bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution and optimization of clinical trial endpoints and design in pulmonary arterial hypertension
Authors: Caccamo Marco , Harrell Frank E. , Hemnes Anna R.
Published: August 2023

Selection of endpoints for clinical trials in pulmonary arterial hypertension (PAH) is challenging because of the small numbers of patients and the changing expectations of patients, clinicians, and regulators in this evolving therapy area. The most commonly used primary endpoint in PAH trials has been 6‐min walk distance (6MWD), leading to the approval of several targeted therapies. However, single surrogate endpoints such as 6MWD or hemodynamic parameters may not correlate with clinical outcomes. Composite endpoints of clinical worsening have been developed to reflect patients' overall condition more accurately, although there is no standard definition of worsening. Recently there has been a shift to composite endpoints assessing clinical improvement, and risk scores developed from registry data are increasingly being used. Biomarkers are another area of interest, although brain natriuretic peptide and its N‐terminal prohormone are the only markers used for risk assessment or as endpoints in PAH. A range of other genetic, metabolic, and immunologic markers is currently under investigation, along with conventional and novel imaging modalities. Patient‐reported outcomes are an increasingly important part of evaluating new therapies, and several PAH‐specific tools are now available. In the future, alternative statistical techniques and trial designs, such as patient enrichment strategies, will play a role in evaluating PAH‐targeted therapies. In addition, modern sequencing techniques, imaging analyses, and high‐dimensional statistical modeling/machine learning may reveal novel markers that can play a role in the diagnosis and monitoring of PAH.
An extensive screening method for the identification and quantitation of ecdysteroids in equine urine and plasma using liquid chromatography coupled with mass spectrometry
Authors: Karatt Tajudheen K. , Sathiq M. Anwar , Laya Saraswathy , Ajeebsanu M. P. Muhammed , Karakka Kal Abdul Khader , Subhahar Michael Benedict , Perwad Zubair
Published: August 2023

Rationale

Recently, there has been a report suggesting that ecdysteroids can enhance sports performance, making them relevant substances in doping control. Hence, it is imperative to examine the analytical characteristics of ecdysteroids in biological samples to identify their misuse in competitive sports.

Methods

To assess the doping of ecdysteroids such as ecdysone, ecdysterone, ponasterone A, turkesterone, and ajugasterone C, a fast and sensitive extraction and detection method was developed, optimized, and validated using equine urine and plasma. Different extraction techniques, namely, solid‐phase extraction, liquid–liquid extraction, and dilute‐and‐inject, were explored to detect ecdysteroids from equine urine and plasma.

Results

The most suitable method of detection was solid‐phase extraction using ABS Elut‐NEXUS, while liquid–liquid extraction and dilute‐and‐inject methods encountered difficulties due to the high polarity of ecdysteroids and the presence of significant matrix interferences. Mass spectrometric parameters are optimized on both the Q Exactive high‐resolution mass spectrometer and the TSQ Altis triple quadrupole mass spectrometer. However, the study indicated that the triple quadrupole mass spectrometer exhibited improved limit of detection when analyzing samples. To achieve optimal separation of the analytes under investigation from the matrix interferences, various liquid chromatography columns were compared. The Selectra PFPP LC column with a mobile phase consisting of 0.2% formic acid in water (mobile phase A) and acetonitrile (mobile phase B) at a flow rate of 0.5 mL/min demonstrated superior performance.

Conclusions

The findings of this study will significantly contribute to the accurate identification of ecdysteroids, facilitating the investigation of their illicit use in horse racing.
A sustainable system for decontamination of cephalexin antibiotic using electrocoagulation technology and response surface methodology
Authors: Arab Maliheh , Danesh Shahnaz
Published: August 2023

The emergence of synthetic micropollutants in wastewater due to domestic and industrial use has presented new challenges for treatment processes. Among these pollutants, pharmaceutical and personal care products (PPCPs) are considered emerging contaminants due to their potential to enter drinking water sources. Antibiotics, in particular, are of significant concern due to their high consumption in veterinary and human applications. In this study, the electrocoagulation (EC) process is used as an efficient technique for the removal of cephalexin (CFX) from pharmaceutical wastewater. The study aims to explore the ability of the EC process to remove CFX and optimize its performance using the response surface method based on Central Composite Design (RSM‐CCD). The effects of initial CFX concentration, electrolysis time, initial pH, and electrode type (non‐insulated and insulated) were considered in the optimization process. This research is distinct as it examines the influence of key factors on the elimination of CFX. The results showed that electrolysis time had the most significant effect on CFX removal using the EC process. The analysis of variance (ANOVA) test was used to evaluate the importance of independent variables and their interaction. The optimal operating conditions for maximum removal efficiency (86.53%) were an initial CFX concentration, reaction time, and initial pH of 34 mg/L, 34.35 min, and 6.5, respectively, using an insulated electrode. Under these optimal conditions, predicted CFX removal was 93.54%. These findings demonstrate that RSM‐CCD is a useful tool for optimizing electrochemical removal processes for micropollutants such as CFX from wastewater streams. The study highlights the importance of considering electrode type in optimizing EC processes for micropollutant removal from wastewater.
Integrating density functional theory into reductive dechlorination research
Authors: Das Schober Jaya , Kurwadkar Sudarshan , Harper Willie F.
Published: August 2023

Chlorinated organics have been frequently detected in groundwaters, threatening the quality of drinking water supplies worldwide. A promising method for groundwater remediation involves reductive dechlorination (RD), in which chlorine atoms are sequentially removed and substituted by hydrogen, producing less harmful byproducts. In this paper, for the first time, RD research is reviewed in light of the growing incorporation of density functional theory (DFT) as a research tool. DFT has been used to uncover a variety of reaction properties for a range of relevant groundwater pollutants, including 1,2,3‐trichloropropane, hexachlorobenzene, and various dioxins. DFT models have revealed the role of surface interactions in driving the kinetics of catalytically driven RD. Mechanisms involved with biologically mediated RD have also been elucidated with insights gleaned from DFT. Issues and challenges for future research are also discussed.
Effects of drought on the physicochemical, nutrient, and carbon metrics of flows in the Savannah River, Georgia, USA
Authors: Wilbanks Kelsey A. , Sutter Lori A. , Amurao Jillian M. , Batzer Darold P.
Published: August 2023

Hydrological drought has wide‐ranging impacts on water quality, nutrient and carbon metrics, and given the uncertainty of climate change and the predicted increased frequency and intensity of drought in the future, investigations into changes induced by drought become increasingly important. This study compared physicochemical parameters (temperature, conductivity, pH and DO), nutrients (TN, NOX [NO2 + NO3], NH3 and TP) and carbon (TOC and DOC) between hydrological drought conditions (2006–2008) and hydrological normal conditions (2016–2019) at five sites along the lower Savannah River (Georgia, USA). Although we had predicted that water temperatures would increase from drought, we instead found temperature was significantly lower during drought conditions. Levels of pH and DO were significantly higher during drought. Further, TN, TOC and DOC concentrations were significantly lower during drought, but NOX concentrations were significantly higher during drought. Conductivity varied at the lower river sites, being significantly higher during drought at sites located below the city of Augusta, GA. These complex changes could be attributed to volume reductions coupled with an increase in the percentage of total flow originating from groundwater as well as limnetic reservoir inputs, persistent point source pollution, reduced natural catchment inputs and/or reduced floodplain interactions. The changes that occurred during drought may be disruptive to aquatic life, not only from reduced water quantity but also due to a scarcity of some biologically essential materials and lower food resources, combined with artificially high levels of some other potentially stressful materials.
Rank intraclass correlation for clustered data
Authors: Tu Shengxin , Li Chun , Zeng Donglin , Shepherd Bryan E.
Published: August 2023

Clustered data are common in biomedical research. Observations in the same cluster are often more similar to each other than to observations from other clusters. The intraclass correlation coefficient (ICC), first introduced by R. A. Fisher, is frequently used to measure this degree of similarity. However, the ICC is sensitive to extreme values and skewed distributions, and depends on the scale of the data. It is also not applicable to ordered categorical data. We define the rank ICC as a natural extension of Fisher's ICC to the rank scale, and describe its corresponding population parameter. The rank ICC is simply interpreted as the rank correlation between a random pair of observations from the same cluster. We also extend the definition when the underlying distribution has more than two hierarchies. We describe estimation and inference procedures, show the asymptotic properties of our estimator, conduct simulations to evaluate its performance, and illustrate our method in three real data examples with skewed data, count data, and three‐level ordered categorical data.
Posttraumatic growth and health‐related quality of life in cancer survivors: Does fatigue moderate the link?
Authors: Onyedibe Maria‐Chidi C. , Blickle Patricia , Schmidt Martina E. , Steindorf Karen
Published: August 2023

Interest in post‐traumatic growth (PTG) as a predictor of health‐related quality of life (HRQoL) is currently gaining attention. However, current evidence is still inconclusive on the nature of this relationship. The first objective of this study was to investigate the relationship between PTG and global HRQoL among cancer survivors. We further investigated the moderating role of fatigue in the association between PTG and global HRQoL. In the FiX study (Fatigue in Germany ‐ Examination of prevalence, severity, and state of screening and treatment) cancer‐related fatigue (EORTC QLQ‐FA12), PTG inventory and global HRQoL (EORTC QLQ‐C30) were assessed four years after cancer diagnosis in 1316 cancer‐free survivors (mean age = 67.28, SD = 11.05, 51.4% female). Multiple linear regression analysis and moderation analysis were performed. The results showed that PTG had a convex quadratic relationship with global HRQoL (p < 0.001). Contrary to our hypothesis, fatigue did not moderate the relationship between PTG (linear and quadratic terms) and global HRQoL, neither when considering the overall PTG score nor for any PTG subdimension. In conclusion, PTG has a convex quadratic relationship with long‐term global HRQoL that was not modified by persisting fatigue. Future statistical models investigating PTG and global HRQoL should take this non‐linear relationship into account. Aiming to increase PTG might contribute to, but is likely not sufficient for high levels of global HRQoL in cancer survivors in the long run.
Massively Parallel High‐Throughput Single‐Cell Patterning and Large Biomolecular Delivery in Mammalian Cells Using Light Pulses
Authors: R Gayathri , Kar Srabani , Nagai Moeto , Mahapatra Pallab Sinha , Santra Tuhin Subhra
Published: August 2023

The recent advancements of single‐cell analysis have significantly enhanced the ability to understand cellular physiology when compared to bulk cellular analysis. Here a massively parallel single‐cell patterning and very large biomolecular delivery is reported. Micro‐pillar polydimethyl siloxane stamp with different diameters (40–100 µm with 1 cm × 1 cm patterning area) is fabricated and then imprint distinct proteins and finally pattern single‐cell to small clusters of cells depending on the micro‐pillar diameters. The maximum patterning efficiency is achieved 99.7% for SiHa, 96.75% for L929, and 98.6% for MG63 cells, for the 100 µm micro‐pillar stamp. For intracellular delivery of biomolecules into the patterned cells, a titanium micro‐dish device is aligned on top of the cells and exposed by infrared light pulses. The platform successfully delivers small to very large biomolecules such as PI dyes (668 Da), dextran 3000 Da, siRNA (20‐24 bp), and large size enzymes (464 KDa) in SiHa, L929 and MG63 cells. The delivery efficiency for PI dye, Dextran 3000, siRNA, and enzyme for patterned cells are ≈95 ± 3%, 97 ± 1%, 96 ± 1% and 94 ± 3%, with cell viability of 98 ± 1%. Thus, the platform is compact, robust, easy for printing, and potentially applicable for single‐cell therapy and diagnostics.
Boosting Microwave Thermo‐Dynamic Cancer Therapy of TiMOF via COF‐Coating
Authors: Wang Yuxin , Ren Xiangling , Zheng Yingjuan , Tan Longfei , Li Bingyan , Fu Changhui , Wu Qiong , Chen Zengzhen , Ren Jun , Yang Daoke , Yu Shiping , Meng Xianwei
Published: August 2023

Microwave (MW) dynamic therapy (MDT) can efficiently eliminate tumor residue resulting from MW thermal therapy. However, MDT is currently in its infancy, and luck of effective MDT sensiters severely limits its clinical therapeutic effect. Herein, based on TiMOF (TM), a high‐efficiency MW sensitizer is designed for MW thermo‐dynamic therapy. TM can generate heat and cytotoxic reacyive oxygen species (ROS) under MW irradiation and has the potential to be used as an MW sensitizer, while the suboptimal MW dynamic sensitization effect of TM limits its application. Inorder to improve the MW dynamic sensitization performance, a covalent organic framework (COF) with good stability and a large conjugate system is used to cover TM, which is conductive to electron and energy transfer, thus increasing the ROS generation rate and prolonging the ROS lifetime. In addition, loading Ni NPs endow nanomaterials with magnetic resonance imaging capabilities. Therefore, this work develops an MW sensitizer based on TM for the first time, and the mechanism of COF coating to enhance the MW dynamic sensitization of TM is preliminarily explored, which provides a new idea for the further development of MW sensitizer with great potential.
Relationship between Structure and Performance of Atomic‐Scale Electrocatalysts for Water Splitting
Authors: Choi Jungsue , Seo Sohyeon , Kim Minsu , Han Yeonsu , Shao Xiaodong , Lee Hyoyoung
Published: August 2023

Atomic‐scale electrocatalysts greatly improve the performance and efficiency of water splitting but require special adjustments of the supporting structures for anchoring and dispersing metal single atoms. Here, the structural evolution of atomic‐scale electrocatalysts for water splitting is reviewed based on different synthetic methods and structural properties that create different environments for electrocatalytic activity. The rate‐determining step or intermediate state for hydrogen or oxygen evolution reactions is energetically stabilized by the coordination environment to the single‐atom active site from the supporting material. In large‐scale practical use, maximizing the loading amount of metal single atoms increases the efficiency of the electrocatalyst and reduces the economic cost. Dual‐atom electrocatalysts with two different single‐atom active sites react with an increased number of water molecules and reduce the adsorption energy of water derived from the difference in electronegativity between the two metal atoms. In particular, single‐atom dimers induce asymmetric active sites that promote the degradation of H2O to H2 or O2 evolution. Consequently, the structural properties of atomic‐scale electrocatalysts clarify the atomic interrelation between the catalytic active sites and the supporting material to achieve maximum efficiency.
Understanding the quality and evolution of Android app build systems
Authors: Liu Pei , Li Li , Liu Kui , McIntosh Shane , Grundy John
Published: August 2023

Build systems are used to transform static source code into executable software. They play a crucial role in modern software development and maintenance. As such, much research effort has been invested in understanding the quality and evolution of build systems, including Apache ANT, Apache Maven, and Make‐based ones. However, the quality and evolution of build systems for mobile apps, such as on the Android platform, have not as yet been investigated in detail. Mobile app development, and the Android development context in particular, impose unique constrains, such as different device conditions and capabilities. It presents unique challenges, such as frequently upgraded Android frameworks, which those who implement and maintain build systems must tackle. In this paper, we present an exploratory empirical study of the build systems of 5222 Android projects to better understand their quality and evolution. We (a) study the build technology choices that Android developers make (Gradle being recommended and the most popular choice), (b) explore the sustainability of the official Gradle build system (parts of build files are updated more frequent that others and the update of the special Gradle plugin would induce unrecommended configurations), and (c) analyze the quality of Gradle scripts for Android apps—more than a half of the open‐source Android apps cannot be successfully built due to five common root causes.
Retrograde cricopharyngeal dysfunction (R‐CPD): What do we know so far?
Authors: Alotaibi Fahad Z.
Published: August 2023

Objective

This comprehensive review aims to explain the disease pathophysiology, clinical presentation, and management options.

Methods

A review was carried out in the following databases: Medline, Scopus, Web of Science, and Cochrane. The following terms were used alone and combined: Retrograde, Cricopharyngeus muscle, Dysfunction, Abelchia, and inability to burp.

Results

A total of 68 articles were identified, and only 11 were found to be relevant and included in writing this review. Retrograde cricopharyngeal dysfunction (R‐CPD) is a relatively new disease entity that has recently been described in clinical literature. It is caused by the inability of the cricopharyngeus muscle to relax. Unlike cricopharyngeal dysfunction (CPD), which is well‐known and characterized by dysphagia, R‐CPD is characterized by the inability to belch in almost all patients, which is considered diagnostic for the condition.

Conclusions

High‐resolution manometry (HRM) is the definitive diagnostic modality. Most patients reported in the literature responded well to treatment with botulinum toxin injection.
Information Security Behaviour in an Organisation Providing Critical Infrastructure: A Pre-post Study of Efforts to Improve Information Security Culture
Authors: Nævestad T.-O. , Honerud J. Hovland , Meyer S. Frislid
Published: August 2023

The study examines whether information security behaviour (ISB) in an organisation providing critical infrastructure improved after systematic efforts to improve information security culture (ISC) through the implementation of an information security management system (ISMS). The data are based on quantitative surveys before (N = 323) and after (N = 446) efforts to improve ISC in the organisation. Qualitative interviews were also conducted before (N = 22) and after (N = 12). The study finds that the organisation has managed to improve its ISC through systematic efforts over a two-year period (2014–2016), and that this also has led to improvements in ISB among the personnel in the organisation. Multivariate regression analyses indicate that ISC is the most important variable influencing ISB, while ISMS measures is the most important variables influencing ISC. Thus, our results indicate that it is important to work with ISMS and ISC to increase IS in our increasingly digitalised society, especially in organisations providing critical infrastructure.
AI at Work, Working with AI. First Lessons from Real Use Cases
Authors: Ferguson Yann
Published: August 2023

This chapter deals with the transformations of employment and work associated with recent developments in artificial intelligence. It proposes a classification based on five figures of the worker: replaced, dominated, augmented, divided and rehumanised. This taxonomy is illustrated by use cases from the catalogue of the Global Partnership on AI, a multistakeholder initiative which aims to bridge the gap between theory and practice on AI. We conclude by highlighting three shifts in the forms of work engagement that are likely to impact safety issues: the distancing of the object of work, the work on the machine itself and the reconfiguration of professional identity.
The Digitalisation of Risk Assessment: Fulfilling the Promises of Prediction?
Authors: Demortain David
Published: August 2023

Risk assessment is a scientific exercise that aims at anticipating hazards. Prediction has always been a rallying call for the scientists that gave birth to this interdisciplinary movement in the 1970s. Several decades later, the broad movement of digitalisation and the promises of artificial intelligence seem to be pushing the limits of risk assessment and herald an era of faster and more precise predictions. This chapter briefly reviews the history of chemical risk assessment methods developed by regulatory bodies and associated research groups, and the complex ways it has digitalised. It unpacks digitalisation, to probe how its various aspects—datafication, computational innovation and modelling theories—align to meaningfully transform it, and determine whether the ever-revamped technological promise of prediction is within a closer reach than it was before.
Key Dimensions of Algorithmic Management, Machine Learning and Big Data in Differing Large Sociotechnical Systems, with Implications for Systemwide Safety Management
Authors: Roe Emery , Fortmann-Roe Scott
Published: August 2023

The time is ripe for more case-by-case analyses of “big data”, “machine learning” and “algorithmic management”. A significant portion of current discussion on these topics occurs under the rubric of Automation (or, artificial intelligence) and in terms of broad political, social and economic factors said to be at work. We instead focus on identifying sociotechnical concerns arising out of software development in the topic areas. In so doing, we identify trade-offs and at least one longer-term system safety concern not typically included alongside notable political, social and economic considerations. This is the system safety concern of obsolescence. We end with a speculation on how skills in making these trade-offs might be noteworthy when system safety has been breached in emergencies.
Considering Severity of Safety-Critical System Outcomes in Risk Analysis: An Extension of Fault Tree Analysis
Authors: Kaber David B. , Liu Yunmei , Lau Mei
Published: August 2023

With the advent of digitalisation and big data sources, new advanced tools are needed to precisely project safety-critical system outcomes. Existing systems safety analysis methods, such as fault tree analysis (FTA), lack systematic and structured approaches to specifically account for system event consequences. Consequently, we proposed an algorithmic extension of FTA for the purposes of: (a) analysis of the severity of consequences of both top and intermediate events as part of a fault tree (FT) and (b) risk assessment at both the event and cut set level. The ultimate objective of the algorithm is to provide a fine-grained analysis of FT event and cut set risks as a basis for precise and cost-effective safety control measure prescription by practitioners.
Are We Going Towards “No-Brainer” Safety Management?
Authors: Paltrinieri Nicola
Published: August 2023

Industry is stepping into its 4.0 phase by implementing and increasingly relying on cyber-technological systems. Wider networks of sensors may allow for continuous monitoring of industrial process conditions. Enhanced computational power provides the capability of processing the collected “big data”. Early warnings can then be picked and lead to suggestion for proactive safety strategies or directly initiate the action of autonomous actuators ensuring the required level of system safety. But have we reached these safety 4.0 promises yet, or will we ever reach them? A traditional view on safety defines it as the absence of accidents and incidents. A forward-looking perspective on safety affirms that it involves ensuring that “as many things as possible go right”. However, in both the views there is an element of uncertainty associated to the prediction of future risks and, more subtly, to the capability of possessing all the necessary information for such prediction. This uncertainty does not simply disappear once we apply advanced artificial intelligence (AI) techniques to the infinite series of possible accident scenarios, but it can be found behind modelling choices and parameters setting. In a nutshell, any model claiming superior flexibility usually introduces extra assumptions (“there ain’t no such thing as a free lunch”). This contribution will illustrate a series of examples where AI techniques are used to continuously update the evaluation of the safety level in an industrial system. This will allow us to affirm that we are not even close to a “no-brainer” condition in which the responsibility for human and system safety is entirely moved to the machine. However, this shows that such advanced techniques are progressively providing a reliable support for critical decision making and guiding industry towards more risk-informed and safety-responsible planning.
Looking at the Safety of AI from a Systems Perspective: Two Healthcare Examples
Authors: Sujan Mark A.
Published: August 2023

There is much potential and promise for the use of artificial intelligence (AI) in healthcare, e.g., in radiology, mental health, ambulance service triage, sepsis diagnosis and prognosis, patient-facing chatbots, and drug and vaccine development. However, the aspiration of improving the safety and efficiency of health systems by using AI is weakened by a narrow technology focus and by a lack of independent real-world evaluation. It is to be expected that when AI is integrated into health systems, challenges to safety will emerge, some old, and some novel. Examples include design for situation awareness, consideration of workload, automation bias, explanation and trust, support for human–AI teaming, training requirements and the impact on relationships between staff and patients. The use of healthcare AI also raises significant ethical challenges. To address these issues, a systems approach is needed for the design of AI from the outset. Two examples are presented to illustrate these issues: 1. Design of an autonomous infusion pump and 2. Implementation of AI in an ambulance service call centre to detect out-of-hospital cardiac arrest.
Kapitel 1: Einleitung
Authors: Wiedemann Klaus
Published: August 2023

Die vorliegende Arbeit untersucht, wie datenbasiertes Profiling und automatisierte Entscheidungen funktionieren, funktional miteinander zusammenhängen und reguliert sind (Teil I). Im Anschluss analysiert sie, welche Möglichkeiten der Nutzung von Profiling bestehen, um im Online-Handel Preise zu personalisieren (Teil II). Aufbauend auf den so gefundenen Erkenntnissen behandelt die Arbeit schließlich die Frage, ob das geltende materielle Recht ausreichende Schutzmechanismen vor Diskriminierung bereithält, die aus der Zugehörigkeit zu geschützten Gruppen resultiert und in ihrer systematischen preislichen Schlechterstellung zum Ausdruck kommt (Teil III). Die Arbeit ist modular aufgebaut. Der erste Teil erarbeitet eine Grundlage für die weiteren Untersuchungen. Der zweite und dritte Teil bauen auf dem jeweils vorhergehenden auf. Preispersonalisierung stellt nur einen von zahlreichen denkbaren Anwendungsfällen der im ersten Teil entwickelten Grundlagen dar. Bei der Analyse des bestehenden Diskriminierungsschutzes handelt es sich, daran anknüpfend, um die Behandlung einer speziellen rechtlichen Fragestellung.
Kapitel 10: Relevante Rechtsregime
Authors: Wiedemann Klaus
Published: August 2023

Der folgende Überblick dient dazu, die (möglicherweise) einschlägigen Regelwerke zu eruieren und festzustellen, ob ihnen grundsätzliche Relevanz und Anwendbarkeit im Kontext von Preispersonalisierung zukommt. Im darauf folgenden Kap. 11 erfolgt die eigentliche rechtliche Analyse unter Rückgriff auf das 3-stufige Modell.
Kapitel 11: Rechtliche Analyse anhand des 3-stufigen Modells
Authors: Wiedemann Klaus
Published: August 2023

Im Kontext der Datenschutz-Grundverordnung stellt sich zunächst die Frage, in welchen Konstellationen Preispersonalisierung mit der Verarbeitung personenbezogener Daten i. S. d. Art. 4 Nr. 1 DSGVO einhergeht. Nur dann ist sie anwendbar, Art. 2 I DSGVO. Sofern personenbezogene Daten verarbeitet werden, muss gem. Art. 6 I bzw. 9 II DSGVO eine geeignete Rechtsgrundlage vorliegen. Zudem steht zu untersuchen, welche datenschutzrechtlichen Transparenzpflichten der Anbieter zu befolgen hat und wie weitreichend diese im Fall des Personalised Pricings sind. In Frage kommen Informationspflichten (Art. 13 und 14 DSGVO) sowie das Auskunftsrecht des Art. 15 DSGVO.
Kapitel 12: Abschließende Bemerkungen
Authors: Wiedemann Klaus
Published: August 2023

Profiling nach dem Verständnis der Datenschutz-Grundverordnung ist ein technisches Erkenntnisverfahren, das auf dem Prinzip der Gruppenbildung basiert. Diesem Verfahren wohnen signifikante persönlichkeitsrechtliche Implikationen inne, erlaubt es doch die Schaffung „neuer“ personenbezogener Daten, die dem Betroffenen zugewiesen werden und teilweise tiefgehende Einblicke in seine persönlichen Aspekte erlauben. Für die rechtliche Bewertung ist die Erkenntnis bedeutsam, dass Profiling letztlich nichts anderes ist als eine Wahrscheinlichkeitsberechnung. Im Einzelfall falsche Ergebnisse – sog. false positives bzw. false negatives – sind diesem Verfahren deshalb systemimmanent. Dies unterstreicht die Notwendigkeit der gedanklichen Trennung von Profiling und darauf basierenden Entscheidungen sowie die Berechtigung der Regulierung automatisierter Einzelentscheidungen in Art. 22 DSGVO.
Kapitel 3: Profiling und automatisierte Entscheidungen: Ein 3-stufiges Modell
Authors: Wiedemann Klaus
Published: August 2023

Die beschriebenen kritischen Aspekte von Profiling wurden ausgehend von der Legaldefinition des Art. 4 Nr. 4 DSGVO und dem Einsatz von Profiling in der Praxis entwickelt. Bei der Beschreibung der mit Profiling zusammenhängenden tatsächlichen Problemlagen tritt eine wesentliche Erkenntnis zutage. Es bietet sich an, eine Unterscheidung in qualitativer sowie chronologischer Hinsicht zu treffen zwischen Profiling einerseits, also der „bloßen“ Erstellung von Bewertungen, und dem darauf aufbauenden Prozess der Entscheidungsfindung (ggf. mitsamt der Ausführung dieser Entscheidung) andererseits. Denn „Profiling – als automatisierte Datenverarbeitung – bildet die Grundlage, auf der eine Entscheidung des Verantwortlichen aufsetzt, die für die betroffene Person dann eine rechtliche Wirkung oder sonstige Konsequenz mit sich bringt.“ Diese beiden Stufen können erst durchgeführt werden, wenn eine ausreichende Datengrundlage vorliegt. Die Datensammlung muss also logischerweise den ersten Schritt in diesem Modell darstellen.
Kapitel 5: Zusammenfassung
Authors: Wiedemann Klaus
Published: August 2023

Profiling i. S. d. Art. 4 Nr. 4 DSGVO stellt ein statistisches Erkenntnisverfahren dar, welches sich der Verarbeitung personenbezogener Daten bedient. Es dient dazu, die persönlichen Aspekte natürlicher Personen wertend zu analysieren bzw. vorherzusagen. Diese Bewertungen können in einer Vielzahl von Lebensbereichen und mit ganz verschiedenen Zielrichtungen zum Einsatz kommen. Ihr potenzieller Anwendungsbereich ist damit äußerst breit. Als typische Beispiele lassen sich Kredit-Scoring und personalisierte Werbung nennen.
Kapitel 6: Preisdiskriminierung
Authors: Wiedemann Klaus
Published: August 2023

Der Begriff Preisdiskriminierung wird in den Wirtschaftswissenschaften unterschiedlich definiert. Als Annäherung an die Thematik wird hier zunächst eine vereinfachte Definition herangezogen. Diese besagt, dass Preisdiskriminierung vorliegt, wenn ein Anbieter zum selben Zeitpunkt für das gleiche Gut von verschiedenen Käufern verschiedene Preise verlangt. Diese Formulierung ist aber aus verschiedenen Gründen irreführend und ungenau. So wäre nach dieser Definition Preisdiskriminierung z. B. auch dann gegeben, wenn ein Anbieter nur deshalb von Kunden unterschiedliche Preise verlangt, weil er tatsächlich unterschiedliche Kosten hat. Ein Beispiel hierfür wäre der Fall, dass ein Anbieter aufgrund höherer Versandkosten vom Kunden A einen höheren Gesamtpreis als vom Kunden B verlangt, da A – im Gegensatz zu B – im Ausland lebt und dementsprechend höhere Portokosten anfallen. Zugleich würden Situationen von dieser Definition mangels „verschiedener Preise“ nicht erfasst, in denen alle Betroffenen denselben Preis zahlen, dieser de facto aber diskriminierend ist, weil beim Anbieter verschiedene Kosten anfallen. Dies ist in der Praxis zum Beispiel der Fall, wenn Industriegüter, deren Versand besonders kostenintensiv ist (etwa Zement), an Kunden unabhängig vom Lieferort zum gleichen Preis verkauft werden und die Versandkosten immer im Endpreis enthalten sind. Hierdurch werden die Kunden, bei denen besonders hohe Transportkosten anfallen, gegenüber den günstiger zu erreichenden bevorzugt.
Kapitel 7: Preispersonalisierung
Authors: Wiedemann Klaus
Published: August 2023

Der vorhergegangene Abschnitt hat eine allgemeine Definition des Begriffs Preisdiskriminierung entwickelt, welche auf der Definition von Stigler aufbaut und diese konkretisiert. Zudem wurden die in der ökonomischen Literatur beschriebenen allgemeinen Voraussetzungen für die erfolgreiche Umsetzung von Preisdiskriminierung sowie die drei traditionell unterschiedenen Grade beschrieben, voneinander abgegrenzt und mit Blick auf ihre datenschutzrechtliche Relevanz analysiert.
Kapitel 9: Einleitung
Authors: Wiedemann Klaus
Published: August 2023

Preispersonalisierung ist ein Unterfall von Preisdiskriminierung. Sie hat der Natur der Sache nach stets ökonomische Auswirkungen, da von ihr Zahlungsströme zwischen den Kunden und den Anbietern und damit die Verteilung von finanziellen Ressourcen und Wohlstand abhängen. Die ökonomische Betrachtungsweise ist neutral und wertfrei: Sie stellt auf Faktoren wie Effizienz und Wohlfahrt ab, ohne die unterschiedliche Behandlung Einzelner mit einer darüber hinausgehenden Wertung zu verbinden.
Signals of millicharged dark matter in light-shining-through-wall experiments
Authors: Berlin Asher , D’Agnolo Raffaele Tito , Ellis Sebastian A. R. , Radkovski Jury I.
Published: August 2023

Abstract

We discuss a novel detection technique for millicharged dark matter that makes use of existing light-shining-through-wall (LSW) experiments searching for massive dark photons. Since millicharged particles interact with both the visible and dark sectors, a small background of such particles enables the search for visible signals even in the limit of a massless dark photon. Furthermore, for sufficiently large couplings, a small dark matter subcomponent consisting of millicharged particles can have a terrestrial abundance that is significantly enhanced with respect to its galactic abundance. We leverage this fact to show that in certain parts of parameter space, future runs of the LSW Dark SRF experiment can be used to set the strongest limits on millicharged relics.
Patient-Reported Outcome Measures zur Erfassung der gesundheitsbezogenen Lebensqualität bei Patienten mit Stimm- und Schluckstörungen
Authors: Bohlender Jörg E.
Published: August 2023

Standardisierte und validierte Patientenbefragungen in Form von Fragebögen haben in der HNO-Heilkunde eine zunehmende Bedeutung. Die subjektive Bewertung von Symptomen und funktionellen Einschränkungen, aber auch der gesundheitsbezogenen Lebensqualität lassen sich mit sog. Patient-Reported Outcome Measures (PROM) erfragen. Diese Erhebungsinstrumente können neben der Anamnese und den objektiven Befunden als weitere wichtige Quelle zur Qualitätssicherung einer patientenzentrierten Versorgung genutzt werden. Im deutschsprachigen Raum gibt es mittlerweile einige PROM, die gezielt die Patientenperspektive bei Stimm- und Schluckstörungen erfragen. Bei Stimmpatienten werden v. a. die folgenden Fragebögen auf Basis des Voice Handicap Index (VHI), die auch international eingesetzt werden, angewandt: VHI-30, VHI-12i, VHI-9i. Im Bereich der oropharyngealen Dysphagie werden derzeit überwiegend die deutschen Versionen des Eating Assessment Tool-10 (EAT-10), des Sydney Swallow Questionnaire, SSQ (SSQ-G), des Swallowing Quality-of-Life Questionnaire (SWAL-QoL) und des MD Anderson Dysphagia Inventory (MDADI) eingesetzt.
Associations of continuum beliefs with personality disorder stigma: correlational and experimental evidence
Authors: Stricker Johannes , Jakob Louisa , Pietrowsky Reinhard
Published: August 2023

Purpose

A pervasive and deeply entrenched stigma of personality disorders exists. For other mental disorders, a large body of research suggests that continuum beliefs (i.e., the endorsement of continuum perspectives on mental health and psychopathology) stimulate more favorable attitudes toward affected persons. Additionally, mental disorder classification systems increasingly incorporate continuous personality disorder models. Yet, it is unclear how continuum beliefs are related to personality disorder stigma. This study evaluated the link of continuum beliefs with personality disorder stigma based on correlational and experimental data.

Methods

A large general population sample (N = 848) completed self-report measures of continuum beliefs regarding personality disorders, desired social distance, and prejudice toward persons with personality disorders. Additionally, participants were randomly presented with information supporting a continuous or a dichotomous view of personality disorders.

Results

Continuum beliefs were associated with lower desired social distance (r = − 0.19) and prejudice (r = − 0.22). Additionally, the brief continuum intervention was associated with increased continuum beliefs (d = 0.99) and decreased desired social distance (d = − 0.14) and prejudice (d = − 0.17). Finally, the intervention effects on desired social distance and prejudice were mediated by continuum beliefs.

Conclusion

This study suggests that highlighting continuum views on personality disorders in public communication and interventions might reduce personality disorder stigma.
Electrostatic levitations of anisotropic dielectric oblate and prolate spheroids
Authors: Spałek Dariusz
Published: August 2023

The paper presents analytical approach to electrostatic field for dielectric spheroids problem. For both oblate and prolate spheroids fields distributions are derived. The variable separation method is applied. Electrostatic force is evaluated with the help of the Maxwell stress tensor generalized method, material force density, coenergy and equivalent dipole. Levitation forces for both oblate and prolate dielectric spheroids versus axis permittivities and spheroids height are presented.
Helicobacter pylori in the post-antibiotics era: from virulence factors to new drug targets and therapeutic agents
Authors: Al-Fakhrany Omnia Momtaz , Elekhnawy Engy
Published: August 2023

Helicobacter pylori is considered one of the most prevalent human pathogenic microbes globally. It is the main cause of a number of gastrointestinal ailments, including peptic and duodenal ulcers, and gastric tumors with high mortality rates. Thus, eradication of H. pylori is necessary to prevent gastric cancer. Still, the rise in antibiotic resistance is the most important challenge for eradication strategies. Better consideration of H. pylori virulence factors, pathogenesis, and resistance is required for better eradication rates and, thus, prevention of gastrointestinal malignancy. This article is aimed to show the role of virulence factors of H. pylori. Some are involved in its survival in the harsh environment of the human gastric lumen, and others are related to pathogenesis and the infection process. Furthermore, this work has highlighted the recent advancement in H. pylori treatment, as well as antibiotic resistance as a main challenge in H. pylori eradication. Also, we tried to provide an updated summary of the evolving H. pylori control strategies and the potential alternative drugs to fight this lethal resistant pathogen. Recent studies have focused on evaluating the efficacy of alternative regimens (such as sequential, hybrid, concomitant treatment, vonoprazan (VPZ)-based triple therapy, high-dose PPI-amoxicillin dual therapy, probiotics augmented triple therapy, or in combination with BQT) in the effective eradication of H. pylori. Thus, innovating new anti-H. pylori drugs and establishing H. pylori databanks are upcoming necessities in the near future.
Modulating Nrf-2/HO-1, apoptosis and oxidative stress signaling pathways by gabapentin ameliorates sepsis-induced acute kidney injury
Authors: Abdelnaser Mahmoud , Alaaeldin Rania , Attya Mina Ezzat , Fathy Moustafa
Published: August 2023

Purpose

Globally, sepsis, which is a major health issue resulting from severe infection-induced inflammation, is the fifth biggest cause of death. This research aimed to evaluate, for the first time, the molecular effects of gabapentin's possible nephroprotective potential on septic rats by cecal ligation and puncture (CLP).

Methods

Sepsis was produced by CLP in male Wistar rats. Evaluations of histopathology and renal function were conducted. MDA, SOD, GSH, TNF-α, IL-1β, and IL-6 levels were measured. qRT-PCR was utilized to determine the expression of Bax, Bcl-2, and NF-kB genes. The expression of Nrf-2 and HO-1 proteins was examined by western blotting.

Results

CLP caused acute renal damage, elevated the blood levels of creatinine, BUN, TNF-α, IL-1β, and IL-6, reduced the expression of Nrf-2 and HO-1 proteins and the Bcl-2 gene expression, and upregulated NF-kB and Bax genes. Nevertheless, gabapentin dramatically diminished the degree of the biochemical, molecular, and histopathological alterations generated by CLP. Gabapentin reduced the levels of proinflammatory mediators and MDA, improved renal content of GSH and SOD, raised the expression of Nrf-2 and HO-1 proteins and Bcl-2 gene, and reduced the renal expression of NF-kB and Bax genes.

Conclusion

Gabapentin mitigated the CLP-induced sepsis-related acute kidney injury through up-regulating Nrf-2/HO-1 pathway, repressing apoptosis, and attenuating the oxidative stress status by reducing the levels of the proinflammatory mediators and enhancing the antioxidant status.
Study on the mechanism of puerarin against osteoarthritis from ferroptosis based on network pharmacology and bioinformatics
Authors: Deng Wenxiang , Zhang Wenan , He Qinghu
Published: August 2023

Network pharmacology and bioinformatics were used to study puerarin’s molecular mechanism in treating osteoarthritis from the perspective of ferroptosis, revealing a new treatment target. Ferroptosis-related targets were obtained from FerrDb. Puerarin action targets were retrieved from TCMSP, Pharmmappe, SwissTargetPrediction, and Targetnet databases, and supplemented with PubMed. The gene expression profiles of GSE12021, GSE55235, and GSE82107 were obtained using “Osteoarthritis” as the search term in the GEO database, and the differential expression gene screening analysis was performed for osteoarthritis. The intersection targets between puerarin, iron death, and osteoarthritis were obtained using Venn diagrams. GO and KEGG analyses were conducted with R software. Molecular docking and visualization of puerarin and core targets were performed using Autodock Vina and PyMol software. The effects of puerarin on the cell viability and the TNFα, IL6, and Ilβ levels of human inflammation articular chondrocytes were tested in vitro experiments. Puerarin, ferroptosis, and osteoarthritis share four targets: PLIN2, PTGS2, VEGFA, and IL6. GO enrichment analysis showed that puerarin maintained the blood-brain barrier, regulated peptide serine phosphorylation, and had anti-inflammatory effects. KEGG analysis showed that puerarin’s anti-inflammatory effects were mainly through VEGF, IL-17, C-type lectin receptor, HIF-1, TNF, and other signaling pathways. Puerarin closely bound PLIN2, PTGS2, VEGFA, and IL6 targets in molecular docking. In vitro, puerarin prevented osteoarthritis. Network pharmacology and bioinformatics explained puerarin’s multi-target and multi-pathway treatment of OA, which may be related to ferroptosis, and confirmed its anti-inflammatory effect.
Structure and enzymatic characterization of CelD endoglucanase from the anaerobic fungus Piromyces finnis
Authors: Dementiev Alexey , Lillington Stephen P. , Jin Shiyan , Kim Youngchang , Jedrzejczak Robert , Michalska Karolina , Joachimiak Andrzej , O’Malley Michelle A.
Published: August 2023

Anaerobic fungi found in the guts of large herbivores are prolific biomass degraders whose genomes harbor a wealth of carbohydrate-active enzymes (CAZymes), of which only a handful are structurally or biochemically characterized. Here, we report the structure and kinetic rate parameters for a glycoside hydrolase (GH) family 5 subfamily 4 enzyme (CelD) from Piromyces finnis, a modular, cellulosome-incorporated endoglucanase that possesses three GH5 domains followed by two C-terminal fungal dockerin domains (double dockerin). We present the crystal structures of an apo wild-type CelD GH5 catalytic domain and its inactive E154A mutant in complex with cellotriose at 2.5 and 1.8 Å resolution, respectively, finding the CelD GH5 catalytic domain adopts the (β/α)8-barrel fold common to many GH5 enzymes. Structural superimposition of the apo wild-type structure with the E154A mutant-cellotriose complex supports a catalytic mechanism in which the E154 carboxylate side chain acts as an acid/base and E278 acts as a complementary nucleophile. Further analysis of the cellotriose binding pocket highlights a binding groove lined with conserved aromatic amino acids that when docked with larger cellulose oligomers is capable of binding seven glucose units and accommodating branched glucan substrates. Activity analyses confirm P. finnis CelD can hydrolyze mixed linkage glucan and xyloglucan, as well as carboxymethylcellulose (CMC). Measured kinetic parameters show the P. finnis CelD GH5 catalytic domain has CMC endoglucanase activity comparable to other fungal endoglucanases with kcat = 6.0 ± 0.6 s−1 and Km = 7.6 ± 2.1 g/L CMC. Enzyme kinetics were unperturbed by the addition or removal of the native C-terminal dockerin domains as well as the addition of a non-native N-terminal dockerin, suggesting strict modularity among the domains of CelD.

Key points

• Anaerobic fungi host a wealth of industrially useful enzymes but are understudied.

• P. finnis CelD has endoglucanase activity and structure common to GH5_4 enzymes.

• CelD’s kinetics do not change with domain fusion, exhibiting high modularity.