bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrinsic Ohmic Contacts and Polarity‐Tunable Schottky Barriers in M8X12–Graphene (M = Mo, W; X = S, Se) van der Waals Heterostructures for High‐Performance and Bipolar Device Applications
Authors: Xu Yuehua , Zeng Qiang
Published: July 2024

Considering the synthesis of novel 2D monolayers such as W8Se12, which are ideal for nanoelectronics, in this study, density‐functional theory is utilized to examine M8X12/G (M = Mo, W; X = S, Se) van der Waals heterostructures (vdWHs). Herein, the crucial role of intrinsic Ohmic contacts and Schottky barrier heights (SBH) at metal/semiconductor interfaces in these heterojunctions, which are vital for efficient current flow and minimal resistance, and their impact on high‐performance electronic and bipolar device applications are focused on. In these findings, it is revealed that W8Se12/G forms an Ohmic contact with a 75.4% tunneling probability, while Mo8S12/G, W8S12/G, and Mo8Se12/G develop n‐type Schottky contacts with remarkably low SBHs of 0.110, 0.136, and 0.064 eV, respectively. The adaptability of these Schottky barriers is demonstrated by modifying the interlayer distance or applying an electric field, leading to transitions from n‐type to p‐type contacts. Additionally, mechanical strain influences the contact type, offering valuable insights for future nanoelectronic and bipolar device technologies. This comprehensive analysis underlines the versatile electronic behavior of M8X12/G vdWHs, highlighting their potential in advancing nanoelectronic devices.
Critical Posthumanist Literacy: Building Theory for Reading, Writing, and Living Ethically with Everyday Artificial Intelligence
Authors: Burriss Sarah K. , Leander Kevin
Published: July 2024

Literacy has become inextricably bound with machine processes, especially in the age of ubiquitous, consequential artificial intelligence (AI). Despite a relatively long history of AI involvement in our everyday reading and writing practices, the public availability of generative AI tools has set off a wave of heated debate—and concern—about AI's role in our lives. We argue that critical literacy theory and tools can serve as a foundation, when combined with posthumanist ideas and some technical knowledge, for understanding, teaching, and participating in our AI‐infused world. In this paper, we outline our theory of critical posthumanist literacy, which draws on posthumanist scholarship to re‐imagine critical literacy with respect to concepts of ontology, agency, ethics and justice, and pedagogy. For each concept, we build on humanist, critical perspectives to show how posthumanist scholarship can help theorize for literacy in the age of AI, especially as AI presents both lingering and new challenges to conceptions of human text production and consumption. Posthumanism provides us with alternative modes of thinking about the nature of “things” (and ourselves); with an understanding of agency as not a human possession but an accomplishment among/within many human and non‐human actors; with an expanded ethics that accounts more deeply for non‐humans; and with pedagogy that embraces ambiguity, movement, and speculation. Using these ideas to expand critical literacy practices, we offer concepts and questions for guiding literacy practice and research, with the understanding that these are no longer separable from complex computational systems.
Cover and hitting times of hyperbolic random graphs
Authors: Kiwi Marcos , Schepers Markus , Sylvester John
Published: July 2024

We study random walks on the giant component of Hyperbolic Random Graphs (HRGs), in the regime when the degree distribution obeys a power law with exponent in the range . In particular, we first focus on the expected time for a random walk to hit a given vertex or visit, that is, cover, all vertices. We show that, a.a.s. (with respect to the HRG), and up to multiplicative constants: the cover time is , the maximum hitting time is , and the average hitting time is . We then determine the expected time to commute between two given vertices a.a.s., up to a small factor polylogarithmic in , and under some mild hypothesis on the pair of vertices involved. Our results are proved by controlling effective resistances using the energy dissipated by carefully designed network flows associated to a tiling of the hyperbolic plane, on which we overlay a forest‐like structure.
An AIoT‐driven smart healthcare framework for zoonoses detection in integrated fog‐cloud computing environments
Authors: Verma Prabal , Gupta Aditya , Jain Vibha , Shashvat Kumar , Kumar Mohit , Gill Sukhpal Singh
Published: July 2024

The escalating threat of easily transmitted diseases poses a huge challenge to government institutions and health systems worldwide. Advancements in information and communication technology offer a promising approach to effectively controlling infectious diseases. This article introduces a comprehensive framework for predicting and preventing zoonotic virus infections by leveraging the capabilities of artificial intelligence and the Internet of Things. The proposed framework employs IoT‐enabled smart devices for data acquisition and applies a fog‐enabled model for user authentication at the fog layer. Further, the user classification is performed using the proposed ensemble model, with cloud computing enabling efficient information analysis and sharing. The novel aspect of the proposed system involves utilizing the temporal graph matrix method to illustrate dependencies among users infected with the zoonotic flu and provide a nuanced understanding of user interactions. The implemented system demonstrates a classification accuracy of around 91% for around 5000 instances and reliability of around 93%. The presented framework not only aids uninfected citizens in avoiding regional exposure but also empowers government agencies to address the problem more effectively. Moreover, temporal mining results also reveal the efficacy of the proposed system in dealing with zoonotic cases.
Learning to evaluate sources of science (mis)information on the internet: Assessing students' scientific online reasoning
Authors: Pimentel Daniel R.
Published: July 2024

Students frequently turn to the internet for information about a range of scientific issues. However, they can find it challenging to evaluate the credibility of the information they find, which may increase their susceptibility to mis‐ and disinformation. This exploratory study reports findings from an instructional intervention designed to teach high school students to engage in scientific online reasoning (SOR), a set of competencies for evaluating sources of scientific information on the internet. Forty‐three ninth grade students participated in eleven instructional activities. They completed pre and post constructed response tasks designed to assess three constructs: evaluating conflicts of interest, relevant scientific expertise, and alignment with scientific consensus. A subset of students (n = 6) also completed pre and post think‐aloud tasks where they evaluated websites of varying credibility. Students' written responses and screen‐capture recordings were scored, coded, and analyzed using a mixed‐methods approach. Findings from the study demonstrate that after the intervention: (1) students' assessment scores improved significantly on all three tasks, (2) students improved in their ability to distinguish between sources of online scientific information of varying credibility, and (3) more students used online reasoning strategies and outside sources of information. Areas for student growth are also identified, such as improving coordinated use of credibility criteria with online reasoning strategies. These results suggest that teaching criteria for the credibility of scientific information, along with online reasoning strategies, has the potential to help students evaluate scientific information encountered on the internet.
Efficient and Powerful Integration of Targeted Metabolomics and Transcriptomics for Analyzing the Metabolism Behind Desirable Traits in Plants
Authors: Johnston Christopher R. , Arias Cintia L. , Alonso Ana Paula
Published: July 2024

Through current mass spectrometry methods and multiple RNA-Seq technologies, large metabolomics and transcriptomics datasets are readily obtainable, which provide a powerful and global perspective on metabolism. Indeed, one “omics” method is often not enough to draw strong conclusions about metabolism. Combining and interpreting multiple “omics” datasets remains a challenging task that requires careful statistical considerations and pre-planning. Here we describe a protocol for obtaining high-quality metabolomics and transcriptomics datasets in developing plant embryos followed by a robust approach to integration of the two. This protocol is readily adjustable and scalable to any other metabolically active organ or tissue.
How Are Gene Editing Technologies Regulated in the Agrifood System?
Authors: Clark Lisa F. , Hobbs Jill E.
Published: July 2024

This chapter examines current governance and regulatory frameworks for gene edited agrifoods. We outline the role of international organizations, particularly the OECD, in facilitating the development of national-level policies toward gene editing. We detail the risk assessment regimes of countries with regulatory frameworks for biotechnologies, providing a summary of the current state of gene editing regulations in these countries. Our analysis places national-level regulatory frameworks into five categories: light regulation, strongly regulated and prohibited, proposed regulation, modified process, and no regulation. We describe how governing gene edited agrifoods requires balancing innovation with considerations of risk and benefits to the economy, society, and the environment. Finally, we discuss the Canadian case in greater detail to illustrate how deliberative governance has been employed in the regulation of gene edited agricultural plants.
Novel Genomic Techniques and Applications on the Horizon
Authors: Clark Lisa F. , Hobbs Jill E.
Published: July 2024

This chapter discusses new breeding techniques (NBTs) and their applications for plants in the agrifood system. We discuss how NBTs can enable other technologies and platforms, then explore new classes of gene editing products in the pipeline. We discuss the pros and cons of gene drive technology. We examine what effect new applications of NBTs may have on the agrifood system, including the potential for future applications of gene editing technology to address pressing issues related to climate change and sustainability. Applications to orphan crops and re-wilding are highlighted. Finally, we explore emerging agrifood applications of gene editing platforms beyond CRISPR-Cas9, including MAD7, base editing, prime editing, and RNAi technologies.
Governing the Unknown: Regulating Future Technologies
Authors: Clark Lisa F. , Hobbs Jill E.
Published: July 2024

This chapter examines how governance structures and regulatory frameworks can respond to emergent new breeding techniques. We discuss how the Cartagena Protocol on Biosafety and the Precautionary Principle continue to shape regulatory systems. Recent developments in the EU’s approach to regulating future biotechnologies are examined. The complex patent, licensing, and freedom to operate landscape for CRISPR and other gene editing technologies is explored. Looking ahead, we argue that using deliberative elements of governance helps stakeholders better identify opportunities and respond to future, unknown technologies that may offer benefits to the challenges facing agricultural food production in the twenty-first century.
Regel als Folter: Gefängnisalltag und die Rolle der guards
Authors: Breger Max
Published: July 2024

Das Kapitel behandelt den Gefängnisalltag in Guantánamo mit seinen strikten Regeln als Teil der Folter und diskutiert die besondere Rolle der guards. Dabei führe ich die These der Dezentralität der Foltergewalt weiter. Denn wie die raumzeitlichen Übergänge im vorangegangenen Kapitel war auch der Alltag außerhalb der Verhöre in den – vor allem militärisch-kontrollierten – Folterorten elementarer Bestandteil der Foltererfahrungen der Gefangenen. Der hierarchisch niedrigen Akteursgruppe der guards kommt dabei deshalb eine große Bedeutung zu, weil sie alltäglich mit den Gefangenen interagierte und als die primäre Vermittlerin der organisationalen Interessen auftrat. Nicht nur hielt sie durch Bewachung der Insassen und Nahrungsvergabe die Gefangenschaft aufrecht. Sie beteiligte sich auch unmittelbar an der Folter, indem sie ein konditionierendes Privilegiensystem durchsetzte und Strafgewalt ausführte.
Gefolterte zwischen Ohnmacht und Widerständigkeit
Authors: Breger Max
Published: July 2024

Das Kapitel diskutiert die massiv eingeschränkte und ambivalente Handlungsfähigkeit von Gefolterten. Phänomenologisch-theoretische Auseinandersetzungen mit Folter skizzieren in Anschluss an Jean Amery und Elaine Scarry für gewöhnlich eine maximale Machtdifferenz, die dem Opfer keine agency mehr lässt. Bei genauerer Betrachtung erfahren sich Gefolterte ihres Ausgeliefertseins zum Trotz durchaus als handelnd und teils sogar widerständig. Denn zum einen adressiert die Folter sie, beispielsweise bei instrumenteller Machtausübung über Konditionierungslogik, als handlungsfähige Subjekte. Zum anderen können Gefolterte auch eigenständige agency entwickeln, also solche, die nicht von den Folternden intendiert (oder ‚gesteuert‘) wurde wie kollektive Hungerstreiks oder religiöse Handlungen.
Methodisches Vorgehen I: Theoretische Zugänge
Authors: Breger Max
Published: July 2024

Leiblicher Schmerz ist nicht direkt kommunizierbar. Daher stellt sich die Frage, wie er und andere leibliche Erfahrungen in sozialwissenschaftlicher Erforschung von Folter beschreibbar gemacht und in empirische Analysen einbezogen werden können. Dieses Problem wird noch dadurch verstärkt, dass der Zugang zu Folter nur indirekt ist. Zum anderen stellt sich die forschungsethische Frage, wie mit einem solch sensiblen Thema umgegangen werden sollte, insbesondere, wenn man empirisch auf Foltersituationen schauen möchte und nicht nur auf legitimierende Diskurse. In diesem Kapitel lege ich dar, wie ich diesen Problemen begegnet bin, und stelle meinen methodischen Zugang im Stil der Grounded Theory und Situationsanalyse vor.
Foltersituationen: Phänomenologische und soziologische Vorüberlegungen
Authors: Breger Max
Published: July 2024

Das Kapitel stellt theoretische Überlegungen anhand der Folterdefinition der Vereinten Nationen sowie von soziologischer, phänomenologischer sowie weiterer folterbezogener Literatur darüber an, was Folter(-situationen) und ihre Funktionsweise ausmacht. Ausgangspunkt ist ein interaktionstheoretisches Verständnis von sozialen Situationen als raumzeitliche Einheiten, die im Sinne Erving Goffmans durch gegenseitige Präsenz und Wahrnehmbarkeit von Interaktionspartner:innen definiert ist. Foltersituationen zeichnen sich durch eine extreme Machtungleichheit aus, denn Folternde nutzen ihre Übermacht und die vielfältigen Verletzbarkeiten des Menschen aus, um Gefangene mittels Gewalt in Leiden zu versetzen. Dabei ist Folter als ein intersubjektiver Prozess zu verstehen. Gefolterte sind zudem nicht rein passiv leidende Opfer, deren agency vollständig zerstört ist. Foltersituationen sind daher trotz ihrer extremen Asymmetrie soziale Situationen.
Methodisches Vorgehen II: Datenkorpus
Authors: Breger Max
Published: July 2024

Das Kapitel setzt die methodischen Überlegungen von Kapitel 2 fort und führt in das heterogene Datenkorpus ein. Ich nutze (ursprünglich geheime) Dokumente der CIA und des US-Militärs, in denen häufig Wörter oder ganze Passagen geschwärzt sind, Reports von staatlichen oder nicht-staatlichen Untersuchungen, Buchveröffentlichungen und andere Formen von Zeugnissen Folterüberlebender und weiterer Beteiligter, juristische Dokumente sowie vereinzelt Teile von journalistischen Texten. Ich erläutere in diesem Kapitel mein Vorgehen bei Datenerhebung, -selektion und -analyse im Stil der Grounded Theory. Insbesondere reflektiere ich die unterschiedlichen Perspektiven, die in die teils fragmentierten Daten eingeschrieben sind, und die unterschiedliche soziologische Aussagekraft der Daten.
Transfer und Transformation von organisationalem Folterwissen
Authors: Breger Max
Published: July 2024

Das Kapitel betrachtet diachrone 'Flüsse' von Folterwissen. Zum einen fragt das Kapitel nach den historischen Kontinuitäten der im vorangegangenen Kapitel rekonstruierten CIA-Foltertheorie mit militärischen Trainingsprogrammen und dem CIA-Folterwissen im Kalten Krieg. Dabei spielt die Erforschung ‚feindlicher‘ Foltertechniken im Auftrag von US-Militär und CIA ab den 1950er Jahre eine entscheidende Rolle als Wissensquelle. Zum anderen zeichne ich nach, wie sich Folterwissen im War on Terror im militärischen Teil des US-Folterkomplexes ausgehend von Guantánamo verbreitete und in welchem Zusammenhang es mit dem des CIA-Folterprogramm steht.
Jet angularities in dijet production in proton-proton and heavy-ion collisions at RHIC
Authors: Chien Yang-Ting , Fedkevych Oleh , Reichelt Daniel , Schumann Steffen
Published: July 2024

Abstract

We study jet angularities for dijet production at the Relativistic Heavy Ion Collider (RHIC) in proton-proton (pp) and nucleus-nucleus (AA) collisions at 200 GeV nucleon-nucleon center-of-mass collision energy. In particular, we provide NLL resummed predictions for angularity observables of groomed and ungroomed jets produced in pp collisions matched to next-to-leading order QCD calculations resulting in NLO + NLL′ accuracy. Our parton-level predictions are corrected for non-perturbative effects, such as hadronization and underlying event, using parton-to-hadron level transfer matrices obtained with the Sherpa event generator. Furthermore, we use the Q-Pythia and Jewel generators to estimate the impact of the interaction between quarks and gluons produced by the parton shower with the dense medium formed in heavy-ion collisions on the considered jet angularities.
Exploring oak processionary caterpillar induced lepidopterism (Part 1): unveiling molecular insights through transcriptomics and proteomics
Authors: Seldeslachts Andrea , Maurstad Marius F. , Øyen Jan Philip , Undheim Eivind Andreas Baste , Peigneur Steve , Tytgat Jan
Published: July 2024

Lepidopterism, a skin inflammation condition caused by direct or airborne exposure to irritating hairs (setae) from processionary caterpillars, is becoming a significant public health concern. Recent outbreaks of the oak processionary caterpillar (Thaumetopoea processionea) have caused noteworthy health and economic consequences, with a rising frequency expected in the future, exacerbated by global warming promoting the survival of the caterpillar. Current medical treatments focus on symptom relief due to the lack of an effective therapy. While the source is known, understanding the precise causes of symptoms remain incomplete understood. In this study, we employed an advanced method to extract venom from the setae and identify the venom components through high-quality de novo transcriptomics, venom proteomics, and bioinformatic analysis. A total of 171 venom components were identified, including allergens, odorant binding proteins, small peptides, enzymes, enzyme inhibitors, and chitin biosynthesis products, potentially responsible for inflammatory and allergic reactions. This work presents the first comprehensive proteotranscriptomic database of T. processionea, contributing to understanding the complexity of lepidopterism. Furthermore, these findings hold promise for advancing therapeutic approaches to mitigate the global health impact of T. processionea and related caterpillars.
Increased copy-number variant load of associated risk genes in sporadic cases of amyotrophic lateral sclerosis
Authors: Guarnaccia Maria , Morello Giovanna , La Cognata Valentina , La Bella Vincenzo , Conforti Francesca Luisa , Cavallaro Sebastiano
Published: July 2024

Amyotrophic lateral sclerosis (ALS) is an age-related neurodegenerative disease characterized by selective loss of motor neurons in the brainstem and spinal cord. Several genetic factors have been associated to ALS, ranging from causal genes and potential risk factors to disease modifiers. The search for pathogenic variants in these genes has mostly focused on single nucleotide variants (SNVs) while relatively understudied and not fully elucidated is the contribution of structural variants, such as copy number variations (CNVs). Here, we applied an exon-centric aCGH method to investigate, in sporadic ALS patients, the load of CNVs in 131 genes previously associated to ALS. Our approach revealed that CNV load, defined as the total number of CNVs or their size, was significantly higher in ALS cases than controls. About 87% of patients harbored multiple CNVs in ALS-related genes, and 75% structural variants compromised genes directly implicated in ALS pathogenesis (C9orf72, CHCHD10, EPHA4, FUS, HNRNPA1, KIF5A, NEK1, OPTN, PFN1, SOD1, TARDBP, TBK1, UBQLN2, UNC13A, VAPB, VCP). CNV load was also associated to higher onset age and disease progression rate. Although the contribution of individual CNVs in ALS is still unknown, their extensive load in disease-related genes may have relevant implications for the diagnostic, prognostic and therapeutical management of this devastating disorder.
SARS-CoV-2 E protein interacts with BRD2 and BRD4 SEED domains and alters transcription in a different way than BET inhibition
Authors: Lara-Ureña Nieves , Gómez-Marín Elena , Pozuelo-Sánchez Isabel , Reyes José C. , García-Domínguez Mario
Published: July 2024

Bromodomain and extra-terminal (BET) proteins are relevant chromatin adaptors involved in the transcriptional control of thousands of genes. Two tandem N-terminal bromodomains are essential for chromatin attachment through acetyl-histone recognition. Recently, the BET proteins members BRD2 and BRD4 were found to interact with the SARS-CoV-2 envelope (E) protein, raising the question of whether the interaction constitutes a virus hijacking mechanism for transcription alteration in the host cell. To shed light on this question, we have compared the transcriptome of cells overexpressing E with that of cells treated with the BET inhibitor JQ1. Notably, E overexpression leads to a strong upregulation of natural immunity- and interferon response-related genes. However, BET inhibition results in the downregulation of most of these genes, indicating that these two conditions, far from causing a significant overlap of the altered transcriptomes, course with quite different outputs. Concerning the interaction of E protein with BET members, and differing from previous reports indicating that it occurs through BET bromodomains, we find that it relies on SEED and SEED-like domains, BET regions rich in Ser, Asp, and Glu residues. By taking advantage of this specific interaction, we have been able to direct selective degradation of E protein through a PROTAC system involving a dTAG-SEED fusion, highlighting the possible therapeutic use of this peptide for targeted degradation of a viral essential protein.
Brown fat-specific mitoribosomal function is crucial for preventing cold exposure-induced bone loss
Authors: Tian Jingwen , Moon Ji Sun , Nga Ha Thi , Lee Ho Yeop , Nguyen Thi Linh , Jang Hyo Ju , Setoyama Daiki , Shong Minho , Lee Ju Hee , Yi Hyon-Seung
Published: July 2024

This study examines the interplay between ambient temperature, brown adipose tissue (BAT) function, and bone metabolism, emphasizing the effects of cold exposure and BAT mitochondrial activity on bone health. Utilizing ovariectomized (OVX) mice to model primary osteoporosis and BAT-specific mitochondrial dysfunction (BKO) mice, we evaluated the impact of housing temperature on bone density, immune modulation in bone marrow, and the protective role of BAT against bone loss. Cold exposure was found to universally reduce bone mass, enhance osteoclastogenesis, and alter bone marrow T-cell populations, implicating the immune system in bone remodeling under cold stress. The thermogenic function of BAT, driven by mitochondrial oxidative phosphorylation, was crucial in protecting against bone loss. Impaired BAT function, through surgical removal or mitochondrial dysfunction, exacerbated bone loss in cold environments, highlighting BAT’s metabolic role in maintaining bone health. Furthermore, cold-induced changes in BAT function led to systemic metabolic shifts, including elevated long-chain fatty acids, which influenced osteoclast differentiation and activity. These findings suggest a systemic mechanism connecting environmental temperature and BAT metabolism with bone physiology, providing new insights into the metabolic and environmental determinants of bone health. Future research could lead to novel bone disease therapies targeting these pathways.
Asymptotic Criticality of the Navier–Stokes Regularity Problem
Authors: Grujić Zoran , Xu Liaosha
Published: July 2024

The problem of global-in-time regularity for the 3D Navier-Stokes equations, i.e., the question of whether a smooth flow can exhibit spontaneous formation of singularities, is a fundamental open problem in mathematical physics. Due to the super-criticality of the equations, the problem has been super-critical in the sense that there has been a ‘scaling gap’ between any regularity criterion and the corresponding a priori bound (regardless of the functional setup utilized). The purpose of this work is to present a mathematical framework-based on a suitably defined ‘scale of sparseness’ of the super-level sets of the positive and negative parts of the components of the higher-order spatial derivatives of the velocity field—in which the scaling gap between the regularity class and the corresponding a priori bound vanishes as the order of the derivative goes to infinity.
Waveforms from Nuclear Explosions (WFNE) Repository
Authors: Oancea Victoria , Kung Yu-Long , Murphy John R. , Piraino Paul , Given Jeffrey W.
Published: July 2024

A key element of successful nuclear monitoring involves the assessment of any newly acquired data in the light of the vast amount of data previously recorded from historical nuclear explosions. To support this effort, the “Waveforms From Nuclear Explosions (WFNE)” repository was developed and is maintained by Leidos under sponsorship of the Defense Threat Reduction Agency (DTRA) to provide convenient access to such historical data. It is built as a trusted data set, starting from the previous data repository “Nuclear Explosion Database (NEDB)” that was accessed in the past by numerous users in the US and international nuclear explosion monitoring community. WFNE includes detailed information (origin, bulletin, other geophysical data) on all the known 2157 atmospheric, underground, and underwater nuclear explosions detonated in the world between 1945 and 2017. It includes over 82,000 waveforms associated to 802 of the nuclear explosions ranging from digitized analog recordings for the oldest explosions to recent International Monitoring System (IMS) data, in CSS and SAC formats, and their station/instrument information, as collected from many sources. The web-based access and the presentation were updated and modernized and rendered ready for active user access. Users can search, visualize, and download data of interest for their own research. Data continues to be collected from newly identified sources. Recent efforts to rescue pre-digital seismic data via scanning and digitization provide interesting information to be added to WFNE, after completeness and quality checks. WFNE is open for the research community’s access to source parameter data and associated waveforms from worldwide nuclear explosions.
Empagliflozin demonstrates cytotoxicity and synergy with tamoxifen in ER-positive breast cancer cells: anti-proliferative and anti-survival effects
Authors: Karzoon Ahmad , Yerer Mükerrem Betül , Cumaoğlu Ahmet
Published: July 2024

Accumulating evidence suggests that sodium–glucose cotransporter 2 (SGLT2) inhibitors may be effective at eliminating tumor cells. While empagliflozin exhibits nearly the highest selectivity for SGLT2 over SGLT1, its specific impact alone and in combination with tamoxifen remains largely unexplored in estrogen receptor α-positive (ERα +) breast cancer. This study investigated the anticancer effects of empagliflozin and its potential synergy with tamoxifen in MCF-7 breast cancer cells. The individual and combined cytotoxic effects of empagliflozin and tamoxifen were assessed using the xCELLigence system. The activities of AMP-activated protein kinase α (AMPKα), p38 mitogen-activated protein kinase (p38 MAPKα), p70-S6 kinase 1 (p70S6K1), and protein kinase B (Akt) were assessed using Western blotting. The gene expression levels of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and Forkhead box O3a (FOXO3a) were assessed via qPCR. Our results revealed time- and concentration-dependent cytotoxic effects of empagliflozin and tamoxifen whether administered separately or in combination. While tamoxifen exhibits potency with an IC50 value of 17 μM, approximately ten times greater than that of empagliflozin (IC50 = 177 μM), synergistic effects are observed when the concentrations of the two agents approach their respective IC50 values. Additionally, empagliflozin significantly increases AMPKα activity while concurrently inhibiting Akt, p70S6K1, and p38 MAPKα, and these effects are significantly enhanced when empagliflozin is combined with tamoxifen. Moreover, empagliflozin modulates the gene expression, downregulating PGC-1α while upregulating FOXO3a. Empagliflozin exerts anti-proliferative and anti-survival effects by inhibiting mTOR, Akt, and PGC-1α, and it exhibits synergy with tamoxifen in MCF-7 breast cancer cells.

Graphical Abstract

Proposed anticancer mechanism of empagliflozin in MCF-7 breast cancer cells.
Lead and arsenic intoxications by traditional and alternative medicine: men are more sensitive than women
Authors: Gerke Lucia , Seifert Roland
Published: July 2024

Traditional and alternative medicines are widely used around the world and include for example herbal medicine, Ayurveda, traditional Chinese medicine, and indigenous therapies. Due to the long history and the mostly natural origin of traditional remedies, it is often assumed that they are harmless, but in recent decades more and more case reports have been published in which traditional medicine has caused metal poisoning. This paper provides an analysis of published cases in which patients have suffered metal poisoning due to traditional or alternative medicines. A systematic literature search was performed on PubMed, whereby 210 patient cases from a total of 102 case reports and 30 case series were identified and then analyzed about various aspects. Most of the traditional medicines involved come from Asia and are mainly contaminated with lead and arsenic. The analyzed patient cases show a high degree of heterogeneity with regard to age, sex, intake reason, symptoms, and severity of intoxication. The metal intoxication itself and the cause of the poisoning often remained unrecognized for a long time, which resulted in many patients undergoing unnecessary diagnostic methods and ineffective therapeutic approaches before the correct diagnosis was made. The evaluation of the available patient cases revealed a higher sensitivity to metal poisoning in children compared to adults and a higher sensitivity in men compared to women. Anemia and basophilic stippling were frequently observed and became more common as the metal content in the blood increased. Hopefully, this paper raises awareness of the potential dangers of traditional and alternative medicines, both from the patient’s and the doctor’s perspective, so that in case of intoxication, treatment can be initiated quickly using the correct diagnostic methods. As ingested metals do not only circulate in the blood but also accumulate in soft tissues and bones, long-term monitoring is necessary to ensure that patients make a full recovery. Doctors should be aware that, in contrast to common belief, men are more sensitive to this type of intoxication than women, necessitating particular attention for diagnosis and treatment.
Ultrasound-Guided Versus Palpation-Guided Techniques to Achieve Vascular Access in Children Undergoing Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Ibrahim Ahmed A. , Allam Abdallah R. , Amin Ahmed Mazen , Rakab Mohamed Saad , Alhadeethi Abdulhameed , Hageen Ahmed W. , Mahmoud Abdelrahman , Abuelazm Mohamed , Abdelazeem Basel
Published: July 2024

Pediatric heart surgery is a vital therapeutic option for congenital heart disease, which is one of the most prevalent causes of death in children. Arterial cannulation (AC) and central venous catheter (CVC) are required in pediatric cardiac surgery for continuous monitoring of the central venous pressure (CVP), replacement of fluid or blood products, close hemodynamic monitoring, and frequent sampling for arterial blood gases (ABG). A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) retrieved from PubMed, Embase Cochrane, Scopus, and WOS until February 2024. Risk ratio (RR) was used to report dichotomous outcomes, and mean difference (MD) was used to report continuous outcomes, both with a 95% confidence interval (CI) using the random-effects model. Thirteen RCTs with 1060 children were included. Regarding arterial cannulation, the ultrasound-guided technique (US) was associated with a statistically significant increase in successful cannulation [RR: 1.31 with 95% CI (1.10, 1.56), P < 0.0001], and first-attempt success [RR: 1.88 with 95% CI (1.35, 2.63), P < 0.0001]. However, US was not associated with any statistically significant difference in venous cannulation in both outcomes with [RR: 1.13 with 95% CI (0.98, 1.30), P = 0.10], [RR: 1.53 with 95% CI (0.86, 2.71), P = 0.15] respectively. Moreover, US was associated with a statistically significant decrease in the number of attempts either in arterial cannulation with [MD: − 0.73 with 95% CI (− 1.00, − 0.46), P < 0.0001] or in venous cannulation with [MD: − 1.34 with 95% CI (− 2.55, − 0.12), P = 0.03], and the time of attempted cannulation also either in arterial cannulation with [MD: − 2.27 with 95% CI (− 3.38, − 1.16), P < 0.0001] or in venous cannulation with [MD: − 4.13 with 95% CI (− 7.06, − 1.19), P < 0.0001]. US guidance improves successful cannulation rates and first-attempt success in arterial access and reduces the number of attempts and procedural time for arterial and venous access. It was also associated with a lower incidence of complications and procedure failure, particularly in arterial access. However, it was associated with a higher incidence of venous puncture.
Biovalorisation of agro-industrial wastes into astaxanthin by Xanthophyllomyces dendrorhous
Authors: Kanwugu Osman N. , Ibn-Wuni Ibrahim , Shevyrin Vadim A. , Williams Thomas C. , Glukhareva Tatiana V.
Published: July 2024

Astaxanthin is a red xanthophyll with high economic and industrial value in the pharmaceutical, nutraceutical, cosmetic and food industries. In recent years, the biotechnological production of astaxanthin has attracted much attention as a sustainable alternative to the predominating petrochemical-dependent chemical synthesis. In this regard, Xanthophyllomyces dendrorhous is regarded as a promising microorganism for industrial production of astaxanthin. Unfortunately, biotechnological production of the carotenoid is currently expensive. The present study investigated soy molasses (SM) and residual brewers’ yeast as cheap fermentation feedstocks for the cultivation of X. dendrorhous and astaxanthin production. Yeast extract was obtained from residual brewers’ yeast using various techniques and then combined with SM to formulate a two-component growth medium which was subsequently used to cultivate X. dendrorhous. Generally, the yeast extract produced from residual brewers’ yeast supported X. dendrorhous growth and astaxanthin production at levels comparable to those seen with commercial yeast extract. Overall, cultivating X. dendrorhous in an SM-based medium containing 5% SM and 0.2% yeast extract obtained from residual brewers’ yeast resulted in significantly higher (> 20% more) biomass accumulation compared to the control media (YPD). A similar slightly higher astaxanthin output (up to 14% more) was recorded in the SM-based medium compared to YPD. The formulated cultivation medium in this study provides an opportunity to reduce the production cost of astaxanthin from X. dendrorhous while simultaneously reducing the environmental impact related to the disposal of the industrial waste used as feedstock.

Key points

• Cheap culture media were formulated from soy molasses and brewers’ spent yeast

• The formulated medium resulted in at least 20% more biomass than the control

• Up to 14% more astaxanthin was produced in molasses-based medium

Graphical Abstract
Clinical outcomes of two-stage revision arthroplasty using a spiked tibial cement spacer in infected total knee arthroplasty
Authors: Park Ki-Bong , Kim Jong-Min , Lee Bum-Sik , Kim Min-Seok , Park Jae-Hwan
Published: July 2024

Purpose

A tibial cement spacer (TCS) with spikes offers better initial stability than a conventional TCS and reduces spacer-related problems in two-stage revision total knee arthroplasty (R-TKA) for infection. We compared the clinical outcomes of two-stage revision arthroplasty for infected TKA using spiked TCS with that of conventional TCS.

Methods

This retrospective cohort study included 29 patients who underwent two-stage revision arthroplasty using an articulating cement spacer and who could be followed up for at least one year. Group S comprised 14 patients using spiked TCS, whereas Group C comprised 15 patients using conventional TCS. Demographic data, the interval from first to second stage revision, motion arc, numerical rating scale (NRS), Knee Society (KS) score, serum levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and frequency of repeating the first-stage and infection recurrence after R-TKA between the groups were analyzed.

Results

No significant differences were observed in the female ratio and mean age between both groups. The mean interval between the first and second stage revision was significantly shorter in Group S than in Group C. The mean motion arc was significantly larger in Group S than in Group C. The mean NRS was significantly lower in Group S than in Group C. The mean KS score in Group S was significantly higher than that in Group C. Serum ESR and CRP levels did not differ between the groups. The frequency of repeating the first stage was lower in Group S than in Group C. However, the recurrence rate after R-TKA was higher in Group S than in Group C.

Conclusion

Compared with conventional TCS, spiked TCS shortened the period until R-TKA and improved pain and function levels. However, no significant difference existed in the rate of infection recurrence after R-TKA.
Spatio-temporal migratory patterns, habitat crossing and within-individual movement repeatability of Central Mediterranean European Rollers Coracias garrulus
Authors: Monti Flavio , Cannarella Sebastian , Ćiković Davor , Tutiš Vesna , Kralj Jelena , Catoni Carlo , Barišić Sanja
Published: July 2024

Populations of long-distance migratory species may exhibit dissimilarities in the leeway of scheduled annual migration programs, the routes they follow and their convergence at ecological barriers. The aim of this study was to fill the current geographical gap, spanning over 1,100 km longitudinally between southern France and eastern Austria, in the pan-European assessment of the migration ecology of the European Roller Coracias garrulus, and contribute to completing the puzzle of spatio-temporal patterns of migration, stopover and wintering at the Western-Palearctic scale for this species. We utilized high-resolution GPS tracking data from adult Rollers breeding in Italy and Croatia, tracked on their intercontinental seasonal journeys between 2018 and 2022 and modelled the variation of migratory components both at individual and population levels. Rollers from the Central Mediterranean exhibited a clockwise spring migration loop, following a Central African migration route and wintering across a wide longitudinal belt spanning from Namibia to Mozambique. Northern savannah zones were used as long stopovers, both in autumn (Chad/Sudan) and spring (Central African Republic/Cameroon). The probability of movement was significantly higher during the night and in spring. Migration speed varied according to season (> in spring) and the habitat crossed (sea > desert > rainforest > savannah). Individuals tracked in successive years showed high consistency of key migratory parameters and partial winter home ranges overlap, in contrast with the large variability of migratory parameters at the population level. This work bridges the current geographical gap of Roller migration ecology at the European level and helps meet conservation needs at the scale of the species’ flyway, with new ecological information valuable for the implementation of International Single Species Action Plans (ISSAP) dedicated to the Roller.

Significance statement

Tracking studies help to disentangle intraspecific variation in migratory strategies and wintering destinations among populations, as well as investigate individual-level decisions taken en route across seasonal journeys. By GPS tracking the intercontinental migration of adult Rollers we found that spatio-temporal components of migratory and flight strategy largely depend on extrinsic factors such as daytime, season and the habitat they traversed, and vary at population level. In contrast, within-individual consistency in migratory and wintering patterns emerged across years. Our findings emphasize the need for effective conservation strategies at the flyway scale.
Local conditions modulated the effects of marine heatwaves on coral bleaching in subtropical Hong Kong waters
Authors: Chung Tzu Hao , Dellisanti Walter , Lai Keng Po , Wu Jiajun , Qiu Jian-Wen , Chan Leo Lai
Published: July 2024

A mass coral bleaching event occurred in the summer of 2022 in subtropical Hong Kong, driven by two marine heatwaves (MHWs) with high intensities of 1.56 and 0.86 °C above a mean climate condition, both MHWs 7 days with a short gap of 4 days during the strong La Niña year. A transect survey was conducted at nine study sites in three regions, which revealed widespread coral bleaching with bleached coral cover ranging from 2.4 to 70.3%. In situ environmental data revealed the presence of a thermocline and halocline. Local conditions, including depth and wave exposure, significantly influenced the bleaching response. Shallow-water (2–4 m) corals were primarily affected, particularly in sheltered and moderately sheltered sites that exhibited higher levels of bleached coral cover (42.97 ± 15.4% and 44.93 ± 29.4%, respectively) compared to the exposed sites (31.8 ± 5.2%). Bleaching in deep waters (4–6 m) was minimal, with only a few colonies of Goniopora at two of the three sheltered sites exhibiting bleaching (1.7 ± 1.5%). Heat stress resistance differed between coral genera. Recovery rate for four common coral genera is low for Acropora tumida. Additionally, a minor hypoxia event was found to cause mortality of non-coral benthos at a sheltered site (Sharp Island). These findings highlight the alarming impact of extreme heatwaves on subtropical coral communities and underscore the importance of monitoring coral bleaching.
The Robust Chromatic Number of Graphs
Authors: Bacsó Gábor , Patkós Balázs , Tuza Zsolt , Vizer Máté
Published: July 2024

A 1-removed subgraph $$G_f$$

G
f

of a graph $$G=(V,E)$$

G
=
(
V
,
E
)

is obtained by

(i)

selecting at most one edge f(v) for each vertex $$v\in V$$

v
∈
V

, such that $$v\in f(v)\in E$$

v
∈
f
(
v
)
∈
E

(the mapping $$f:V\rightarrow E \cup \{\varnothing \}$$

f
:
V
→
E
∪
{
∅
}

is allowed to be non-injective), and

(ii)

deleting all the selected edges f(v) from the edge set E of G.

Proper vertex colorings of 1-removed subgraphs proved to be a useful tool for earlier research on some Turán-type problems. In this paper, we introduce a systematic investigation of the graph invariant 1-robust chromatic number, denoted as $$\chi _1(G)$$

χ
1

(
G
)

. This invariant is defined as the minimum chromatic number $$\chi (G_f)$$

χ
(

G
f

)

among all 1-removed subgraphs $$G_f$$

G
f

of G. We also examine other standard graph invariants in a similar manner.
On the suitability of a convolutional neural network based RCM-emulator for fine spatio-temporal precipitation
Authors: Doury Antoine , Somot Samuel , Gadat Sebastien
Published: July 2024

High resolution regional climate models (RCM) are necessary to capture local precipitation but are too expensive to fully explore the uncertainties associated with future projections. To resolve the large cost of RCMs, Doury et al. (2023) proposed a neural network based RCM-emulator for the near-surface temperature, at a daily and 12 km-resolution. It uses existing RCM simulations to learn the relationship between low-resolution predictors and high resolution surface variables. When trained the emulator can be applied to any low resolution simulation to produce ensembles of high resolution emulated simulations. This study assesses the suitability of applying the RCM-emulator for precipitation thanks to a novel asymmetric loss function to reproduce the entire precipitation distribution over any grid point. Under a perfect conditions framework, the resulting emulator shows striking ability to reproduce the RCM original series with an excellent spatio-temporal correlation. In particular, a very good behaviour is obtained for the two tails of the distribution, measured by the number of dry days and the 99th quantile. Moreover, it creates consistent precipitation objects even if the highest frequency details are missed. The emulator quality holds for all simulations of the same RCM, with any driving GCM, ensuring transferability of the tool to GCMs never downscaled by the RCM. A first showcase of downscaling GCM simulations showed that the RCM-emulator brings significant added-value with respect to the GCM as it produces the correct high resolution spatial structure and heavy precipitation intensity. Nevertheless, further work is needed to establish a relevant evaluation framework for GCM applications.