bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetocaloric Effect in the Full‐Heusler Alloy Ga2MnNi for Magnetic Refrigeration: A First‐Principles and Monte Carlo Study
Authors: Kerrai Hamza , Zaim Ahmed , Kerouad Mohamed
Published: November 2024

In this manuscript, the magnetic and magnetocaloric properties of the MnNi compound are investigated using Monte Carlo simulations and first‐principles calculations. Initially, the electronic, structural, and magnetic characteristics of the alloy are explored. The findings indicate that the ferromagnetic state in the Fm (No. 216) structure, with an optimal lattice parameter of 5.88 Å, was the most stable state compared to nonmagnetic (NM) and antiferromagnetic (AFM) states. Phonon dispersion studies confirm the alloy's dynamic stability, while the density of states reveal metallic behavior at the Fermi level. The total magnetic moment is calculated to be 3.48  . Additionally, exchange interactions are computed for Monte Carlo simulations, predicting a Curie temperature () of 331 K, consistent with experimental measurements ( = 330 K). Furthermore, the alloy exhibited a relative cooling power (RCP) of 1133.16 J kg−1 and a magnetocaloric effect of 19.65 J kg−1 K−1 at an applied magnetic field of 5 T. These results indicate that the MnNi full‐Heusler alloy is a potential option for use in magnetic refrigeration applications.
Financing methods for solid waste management: A review of typology, classifications, and circular economy implications
Authors: Ezeudu Obiora B. , Bristow David
Published: November 2024

The operations that underpin efficient municipal solid waste management delivery require economic funds. These funds are needed for both capital and recurrent expenditures. Municipalities (local governments) often being the main entities responsible for waste management in cities across the globe, have implemented several funding methods. Yet not all attempts at raising funds for waste management operations have been successful due to the existence of barriers preventing their sustainability in the long term. As such, municipal authorities and decision‐makers are frequently confronted with the dilemma of understanding different methods of financing waste management operations and making the appropriate choices among the available options for maximum operational flexibility. Based on locations, convenience, requirements, technical possibilities, institutional arrangement, and regulatory framework, several waste management financing methods have been adopted and applied with varying degrees of outcomes. However, this information is fragmented and scattered both in the academic and grey literature. In this work, we first collate and categorize the operating procedures of various municipal solid waste management finance strategies in a typology. We base our actions on several policy frameworks and areas of focus for waste management finance that have been implemented in many nations. Second, we provide a classification system by combining several strands of information on reported combinations of waste finance strategies, possibilities, and restrictions in the context of urban waste management. Finally, we discuss other essential elements related to financial sustainability and the implications on the circular economy. Therefore, this article presents a comprehensive review of the pros and cons of various municipal solid waste management financing methods.
Electrochemical Probing of Dopamine Dynamics During Poly(I:C)‐Induced Neuroinflammation
Authors: Wang Jian , Zhou Qiang , Zhang Yuchan , Zhao Shuang , Li Li , Zeng Zhongyuan , Chen Jiajia , Meng Yangmingxu , Zhao Xianglong , Wang Tianqi , Meng Zexuan , Yuan Haihan , Ran Jianhua , Wang Guixue , Li Chen‐zhong , Zang Guangchao
Published: November 2024

Viruses can infiltrate the central nervous system and contribute to depression, which may include alterations in dopamine (DA) metabolism triggered by immune responses though the specific mechanisms involved remain unclear. Here, an electrochemical system to realize the real‐time dynamic monitoring of DA with high sensitivity is proposed and it is demonstrated that the viral simulator polyinosinic‐polycytidylic acid (poly(I:C)) can inhibit the release of DA (from 5.595 to 0.137 µm) in neurons from the perspective of single cells, cell populations and even in vivo through the combination of multiscale electrodes, including single nanowires, carbon fibers (CFs) and 2D flexible electrodes. These findings are associated with the increase in reactive oxygen species (ROS) produced by microglia. At the molecular level, poly(I:C) significantly decreases the expression of α‐synuclein and increases its phosphorylation level, whereas ROS inhibitors can reverse these pathological changes and salvage DA release to half the initial level (≈2.6 µM). These results suggest that viruses may indirectly inhibit DA system function through ROS produced in inflammatory responses and that antioxidant activity may be a potential therapeutic strategy.
A Study of Factors That Influence the Software Project Success
Authors: Monserrat Maria , Mas Antonia , Mesquida Antoni‐Lluís
Published: November 2024

Most software development organizations are project based. However, statistics show that the failure rate of projects is very high. Different authors have identified factors (critical success factors) that can influence the success or failure of software projects, and that must be considered when carrying out a software project. This study is part of a research aimed at defining a framework that allows software development companies to assess the extent of the impact of critical success factors on their projects and increase the probability of project success. To achieve this goal, the first step was to identify the factors influencing software project success as reported in recent literature, as presented in this paper. A systematic literature review was conducted to obtain the list of factors that can influence the success of software projects. The list of 50 critical success factors resulting from this literature review can be used as a guide of critical aspects to be taken into consideration by the project manager when managing a project. Several gaps were identified through the literature review, such as the lack of indicators to measure the level of impact of each factor and the absence of descriptions for these factors.
Mode shape area difference method for sparse damage detection in beam‐like structures
Authors: Pajan Jurica , Duvnjak Ivan , Bartolac Marko , Ereiz Suzana
Published: November 2024

This article develops the mode shape area difference (MSAD) method for detecting sparse damage in beam‐like structures under serviceability conditions. MSAD enhances the static deformation area difference (DAD) damage detection method by extending its application to the modal domain. MSAD leverages the sensitivity of mode shapes to the damage, enabling damage detection and localization through the quantification of area differences between functions of modal displacements and their derivatives. To test the applicability of the method to real modal data that is affected by measurement noise resulting in different accuracies on which the modal displacements are estimated, method is evaluated under different levels of artificial noise added to the theoretical mode shapes derived from numerical model of a simply supported reinforced concrete beam. The noise level is defined by a maximum noise amplitude representing the maximal permutation in each component of normalized mode shape. Additionally, the threshold value of noise level from within the reliable estimation of damage based on MSAD method is determined. It is confirmed that MSAD method requires mode shapes with exceptionally low noise levels and demands precise estimation of all mode shape components, thereby reducing its applicability to real experimental data.
Towards a microRNA‐based Johne's disease diagnostic predictive system: Preliminary results
Authors: Capewell Paul , Lowe Arianne , Athanasiadou Spiridoula , Wilson David , Hanks Eve , Coultous Robert , Hutchings Michael , Palarea‐Albaladejo Javier
Published: November 2024

Background

Johne's disease, caused by Mycobacterium avium subspecies paratuberculosis (MAP), is a chronic enteritis that adversely affects welfare and productivity in cattle. Screening and subsequent removal of affected animals is a common approach for disease management, but efforts are hindered by low diagnostic sensitivity. Expression levels of small non‐coding RNA molecules involved in gene regulation (microRNAs), which may be altered during mycobacterial infection, may present an alternative diagnostic method.

Methods

The expression levels of 24 microRNAs affected by mycobacterial infection were measured in sera from MAP‐positive (n = 66) and MAP‐negative cattle (n = 65). They were then used within a machine learning approach to build an optimal classifier for MAP diagnosis.

Results

The method provided 72% accuracy, 73% sensitivity and 71% specificity on average, with an area under the curve of 78%.

Limitations

Although control samples were collected from farms nominally MAP‐free, the low sensitivity of current diagnostics means some animals may have been misclassified.

Conclusion

MicroRNA profiling combined with advanced predictive modelling enables rapid and accurate diagnosis of Johne's disease in cattle.
Introduction
Authors: Santilli Cecilia , Scaramuzzino Roberto
Published: November 2024

This introductory chapter explores the development of the civil society sector in Europe, emphasising the processes of professionalisation and NGOisation that result in the concentration of power and resources among a few key actors. By integrating insights from civil society studies and elite studies, the book addresses a significant research gap concerning power stratification within civil society. The concept of a “civil society elite” is central, focusing on individuals in leading positions within major organisations. The Italian context is highlighted, underscoring the third sector’s dual role in providing social services and advocacy. Key terms like “Third Sector” and “Ruling Class” are introduced, with the term “elite” being justified with reference to C. Wright Mills’ perspective on power elites. This chapter outlines the book’s structure, which includes an in-depth analysis of the Italian context, the organisational landscape, and leader composition, comparisons with professionalisation processes within the UK, career trajectories at the EU level, and subjective perspectives on elites in Sweden. This comprehensive framework sets the stage for a detailed examination of power dynamics and elitisation within the civil society sector in Italy, offering comparative insights from other European contexts and discussing the implications for civil society’s role in democracy.
Professionalisation and Elitisation
Authors: Santilli Cecilia , Scaramuzzino Roberto
Published: November 2024

This chapter investigates the process of professionalisation within civil society elites, defined as the shift from unpaid voluntary engagement to paid employment within CSOs. Comparing Italy’s corporatist civil society tradition with the UK’s liberal model reveals contrasting dynamics. Italy exhibits lower levels of professionalisation, with a predominance of unpaid leaders and minimal reliance on salaried staff roles. In contrast, the UK’s civil society landscape demonstrates advanced professionalisation, marked by a higher proportion of remunerated positions and greater dependence on state funding. Leadership composition reflects these divergent trajectories. Italy’s elite predominantly comprises presidents aligned with political advocacy, while the UK’s leadership cadre features a stronger presence of directors embodying managerial expertise. Demographic analyses reveal greater diversity among the UK’s elite regarding gender, age, and education, suggesting inclusive yet socioeconomically stratified leadership pathways influenced by professionalisation. Qualitative insights from Italian leaders illuminate tensions between the merits of professionalisation in fostering meritocracy and apprehension about compromising the sector’s historical identity. This dichotomy underscores the delicate equilibrium between tradition and innovation within civil society’s evolving governance structures. Ultimately, this comparative exploration elucidates how professionalisation intersects with elitisation processes, power dynamics, and institutional biases, offering a nuanced perspective on civil society’s transformative role in championing inclusive leadership and equitable social progress.
Decay and non-decay for the massless Vlasov equation on subextremal and extremal Reissner–Nordström black holes
Authors: Weissenbacher Max
Published: November 2024

We study the massless Vlasov equation on the exterior of the subextremal and extremal Reissner–Nordström spacetimes. We prove that moments decay at an exponential rate in the subextremal case and at a polynomial rate in the extremal case. This polynomial rate is shown to be sharp along the event horizon. In the extremal case we show that transversal derivatives of certain components of the energy momentum tensor do not decay along the event horizon if the solution and its first time derivative are initially supported on a neighbourhood of the event horizon. The non-decay of transversal derivatives in the extremal case is compared to the work of Aretakis on instability for the wave equation. Unlike Aretakis’ results for the wave equation, which exploit a hierarchy of conservation laws, our proof is based entirely on a quantitative analysis of the geodesic flow and conservation laws do not feature in the present work.
A novel approach to authentication of highbush and lowbush blueberry cultivars using image analysis, traditional machine learning and deep learning algorithms
Authors: Ropelewska Ewa , Koniarski Michał
Published: November 2024

The objective of this study was to classify blueberry cultivars based on image texture parameters using models built using traditional machine learning and deep learning algorithms. The blueberries belonging to highbush cultivars (‘Bluecrop’, ‘Herbert’, ‘Jersey’, and ‘Nelson’) and lowbush cultivars (‘Emil’ and ‘Putte’) were subjected to imaging using a digital camera. The texture parameters from blueberry images in color channels R, G, B, L, a, b, X, Y, Z, U, V, and S were determined. After selection image textures were used to build models for the classification of all highbush and lowbush blueberry cultivars, and highbush blueberry cultivars and lowbush blueberry cultivars, separately. In the case of distinguishing all cultivars, such as ‘Bluecrop’, ‘Herbert’, ‘Jersey’, and ‘Nelson’, ‘Emil’ and ‘Putte’, the classification accuracy reached 92.33% for a model built using a deep learning algorithm. Models built to distinguish only highbush cultivars provided an average accuracy of up to 91.25% (WiSARD). For models developed to classify two lowbush cultivars, an average accuracy reaching 96% (WiSARD) was found. The applied procedure can be used in practice to distinguish blueberry cultivars before their consumption or processing.
Biological Nitrification Inhibitors with Antagonistic and Synergistic Effects on Growth of Ammonia Oxidisers and Soil Nitrification
Authors: Issifu Sulemana , Acharya Prashamsha , Kaur-Bhambra Jasmeet , Gubry-Rangin Cecile , Rasche Frank
Published: November 2024

Biological nitrification inhibition (BNI) refers to the plant-mediated process in which nitrification is inhibited through rhizospheric release of diverse metabolites. While it has been assumed that interactive effects of these metabolites shape rhizosphere processes, including BNI, there is scant evidence supporting this claim. Hence, it was a primary objective to assess the interactive effects of selected metabolites, including caffeic acid (CA), vanillic acid (VA), vanillin (VAN), syringic acid (SA), and phenylalanine (PHE), applied as single and combined compounds, against pure cultures of various ammonia-oxidising bacteria (AOB, Nitrosomonas europaea, Nitrosospira multiformis, Nitrosospira tenuis, Nitrosospira briensis) and archaea (AOA, Nitrososphaera viennensis), as well as soil nitrification. Additionally, benzoic acid (BA) was examined as a novel biological nitrification inhibitor. All metabolites, except SA, tested as single compounds, achieved varied levels of inhibition of microbial growth, with CA exhibiting the highest inhibitory potential. Similarly, all metabolites applied as single compounds, except PHE, inhibited soil nitrification by up to 62%, with BA being the most potent. Inhibition of tested nitrifying microbes was also observed when compounds were assessed in combination. The combinations VA + PH, VA + CA, and VA + VAN exhibited synergism against N. tenuis and N. briensis, while others showed antagonism against N. europaea, N. multiformis, and N. viennensis. Although all combinations suppressed soil nitrification, their interactions against soil nitrification revealed antagonism. Our findings indicate that both antagonism and synergism are possible in rhizospheric interactions involving BNI metabolites, resulting in growth inhibition of nitrifiers and suppression of soil nitrification.
Bioprospecting a Natural Antioxidant Peptide for Tomato Biostimulation Under Water Limitations: Physiological Approach
Authors: Silva Sónia , Teixeira Cátia , Dias Maria Celeste , Pereira Renato B. , Gomes Paula , Silva Artur M. S.
Published: November 2024

Drought causes major agricultural losses, threatening food security worldwide. Thus, innovative strategies have been explored to improve crop tolerance to drought. This work focused on one natural peptide (PpT-2) with antioxidant activity, unexplored in plant applications, to evaluate its effectiveness in mitigating drought effect on Solanum lycopersicum L. plants. For that, tomato plants were foliar sprayed with different doses of PpT-2 (0, 15 or 150 mg L−1) and exposed to water Stressed and UnStressed conditions. The plant growth, photosynthesis and oxidative stress-related parameters were evaluated. Plant treatment with PpT-2, mostly at the highest concentration, alleviated diverse effects induced by water restriction: stimulated CO2 assimilation; improved ΦPSII, Fv/Fm and Fv’/Fm’; amended net CO2 assimilation rate and water use efficiency; restricted H2O2 accumulation and lipid peroxidation; stimulated SOD activity. Under UnStressed conditions, PpT-2 induced some degree of stomatal closure, nevertheless without restricting CO2 availability for the non-photochemical processes of photosynthesis, besides of decreasing H2O2 content and CAT activity. Overall, PpT-2 application controlled H2O2 accumulation, and under water limitations improved both photochemical and non-photochemical processes of photosynthesis and promoted drought tolerance, underscoring its potential for managing drought stress in crop species.
RV-PA uncoupling is associated with increased mortality in transthyretin amyloid cardiomyopathy treated with tafamidis
Authors: Schwarting Stéphanie K. , Poledniczek Michael , Metodiev Yuliyan , Stolz Lukas , Hofmann Eva , Hegenbart Ute , Schönland Stefan , Kääb Stefan , Massberg Steffen , Frey Norbert , aus dem Siepen Fabian
Published: November 2024

Background

The right ventricle to pulmonary artery coupling (RV-PAc) describes the right ventricle’s ability to adjust to an increased afterload. In case of transthyretin amyloid cardiomyopathy (ATTR-CM), impaired RV-PAc can result from increased left ventricular diastolic stiffness due to fibril deposition.

Objectives

While RV-PAc is a validated prognostic parameter in pulmonary arterial hypertension (PAH), its prognostic relevance in ATTR-CM remains unknown. We sought to evaluate the prognostic implications of impaired RV-PAc on survival in ATTR-CM.

Methods

In this multicentre study, RV-PAc was investigated by the echocardiographic surrogate of ratio of tricuspid annular plane systolic excursion to estimated pulmonary arterial systolic pressure (TAPSE/PASP) in 418 ATTR-CM patients, all treated with a TTR stabilizer. The primary outcome was all-cause mortality.

Results

Within a median time of 1.52 [IQR 0.72–2.56] years after diagnosis, 49 (11.7%) patients died. In multivariate Cox regression analysis impaired RV-PAc was a strong independent predictor of mortality (Hazard Ratio (HR) 2.16, 95% Confidence Interval (CI) 1.14–4.07, p = 0.018). RV-PAc ratio at first presentation emerged as a robust marker for risk stratification with a determined optimal cut-off of 0.382 mm/mmHg (area under the curve (AUC) 0.73, 95% CI 0.65–0.81). Patients with RV-PAc ratio ≤ 0.382 mm/mmHg exhibited significantly lower survival (HR 4.17, 95% CI 2.21–7.87, p < 0.001) within 3 years of follow up than those with RV-PAc ratio above the cut-off (Graphical Abstract).

Conclusion

Impaired adaptation of the RV to increased afterload is associated with worse outcome in ATTR-CM patients. RV-PAc ratio can serve as an echocardiographic predictor for all-cause mortality. Therefore, the determination of RV-PAc could improve risk stratification for ATTR-CM patients.

Graphical Abstract

RV-PA coupling in ATTR-CM patients. This two-center study included patients with transthyretin cardiomyopathy, all treated with specific stabilizer. Tricuspid annular plane systolic excursion (TAPSE, green arrow) to systolic pulmonary artery pressure (PASP, light purple arrows) ratio was investigated retrospectively as correlate for rightventricle to pulmonary artery coupling (RV-PAc). Impaired RV-PAc was associated with higher risk for all-cause mortality, reduced left ventricular function and advanced stages of disease.
Production of the antimalarial drug precursor amorphadiene by microbial terpene synthase-like from the moss Sanionia uncinata
Authors: Kim Hyeonjin , Lee Yelim , Yu Jihyeon , Park Jong-Yoon , Lee Jungeun , Kim Sang-Gyu , Hyun Youbong
Published: November 2024

Main conclusion

The microbial terpene synthase-like of the moss Sanionia uncinata displays the convergent evolution of a rare plant metabolite amorpha-4,11-diene synthesis.

Despite increasing demand for the exploration of biological resources, the diversity of natural compounds synthesized by organisms inhabiting various climates remains largely unexplored. This study focuses on the moss Sanionia uncinata, known as a predominant species within the polar climates of the Antarctic Peninsula, to systematically explore its metabolic profile both in-field and in controlled environments. We here report a diverse array of moss-derived terpene volatiles, including the identification of amorpha-4,11-diene, a rare sesquiterpene compound that is a precursor for antimalarial drugs. Phylogenetic reconstruction and functional validation in planta and in vitro identified a moss terpene synthase, S. uncinata microbial terpene synthase-like 2 (SuMTPSL2), which is associated with amorpha-4,11-diene production. We demonstrate that expressing SuMTPSL2 in various heterologous systems is sufficient to produce amorpha-4,11-diene. These results highlight the metabolic diversity in Antarctica, but also provide insights into the convergent evolution leading to the synthesis of a rare plant metabolite.
Proximal Galerkin: A Structure-Preserving Finite Element Method for Pointwise Bound Constraints
Authors: Keith Brendan , Surowiec Thomas M.
Published: November 2024

The proximal Galerkin finite element method is a high-order, low iteration complexity, nonlinear numerical method that preserves the geometric and algebraic structure of pointwise bound constraints in infinite-dimensional function spaces. This paper introduces the proximal Galerkin method and applies it to solve free boundary problems, enforce discrete maximum principles, and develop a scalable, mesh-independent algorithm for optimal design with pointwise bound constraints. This paper also introduces the latent variable proximal point (LVPP) algorithm, from which the proximal Galerkin method derives. When analyzing the classical obstacle problem, we discover that the underlying variational inequality can be replaced by a sequence of second-order partial differential equations (PDEs) that are readily discretized and solved with, e.g., the proximal Galerkin method. Throughout this work, we arrive at several contributions that may be of independent interest. These include (1) a semilinear PDE we refer to as the entropic Poisson equation; (2) an algebraic/geometric connection between high-order positivity-preserving discretizations and certain infinite-dimensional Lie groups; and (3) a gradient-based, bound-preserving algorithm for two-field, density-based topology optimization. The complete proximal Galerkin methodology combines ideas from nonlinear programming, functional analysis, tropical algebra, and differential geometry and can potentially lead to new synergies among these areas as well as within variational and numerical analysis. Open-source implementations of our methods accompany this work to facilitate reproduction and broader adoption.
MSME/SME Financial Literacy: A Systematic Literature Review and Bibliometric Analysis
Authors: IS Rekha , KV Sriram , Hungund Sumukh
Published: November 2024

Although there has been an increase in publications in the field of financial literacy in recent years, the articles related to financial literacy in connection to MSMEs/SMEs are limited. Hence, the purpose of this article is to analyze the trend in publication (for long-term, medium-term, and short-term) and literature review of key empirical studies to understand the definition, dimensions, and common variables that are influenced by financial literacy of MSME/SME owner/manager/CFO, etc. The descriptive bibliometric analysis reveals that overall business, management, and accounting is the leading subject area (in all three timelines) in which the articles are published, and the focus seems to be shifting to economics, econometrics, and finance in the short term with increase in percentage contribution in top 3 subject area list. The findings of our literature review reveal four aspects i.e., (i) The common dimensions of financial literacy were knowledge, awareness, and skill; (ii) There is no standardized scale for measuring the financial literacy of owner-managers of MSMEs; and (iii) Financial literacy is a common and significant antecedent to access to finance and enterprise performance. Financial literacy and access to finance are the challenges faced by MSMEs, these findings are of significance to both MSMEs and policymakers. Training and development programs to create awareness on policies related to MSMEs, sources of finance, and knowledge on basic financial aspects will not only improve the access to finance but also will improve the financial health and performance of MSMEs which are backbone of many developing economies. Further, academicians/researchers can work can developing a suitable scale measuring FL of owner-managers of MSMEs.
Evaluation of physical and chemical modifications to drug reservoirs for stimuli-responsive microneedles
Authors: Li Luchi , Anjani Qonita Kurnia , Hutton Aaron R. J. , Li Mingshan , Sabri Akmal Hidayat Bin , Vora Lalitkumar , Naser Yara A. , Tao Yushi , McCarthy Helen O. , Donnelly Ryan F.
Published: November 2024

Hydrogel-forming microneedle (MN) arrays are minimally-invasive devices that can penetrate the stratum corneum, the main barrier to topical drug application, without causing pain. However, drug delivery using hydrogel-forming MN arrays tends to be relatively slow compared to rapid drug delivery using conventional needles and syringes. Therefore, in this work, for the first time, different physical and chemical delivery enhancement methods were employed in combination with PVA-based hydrogel-forming MN arrays. Using a model drug, ibuprofen (IBU) sodium, the designed systems were assessed in terms of the extent of transdermal delivery. Iontophoresis (ITP) and heat-assisted drug delivery technology were investigated as physical permeation enhancement techniques. Ex vivo studies demonstrated that the ITP (0.5 mA/cm2)-mediated combination strategy significantly enhanced the transdermal permeation of IBU sodium over the first 6 h (~ 5.11 mg) when compared to MN alone (~ 1.63 mg) (p < 0.05). In contrast, heat-assisted technology showed almost no promoting effect on transdermal delivery. Furthermore, IBU sodium-containing rapidly dissolving lyophilised and effervescent reservoirs, classified as chemical modification methods, were prepared. Both strategies achieved rapid and effective ex vivo IBU sodium permeation, equating to ~ 78% (30.66 mg) and ~ 71% (28.43 mg) from lyophilised and effervescent reservoirs, respectively. Moreover, in vivo pharmacokinetic studies showed that the IBU sodium plasma concentration within lyophilised and effervescent groups reached a maximum concentration (Cmax) at 4 h (~ 282.15 µg/mL) and 6 h (~ 140.81 µg/mL), respectively. These strategies not only provided rapid achievement of therapeutic levels (10–15 µg/ml), but also resulted in sustained release of IBU sodium for at least 48 h, which could effectively reduce the frequency of administration, thereby improving patient compliance and reducing side effects of IBU sodium.

Graphical Abstract
A quality by design strategy for cocrystal design based on novel computational and experimental screening strategies: part A
Authors: Ross Steven A. , Ward Adam , Basford Patricia , McAllister Mark , Douroumis Dennis
Published: November 2024

While pharmaceutical Cocrystals have long been acknowledged as a promising method of enhancing a drugs bioavailability, they have not yet experienced widespread industrial adoption on the same scale as other multi-component drugs, such as salts and amorphous solid dispersions. This is partly due to the lack of a being no definitive screening strategy to identify suitable coformers, with the most cocrystal screening strategies heavily relying on trial and error approaches, or through utilizing a multiple and often conflicting, computational screening techniques combined with high material consumption experimental techniques. From the perspective of industry, this can often lead to high material waste and increased costs, encouraging the prioritization of more traditional bioenhancement techniques. Here we present a strategy for the selection of multicomponent systems involving computational modelling for screening of drug– former pairs based on a combination of molecular complementarity and H-bond propensity screening. Jet dispensing printing technology is co-opted as a mechanism for High-Throughput Screening (HTS) of different stoichiometric ratios, as a low material consumption screening strategy. This strategy is presented herein as a Quality by Design (QbD) crystal engineering approach, combined with experimental screening methods to produce cocrystals of a novel 5-Lipoxygenase (5‐LO) inhibitor, PF-04191834 (PF4). Through this methodology, three new cocrystals were indicated for PF4, confirmed via DSC and XRPD, from less than 50 mg of original testing material. Part B of this study will demonstrate the scalability of this technique continuous extrusion.

Graphical Abstract
On Galois covers of a union of zappatic surfaces of type $$R_k$$
Authors: Amram Meirav , Gong Cheng , Mo Jia-Li
Published: November 2024

We investigate the topological structures of Galois covers of a union of two Zappatic surfaces of type $$R_k$$

R
k

. We prove that the Galois covers of such surfaces are simply connected surfaces of general type. We also compute their Chern numbers and topological indices.
Context Matters: Exploring the Structural Relationships Between ICT Usage, Support, Perceived Usefulness, Intention to Use, and Learning Motivation
Authors: Huang Xueqin , Gao Xingjian , Kim Sangmi , Ohno Shiroh
Published: November 2024

Previous research has extensively explored the integration of Information and Communication Technology (ICT) in education. However, much of previous research has not differentiated between the environments where ICT is used, particularly in terms of its perceived usefulness in school versus at home. This gap in understanding the contextual influence of ICT on students’ learning motivation forms the basis for this study. In particular, this research aims to clarify how different environments influence the effectiveness of ICT in motivating students. Using data from 737 high school students, collected through two surveys, and employing Structural Equation Modeling, the study found that ICT usage in schools is positively linked to its perceived usefulness in both school and home environments. Additionally, ICT support from teachers enhances the perceived usefulness of ICT in both contexts. Furthermore, the perceived usefulness of ICT in both school and home environments significantly predicts students’ intentions to use ICT. However, only the perceived usefulness of ICT at home significantly predicts learning motivation, contrary to initial expectations that school-related ICT would also be a significant predictor. These findings suggest that enhancing students’ learning motivation through ICT integration may require more emphasis on the home environment. The implications for educational policy and practice are discussed, emphasizing a more efficient strategy in incorporating ICT into education.
Social Media Democracy Mirage
Authors: Gil de Zúñiga Homero , Marné Hugo Marcos , Goyanes Manuel , Scheffauer Rebecca
Published: November 2024

For over two decades, political communication research has hailed the potentially reinvigorating effect of social media on democracy. Social media was expected to provide new opportunities for people to learn about politics and public affairs, and to participate politically. Building on two systematic literature reviews on social media, and its effects on political participation and knowledge (2000–2020), and introducing empirical evidence drawing on four original US survey data that expands for over a decade (2009–2020), this Element contends that social media has only partially fulfilled this tenet, producing a Social Media Democracy Mirage. That is, social media have led to a socio-political paradox in which people are more participatory than ever, yet not necessarily more informed.
Edom in Judah
Authors: Danielson Andrew J.
Published: November 2024

During the late Iron Age (800–539 BCE) in the semi-arid southern Levant, small competing kingdoms navigated a tenuous position between their local populace and the external empires who dominated the region. For kingdoms such as Judah and Edom, this period was also one of opportunity due to their location at the intersection of lucrative trade networks connecting the Mediterranean and Arabian worlds. Such economic opportunity, together with subsistence practices rooted in mobility, resulted in a diverse and contested social landscape in the northeastern Negev borderland region between these two kingdoms. This Element explores the multifaceted interactions in this landscape. Insightful case studies highlight patterns of cross-cultural interaction and identity negotiation through the lenses of culinary practices, religion, language, and text. Ultimately, this analysis explores the lived realities of the region's inhabitants, migrants, and traders over multiple generations, emphasizing social diversity and entanglement as an integral feature of the region.
The Nordic Beowulf
Authors: Gräslund Bo
Published: November 2024

In such a wide-ranging, long-standing, and international field of scholarship as Beowulf, one might imagine that everything would long since have been thoroughly investigated. And yet as far as the absolutely crucial question of the poem's origins is concerned, that is not the case. This cross-disciplinary study by Bo Gräslund argues that the material, geographical, historical, social, and ideological framework of Beowulf cannot be the independent literary product of an Old English Christian poet, but was in all essentials created orally in Scandinavia, which was a fertile seedbed for epic poetry.
Franciscan Books and their Readers
Authors: Hernández Vera René
Published: November 2024

The book explores the manuscripts written, read, and studied by Franciscan friars from the thirteenth to the fifteenth centuries in Northern Italy, and specifically Padua, assessing four key aspects: ideal, space, form and readership. The ideal is studied through the regulations that determined what manuscripts should aim for. Space refers to the development and role of Franciscan libraries. The form is revealed by the assessment of the physical configuration of a set of representative manuscripts read, written, and manufactured by the friars. Finally, the study of the readership shows how Franciscans were skilled readers who employed certain forms of the manuscript as a portable, personal library, and as a tool for learning and pastoral care. By comparing the book collections of Padua's reformed and unreformed medieval Franciscan libraries for the first time, this study reveals new features of the ground-breaking cultural agency of medieval friars.
Exploitation’s grounding problem
Authors: Ferguson Benjamin
Published: November 2024

Standard accounts of what makes exploitation wrong ground its wrong in distributive unfairness: when A exploits B he wrongs her by taking a greater share of the benefits from their interaction than he ought. I argue that this standard account does not succeed; distributive unfairness is neither the sole, nor the primary wrong of exploitation. I assume that distributive unfairness is pro tanto wrong. However, I argue that in situations where transactors’ consent to a transaction is morally valid, it is also morally transformative and overrides distributive unfairness’s pro tanto wrong. Thus, wrongful exploitation requires morally invalid consent.
Maternal environmental control of progeny seed physiology: a review of concepts, evidence and mechanism
Authors: Bezodis William , Penfield Steven
Published: November 2024

The environment experienced by a plant before and after reproduction can have a profound effect on the behaviour of the progeny after shedding. Maternal environmental effects on seeds are important for phenology and fitness in plants, especially for bet-hedging reproductive strategies. Maternal tissues that disperse with seeds are important for dormancy in many species, particularly those with coat-imposed dormancy and those that disperse in indehiscent fruits. Maternal nitrogen status, temperature and photoperiod modify maternal tissues and also influence the developing zygote. During seed development on the mother, the progeny may acquire environmental information directly, but there is also evidence for maternal–filial signalling and the epigenetic inheritance of environmental information through the germline.
Revisiting dose-response: concepts of hormesis, toxicological thresholds and data analysis
Authors: Milosevic Luka , Knezevic Stevan Z.
Published: November 2024

Several publications and web-based tools are available in weed science literature to help weed scientists to carry out basic analysis of dose-response studies. Given the nature of the complicated relationship between the explanatory variable (dose as x-axis) evaluated against response variables of interest (y-axis), using regression curves should be the preferred method for handling data analysis. The objective of this manuscript is to provide user-friendly instructions for conducting and analyzing several types of dose-response studies that were lacking in current weed science literature. A better understanding of less commonly used concepts of hormesis and toxicological safety thresholds (no-observable-adverse-effect-level [NOAEL] and lowest-observable-adverse-effect-level [LOAEL]) is needed to help address the potential risks and benefits associated with herbicide use while minimizing environmental impacts. Basic codes available in cost-free R software are provided for data analysis and to foster collaboration among weed scientists.
A Simple Model for the Evaporation of Hydrometeors and Their Isotopes
Authors: de Szoeke Simon P. , Sarkar Mampi , Quiñones Meléndez Estefanía , Blossey Peter N. , Noone David
Published: November 2024

Cloud condensation and hydrometeor evaporation fractionate stable isotopes of water, enriching liquid with heavy isotopes; whereupon updrafts, downdrafts, and rain vertically redistribute water and its isotopes in the lower troposphere. These vertical water fluxes through the marine boundary layer affect low cloud climate feedback and, combined with isotope fractionation, are hypothesized to explain the depletion of tropical precipitation at higher precipitation rates known as the “amount effect.” Here, an efficient and numerically stable quasi‐analytical model simulates the evaporation of raindrops and enrichment of their isotope composition. It is applied to a drop size distribution and subcloud environment representative of Atlantic trade cumulus clouds. Idealized physics experiments artificially zero out selected processes to discern the separate effects on the isotope ratio of raindrops, of exchange with the environment, evaporation, and kinetic molecular diffusion. A parameterization of size‐dependent molecular and eddy diffusion is formulated that enriches raindrops much more strongly (+5‰ for deuterated water [HDO] and +3.5‰ for O) than equilibrium evaporation as they become smaller than 1 mm. The effect on evaporated vapor is also assessed. Rain evaporation enriches subcloud vapor by +12‰ per mm rain (for HDO), explaining observations of enriched vapor in cold pools sourced by evaporatively cooled downdrafts. Drops smaller than 0.5 mm evaporate completely before falling 700 m in typical subtropical marine boundary layer conditions. The early and complete evaporation of these smaller drops in the rain size distribution enriches the vapor produced by rain evaporation.
Ecological diversification of sea catfishes is accompanied by genome-wide signatures of positive selection
Authors: Rincon-Sandoval Melissa , De-Kayne Rishi , Shank Stephen D. , Pirro Stacy , Ko’ou Alfred , Abueg Linelle , Tracey Alan , Mountcastle Jackie , O’Toole Brian , Balacco Jennifer , Formenti Giulio , Jarvis Erich D. , Arcila Dahiana , Kosakovsky Pond Sergei L. , Davis Aaron , Bloom Devin D. , Betancur-R Ricardo
Published: November 2024

Habitat transitions have shaped the evolutionary trajectory of many clades. Sea catfishes (Ariidae) have repeatedly undergone ecological transitions, including colonizing freshwaters from marine environments, leading to an adaptive radiation in Australia and New Guinea alongside non-radiating freshwater lineages elsewhere. Here, we generate and analyze one long-read reference genome and 66 short-read whole genome assemblies, in conjunction with genomic data for 54 additional species. We investigate how three major ecological transitions have shaped genomic variation among ariids over their ~ 50 million-year evolutionary history. Our results show that relatively younger freshwater lineages exhibit a higher incidence of positive selection than their more ancient marine counterparts. They also display a larger disparity in body shapes, a trend that correlates with a heightened occurrence of positive selection on genes associated with body size and elongation. Although positive selection in the Australia and New Guinea radiation does not stand out compared to non-radiating lineages overall, selection across the prolactin gene family during the marine-to-freshwater transition suggests that strong osmoregulatory adaptations may have facilitated their colonization and radiation. Our findings underscore the significant role of selection in shaping the genome and organismal traits in response to habitat shifts across macroevolutionary scales.
Premature mortality analysis of 52,000 deceased cats and dogs exposes socioeconomic disparities
Authors: Farrell Sean , Anderson Katharine , Noble Peter-John Mäntylä , Al Moubayed Noura
Published: November 2024

Monitoring mortality rates offers crucial insights into public health by uncovering the hidden impacts of diseases, identifying emerging trends, optimising resource allocation, and informing effective policy decisions. Here, we present a novel approach to analysing premature mortality in companion animals, utilising data from 28,159 deceased dogs and 24,006 deceased cats across the United Kingdom. By employing PetBERT-ICD, an automated large language model (LLM) based International Classification of Disease 11 syndromic classifier, we reveal critical insights into the causes and patterns of premature deaths. Our findings highlight the significant impact of behavioural conditions on premature euthanasia in dogs, particularly in ages one to six. We also identify a 19% increased risk of premature mortality in brachycephalic dog breeds, raising important animal welfare concerns. Our research establishes a strong correlation between socioeconomic status and premature mortality in cats and dogs. Areas with the lowest Index of Multiple Deprivation (IMD) scores show nearly a 50% reduction in the risk of premature mortality across cats and dogs, underscoring the powerful impact that socioeconomic factors can have on pet health and longevity. This research underscores the necessity of examining the socioeconomic disparities affecting animal health outcomes. By addressing these inequities, we can better safeguard the well-being of our companion animals.
Transcriptomic analysis reveals a critical role for activating Gsα mutations in spontaneous feline hyperthyroidism
Authors: Hiron Thomas K. , Aguiar Joana , Williams Jonathan M. , Falcone Sara , Norman Paul A. , Elliott Jonathan , Fowkes Robert C. , Syme Harriet M. , Davison Lucy J.
Published: November 2024

Feline hyperthyroidism (FHT) is a debilitating disease affecting > 10% of elderly cats. It is generally characterised by chronic elevation of thyroid hormone in the absence of circulating TSH. Understanding of the molecular pathogenesis of FHT is currently limited. However, FHT shares clinical and histopathological similarities with human toxic multinodular goitre, which has been associated with activating mutations in TSH receptor (TSHR) and Gsα encoding genes. Using RNA-seq transcriptomic analysis of thyroid tissue from hyperthyroid and euthyroid cats, we identified differentially expressed genes and dysregulated pathways in FHT, many of which are downstream of TSHR. In addition, we detected missense variants in thyroid RNA-seq reads that alter the structure of both TSHR and Gsα. All FHT-associated mutations were absent in germline sequence from paired blood samples. Only a small number of hyperthyroid cats demonstrated TSHR variation, however all thyroids from advanced cases of FHT carried at least one missense variant affecting Gsα. The activating nature of the acquired Gsα mutations was demonstrated by increased cAMP production in vitro. These data indicate that constitutive activation of signalling downstream of TSHR is central to the TSH-independent production of thyroid hormone in FHT, offering a novel therapeutic target pathway in this common disease.