bluuebunny/crossref_metadata_2025 huggingface dataset:
Tough, Transparent, and Slippery PVA Hydrogel Led by Syneresis
Authors: Liu Desheng , Cao Yufei , Jiang Pan , Wang Yixian , Lu Yaozhong , Ji Zhongying , Wang Xiaolong , Liu Weimin
Published: January 2023

Slippery and transparent polyvinyl alcohol (PVA) hydrogels with mechanical robustness exhibit broad applications in artificial biological soft tissues, flexible wearable electronics, and implantable biomedical devices. Most of the current PVA hydrogels, however, are unable to integrate these features, which compromises its performance in biological and engineering applications. To achieve such purpose, herein, a novel tactic is proposed, salting‐out‐after‐syneresis of PVA, to realize a mechanically robust and highly transparent slippery PVA hydrogel. The syneresis of PVA sol is first conducted to form highly dense and transparent PVA polymer networks, then the salting‐out effect tunes the aggregation of the polymer chains to rapidly induce the phase separation and crystallization. The resultant hydrogels show the transparency up to 98% in the visible region, the tribological coefficient down to 0.0081, and the excellent mechanical properties with strength, modulus, and toughness of 26.72 ± 1.05, 6.66 ± 0.29 MPa, and 55.21 ± 1.62 MJ m−3, respectively. To reveal the potentials, PVA contact lens that combine remarkable lubrication, anti‐protein adhesion, biocompatibility, and drug‐loading functions are demonstrated. This strategy provides a simple and new avenue for developing the mechanically robust, transparent, and hydrated hydrogels, showing the potential in biomedicine and wearable devices.
A Detection Method of Atrial Fibrillation from 24‐hour Holter‐ECG Using CNN
Authors: Kamozawa Hidefumi , Muroga Sho , Tanaka Motoshi
Published: January 2023

A method for detecting atrial fibrillation (AF) from electrocardiogram (ECG) measured by a 24‐hour Holter electrocardiograph (Holter‐ECG) is proposed using convolutional neural network (CNN). In the preprocessing stage, artifacts and noises on Holter‐ECG are removed by a bandpass filter. The detection method consists of two stages: extraction of abnormal waveforms using one‐dimensional CNN trained with segmented ECG waveform and its spectral entropy, and identification of AF using two‐dimensional CNN trained with segmented ECG spectrogram. A total of 47 520 datasets obtained from Holter‐ECG were prepared, and used for training at both CNN stages. Newly prepared (untrained) datasets of 24‐hour Holter‐ECG of 10 subjects and MIT‐BIH databases are tested, and the proposed method showed sufficient performance for detecting AF, with the accuracy of approximately 90%. This result indicates the feasibility of the proposed method. © 2023 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Concurrent right atrial myxoma with visceral haemangiosarcoma in a dog
Authors: Brewer David John , Marwood Rachel , Leeming Gail , Ressel Lorenzo , Dukes‐McEwan Joanna
Published: January 2023

A 10‐year‐old crossbreed (labradoodle) was presented with an acute history of vomiting and diarrhoea, with supraventricular tachycardia and ventricular premature complexes. Physical examination revealed mild tachycardia, but no significant abnormalities otherwise. Investigations with echocardiogram and computed tomography identified a right atrial mass, nodular interstitial lung pattern, multiple nodules throughout the hepatic parenchyma and peritoneal effusion. Abdominocentesis confirmed a haemoabdomen. Treatment was declined and the dog was euthanased the same day. Histopathology of the cardiac mass confirmed a cardiac myxoma, which stained Alcian blue‐positive, demonstrating the mucin content of the tumour. The hepatic lesions were factor VIII‐positive, consistent with a visceral haemangiosarcoma.
Dynamics and Hydration of Proteins Viewed by Fluorescence Methods: Investigations for Protein Engineering and Synthetic Biology
Authors: Sykora Jan , Prokop Zbynek , Damborsky Jiri , Abhinav  , Hof Martin , Amaro Mariana
Published: January 2023

Protein engineering and synthetic biology are currently very active areas of research and development. In the pursuit of engineering proteins with specific capabilities, it has become evident that the scrutiny of structural and geometrical properties does not suffice to achieve the proposed goals. The dynamics and hydration of specific protein areas seem to be of higher influence than it has been once thought. This chapter introduces three different fluorescence spectroscopy techniques (time-dependent fluorescent shift, HMC hydration assay based on unnatural amino acid fluorescence, and photoinduced electron transfer–fluorescence correlation spectroscopy) that allow for assessing the dynamics and hydration of proteins in a site-specific fashion and showcase their usefulness in advancing the design of more efficient enzymes. Systematic application of these techniques to various biomolecular systems will allow a thorough description of these important protein properties, which are rarely taken into account during protein engineering and synthetic biology projects.
Metabolism in Crisis? A New Interplay Between Physiology and Ecology
Authors: Bognon-Küss Cécilia
Published: January 2023

This chapter investigates the hybrid relationships between metabolism, broadly and a-historically understood as the set of processes through which alien matter is made homogeneous to that of the organism, and forms of vitalism from the eighteenth century on. While metabolic processes have long been modeled in a reductionist fashion as a straightforward function of repair and expansion of a given structure (either chemically, or mechanistically), a challenging vitalist view has characterized metabolism as a creative, organizing, vital faculty. I suggest that this tension was overcome in Claude Bernard’s works on “indirect nutrition”, in which nutrition, rightly conceived as a general vital phenomenon common to plants and animals, was both characterized as an instance of the general physico-chemical determinism of all phenomena and as the sign and condition of the “freedom and independence” of the organism with respect to the environment. I propose that Bernard’s theory of indirect nutrition was central in the elaboration of his general physiology and has, at the same time, underpinned a self-centered view of biological identity in which the organism creates itself continuously at the detriment of its externalmilieu. I further argue that this conception of biological individuality as metabolically constructed has since, and paradoxically, supported a view in which the organism appears as an autonomous and self-creating entity. I then contrast this classical view of the metabolic autonomy of the organism with the challenges raised by microbiome studies and suggest that these emerging fields contribute to sketch an ecological conception of the organism and its metabolism through the reconceptualization of its relationship with the environment. The recent focus on a “microbiota – host metabolism” axis contributes to shift the focus away from the classical concept of organism, somehow externalizing vitalism out of the autonomous individual in favor of an ecological, collaborative, and interactionist view of the living.
Vitalist Arguments in the Struggle for Human (Im)Perfection: The Debate Between Biologists and Theologians in the 1960s–1980s
Authors: Shmidt Victoria
Published: January 2023

In this chapter, I explore and offer critical reflections on the widespread practice of attributing negative value to “vital forces” in debates on health and disease, as the direct result of the extensive dissemination of genetics and its implications since the late 1960s. This historical reconstruction focuses on the most heated debates in popular science periodicals and editions, having the longest-lasting public “echo,” which have shaped an intergenerational continuity in the reproduction of vitalist arguments in discursive practices regarding health, disease, and their genetic factors.

Mapping attacks on vital forces as various forms of negation addresses three different debates in the historically interrelated repertoire of potentially rival approaches to health, disease, and their genetic components: (1) the attribution of negative value to primal instinct as an obstacle to the progress of human civilization; (2) the normative vitalism mainly associated with French philosophers George Canguilhem, Michel Foucault, and Gilles Deleuze; and (3) the movement for the deinstitutionalization of health care within the negative theology presented by Ivan Illich.

The reproduction of vitalist arguments in the each of the three realms is seen as a historical continuity of the medical vitalism that appeared in the Enlightenment and that produced a less monolithic and more conceptually coherent continuum of the positions regarding health, diseases, and their causes. In line with the Lakatosian division into internalist and externalist histories of science, I focus on the multiple functions of vitalist arguments: as a main force in the contest among rival theories regarding health and disease (as a part of the internalist narrative); as a signifier of the boundary work delineating science and not-science, whether labeled as theology or as “bad” science aimed at legitimizing science (as a part of externalist history); and as an ideological platform for bridging science and its performance in policies concerning reproduction .
Canguilhem and the Greeks: Vitalism Between History and Philosophy
Authors: Holmes Brooke
Published: January 2023

In this essay, I examine the role of ancient Greek medicine and philosophy in Georges Canguilhem’s analysis of vitalism at the intersection of history and philosophy in his essay “Aspects of Vitalism” in light of larger questions about the historicity of “life” as a concept in the history and philosophy of science and contemporary biopolitical theory. Vitalism, for Canguilhem, is not a proper object of the history of science. But nor is it a philosophy that exists outside of historical time. I show how Canguilhem embeds vitalism both historically and trans-historically by threading each of its three “aspects” in the essay through ancient Greece. Canguilhem distinguishes his own understanding of both life and vitalism from that of the “classical” vitalists of the eighteenth century by refusing to read ancient Greece as romantically naïve or pre-technological and instead locating a dialectic between vitalism and mechanism already in antiquity. I argue for a critical re-reading of Canguilhem’s own conjunction of vitalism and Hellenism that resists its figuration of ancient Greece as the place where the human qua species first comes to take itself as an object of knowledge. I instead propose reading ancient Greek medical and philosophical texts that are read and reread in debates about the nature of human life and the life of Nature over millennia as part of a milieu that shapes how contemporary thinkers theorize life in the interest of human flourishing.
Gender Competent Criminal Law
Authors: Acale Sánchez María , Marković Ivana , Strand Susanne
Published: January 2023

The following chapter deals with the general and special part of criminal law from a gender perspective. It analyses, in particular, the provisions from the Council of Europe Convention on preventing and combating violence against women and domestic violence, the Istanbul Convention, from 2011. The Istanbul Convention is the most comprehensive international legal instrument that outlines binding obligations to states to prevent and combat violence against women and girls. Furthermore, the Istanbul Convention contains several institutes and behaviours that have to be criminalised in the respective national jurisdictions, covering and combining dogmatics and criminal policy issues with a foundation substantially based on gender. The chapter also explores gender issues in a more general way, interpreting criminal law and its challenges towards gender equality. The special part raises questions regarding criminal law and its compatibility with the Istanbul Convention and national laws.
Gender Competent Family Law
Authors: Barać Ivana , Blandino Amalia , Coppo Letizia , Frezza Giampaolo , Novaković Uros , Rabadán Fuensanta , Saeidzadeh Zara
Published: January 2023

This chapter discusses the construction of family and family law as central tenets of gender equality projects in law and society. It begins with a review of the evolution of family institution from the traditional nuclear to the models that are not constituted through either heteronormativity or marriage contract. Hence, it draws on LGBTQIA+ family formations including parenthood and intimate partnership. Furthermore, the chapter elaborates on the development of gender equality in family law and marriage contract in various social settings through an intersectional analysis of rights and responsibilities of partners, parents, and children. The chapter also explores domestic violence as a matter of gender equality in family law. It discusses how legal protection and prevention of domestic violence in family law can reduce harmful effects on family members, who are the victims of violence directly or affected by domestic violence as witnesses.
Labour Law and Gender
Authors: Padrón Thais Guerrero , Kovačević Ljubinka , Moreno Mª Isabel Ribes
Published: January 2023

The chapter presents an overview of key labour law institutions, aiming at discussing the importance of the gender perspective in labour law. Therefore, the introductory section of the chapter will put this issue into the context of historical and conceptual framework genesis of regulating employment relationships. These issues are connected with the legal subordination and economic dependence of employees, which produce the need to create and implement norms that protect employees, as a weaker party to the employment relationship. This includes the limitation of employers’ (managerial, normative and disciplinary) prerogatives, in order to create the conditions for effective enjoyment of the right of jobseekers and employees for protection against gender-based discrimination. The labour law is, in this regard, traditionally conceived according to the model of a male worker, who is employed on the basis of a standard employment contract (open-ended full time employment contract). This then results in a failure to recognise or provide sufficient consideration of the specific needs that women have as participants in the labour market. The use of the feminist method, which included the understanding of gender as an analytical category in the field of labour law, opened up a new set of labour law issues. For example, in easing the ban on women working in physically demanding jobs, and the conceptualisation of the need to reconcile the professional and family duties of employees.. On the other hand, contemporary labour law, when creating conditions for achieving gender equality, is aimed primarily at women’s empowerment in the world of work. Persisting with this approach can lead to an oversimplified understanding of the principle of gender equality, ignoring the special needs of men in the world of work, as well as ignoring the importance of their role for consistent implementation of the principle of gender equality and women’s empowerment. The second section of the chapter will provide analysis of gender-based discrimination during the hiring process. Other sections will cover the risk of gender-based discrimination regarding rights, obligations and duties deriving from employment relationship, labour law measures to encourage improvements in the occupational safety and health, work-life balance for parents and caregivers, sexual harassment at work and promotion of gender equality in collective labour law.
Integrating Gender Equality in Economics and Management
Authors: Lopez Lydia Bares , Costanza Francesca , Gil Manuela Ortega , Strid Sofia
Published: January 2023

This chapter deals with gender economics, gender and management, and gender and innovation. After introducing the general concept of feminist economics and its critique of mainstream economics, this chapter explains the meaning of gender indicators, gender parity, gender equality, and gender mainstreaming. It further investigates the factors causing inequalities in the labour market. Gender is afterwards addressed from a managerial perspective, embracing a multidimensional notion of performance, and considering both the management of private and public organisations. Finally, the topic gender and innovation is deepened by explaining the importance of intellectual property rights, as well as the poor visibility of women inventors in society.
Gender, Business and the Law
Authors: Fröhlich Mareike , Jevremović Petrović Tatjana , Lepetić Jelena
Published: January 2023

This chapter deals with gender equality in business law. For some time now, gender diversity has played an important role in the composition of dispute resolution bodies, boards of directors and supervisory boards, forcing the companies concerned to take action. The underlying initiatives of the EU regarding gender quotas in companies, as described in the chapter, are beginning to have an effect, as developments in the banking and financial sector also show. Although the European internal market and its fundamental freedoms do not have a direct impact, the European Union is strongly committed to the protection of gender equality, the economic empowerment of women as well as female entrepreneurship. This chapter explains in detail how forms of enterprises, financing options, education and networking can support women to become entrepreneurs and play a crucial role in business decision-making. Finally, the chapter describes the impact of international trade and investment agreements in this field. Gender mainstreaming now takes place in all recent trade agreements and opens up new opportunities for women. Although investment agreements secure and support foreign investments, which are needed to improve the welfare of states and their citizens, they also could undermine the promotion of gender equality in the investor state. These new changes could jeopardise the investment as national rules will be legally obliged to be changed.
Feminist Judgments
Authors: Evola Marco , Krstić Ivana , Rabadán Fuensanta
Published: January 2023

The chapter discusses how the lack of gender knowledge and approach in judicial decision-making can influence the decision and the result of the case. Particular emphasis is given to the role of gender stereotypes and how gender stereotypes bias the working of the bench and the outcome courts achieve. Feminist judgments projects that have been developed worldwide demonstrate that judging is gendered, and women make a difference in the decision-making process. The rising number of women judges makes the bench more representative, although they face many constraints preventing them from asking the woman question. The analysis of the essential features of rewriting judgments in a gender perspective highlights that feminist judgments could contribute to the enhancement and spreading of gender competent legal knowledge.
The Evolving Recognition of Gender in International and European Law
Authors: Argren Rigmor , Evola Marco , Giegerich Thomas , Krstić Ivana
Published: January 2023

This chapter explains the development of international and European law from a gender perspective and describes how the process from a gender-neutral to a gender-sensitive approach was developed.

Since 1945 and the adoption of the UN Charter, the idea of achieving greater gender equality was merged into many international documents, including the first catalog of women’s rights—Convention on the Elimination of all Forms of Discrimination against Women. Many principal and subsidiary bodies were established, contributing to the elimination of gender discrimination and to awareness-raising on some critical issues which were an impediment to achieving gender equality. Twenty years ago, UN Security Council Resolution 1325 was adopted, due to a global effort to establish a platform as a foundation to national and international policies to ensure greater protection of women and girls, during and after, armed conflicts. International Humanitarian Law, enshrined in the Geneva Conventions, also has rules that specifically seek to protect women during armed conflicts. Also, International Criminal Law has been developed to recognize extreme forms of sexual violence as international crimes.

On the European level, under the auspices of the Council of Europe, several international conventions were adopted to achieve gender equality. One of the main instruments, the European Convention on Human Rights, provides broad protection from discrimination based on gender, established in a comprehensive jurisprudence of the European Court of Human Rights. The EU has a set of primary and secondary sources on anti-discrimination, which provides comprehensive protection from gender discrimination and serves as an inspiring model to States candidates and other European countries.
Flexible Dienstleistungsarbeit gesundheitsförderlich gestalten – zur Einführung
Authors: Becke Guido , Koppelin Frauke
Published: January 2023

Flexible und interaktive Dienstleistungsarbeit ist mit Blick auf ihre gesundheitlichen Auswirkungen und gesundheitsfördernde Interventionsansätze noch unzureichend erforscht. Hier setzt das BMBF-geförderte Verbundprojekt FlexiGesA an. Dieser einführende Beitrag konzeptualisiert zunächst flexible und interaktive Dienstleistungsarbeit. Sodann wird hierzu der gesundheitsbezogene Forschungs- und Gestaltungsbedarf aufgezeigt. Danach wird das Verbundprojekt FlexiGesA einschließlich des Forschungsdesigns und der Verbundarchitektur vorgestellt. Die Coronapandemie bedeutete für FlexiGesA eine tiefgreifende Herausforderung. Daher werden erfolgte Anpassungen von Forschungsdesign und -methoden skizziert und beschrieben, wie die Pandemie als Gegenstand der Forschung adressiert wurde. Abschließend werden Gemeinsamkeiten gesundheitsförderlicher Gestaltung flexibler und interaktiver Dienstleistungsarbeit in der IT-Dienstleistung und den ambulanten sozialen Diensten – als empirische Forschungs- und Entwicklungsfelder in FlexiGesA – herausgestellt.
Gender – eine zentrale Kategorie der gesundheitsfördernden Gestaltung von Interaktionsarbeit
Authors: Pieck Nadine , Koppelin Frauke
Published: January 2023

Gender ist eine zentrale Analysekategorie zur gesundheitsförderlichen Gestaltung von Interaktionsarbeit. Gender und Geschlecht sind soziale Kategorien, die Wahrnehmungs- Deutungs- und Bewertungsmuster strukturieren, unterschiedliche Erwartungen an Frauen und Männer, Aufgabenzuweisungen sowie Ressourcenausstattung zur Folge haben. In Branchen mit einem hohnen Anteil an Interaktionsarbeit arbeiten überwiegend Frauen, die von einer fehlenden Anerkennung und schlechten Gestaltung von Interaktionsarbeit betroffen sind. Die unterschiedlichen Emotionsregeln in Organisationen nach Geschlecht führen zu spezifischen Bewältigungsmöglichkeiten für Frauen und Männer. Zudem ist Gender Gegenstand der Interaktonsarbeit und erfordert einen reflektierten Umgang z. B. mit den Geschlechtsrollenerwartungen der Klient:innen oder Patient:innen. Für eine gesundheitsförderliche Gestaltung ist Gender theoretisch fundiert als Analysekategorie mitzuführen.
Agile Projektarbeit in der Pandemie – Gesundheitsressourcen entwickeln und regenerieren unter widrigen Umständen
Authors: Zenz Cora , Becke Guido , Pöser Stephanie
Published: January 2023

In diesem Beitrag wird untersucht, wie sich Gesundheitsressourcen bei agiler Projektarbeit unter widrigen Umständen der Coronapandemie entwickeln. Am Beispiel der Gesundheitsressourcen des Empowerments und der sozialen Zugehörigkeit wird verdeutlicht, dass Gesundheitsressourcen organisationaler Aufmerksamkeit bedürfen, damit sie langfristig erhalten und – in Krisen bzw. im Falle ihrer Beeinträchtigung – auch regeneriert werden können. Die Beteiligung der Beschäftigten bildet hierzu eine unverzichtbare Voraussetzung.
Quantitative Evaluation gesundheitsbezogener Interventionen im FlexiGesA-Projekt
Authors: Gerdau-Heitmann Cornelia , Mümken Sarah , Schicktanz Christel , Wiese Birgitt , Koppelin Frauke
Published: January 2023

Der Beitrag stellt die quantitativen Evaluationsergebnisse des FlexiGesA-Projektes dar und zeigt inwieweit ausgewählte betriebliche Gesundheitsförderungsmaßnahmen gesundheitliche Verbesserungen bei den Beschäftigten im Zeitverlauf erzielen. Bei den Interventions- und Referenzbetrieben der Branchen IT-Services und ambulante soziale Dienste (ASD) (Unter ambulante soziale Dienste (ASD) sind im Folgenden die ambulante Pflege und auch weitere Dienste, wie insbesondere die haushaltswirtschaftliche Versorgung pflegebedürftiger Menschen in ihrer Häuslichkeit, gemeint) wurden psychische Gefährdungsbeurteilungen eingeleitet. Im linearen Multilevel-Regressionsmodell konnte insgesamt kein signifikanter Effekt für die ausgewählten Outcome-Variablen wie allgemeiner Gesundheitszustand,Präsentismus und Burnout ermittelt werden. Tendenziell zeigen allerdings die deskriptiven Auswertungen aller Skalen und im Abgleich mit einer deutschlandweit erhobenen Datenbank in einigen Bereichen positive Ergebnisse.
Subjektivierung von Arbeitskraft in der ambulanten Pflege und den IT-Dienstleistungen – Ethische Herausforderungen
Authors: Stange Lena
Published: January 2023

Im gesundheitsbezogenen Diskurs um die Subjektivierung von Arbeitskraft und ihre Folgen für die psychische Gesundheit von Beschäftigten wird der Fokus bislang auf Verhaltens- und Verhältnisprävention, die vermehrte Umsetzung der Gefährdungsbeurteilung psychischer Belastung sowie Möglichkeiten des Umgangs mit solchen Belastungen am Arbeitsplatz gelegt. Neue Strukturen der Arbeitsorganisation und ihre vielschichtigen Herausforderungen werfen jedoch auch ethische Fragen guter Führung auf. Der empirisch angereicherte Beitrag widmet sich der Situation psychischer Arbeitsgesundheit in der ambulanten Pflege und den IT-Dienstleistungen und zeigt für den arbeits- und gesundheitswissenschaftlichen Fachdiskurs relevante ethische Problemfelder auf.
Global generalized solvability in a strongly degenerate taxis-type parabolic system modeling migration–consumption interaction
Authors: Winkler Michael
Published: January 2023

The parabolic problem $$\begin{aligned} \left\{ \begin{array}{l} u_t=\Delta \big (u\phi (v)\big ), \\ v_t=\Delta v-uv, \end{array} \right. \end{aligned}$$

u
t

=
Δ

(

u
ϕ

(
v
)

)

,

v
t

=
Δ
v
-
u
v
,

is considered in smoothly bounded subdomains of $${\mathbb {R}}^n$$

R

n

with arbitrary $$n\ge 1$$

n
≥
1

. Under the assumptions that $$\phi \in C^0([0,\infty )) \cap C^3((0,\infty ))$$

ϕ
∈

C
0

(

[
0
,
∞
)

)

∩

C
3

(

(
0
,
∞
)

)

is positive on $$(0,\infty )$$

(
0
,
∞
)

and satisfies $$\begin{aligned} \liminf _{\xi \searrow 0} \frac{\phi (\xi )}{\xi ^\alpha }>0 \quad {\text{ and }} \quad \limsup _{\xi \searrow 0} \big \{ \xi ^\beta |\phi '(\xi )| \big \}<\infty \end{aligned}$$

lim inf

ξ
↘
0

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(
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)

ξ
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>
0

and

lim sup

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{

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|

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)

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}

<
∞

with some $$\alpha >0$$

α
>
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and $$\beta >0$$

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, for all reasonably regular initial data an associated no-flux type initial-boundary value problem is shown to admit a global solution in an appropriately generalized sense. This extends previously developed solution theories on problems of this form, which either concentrated on non-degenerate or weakly degenerate cases corresponding to the choices $$\alpha =0$$

α
=
0

and $$\alpha \in (0,2)$$

α
∈
(
0
,
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, or were restricted to low-dimensional settings by requiring that $$n\le 2$$

n
≤
2

.
Novel fluorinated pyrazole-based heterocycles scaffold: cytotoxicity, in silico studies and molecular modelling targeting double mutant EGFR L858R/T790M as antiproliferative and apoptotic agents
Authors: Fayed Eman A. , Gohar Nirvana A. , Bayoumi Ashraf H. , Ammar Yousry A.
Published: January 2023

Hepatocellular carcinoma (HCC), also known as hepatoma, is the most prevalent type of primary liver cancer. It begins in the hepatocytes, the liver’s major cell type. Cancer that began in another region of the body but has spread to the liver is known as secondary cancer of life; several still unmet demands for better, less toxic therapy to treat this malignant tumor. Several novel pyrazolo[1,5-a]pyrimidine derivatives were synthesized as part of our goal to develop promising anticancer drugs. All the synthesized hybrids have been screened for their cytotoxicity effect against three cancer cell lines which are; HepG-2, HCT-116, and MCF-7. The liver cancer cells were found to be the most sensitive to the effect of the new molecules. A subsequent set of in vitro biological evaluation studies has been conducted on the most promising derivatives to identify their effect on such a cancer type. In HepG-2 cells, four derivatives (8a, 8b, 10c, and 11b) demonstrated good anticancer activity. The most efficacious compounds were 8b and 10c, which had IC50 values of 2.36 ± 0.14 and 1.14 ± 0.063 μM, respectively, higher than the reference medication Imatinib. The latter’s putative molecular effect has been investigated further by looking at its influence on the cell cycle, EGFR, and specific apoptotic and anti-apoptotic markers in HepG-2 cells. These findings indicated that 8b and 10c could trigger apoptosis by upregulating BAX and caspase-3 and cell cycle at the Pre-G1 and G2-M stages. The compounds 8b and 10c showed high potency for EGFR with IC50 equal to 0.098 and 0.079 μM, respectively. Compound 10c had the most effective inhibitory activity for EGFR L858R-TK with IC50 (36.79 nM). Additionally, in silico ADMET and docking studies were done for the most active hits, representing good results.

Graphical Abstract
Bronchialkarzinom: Metastasierungspfade und Involvierung hilärer und mediastinaler Lymphknoten
Authors: Glandorf Julian , Vogel-Claussen Jens
Published: January 2023

Bedeutung des Lungenkarzinoms

Das Lungenkarzinom hat aufgrund seiner hohen Prävalenz und Mortalität enorme sozioökonomische Auswirkungen auf unsere Gesellschaft. Für das Jahr 2022 wurden ca. 59.700 Neuerkrankungen an Lungenkrebs prognostiziert.

TNM-Schema zur Stadieneinteilung

Die korrekte Ausbreitungsdiagnostik ist für die Therapieplanung, Prognoseabschätzung und zukünftige Analysen von grundlegender Bedeutung. Die Stadieneinteilung des Lungenkarzinoms erfolgt nach dem TNM-Schema der Union for International Cancer Control (UICC). Für die Stadien IIB–IIIC wird der Lymphknotenbefall zur Differenzierung herangezogen.

Lymphknotenstationen beim Lungenkarzinom

Die Kenntnis der intrathorakalen Lymphknotenstationen ist für die genaue Klassifikation von entscheidender Bedeutung, und deren Befall hat unmittelbare Auswirkungen auf die Therapie. Die International Association for the Study of Lung Cancer (IASLC) hat eine vereinheitlichte Lymphknotenkarte vorgeschlagen, die sich durch ihre exakten anatomischen Definitionen auszeichnet und in der aktuellen S3-Leitlinie für das Lungenkarzinom berücksichtigt wird. Der Lymphknotenbefall wird abhängig vom Ausmaß in N0–N3 stratifiziert. Je nach Lokalisation des Primärtumors lassen sich bevorzugte Metastasierungspfade nachweisen. Die Krankheitslast hat einen größeren Einfluss auf das Überleben als die Lokalisation der Metastasen.

Ausbreitungsdiagnostik beim Lungenkarzinom

Mit der Computertomographie (CT) kann die Operabilität des Primärtumors meistens sicher beurteilt werden. Invasive Verfahren zur Diagnosesicherung durch Probengewinnung sollten erst im Anschluss an nichtinvasive Diagnostik eingesetzt werden.

Empfehlung für die Praxis

In der aktuellen Leitlinie des Lungenkarzinoms wird bei allen Patienten mit nichtkleinzelligem Lungenkarzinom, die einer kurativen Resektion zugeführt werden, eine systematische Lymphknotenresektion empfohlen.
Favorable rates of return to activity and work following lateral closing wedge distal femoral osteotomy for femoral-based symptomatic varus malalignment: an analysis at a mean 6-year follow-up
Authors: Rupp Marco-Christopher , Themessl Alexander , Merkle Michael , Insam David , Hinz Maximilian , Breulmann Franziska L. , Achtnich Andrea , Mehl Julian , Siebenlist Sebastian , Muench Lukas N.
Published: January 2023

Purpose

To evaluate return to sport (RTS), work (RTW) and clinical outcomes following lateral closing wedge distal femoral osteotomy (LCW-DFO) for symptomatic femoral varus malalignment.

Methods

Consecutive patients who underwent LCW-DFO for symptomatic varus malalignment between 12/2007 and 03/2018 were included. The International Knee Documentation Committee (IKDC) Score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lysholm score, Tegner Activity Scale, and visual analogue scale (VAS) for pain were collected preoperatively and at a minimum of 24 months postoperatively. RTS and RTW were assessed by questionnaire.

Results

Thirty-two patients (mean age: 45.9 ± 12.3 years), who underwent LCW-DFO for femoral-based varus malalignment (6.4 ± 3.0°), were included at a mean follow-up of 72.7 ± 39.1 months. The patient collective significantly improved in IKDC (51.8 ± 12.3 to 61.8 ± 21.5, p = 0.010; 95% CI = 3–21), WOMAC (26.7 ± 17.6 to 12.5 ± 13.5; p < 0.001; 95% CI = 21–6) and Lysholm (46.5 ± 19.4 to 67.9 ± 22.8 points (p < 0.01; 95% CI = 9–31)) scores at final follow-up. The VAS for pain reduced significantly postoperatively (4.8 ± 2.3 points to 2.6 ± 2.3 points (p = 0.002; 95% CI = 0–3)). Following LCW-DFO, 96% of patients returned to sports at a mean of 5.3 ± 2.9 months. Yet, a shift to lower impact sports compared to one year preoperatively was observed, with patients participating in a significantly lower number of high-impact disciplines (p = 0.024) and fewer hours in high-impact sports (p = 0.034). Twenty-three out of 24 patients returned to work at a mean 11.4 ± 10.9 weeks, with 18 patients reporting a similar or superior working ability.

Conclusion

Undergoing isolated LCW-DFO for symptomatic femoral-based varus malalignment enabled the vast majority of patients to RTS and RTW along with a significant functional improvement at mid-term follow-up. However, patients’ expectations have to be adequately managed regarding a limited probability to return to high-impact sports and work after surgery.

Level of evidence

Retrospective case series; Level IV.
Does Surgeon Volume Impact Morbidity Following Parathyroidectomy? A Study of 16,140 Parathyroidectomies from the UK Registry of Endocrine and Thyroid Surgery (UKRETS) Database
Authors: Rajan Sendhil , Gracie Dale , Aspinall Sebastian
Published: January 2023

Background

Outcomes in endocrine surgery have been shown to improve with surgeon volume. We aimed to study the effect of surgeon volume on morbidity following parathyroidectomy.

Methods

UKRETS data from 2004 to 2019 was studied. Parathyroidectomies for primary hyperparathyroidism with complete data were included. Exclusion criteria were age <18 or >80 years; surgeons contributing <10 cases overall; and length of stay >28 days. Multivariable analysis was performed. Primary outcome was persistent hypercalcaemia; secondary outcomes were haemorrhage, length of stay, need for re‐admission, post‐operative hypocalcaemia, and need for calcium/vitamin D supplements to maintain eucalcaemia at 6 months.

Results

153 surgeons undertook mean 22.5 (median 17, range 2–115) parathyroidectomies/year. Persistent hypercalcaemia affected 4.8% (776/16140) overall; 5.7% (71/1242) in surgeons undertaking < 10 cases/year; 5.1% (3339/6617) for 10–30 cases/year; 5.0% (270/5397) for 30–50 cases; and 3.3% (96/2884) for >50 cases/year. High‐volume (>50 parathyroidectomies/year) surgeons operated 23.4% (809/3464) of negative localisation cases compared to 16.4% (2074/12676) of positive localisation cases. Persistent hypercalcaemia was almost twice as common in image negative (7.9%) compared to image‐positive (4%) cases. Persistent hypercalcaemia was significantly more likely to occur in the low volume (<10 parathyroidectomies/year) group than high volume (>50 parathyroidectomies/year), regardless of image positivity (p = 0.0006). Surgeon volume significantly reduced persistent hypercalcaemia on multivariable analysis (OR = 0.878, 95%CI 0.842–0.914, p < 0.001), along with age, sex, and positive localisation. BNE and re‐operation significantly increased persistent hypercalcaemia. Post‐operative hypocalcaemia occurred in 3.2% (509/16040) and was reduced with increasing surgeon volume (OR = 0.951, 95%CI 0.910–0.993, p < 0.001). Haemorrhage and length of stay were not significantly associated with surgeon volume.

Conclusion

The incidence of persistent hypercalcaemia, post‐operative hypocalcaemia, and persistent hypoparathyroidism decreased with increasing surgeon volume. The relative reduction in persistent hypercalcaemia with surgeon volume was similar in image negative and positive groups, but the absolute reduction was higher in image negative cases. Restricting image negative parathyroidectomy to high‐volume surgeons could be considered.
Interannual snowfall variations in Central Asia and their association with ENSO and stratospheric polar vortex during winter
Authors: Chen Ping , Yao Junqiang , Mao Weiyi
Published: January 2023

As a major source of moisture in Central Asia (CA), snowfall may significantly impact agriculture and economics in CA. The study has investigated the dominant modes of snowfall frequency during winter over CA and associated mechanisms. The first EOF mode (EOF1) of snowfall frequency corresponds to a homogeneous pattern over CA. In contrast, the second EOF mode (EOF2) is characterized by reversed anomalies over northern and southern CA. The mechanisms of the interannual variation of the two leading modes are different. EOF1 is influenced by the sea surface temperature anomalies (SSTA) over the North Atlantic and eastern tropical Pacific. Positive SSTA in the eastern tropical Pacific may stimulate a zonal wave train that propagates eastward and induce an anomalous cyclone in CA. The anomalous cyclone associated with ascending motions and water vapor transport convergence can contribute to increased snowfall frequency over CA. Besides, the interaction between the North Atlantic Oscillation and North Atlantic triple SSTA may also strengthen the zonal wave train. EOF2 is affected by the stratospheric polar vortex which is related to the wave reflections in winter. The wave reflections may strengthen the coupling of atmospheric circulation in the stratosphere and the troposphere, inducing a positive (negative) geopotential height anomaly over southern (northern) CA. These geopotential height anomalies may contribute to increased and decreased synoptic-scale wave activity over northern and southern CA which is conducive to the dipole mode of snowfall frequency over CA.
Identification and validation of a PD-L1-related signature from mass spectrometry in gastric cancer
Authors: Chen Xiancong , Mao Deli , Li Dongsheng , Li Wenchao , Wei Hongfa , Deng Cuncan , Chen Hengxing , Zhang Changhua
Published: January 2023

Background

According to the guidelines, PD-L1 expression is a critical indicator for guiding immunotherapy application. According to certain studies, regardless of PD-L1 expression, immunotherapy could be advantageous for individuals with gastric cancer. Therefore, new scoring systems or biomarkers are required to enhance treatment strategies.

Methods

Mass spectrometry and machine learning were used to search for strongly related PD-L1 genes, and the NMF approach was then used to separate gastric cancer patients into two categories. Differentially expressed genes (DEGs) between the two subtypes identified in this investigation were utilized to develop the UBscore predictive model, which was verified by the Gene Expression Omnibus (GEO) database. Coimmunoprecipitation, protein expression, and natural killing (NK) cell coculture experiments were conducted to validate the findings.

Results

A total of 123 proteins were identified as PD-L1 interactors that are substantially enriched in the proteasome complex at the mRNA level. Using random forest, 30 UPS genes were discovered in the GSE66229 cohort, and ANAPC7 was experimentally verified as one of 123 PD-L1 interactors. Depending on the expression of PD-L1 and ANAPC7, patients were separated into two subgroups with vastly distinct immune infiltration. Low UBscore was related to increased tumor mutation burden (TMB) and microsatellite instability-high (MSI-H). In addition, chemotherapy medications were more effective in individuals with a low UBscore. Finally, we discovered that ANAPC7 might lead to the incidence of immunological escape when cocultured with NK-92 cells.

Conclusion

According to our analysis of the PD-L1-related signature in GC, the UBscore played a crucial role in prognosis and had a strong relationship with TMB, MSI, and chemotherapeutic drug sensitivity. This research lays the groundwork for improving GC patient prognosis and treatment response.
Klinische Wirksamkeit der aurikulären Vagusnervstimulation in der Behandlung chronischer und akuter Schmerzen
Authors: Likar Rudolf , Perruchoud Christophe , Kampusch Stefan , Köstenberger Markus , Sator Sabine , Stremnitzer Caroline , Wolf Andreas , Neuwersch-Sommeregger Stefan
Published: January 2023

Hintergrund

Aktuelle Leitlinien empfehlen für die Behandlung chronischer Schmerzen einen personalisierten, multimodalen und interdisziplinären Ansatz. Bereits in der akuten Behandlung postoperativer Schmerzen kann es sinnvoll sein, Risikofaktoren für die Chronifizierung zu minimieren. Die aurikuläre Vagusnervstimulation (aVNS) könnte eine effektive nichtmedikamentöse Therapie zur Behandlung von Schmerzen darstellen.

Ziel der Arbeit

Ziel dieser Arbeit ist die Evaluierung der klinischen Wirksamkeit der aVNS bei chronischen und akuten Schmerzen sowie deren Einfluss auf die begleitende Medikamenteneinnahme.

Material und Methoden

Es wurde eine systematische Literaturrecherche zur Anwendung aurikulärer elektrischer Stimulation bei chronischen und akuten Schmerzen durchgeführt. Die Studien wurden entsprechend ihrem Evidenzgrad klassifiziert, gemäß Jadad-Skala und wissenschaftlicher Validität bewertet, und anschließend in Bezug auf Indikation, Methode, Stimulationsparameter, Behandlungsdauer, Wirksamkeit und Sicherheit analysiert.

Ergebnisse

Es konnten 20 Studien zu chronischen Schmerzindikationen, 10 Studien zu akuten postoperativen Schmerzen sowie 7 Studien zu experimentellen akuten Schmerzen identifiziert und analysiert werden. Die Recherche ergab eine Gesamtanzahl von n = 1105 mit aVNS behandelten Patient*innen. Die beste Evidenz zur Wirksamkeit der aVNS liegt für die Indikationen chronischer Kreuzschmerz, chronisches Zervikalsyndrom, chronischer Unterleibsschmerz und chronischer Migräne sowie zu akutem postoperativen Schmerz bei Oozytenaspiration, laparoskopischer Nephrektomie und offenen kolorektalen Eingriffen vor. In der Mehrzahl der Studien konnte außerdem eine signifikante Reduktion der Schmerzmittel- bzw. Opiateinnahme gezeigt werden. In 3 randomisierten kontrollierten Studien bei chronischen Schmerzpatient*innen konnte eine nachhaltige Schmerzreduktion über einen Zeitraum von bis zu 12 Monaten gezeigt werden. Insgesamt wurde die aVNS sehr gut vertragen.

Schlussfolgerung

Die Studienlage zeigt, dass die aVNS eine ergänzende, effektive nichtmedikamentöse Behandlung für Patient*innen mit chronischen und akuten postoperativen Schmerzen sein kann. Zukünftige Studien in den genannten Indikationen sollten auf eine Standardisierung und Optimierung von Behandlungsparametern, die stärkere Einbeziehung von Quality-of-Life-Outcome-Parametern sowie längere Follow-up-Perioden zum besseren Verständnis der nachhaltigen therapeutischen Wirkung der aVNS fokussieren.
Mental Health, ART Adherence, and Viral Suppression Among Adolescents and Adults Living with HIV in South Africa: A Cohort Study
Authors: Haas Andreas D. , Lienhard Raphael , Didden Christiane , Cornell Morna , Folb Naomi , Boshomane Tebatso M. G. , Salazar-Vizcaya Luisa , Ruffieux Yann , Nyakato Patience , Wettstein Anja E. , Tlali Mpho , Davies Mary-Ann , von Groote Per , Wainberg Milton , Egger Matthias , Maartens Gary , Joska John A.
Published: January 2023

We followed adolescents and adults living with HIV aged older than 15 years who enrolled in a South African private-sector HIV programme to examine adherence and viral non-suppression (viral load > 400 copies/mL) of participants with (20,743, 38%) and without (33,635, 62%) mental health diagnoses. Mental health diagnoses were associated with unfavourable adherence patterns. The risk of viral non-suppression was higher among patients with organic mental disorders [adjusted risk ratio (aRR) 1.55, 95% confidence interval (CI) 1.22–1.96], substance use disorders (aRR 1.53, 95% CI 1.19–1.97), serious mental disorders (aRR 1.30, 95% CI 1.09–1.54), and depression (aRR 1.19, 95% CI 1.10–1.28) when compared with patients without mental health diagnoses. The risk of viral non-suppression was also higher among males, adolescents (15–19 years), and young adults (20–24 years). Our study highlights the need for psychosocial interventions to improve HIV treatment outcomes—particularly of adolescents and young adults—and supports strengthening mental health services in HIV treatment programmes.
Robust Federated Learning for execution time-based device model identification under label-flipping attack
Authors: Sánchez Sánchez Pedro Miguel , Huertas Celdrán Alberto , Buendía Rubio José Rafael , Bovet Gérôme , Martínez Pérez Gregorio
Published: January 2023

The computing device deployment explosion experienced in recent years, motivated by the advances of technologies such as Internet-of-Things (IoT) and 5G, has led to a global scenario with increasing cybersecurity risks and threats. Among them, device spoofing and impersonation cyberattacks stand out due to their impact and, usually, low complexity required to be launched. To solve this issue, several solutions have emerged to identify device models and types based on the combination of behavioral fingerprinting and Machine/Deep Learning (ML/DL) techniques. However, these solutions are not appropriate for scenarios where data privacy and protection are a must, as they require data centralization for processing. In this context, newer approaches such as Federated Learning (FL) have not been fully explored yet, especially when malicious clients are present in the scenario setup. The present work analyzes and compares the device model identification performance of a centralized DL model with an FL one while using execution time-based events. For experimental purposes, a dataset containing execution-time features of 55 Raspberry Pis belonging to four different models has been collected and published. Using this dataset, the proposed solution achieved 0.9999 accuracy in both setups, centralized and federated, showing no performance decrease while preserving data privacy. Later, the impact of a label-flipping attack during the federated model training is evaluated using several aggregation mechanisms as countermeasures. Zeno and coordinate-wise median aggregation show the best performance, although their performance greatly degrades when the percentage of fully malicious clients (all training samples poisoned) grows over 50%.