dependent patterning. Our data indicate that CK acts as substrate adaptor, recruiting SHAGGY46/GSK3-β to DRONC, thereby facilitating caspase-mediated cleavage and localized modulation of kinase activity. Similarly, the mammalian CK counterpart, MYO7A, binds to and impinges on CASPASE-8, revealing a new regulatory axis affecting receptor interacting protein kinase-1 (RIPK1)>CASPASE-8 signalling. Together, our results expose a conserved role for unconventional myosins in transducing caspase-dependent regulation of kinases, allowing them to take part in specific signalling events., Nature Communications, 7, ISSN:2041-1723

Novel therapies capable of reducing myocardial infarct (MI) size when administered prior to reperfusion are required to prevent the onset of heart failure in ST‐segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI). Experimental animal studies have demonstrated that mineralocorticoid receptor antagonist (MRA) therapy administered prior to reperfusion can reduce MI size, and MRA therapy prevents adverse left ventricular (LV) remodeling in post‐MI patients with LV impairment. With these 2 benefits in mind, we hypothesize that initiating MRA therapy prior to PPCI, followed by 3 months of oral MRA therapy, will reduce MI size and prevent adverse LV remodeling in STEMI patients. The MINIMISE‐STEMI trial is a prospective, randomized, double‐blind, placebo‐controlled trial that will recruit 150 STEMI patients from four centers in the United Kingdom. Patients will be randomized to receive either an intravenous bolus of MRA therapy (potassium canrenoate 200 mg) or matching placebo prior to PPCI, followed by oral spironolactone 50 mg once daily or matching placebo for 3 months. A cardiac magnetic resonance imaging scan will be performed within 1 week of PPCI and repeated at 3 months to assess MI size and LV remodeling. Enzymatic MI size will be estimated by the 48‐hour area‐under‐the‐curve serum cardiac enzymes. The primary endpoint of the study will be MI size on the 3‐month cardiac magnetic resonance imaging scan. The MINIMISE STEMI trial will investigate whether early MRA therapy, initiated prior to reperfusion, can reduce MI size and prevent adverse post‐MI LV remodeling.

La placa coronaria inestable es la causa de base más común de síndromes coronarios agudos (SCA) y se puede manifestar como angina inestable, infarto sin elevación del segmento ST (SCASEST), e infarto con elevación del segmento ST (IAMCEST), pero también se puede manifestar como paro cardíaco súbito debido a taquiarritmias inducidas por isquemia. La mortalidad de los SCA ha disminuido significativamente en el curso de los últimos años, especialmente la debida a las manifestaciones más extremas de SCA, IAMCEST, y paro cardíaco. Es probable que esta tendencia continúe gracias a avances terapéuticos recientes, entre los que se incluyen nuevos agentes antiplaquetarios tales como prasugrel, ticagrelor y cangrelor.

Resumen Las recientes innovaciones en el área de la cardiología intervencionista han ampliado drásticamente las opciones terapéuticas aplicables a los pacientes portadores de afecciones cardíacas. La cardiología intervencionista ya no queda limitada al tratamiento de las coronariopatías, sino que permite también tratar valvulopatías, prevenir accidentes cerebrovasculares, hipertensión, etcétera. Una de las principales opciones nuevas es el tratamiento percutáneo de la estenosis de válvula aórtica (implantación de la válvula aórtica transcatéter o percutánea); la valvulopatía aórtica es un problema bastante común en pacientes añosos, muchos de los cuales presentan un alto riesgo quirúrgico. De igual manera, la insuficiencia mitral a menudo se asocia con comorbilidades que determinan un alto riesgo quirúrgico. MitraClip es una promisoria alternativa percutánea que sustituiría la reparación o el reemplazo valvular quirúrgico. Otros procedimientos analizados en esta revisión son el cierre percutáneo de la orejuela de la aurícula izquierda como terapia no farmacológica para evitar accidentes cerebrovasculares y la denervación renal para la hipertensión resistente. Esta revisión explica los principios básicos de estos procedimientos, la evidencia clínica más importante, y también aporta datos clínicos recientes adicionales sobre cada uno de ellos.

Resumen El campo de la cardiología intervencionista sigue avanzando rápidamente. La eficacia de las intervenciones percutáneas con las últimas generaciones de endoprótesis liberadoras de fármacos ha tenido grandes avances en la última década. Esta mejora en los resultados de las endoprótesis ha ampliado el nivel de indicaciones, abarcando ahora otras más complejas, tales como las intervenciones coronarias percutáneas (ICP) de la arteria coronaria izquierda y de múltiples vasos. También continúan los grandes avances en el campo de la terapia médica concomitante, como los tratamientos antiplaquetarios (bivalirudina, prasugrel, ticagrelor), lo que redundará en resultados aun mejores de las ICP. Lo mismo ocurre con los estudios de imagenología intravascular como la ultrasonografía intravascular, (IVUS, por su sigla en inglés) y la tomografía de coherencia óptica (OCT, por su sigla en inglés). Sin embargo, la cardiología intervencionista se ha convertido en un campo muy amplio, incluyendo, entre otras técnicas, la ablación septal con alcohol para casos de miocardiopatía hipertrófica obstructiva. En la actualidad, el área de mayor crecimiento es la de las intervenciones estructurales, sobre todo para la estenosis de la válvula aórtica (implante de la válvula aórtica transcatéter percutáneo, o TAVI, por su sigla en inglés) y clipado (clipping) de la válvula mitral insuficiente. Esta revisión analiza los recientes avances en todos estos campos de la cardiología intervencionista Summary The field of interventional cardiology continues to progress quickly. The efficacy of percutaneous interventions with newer generation drug-eluting stents has advanced a lot over the last decade. This improvement in stent performance has broadened the level of indication towards more complex interventions such as left main and multi- vessel PCI. Major improvements continue in the field of medical co-therapy such as antiplatelet therapies (bivalirudin, prasugrel, ticagrelor) and this will further improve outcomes of PCI. The same is true for intravascular imaging such as ultrasound IVUS and optical coherence tomography OCT. However, interventional cardiology has become a rather broad field, also including alcohol septal ablation for hypertrophic obstructive cardiomyopathy, etc. At the moment, the fastest growing area is the structural interventions, especially for aortic valve stenosis (transcatheter aortic valve implantation TAVI) and for mitral regurgitation (mitral clipping). This review covers recent advances in all these different fields of interventional cardiology.

Caspases have been extensively studied as critical initiators and executioners of cell death pathways. However, caspases also take part in non-apoptotic signalling events such as the regulation of innate immunity and activation of nuclear factor-κB (NF-κB). How caspases are activated under these conditions and process a selective set of substrates to allow NF-κB signalling without killing the cell remains largely unknown. Here, we show that stimulation of the Drosophila pattern recognition protein PGRP-LCx induces DIAP2-dependent polyubiquitylation of the initiator caspase DREDD. Signal-dependent ubiquitylation of DREDD is required for full processing of IMD, NF-κB/Relish and expression of antimicrobial peptide genes in response to infection with Gram-negative bacteria. Our results identify a mechanism that positively controls NF-κB signalling via ubiquitin-mediated activation of DREDD. The direct involvement of ubiquitylation in caspase activation represents a novel mechanism for non-apoptotic caspase-mediated signalling.

Retroperitoneal fibrosis (RF) is a rare disease, typically with an insidious clinical course. The peak incidence is seen in patients 40 to 60 years of age and mostly in man. The characteristic finding in this disease is a periaortic fibrous mass that often surrounds the ureters. Although usually regarded as an obstructive uropathy, there has been growing recognition of the condition as a generalized disease. It may have a wide variety of manifestations including mediastinitis, thyroiditis and sclerosing cholangitis. The most common mode of presentation remains abdominal or flank pain with uremia, anemia and a high sedimentation rate. Although ultrasound and renal scintigraphy may contribute to the general evaluation of patients with RF, CT-scanner is the preferred imaging method. The multiplanar imaging capability of magnetic resonance may facilitate assessment of disease extent. The pathogenesis of the disease remains unknown. Steroids and, more recently tamoxifen, appear to be effective in the treatment of the RF. In most instances, RF does not lead to long-term morbidity or affect survival. The three cases of RF reported herein illustrate the varied mode of presentation and the response to the treatment.

ObjectivesWe sought to compare the nephrotoxicity of the iso-osmolar contrast medium, iodixanol, to low-osmolar contrast media (LOCM).BackgroundContrast-induced acute kidney injury (CI-AKI) is a common cause of in-hospital renal failure. A prior meta-analysis suggested that iodixanol (Visipaque, GE Healthcare, Princeton, New Jersey) was associated with less CI-AKI than LOCM, but this study was limited by ascertainment bias and did not include the most recent randomized controlled trials.MethodsWe searched Medline, Embase, ISI Web of Knowledge, Google Scholar, Current Contents, and International Pharmaceutical Abstracts databases, and the Cochrane Central Register of Controlled Trials from 1980 to November 30, 2008, for randomized controlled trials that compared the incidence of CI-AKI with either iodixanol or LOCM. Random-effects models were used to calculate summary risk ratios (RR) for CI-AKI, need for hemodialysis, and death.ResultsA total of 16 trials including 2,763 subjects were pooled. There was no significant difference in the incidence of CI-AKI in the iodixanol group than in the LOCM group overall (summary RR: 0.79, 95% confidence interval [CI]: 0.56 to 1.12, p = 0.19). There was no significant difference in the rates of post-procedure hemodialysis or death. There was a reduction in CI-AKI when iodixanol was compared with ioxaglate (RR: 0.58, 95% CI: 0.37 to 0.92; p = 0.022) and iohexol (RR: 0.19, 95% CI: 0.07 to 0.56; p = 0.002), but no difference when compared with iopamidol (RR: 1.20, 95% CI: 0.66 to 2.18; p = 0.55), iopromide (RR: 0.93, 95% CI: 0.47 to 1.85; p = 0.84), or ioversol (RR: 0.92, 95% CI: 0.60 to 1.39; p = 0.68).ConclusionsThis meta-analysis including 2,763 subjects suggests that iodixanol, when compared with LOCM overall, is not associated with less CI-AKI. The relative renal safety of LOCM compared with iodixanol may vary based on the specific type of LOCM.

ObjectivesWe sought to test whether myocardial blood flow (MBF) can be quantified by myocardial contrast echocardiography (MCE) using a volumetric model of ultrasound contrast agent (UCA) kinetics for the description of refill curves after ultrasound-induced microsphere destruction.BackgroundAbsolute myocardial perfusion or MBF (ml·min−1·g−1) is the gold standard to assess myocardial blood supply, and so far it could not be obtained by ultrasound.MethodsThe volumetric model yielded MBF= rBV·β/ρT, where ρTequals tissue density. The relative myocardial blood volume rBV and its exchange frequency βwere derived from UCA refill sequences. Healthy volunteers underwent MCE and positron emission tomography (PET) at rest (group I: n = 15; group II: n = 5) and during adenosine-induced hyperemia (group II). Fifteen patients with coronary artery disease underwent simultaneous MCE and intracoronary Doppler measurements before and during intracoronary adenosine injection.ResultsIn vitro experiments confirmed the volumetric model and the reliable determination of rBV and βfor physiologic flow velocities. In group I, 187 of 240 segments were analyzable by MCE, and a linear relation was found between MCE and PET perfusion data (y = 0.899x + 0.079; r2= 0.88). In group II, resting and hyperemic perfusion data showed good agreement between MCE and PET (y = 1.011x + 0.124; r2= 0.92). In patients, coronary stenosis varied between 0% to 89%, and myocardial perfusion reserve was in good agreement with coronary flow velocity reserve (y = 0.92x + 0.14; r2= 0.73).ConclusionsThe volumetric model of UCA kinetics allows the quantification of MBF in humans using MCE and provides the basis for the noninvasive and quantitative assessment of coronary artery disease.

The coronary collateral circulation has a beneficial role regarding all-cause and cardiac mortality. Hitherto, the underlying mechanism has not been clarified. The aim of this prospective study was to assess the effect of the coronary collateral circulation on electrocardiogram (ECG) QTc time change during short-term myocardial ischaemia.

Background The hypothesis of this study was that local anesthesia with monitored anesthesia care (MAC) is not harmful in comparison to general anesthesia (GA) for patients undergoing Transcatheter Aortic Valve Implantation (TAVR). TAVR is a rapidly spreading treatment option for severe aortic valve stenosis. Traditionally, in most centers, this procedure is done under GA, but more recently procedures with MAC have been reported. Methods This is a systematic review and meta-analysis comparing MAC versus GA in patients undergoing transfemoral TAVR. Trials were identified through a literature search covering publications from 1 January 2005 through 31 January 2013. The main outcomes of interest of this literature meta-analysis were 30-day overall mortality, cardiac-/procedure-related mortality, stroke, myocardial infarction, sepsis, acute kidney injury, procedure time and duration of hospital stay. A random effects model was used to calculate the pooled relative risks (RR) with 95% confidence intervals. Results Seven observational studies and a total of 1,542 patients were included in this analysis. None of the studies were randomized. Compared to GA, MAC was associated with a shorter hospital stay (-3.0 days (-5.0 to -1.0); P = 0.004) and a shorter procedure time (MD -36.3 minutes (-58.0 to -15.0 minutes); P

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

Lung squamous cell carcinoma (LSCC) and adenocarcinoma (LADC) are the most common lung cancer subtypes. Molecular targeted treatments have improved LADC patient survival but are largely ineffective in LSCC. The tumor suppressor FBW7 is commonly mutated or down-regulated in human LSCC, and oncogenic KRasG12D activation combined with Fbxw7 inactivation in mice (KF model) caused both LSCC and LADC. Lineage-tracing experiments showed that CC10+, but not basal, cells are the cells of origin of LSCC in KF mice. KF LSCC tumors recapitulated human LSCC resistance to cisplatin-based chemotherapy, and we identified LUBAC-mediated NF-κB signaling as a determinant of chemotherapy resistance in human and mouse. Inhibition of NF-κB activation using TAK1 or LUBAC inhibitors resensitized LSCC tumors to cisplatin, suggesting a future avenue for LSCC patient treatment.

The benefit of the coronary collateral circulation (natural bypass network) on survival is well established. However, data derived from smaller studies indicates that coronary collaterals may increase the risk for restenosis after percutaneous coronary interventions. The purpose of this systematic review and meta-analysis of observational studies was to explore the impact of the collateral circulation on the risk for restenosis.

BACKGROUND Transradial access (TRA) improves outcome compared with trans-femoral access for the management of patients with acute coronary syndromes. In this setting, it is unknown whether the activation of a pre-hospital alarm system (PHAS) confers additional benefit for the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). MATERIALS AND METHODS We retrospectively analyzed a cohort of patients with a first STEMI who underwent a primary percutaneous coronary intervention (PPCI) at a single center within a prospective cohort of acute coronary syndrome patients (SPUM-ACS). TRA was used in 85% of patients. We assessed how PHAS (n=165) vs. no-PHAS (n=166) activation was associated with the composite outcome of all-cause mortality and recurrence of myocardial infarction (MI) at 1-year follow-up. As secondary outcomes, the individual clinical endpoints were separately assessed for association. RESULTS Compared with no-PHAS patients, patients in the PHAS group were predominantly women, and presented more frequently with dyslipidemia and cardiac arrest. A significant reduction in the composite outcome of all-cause mortality and recurrent MI at 1-year was observed in the PHAS group, compared with no-PHAS (3.6% vs. 8.5%, p=0.027). When adjusted for age, sex and resuscitation status, PHAS activation remained associated with decreased all-cause mortality and recurrent MI (HR: 0.36 [95% CI: 0.13-0.95]; p=0.040). CONCLUSIONS This study suggests that the benefit of PHAS activation in STEMI patients undergoing PPCI persists also in the era of TRA.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

Lung squamous cell carcinoma (LSCC) and adenocarcinoma (LADC) are the most common lung cancer subtypes. Molecular targeted treatments have improved LADC patient survival but are largely ineffective in LSCC. The tumor suppressor FBW7 is commonly mutated or down-regulated in human LSCC, and oncogenic KRasG12D activation combined with Fbxw7 inactivation in mice (KF model) caused both LSCC and LADC. Lineage-tracing experiments showed that CC10+, but not basal, cells are the cells of origin of LSCC in KF mice. KF LSCC tumors recapitulated human LSCC resistance to cisplatin-based chemotherapy, and we identified LUBAC-mediated NF-κB signaling as a determinant of chemotherapy resistance in human and mouse. Inhibition of NF-κB activation using TAK1 or LUBAC inhibitors resensitized LSCC tumors to cisplatin, suggesting a future avenue for LSCC patient treatment.