bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammation remains a dynamic component of portal hypertension in regressive alcohol‐related cirrhosis
Authors: Hofer Benedikt Silvester , Simbrunner Benedikt , Königshofer Philipp , Brusilovskaya Ksenia , Petrenko Oleksandr , Taru Vlad , Sorz‐Nechay Thomas , Zinober Kerstin , Regnat Katharina , Semmler Georg , Lackner Carolin , Trauner Michael , Mandorfer Mattias , Schwabl Philipp , Reiberger Thomas
Published: December 2024

Background

Portal hypertension (PH) resulting from static and dynamic intrahepatic changes drives liver‐related complications even after removing the underlying aetiological factor.

Objective

We investigated the impact of inflammation on the dynamic component of PH during disease regression in animal models of toxin‐induced cirrhosis and patients with alcohol‐related cirrhosis.

Methods

In mice, cirrhosis was induced via toxin application for 12 weeks followed by toxin‐withdrawal allowing for one or 2 weeks of regression. Furthermore, 128 patients with alcohol‐related cirrhosis and alcohol abstinence undergoing same‐day hepatic venous pressure gradient (HVPG) and liver stiffness measurement (LSM) were included. The influence of inflammation on the dynamic PH component was assessed using linear models. Specifically, we explored proinflammatory changes in mice/patients in whom the measured portal pressure (PP)/HVPG was significantly higher than the PP/HVPG expected from the static PH component (histological collagen proportionate area [CPA; %] in mice, LSM in patients).

Results

In mice, toxin discontinuation induced a significant decrease in PP, CPA, histological hepatic inflammation and hepatic expression of proinflammatory genes (Tnfa, Il6, Cxcl1, Mcp1; all p < 0.05 for one/2 week regression vs. peak disease). Similarly, prolonged abstinence in alcohol‐related cirrhosis was linked to lower HVPG/LSM and longer abstinence was correlated to lower C‐reactive protein (CRP), IL‐6, immunoglobulin A (IgA) and IgG levels (all p < 0.05). Nevertheless, the persistence of a low‐grade proinflammatory state during regression was linked to a higher PP/HVPG than expected from static PH components. In regressive mice, higher hepatic proinflammatory gene expression (Tnfa, Il6, Il1b; all p < 0.05) was linked to higher‐than‐expected PP. Similarly, higher CRP, IL‐6, IgA and IgG and lower complement factor C3c (all p < 0.05) were associated with higher‐than‐expected HVPG in abstinent patients with alcohol‐related cirrhosis.

Conclusions

Although removing the underlying aetiological factor resulted in significant improvements, a persistent hepatic proinflammatory environment remained a key driver of the dynamic PH component in regressive liver disease.

Clinical trial number

NCT03267615.
Impact of Lysine to Methionine Ratios on Antioxidant Capacity and Immune Function in the Rumen of Tibetan Sheep: An RNA‐Seq Analysis
Authors: Zhang Fengshuo , Su Quyangangmao , Gao Zhanhong , Wu Zhenling , Ji Qiurong , He Tingli , Zhu Kaina , Chen Xuan , Zhang Yu , Hou Shengzhen , Gui Linsheng
Published: December 2024

With global protein prices on the rise, lowering protein levels in animal feed, together with balancing diet composition and reducing nitrogen emissions, can both reduce the environmental impact of agriculture and save on feed costs. However, the formulation of an ideal amino acid (AA) composition is crucial for better protein utilization by livestock. This study aimed to investigate the effects of different lysine to methionine ratios on the antioxidant capacity and immune function of the rumen in Tibetan sheep. Ninety male Tibetan sheep, weaned at 2 months of age, were randomly divided into three groups (1:1, 2:1 and 3:1 lysine ratios) and subjected to a 100‐day feeding trial. RNA sequencing (RNA‐seq) was utilized to analyse the impact of different AA ratios on gene expression in rumen tissue, whereas the levels of antioxidant enzymes (total antioxidant capacity [T‐AOC], superoxide dismutase [SOD], glutathione peroxidase [GSH‐Px] and catalase [CAT]) and immunoglobulins (immunoglobulin A [IgA], immunoglobulin G [IgG] and immunoglobulin M [IgM]) were evaluated. The results indicated that the 1:1 group significantly upregulated the expression of PTGS2, PLA2G12A and PLA2G4 genes, enhancing antioxidant enzyme activity, reducing free radical production and modulating systemic immune responses. COL16A1 and KCNK5 were highly expressed in the protein digestion and absorption pathway, maintaining the structural integrity and function of the rumen epithelium. BMP4 and TGFBR2 were significantly enriched in the cytokine–cytokine receptor interaction pathway and positively correlated with CAT and T‐AOC. ITGA8 was upregulated in the 1:1 group, participating in the regulation of various cellular signalling pathways. ATP2B1 was enriched in the cyclic guanosine monophosphate (cGMP)– protein kinase G (PKG) signalling and mineral absorption pathways, primarily influencing oxidative stress and immune responses by regulating intracellular calcium ion concentration. This study demonstrates that a 1:1 lysine to methionine ratio is most beneficial for enhancing the antioxidant capacity and immune function of the rumen in Tibetan sheep.
Introducing Energy Citizenship
Authors: Fahy Frances , Vadovics Edina , Pel Bonno
Published: December 2024

The first chapter introduces the concept of energy citizenship and the innovative approach this book has adopted to investigate it, as well as provides a road map for the remaining chapters. Specifically, the chapter discusses the origins of the concept of energy citizenship and the many forms in which it exists. It then briefly introduces the EnergyPROSPECTS project, the driver behind the production of this collection. This introductory chapter explains how each of the core chapters, drawing on eight national contexts, highlights the geographical differences, the contextual challenges, and the socio-political histories out of which energy citizenship develops.
Energy Citizenship in Hungary: Diversity, Actors, Focus and System-Contestation
Authors: Vadovics Edina , Szőllőssy Anita
Published: December 2024

Researchers often find that the systemic conditions for supporting active energy citizenship are lacking in many respects in Hungary. Nevertheless, despite this unfavourable context, there are numerous and diverse examples of energy citizenship in the country, 56 of which have been mapped and studied in the framework of the EnergyPROSPECTS project. In this chapter, we provide an overview of these cases, focusing on the following four aspects. First, we take a closer look at the actors initiating and involved in the cases at the time of our process of data collection (2021–2022), followed by an analysis of the focus and objectives of the cases. Then, we examine to what extent the cases mapped in Hungary are progressive, i.e. whether they can be considered frontrunners in their own national context and a European context. Finally, we look at the system-contesting capacity of the cases from the point of view of their participation in creating a more just, equitable and environmentally sustainable energy system.
Energy Citizenship in Ireland: Beyond Individual Private Agency
Authors: Schmid Benjamin , Fahy Frances
Published: December 2024

This chapter uses several case studies to illustrate how energy citizenship has developed in Ireland since the Irish government first explicitly used the term “energy citizenship” in its 2015 “White Paper on Ireland’s Transition to a Low Carbon Energy Future 2015–2030”. In particular, the chapter demonstrates that citizen participation has extended beyond direct individual engagement in the energy system. Energy communities, as a collective form of energy citizenship, have become an important element of the Irish energy transition landscape and governance. Furthermore, mechanisms have emerged through which citizens have increasingly been able to participate directly in the shaping of energy policy. Interestingly, these forms of energy citizenship do not appear to be independent but rather interrelated and mutually influential. Overall, the findings on diversity of energy citizenship in Ireland in this chapter highlight the importance of understanding energy citizenship beyond individual private agency.
Advancing Energy Citizenship: Hindering and Supporting Factors in Latvia’s Energy Transition
Authors: Lagzdiņa Ērika , Brizga Jānis , Kudreņickis Ivars , Ikstena Rasa , Ernšteins Raimonds
Published: December 2024

This chapter explores the hindering and supporting factors in the development of energy citizenship in Latvia. This contribution identifies key threats arising from the complex economic landscape shaped by geopolitical dynamics and escalating energy costs, as well as the level of political commitment in the field of climate policy and renewable energy. The chapter identifies a lack of confidence in public institutions and collective efforts as one of the critical obstacles to broader engagement with energy citizenship initiatives. The chapter also highlights several factors that contribute to the development of a framework energy citizenship. These include robust financing and investment prospects in this field, initiated by the EU and national level support schemes; the pivotal role of decarbonisation technologies and renewable energy sources, particularly household solar installations as well as Latvia's natural resources, encompassing residual forestry materials and solid biomass. National policy recommendations are included to conclude this chapter. Overall, this contribution broadens the understandings of energy citizenship development in Latvia, paving the way for future potential policy decisions and strategic interventions.
Building Trust Through Energy Citizenship? The Developing Landscape of Energy Citizenship in France
Authors: Thalberg Karin , Defard Camille
Published: December 2024

In 2020, France was the only European Union Member State unable to meet its renewable energy targets. At the same time, the country strives to be a leader in the climate and energy transition and has recently launched an ecological planning strategy to accelerate its pace. In a highly centralised energy and political system, characterised by a stark polarisation between renewables and nuclear energy, what route will the energy transition take, and which roles do citizens, local authorities, civil society, and other stakeholders play now and in the future? This chapter sketches the current French landscape for energy citizenship, understood as citizen engagement and involvement in the energy production, consumption, and governance. Through three case studies across France, it portrays burgeoning engagement and cooperation among local and regional authorities, citizen-led energy initiatives, and the private sector. Notably, these advancements occur within a societal context where trust in the national government is low. For France to realise its aspiration of leading in the energy transition, building trust and bolstering collective mobilisation towards a shared vision of a carbon-neutral future appear crucial. Could energy citizenship be the way forward?
Imperative of Paradata
Authors: Huvila Isto
Published: December 2024

Heritage visualisation has been one of the pioneers in acknowledging the imperative of paradata i.e. that of documenting not only the outputs of knowledge making but also the practices and processes, including decisions and intellectual work underpinning of how they came into being. However, even if the need and technical means to represent such information exist, the practical understanding of how to capture such information remain underdeveloped. The aim of this chapter is to delve into the imperative of paradata as a theoretical and practical challenge and to outline how to get grips with it: what is possible and how, and what is probably unachievable and why. A model of a process for identifying and acquiring usable paradata is outlined and major pitfalls of paradata generation, relating to non-actionable standards and exceeding data cleaning are discussed.
A Metadata/Paradata Design Framework for Historic BIM
Authors: Murphy Maurice , Krajacic Petra , Meegan Eimear , Reilly Rebecca O. , Keenaghan Garrett , Chenaux Alain , Dionizio Rafael Fernandes , DezenKempter Eloisa
Published: December 2024

In this paper a systematic examination of metadata/paradata is presented to support the creation and reuse of digital heritage data as a means of engaging in some way with the experience of past material cultural discourse. The contextual and procedural information generated throughout Historic Building Information Modelling (HBIM) workflows are presented through a series of case studies. The three phases of data capture, modelling and knowledge dissemination for HBIM workflows are reflected in the presented case studies. The first case study illustrate how metadata is recorded automatically by the terrestrial and aerial laser scanning instruments and software, whereas it is necessary to document paradata. Case study 2, shows how shape grammar libraries of architectural elements and procedural modelling both contained metadata within the HBIM software platforms. Again, there is a need to document the paradata using both graphic and text format, proving the need for standards and guidelines for HBIM. Finally, additional software platforms were reviewed to ensure survival of metadata (geometry, geolocation and other semantic attributes) when the virtual model is disseminated outside of HBIM in this case using Heritage GIS. The HBIM design framework is presented as a set of Data Cards, a standardised documentation to record key information about datasets, allowing for enhanced reuse of the data recorded in such a way as to contribute more meaningfully to the consideration of the many and various ways of living in the past.
Paradata to Reuse Holistic HBIM Quality Models in the SCAN-to-HBIM-to-VR Process. The Mausoleum of Cecilia Metella and the Castrum Caetani
Authors: Brumana Raffaella , Roascio Stefano , Attico Dario , Gerganova Maria Radoslavova , Genzano Nicola
Published: December 2024

The multiplication of efforts to digitize complex architectural and archaeological heritage sites in the form of informative models increasingly requires to document survey and modelling methods through qualitative and quantitative parameters to ensure mutual trustworthiness and proper re-use for different purposes by the potential multiple users, as well as the citation of the contributors’ data source (archaeologists, designers, conservators, civil engineers, geologists, XR-VR developers). The HBIM of the Mausoleum of Cecilia Metella and the Castrum Caetani (Rome, Italy), is part of the digitization of the PAAA (Parco Archeologico dell’Appia Antica, Archaeological Park of the Appian Way): it is emblematic for the complexity of the interconnections among users and contributors across the time. The article discusses needs and definition of Paradata for the re-use of holistic HBIM quality information models documenting the entire SCAN-to-HBIM-to-XR process, through diverse Levels of Development and Levels of Geometry (LODs100-600, LOGs100-600) from the surveys to the modelling phases including Virtual Reality experiences built on informative models, as well as remote environmental risk applications as part of long life management and monitoring. Being the models generated for different HBIM-USES and users, parameters that document the Grade of Accuracy of the Survey and of the Object Models generated in various times are identified. It is the case of the construction technologies associated to the transformation phases for potential future HBIM-uses, as for BIM-to-FEA and Seismic Vulnerability Plan exploitation, remote monitoring or XR (eXtended Reality) in a holistic process.
Usable, Useful, Reviewable and Reusable Metadata
Authors: Champion Erik
Published: December 2024

Approaches to both metadata in 3D cultural heritage and strengthening the integration of paradata have been clearly focused on developing new technological solutions. New technologies allow novel and richer communication participation yet metadata in 3D cultural heritage has been decided by a combination of specialized individuals and by frameworks of quantitative standards, but this does not address how to engage and educate the public. As a potential solution, this paper will suggest that metadata and paradata should be linked to UXdata (data recording participant feedback).
Making the Europeana Data Model a Better Fit for Documentation of 3D Objects
Authors: Isaac Antoine , Fernie Kate , Bachi Valentina , Tsoupra Eleftheria , Medici Marco , Alkemade Henk , Münster Sander , Charles Valentine , Heslinga Lianne
Published: December 2024

The current effort in 3D digitisation of heritage items poses new challenges in accommodating more and higher quality information to be associated with the 3D models that are of interest to users and stakeholders. The Europeana Data Model (EDM) is a metadata schema that distinguishes between the information related to the cultural heritage object as such (represented by the class edm:ProvidedCHO) and the information related to its digital representation (edm:WebResource), brought together in the class ore:Aggregation. Work done in the context of the new common European data space for cultural heritage collected inputs from various experts and initiatives working on 3D data, metadata and paradata, in the light of studying requirements for the extension and adaptation of EDM classes to the more complex scenario of representing and sharing 3D digitised cultural heritage collections.
Anliegen und Struktur der Studie
Authors: Lorenz Astrid , Pischtschan Luisa
Published: December 2024

Gleichwertige Lebensverhältnisse zu gewährleisten ist in Deutschland „ein rechtlich verankertes, politisch unstrittiges Ziel“, laut dem ersten Gleichwertigkeitsbericht von 2024 sogar „ein prioritäres Ziel der Bundesregierung“. Aber welche Aspekte sind Menschen wichtig, wenn es um ein gutes Leben geht? Mit welchen Orten oder Regionen vergleichen sie ihre Lebensverhältnisse? Und was erscheint ihnen politisch sinnvoll, um etwas für gleichwertige Lebensverhältnisse zu tun? Darüber berichtet die vorliegende Studie und erkundet zugleich, ob diese Sichtweisen Potenzial für räumliche Konflikte und damit Sprengstoff für den gesellschaftlichen Zusammenhalt bergen und ob sie von den Themen abweichen, die in der Politik als Kennzeichen für „gleichwertige Lebensverhältnisse“ betrachtet werden. Dafür wurden 913 Seiten Datenmaterial aus Gruppendiskussionen in 24 deutschen Kommunen, 915 Seiten ergänzende schriftliche Befragungen sowie 203 Seiten Transkripte von einordnenden Interviews mit Vertretern kommunaler Spitzenverbände ausgewertet.
Politik für ein gutes Leben: lokale Gewichtungen von Themenfeldern
Authors: Lorenz Astrid , Pischtschan Luisa
Published: December 2024

In diesem Kapitel analysieren wir unter anderem, wofür die Teilnehmer unserer Gruppendiskussionen in 24 Kommunen Geld ausgeben würden, wenn sie politisch entscheiden könnten. Die Antwort auf diese Frage fiel für viele typische Themen der öffentlichen Daseinsvorsorge eindeutig und unkritisch aus. Gesundheit, Bildung/Soziale Dienste, Wohnen, Sicherheit wurden weitgehend unkontrovers als wichtig bewertet – unabhängig vom Ort, in dem die Gruppendiskussion stattfand (Abschn. 6.1). Mehr politisches Konfliktpotenzial ergab sich bei anderen Themen (6.2), zu denen die Meinungen der Gruppen teils räumlich variierten, teils aber auch gruppenintern unterschiedliche Sichtweisen formuliert wurden. Hinsichtlich der weniger wichtigen Themen zeigte sich wieder mehr Einigkeit. Bemerkenswert war auch, dass die Teilnehmer der Gruppendiskussionen bereit waren, Themenfelder als politisches Anliegen zu priorisieren, die für andere wichtiger waren oder ihnen wichtiger schienen als für sie selbst. Dies betrifft v. a. politische Maßnahmen für das Wohnen, obwohl die Lage rund um das Wohnen häufig – v. a. in kleineren Orten – nicht als problematisch geschildert wurde. Dies sind sehr gute Voraussetzungen für die politische Kompromissfindung und den gesellschaftlichen Zusammenhalt.
Vergleiche der Lebensverhältnisse und Vorstellungen von „Gleichwertigkeit“
Authors: Lorenz Astrid , Pischtschan Luisa
Published: December 2024

Dass Politik und Verwaltung mit dem Konzept der „gleichwertigen Lebensverhältnisse“ eine vergleichende Perspektive einnehmen, passt dazu, wie in unseren Gruppendiskussionen über den eigenen Ort, ein gutes Leben und politische Prioritäten gesprochen wurde. In diesem Kapitel zeigen wir: Überall stellten Teilnehmer von sich aus allgemeine oder räumliche Vergleiche an. Den in Politik und Raumplanung verbreiteten Begriff „gleichwertige Lebensverhältnisse“ verwendeten sie dabei allerdings nicht, und ausgerechnet in Bezug auf die Politik waren Vergleiche weniger ausgeprägt. In diesem Kapitel berichten wir außerdem über räumliche Muster bei den Vergleichen. So bezogen Gesprächsrunden in Großstädten kaum kleinere Kommunen in solche Vergleiche ein (Abschn. 7.1). Außerdem zeigen wir, dass der Begriff „gleichwertige Lebensverhältnisse“ nicht nur mit Bemühungen um einen räumlichen Ausgleich, sondern oft auch mit sozialer Gleichheit, d. h. einem individuellen Ausgleich, assoziiert wurde (7.2).
Sichtweisen auf die Politik für gleichwertige Lebensverhältnisse
Authors: Lorenz Astrid , Pischtschan Luisa
Published: December 2024

Dieses Kapitel berichtet darüber, wie die Teilnehmer unserer 24 lokalen Gruppendiskussionen die Politik für gleichwertige Lebensverhältnisse in Deutschland bewerteten. In den ersten Gesprächsabschnitten hatten sie beim Sprechen über die Lebensverhältnisse selten von sich aus die Bundes-, Landes-, Europa- oder Kommunalpolitik, bestimmte Gesetze oder Akteure erwähnt. Gelegentlich wurde Kritik geäußert, aber nicht systematisch und nicht in breitem Umfang. In einem eigenen Abschnitt fragten wir nun: „Finden Sie, die Politik tut genug dafür, dass die Menschen überall in etwa ähnlich gut leben können? Oder was sollte sie anders machen, z. B. auch hier vor Ort?“. Ebenso interessierte uns ihre Sicht darauf, wie dies finanziert werden sollte. In diesem Kapitel analysieren wir, wie die lokalen Gruppen dazu diskutierten, und identifizieren teils deutliche räumliche Unterschiede. Die Befunde ergänzen wir um Auswertungen der separaten schriftlichen Befragung, die von den mündlichen Aussagen abwichen. Ferner analysieren wir die Aussagen zur Rolle der Bürger für die Gewährleistung gleichwertiger Lebensverhältnisse, die räumlich variierten.
Extrakorporale Stoßwellentherapie bei Überlastungssyndromen des Knochens
Authors: Knobloch Karsten
Published: December 2024

Die extrakorporale Stoßwellentherapie (ESWT) kann die Heilung insbesondere am Knochen – aber nicht nur dort – beschleunigen. Die akustischen Wellen werden über Mechanotransduktion in eine Gewebeantwort übersetzt. Neben der Stammzellaktivierung werden auch Effekte auf die Exosomenausschüttung, die Modulation der Inflammation und Wachstumsfaktoren durch die Stoßwellentherapie ausgelöst, welche die positiven Wirkungen auf die Knochenheilung sowohl bei verzögerter Knochenheilung wie bei Pseudarthrosen wie auch bei Stressreaktionen und Stressfrakturen erklären. Kombinationstherapien mit oszillierenden Magnetfeldern (pulsierende Magnetfeldtherapie [PEMF] und extrakorporale Magnetotransduktionstherapie [EMTT]) und orthobiologischen Injektionen können in der Zukunft möglicherweise die gezeigten Effekte noch verstärken helfen.
Oscillations in Wave Map Systems and Homogenization of the Einstein Equations in Symmetry
Authors: Guerra André , Teixeira da Costa Rita
Published: December 2024

In 1989, Burnett conjectured that, under appropriate assumptions, the limit of highly oscillatory solutions to the Einstein vacuum equations is a solution of the Einstein–massless Vlasov system. In a recent breakthrough, Huneau–Luk (Ann Sci l’ENS, 2024) gave a proof of the conjecture in U(1)-symmetry and elliptic gauge. They also require control on up to fourth order derivatives of the metric components. In this paper, we give a streamlined proof of a stronger result and, in the spirit of Burnett’s original conjecture, we remove the need for control on higher derivatives. Our methods also apply to general wave map equations.
Feels Like Home: A Biobased and Biodegradable Plastic Offers a Novel Habitat for Diverse Plant Pathogenic Fungi in Temperate Forest Ecosystems
Authors: Nonthijun Paradha , Tanunchai Benjawan , Schroeter Simon Andreas , Wahdan Sara Fareed Mohamed , Alves Eliane Gomes , Hilke Ines , Buscot François , Schulze Ernst-Detlef , Disayathanoowat Terd , Purahong Witoon , Noll Matthias
Published: December 2024

Poly(butylene succinate-co-adipate) (PBSA), a biodegradable plastic, is significantly colonized and degraded by soil microbes under natural field conditions, especially by fungal plant pathogens, raising concerns about potential economic losses. This study hypothesizes that the degradation of biodegradable plastics may increase the presence and abundance of plant pathogens by serving as an additional carbon source, ultimately posing a risk to forest ecosystems. We investigated (i) fungal plant pathogens during the exposure of PBSA in European broadleaved and coniferous forests (two forest types), with a specific focus on potential risk to tree health, and (ii) the response of such fungi to environmental factors, including tree species, soil pH, nutrient availability, moisture content, and the physicochemical properties of leaf litter layer. Next-generation sequencing (NGS) revealed that PBSA harbored a total of 318 fungal plant pathogenic amplicon sequence variants (ASVs) belonging to 108 genera. Among the identified genera (Alternaria, Nectria, Phoma, Lophodermium, and Phacidium), some species have been reported as causative agents of tree diseases. Plenodomus was present in high relative abundances on PBSA, which have not previously been associated with disease in broadleaved and coniferous forests. Furthermore, the highest number of fungal plant pathogens were detected at 200 days of PBSA exposure (112 and 99 fungal plant pathogenic ASV on PBSA degraded under Q. robur and F. sylvatic-dominated forest, respectively), which was double compared mature leaves and needles from the same forest sites. These findings suggest that PBSA attracts fungal plant pathogens in forests as an additional carbon source, potentially leading to increased disease outbreaks and disrupting the stability of forest ecosystems. The fungal plant pathogenic community compositions were mainly shaped by forest type, PBSA exposure time, site locations, leaf litter layer water content, and N:P ratio from leaf litter layer in both forest types. This study provides valuable insights into the potential risks posed by biodegradable plastic degradation in forests after 200 and 400 days of exposure, respectively. Further comprehensive evaluations of their effects on tree health and ecosystems, ideally on a long-term basis, are needed. These evaluations should include integrating microbial investigation, soil health monitoring, and ecosystem interaction assessments. Nevertheless, it should be noted that our interpretation of plant pathogens is solely based on high-throughput sequencing, bioinformatics, and annotation tools.
Bat Cutaneous Microbial Assemblage Functional Redundancy Across a Host-Mediated Disturbance
Authors: Grisnik Matthew , Walker Donald M.
Published: December 2024

Understanding the processes and factors that influence the structure of host-associated microbial assemblages has been a major area of research as these assemblages play a role in host defense against pathogens. Previous work has found that bacterial taxa within bat cutaneous microbial assemblages have antifungal capabilities against the emerging fungal pathogen, Pseudogymnoascus destructans. However, our understanding of natural fluctuations in these cutaneous microbial assemblages over time due to shifts in host habitat is lacking. The objective of this work was to understand how the taxonomic and functional bat cutaneous microbial assemblage responds to seasonal shifts in host habitat. We hypothesized that at the community level, there will be turnover in taxonomic structure but functional redundancy across seasons. On a finer scale, we hypothesized that there will be differences in the relative abundance of functional genes that code for select pathways across seasons. Results showed that, on a broad scale, the bat cutaneous microbial assemblage is seasonally taxonomically dynamic but functionally redundant. Additionally, although there was almost complete taxonomic turnover between winter and summer bat microbial assemblages, there was no difference in assemblage structure across winters. This functional redundancy was also observed at finer scales, with no differences in the abundance of genes within pathways of hypothesized importance across seasons or winters. Taken together, results suggest species sorting mechanisms correlated with shifts in host habitat use, drive taxonomic but not functional host-associated cutaneous microbial community assembly.
Integration of bulk and single-cell RNA-seq reveals prognostic gene signatures in patients with bladder cancer treated with immune checkpoint inhibitors
Authors: Cho Mina , Chang Hyun , Kim Ju Han
Published: December 2024

Immune checkpoint inhibitors have significantly advanced research in oncology and are used to successfully treat patients with bladder cancer (BC). However, as the benefits of programmed death-1/ programmed death-ligand-1 blockade immunotherapy do not extend to all patients with BC, biomarkers are required to improve prognostic stratification. This study aims to identify reliable biomarkers to enhance the prediction of treatment outcomes. Bulk RNA expression data from a BC cohort (GSE176307) receiving ICI and single-cell sequencing data from patients with BC (GSE135337) were collected. We identified differentially expressed genes (DEGs) within cells that were associated with favorable survival outcomes and developed a predictive bladder cancer gene signature (BC-GS). Subsequently, we performed pathway enrichment analysis using the Reactome database. We used two independent datasets to validate the BC-GS. Patients with low BC-GS had a significantly shorter overall survival (OS) than those with high BC-GS (p < 0.05, p < 0.001, respectively). Additionally, patients with a concurrently low BC-GS score and low tumor mutation burden (TMB) in GSE176307 and the two validation datasets exhibited an increased risk of death. Genes in the BC-GS were predominantly involved in CD8+ T cell activation, antigen presentation, and immune checkpoint pathways. CIBERSORT analysis revealed differences in CD4+ T cells and macrophages between the high and low BC-GS groups. This study demonstrated the prognostic significance of the BC-GS in patients with BC treated with ICI. The combined assessment of the BC-GS and TMB may provide a sophisticated prognostic approach to enhance patient stratification for ICI treatment in BC.
Target trial emulation to evaluate the effect of immune-related adverse events on outcomes in metastatic urothelial cancer
Authors: Pichler Renate , Fritz Josef , Maier Sarah , Hassler Melanie R. , Krauter Johanna , D`Andrea David , Laukhtina Ekaterina , Gust Kilian , Mori Keiichiro , Tully Karl H. , Niedersuess-Beke Dora , Korber Lea , Spiegelberg Jasmin Alija , Bauernhofer Thomas , Subiela José D. , Mayr Roman , Kronbichler Andreas , Moschini Marco , Teoh Jeremy , Pradere Benjamin , Shariat Shahrokh F. , Ulmer Hanno , Mertens Laura S. ,   European Association of Urology–Young Academic Urologists (EAU-YAU): Urothelial Carcinoma Working Group
Published: December 2024

Background

Immune checkpoint inhibitors (ICIs) are an important therapeutic pillar in metastatic urothelial carcinoma (mUC). The occurrence of immune-related adverse events (irAEs) appears to be associated with improved outcomes in observational studies. However, these associations are likely affected by immortal time bias and do not represent causal effects. The aim of this study was to assess the effect of irAEs on outcomes while correcting for immortal time bias, using target trial emulation (TTE).

Methods

TTE was contrasted to adjusted naïve and time-updated Cox models. We performed a multi-institutional retrospective study involving mUC patients under ICI. The primary objective was to assess the impact of irAEs on progression-free survival (PFS) and overall survival (OS). Secondary endpoints included the influence of irAEs on objective response rates (ORRs) to ICI and the influence of systemic corticosteroids on outcomes.

Results

Among 335 patients (median age: 69 yrs), 69.6% received ICI in the second line or further lines. During a median follow-up of 21.1 months, 122 (36.4%) patients developed irAEs of any grade (grade ≥ 3: 14.9%). Hazard ratios (HRs) for PFS ranged from 0.37 for naïve adjusted Cox model to 0.88 (95% confidence interval (CI), 0.59–1.30) with time-updated covariates, and from 0.41 to 1.10 (95% CI, 0.69–1.75) for OS. TTE accounting for immortal time bias yielded a HR of 1.02 (95% CI, 0.72–1.44) for PFS, and 0.90 (95% CI, 0.62–1.30) for OS. In contrast to the naïve Cox model (HR = 2.26, 95% CI 1.26–4.05), the presence of irAEs was no longer a predictive factor for improved ORR in time-updated Cox models (HR = 1.27, 95% CI 0.68–2.36) and TTE (HR = 1.43, 95% CI 0.89–2.29). In patients with irAEs, systemic corticosteroids did not negatively impact survival.

Conclusion

Using TTE, we were able to show that the occurrence of irAEs is no longer associated with better survival or improved response rates to ICI in mUC patients, in contrast to the naïve analysis. These findings demonstrate that TTE is a suitable formal framework to avoid immortal time bias in studies with time-dependent non-interventional exposures.

Graphical abstract
COVID-19–sensitive tumour response: 2-year assessment of the SARS-CoV-2 humoral response in cancer patients in oncology hospital in Poland
Authors: Kosiorek Piotr , Mikołuć Bożena , Stróż Samuel , Hryniewicz Anna , Kazberuk Dorota E. , Milewski Robert , Grzeszczuk Anna , Borkowska Magdalena J. , Stasiak‐Barmuta Anna
Published: December 2024

Vaccination has been considered the most crucial defence against viral infections, including SARS-CoV-2. Numerous reports have demonstrated the effectiveness of the above vaccines in oncological patients. It has also been proven that, apart from vaccinations and oncological therapy, the course of the cancer process itself influences the magnitude of the humoral response, especially in people after infection with SARS-CoV-2. The phenomenon we observe seems to confirm the presence of a "natural" defence potential in a cancer patient's body, in this case, directed against infection with a viral pathogen. A "stronger" antiviral response also explains the asymptomatic course of SARS-CoV-2 infection in some of the above patients. To what extent the SARS-CoV-2 infection weakened the "natural" potential of the anticancer response in these patients remains an open question.

Objective

This study aimed to answer the question about the impact of the cancer process on the humoral response in oncological patients vaccinated against SARS-CoV-2 infection and in patients after COVID-19.

Material and methods

One thousand six hundred and sixty-eight people were observed. Over 2 years, 5,082 SARS-CoV-2 IgG and IgM antibody samples were determined. The concentration of antibodies was assessed in groups of oncological patients: those undergoing anticancer therapy after contracting COVID-19 and those after vaccination against the SARS-CoV-2 infection.

Results

The obtained results indicate a naturally more significant humoral response in oncological patients who have not been vaccinated and have not undergone anticancer therapy, such as radiotherapy, chemotherapy, or surgical intervention. The above observation applies to patients with breast, lung, colon, kidney, and testicular cancer, although the response varies significantly depending on the type of cancer.

Graphical abstract
Subtrochanteric shortening osteotomy in adult sickle cell disease patients with cemented total hip arthroplasty for hip deformities secondary to childhood osteonecrosis: is healing a challenge?
Authors: Hernigou Philippe , Homma Yasuhiro , Bastard Claire , Yoon Byoung-Chol , Lachaniette Charles-Henri Flouzat
Published: December 2024

Purpose

Hip deformity is frequent after childhood osteonecrosis in patients with sickle cell disease (SCD). When they are adults, they present a challenge as candidates for total hip arthroplasty (THA) because of abnormal bone development, their relative youth, and also because of their disease. Performing subtrochanteric osteotomy associated with THA is technically challenging, and healing of osteotomies has never been reported in this population with frequent osteonecrotic bone, whether using cemented or uncemented arthroplasties.

Methods

We retrospectively analyzed 59 cemented THA with femoral corrective osteotomies (subtrochanteric shortening and transverse derotational osteotomy) performed on hip deformities between 1984 and 2018 in 59 sickle cell adult patients. The patient’s age at the onset of osteonecrosis was an average of 8.4 years (6 to 10 years), and at the time of the THA was 28.6 years (19 to 41 years). All the patients had a minimum followup period of six years. Endocrinopathy was frequently associated to SCD Data and consequences were evaluated on bone union. The mechanical variables, such as the length of the resected femur, limb lengthening, the location of the osteotomy site, the size of the stem bridging the osteotomy, and any complications, were also analyzed.

Results

The average length of the resected femoral segment was 38.4 mm. The length of the femoral stem (bridging the osteotomy) was average 13 cm. The mean osteotomy union time was 10.6 months. Twenty-four osteotomies healed in six months, six in nine months, and 29 in twelve months, while five required bone grafts at nine months. The union time of the osteotomy was average 10.6 months. Complications included four cases of transient nerve palsy, and five intraoperative femur perforations. No statistically significant relationship was found between osteotomy union time and mechanical variables. The severity of endocrinopathy associated with sickle cell disease prolonged the healing time. In three cases, cement leakage into the osteotomy gap occurred without resulting in non-healing.

Conclusion

Cemented THA, combined with a subtrochanteric femoral shortening with transverse derotational osteotomy, has a long union time but is effective for adult hip deformities of patients with sickle cell patients.
Combined PCL and anatomic posterolateral corner reconstruction: A tibial slope under 8 degrees and a persisting dorsal instability of 4 mm or more have a negative effect on the clinical outcome
Authors: Fahlbusch H. , Weiß S. , Korthaus A. , Akoto R. , Krause M. , Frosch K. H.
Published: December 2024

Purpose

The failure rate following posterolateral corner reconstruction (PLC) remains high. Previous research indicates that in posterior cruciate ligament (PCL) reconstruction the laxity is affected by the tibial slope (TS). However, there is currently no literature evaluating the impact of TS on surgical outcome in combined reconstruction of PLC/PCL.

Methods

This study analyzed 47 patients in a retrospective cohort study who underwent PCL and anatomical PLC reconstruction according to techniques described by Arciero or LaPrade. TS was measured, and patients were divided into two groups: Group A (n = 16) with TS < 8° and Group B (n = 31) with TS ≥ 8°. After a minimum follow-up of 12 months, the side-to-side difference (SSD) of posterior tibial translation (PTT) was assessed using instrumented stability testing (Rolimeter), and various patient-reported outcome measures (IKDC, Lysholm) were collected and compared.

Results

At a mean follow-up of 17.7 ± 4.7 months, group A exhibited a higher SSD of PTT (A 3.9 mm ± 2.1 vs. B: 2.8 mm ± 1.5; p < 0.05). A negative correlation was observed between SSD of PTT and both TS (r = − 0.43; R2 = 0.18; p < 0.01) and the Lysholm Score (r = − 0.41; R2 = 0.17; p < 0.01) in the overall cohort. Subgroup analysis revealed a higher Lysholm Score in patients with a postoperative SSD of PTT less than 4 mm (85.7 ± 10.1 vs. 79.2 ± 6.6; p = 0.0006).

Conclusion

In combined PCL and anatomic PLC reconstruction a TS < 8° results in elevated SSD of PTT. A flattened TS is linked to higher remaining SSD of PTT, while lower SSD of PTT is associated with improved clinical outcomes.

Level of evidence

Retrospective Cohort Study, IV.
Naturalistic multimodal emotion data with deep learning can advance the theoretical understanding of emotion
Authors: Angkasirisan Thanakorn
Published: December 2024

What are emotions? Despite being a century-old question, emotion scientists have yet to agree on what emotions exactly are. Emotions are diversely conceptualised as innate responses (evolutionary view), mental constructs (constructivist view), cognitive evaluations (appraisal view), or self-organising states (dynamical systems view). This enduring fragmentation likely stems from the limitations of traditional research methods, which often adopt narrow methodological approaches. Methods from artificial intelligence (AI), particularly those leveraging big data and deep learning, offer promising approaches for overcoming these limitations. By integrating data from multimodal markers of emotion, including subjective experiences, contextual factors, brain-bodily physiological signals and expressive behaviours, deep learning algorithms can uncover and map their complex relationships within multidimensional spaces. This multimodal emotion framework has the potential to provide novel, nuanced insights into long-standing questions, such as whether emotion categories are innate or learned and whether emotions exhibit coherence or degeneracy, thereby refining emotion theories. Significant challenges remain, particularly in obtaining comprehensive naturalistic multimodal emotion data, highlighting the need for advances in synchronous measurement of naturalistic multimodal emotion.
Association between FTO gene polymorphism and obesity in down syndrome children
Authors: Mourad Shereen A. , El-Farahaty Reham M , Atwa Mohamed A. , Yahia Sohier , El-Gilany Abdel-Hady , Elzeiny Ahmed A. , Elhennawy Eman S.
Published: December 2024

Children with Down syndrome (DS) have a higher incidence of overweight and obesity compared to typically developing peers. The fat mass and obesity-associated gene (FTO) is one of the early identified genes linked to obesity in various populations. To date, the FTO rs17817449 gene polymorphism has not been investigated in overweight/obese-DS (ODS) individuals. The current study aimed to explore the potential association between the FTO rs17817449 gene polymorphism and obesity-related markers, and to evaluate the ability of this polymorphism in the prediction of overweight/obesity in DS children and adolescents. This case-control study included 100 DS children under the age of 18, classified into three groups according to BMI-percentile; 50 non-obese DS (NODS), 24 overweight DS, and 26 ODS. Genotyping of FTO gene rs17817449 polymorphism was performed using the restriction fragment length polymorphism (RFLP-PCR) method. Serum lipid and thyroid profiles were also assessed. The results revealed significant increase in the frequency of the FTO rs17817449 T allele among overweight /ODS children compared to NODS children (p=0.0099). Overweight/ODS children exhibited significantly higher frequencies of the FTO rs17817449 GT and TT genotypes compared to NODS children.

Conclusion:There is an association between FTO rs17817449 genetic variant and overweight/obesity among the studied DS groups. The FTO rs17817449 GT and TT genotypes, as well as TGs level, were identified as independent risk factors for predicting overweight and obesity in DS children.

What is Known:

• Overweight and obese-DS (ODS) children displayed higher BMI and atherogenic lipid profile than non-obese DS children (NODS). FTO gene polymorphism rs17817449 contributes to obesity development in general population, but there is conflicting information about the risk allele.

What is New:

• FTO rs17817449 TT genotype and T allele were considered as independent risk factors for overweight and obesity development in DS children, so they could be used for obesity prediction in DS children.
Post-coronavirus disease 2019–associated symptoms among children and adolescents in the SARS-CoV-2 Omicron era
Authors: Schlegtendal Anne , Maier Christoph , Stein Julien , Höpner Jakob , Petersmann Astrid , Drinka Denisa , Berner Reinhard , Lücke Thomas , Toepfner Nicole , Brinkmann Folke
Published: December 2024

Purpose

Lack of a control group(s) and selection bias were the main criticisms of previous studies investigating the prevalence of post-coronavirus disease 2019 (COVID-19) syndrome (PCS). There are insufficient data regarding paediatric PCS, particularly in the SARS-CoV-2 Omicron era. As such, our study investigated PCS-associated symptoms in a representative control-matched cohort.

Methods

This multicentre, cross-sectional, cohort study within the “Immunebridge” project of the German Network University Medicine (NUM) recruited children and adolescents (five to 17 years old) between July and October 2022. Children with polymerase chain reaction-confirmed SARS-CoV-2 infection in 2022 (COVID-19 group) were compared with those without history of SARS-CoV-2 infection and negative for SARS-CoV-2 antibodies. Queries included vaccinations, quality of life (QoL), and mental and physical symptoms potentially associated with PCS in the previous three months. An additional composite item, “physical performance”, was created from the responses.

Results

The number of children with ≥ 1 PCS symptom(s) was comparable between the COVID-19 (n = 114 [62.1%]) and control (n = 66 [64.9%]) groups. Concentration disorders were reported more frequently in the COVID-19 group (12.3% versus 1.5%; p = 0.012) and “physical performance” was significantly impaired (p = 0.016) regardless of age, sex, and SARS-CoV-2 vaccination. The frequencies of other symptoms were similar in both groups. The COVID-19 group rated their fitness as worse, with otherwise equal QoL ratings regarding general and mental health.

Conclusion Children with and without previous infections did not differ in most PCS-associated symptoms. Exceptions
included physical performance and cognitive problems, which appeared to be more impaired after Omicron infection than
in controls.

What is Known:• Mainly due to too few controlled studies, knowledge about the prevalence of individual symptoms in paediatric post-COVID-19 syndrome (PCS) for the Omicron era is poor.

What is New:• In a representative control-matched cohort most parent-reported PCS-associated symptoms and quality of life scores in children and adolescents with PCR-confirmed SARS-CoV-2 infection did not differ from those without infection.• Exceptions were physical performance and cognitive problems, which were apparently more severely impaired after SARS-CoV-2-Omicron infection than in the control subjects.