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The current study aimed to determine the molecular mechanisms of carbapenem and colistin resistance among the clinical isolates of Klebsiella pneumoniae from hospitalized patients admitted to a university hospital in Eastern Algeria. In total, 124 non-duplicate isolates of K. pneumoniae were collected from September 2018 to April 2019. Bacterial identification was performed using MALDI-TOF MS. The presence of extended spectrum β-lactamase (ESBL) genes, carbapenemase genes, chromosomal mutation and mcr genes in colistin-resistant K. pneumoniae were evaluated by PCR. ESBLs represented a rate of 49.1% and harbored bla_CTX-M, bla_TEM and bla_SHV genes. Concerning carbapenems, 12 strains (9.6%) were resistant to ertapenem (MIC: 1–32 μg/mL), of which one strain (0.8%) was also resistant to imipenem (MIC: 32 μg/mL). Among these strains, nine (75%) harbored bla_OXA-48 gene. Seven strains (5.6%) expressed resistance to colistin (MIC: 2–32 μg/mL), of which two harbored mcr-8 and mgrB genes simultaneously. The existence of a double resistance to colistin in the same strain is new in Algeria, and this could raise concerns about the increase in levels of resistance to this antibiotic (MIC: 32 μg/mL). The mgrB gene alone was observed in five isolates (71.4%), including two strains harboring bla_OXA-48. This is the first report revealing the presence of K. pneumoniae strains carrying the bla_OXA-48 gene as well as a mutation in the mgrB gene. Large-scale surveillance and effective infection control measures are also urgently needed to prevent the outbreak of various carbapenem- and colistin-resistant isolates. Full article

(This article belongs to the Special Issue Bacterial Infections in Clinical Settings)

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27 pages, 11476 KiB

Open AccessArticle

Numerical Groundwater Model to Assess the Fate of Nitrates in the Coastal Aquifer of Arborea (Sardinia, Italy)

by Gerhard Schäfer, Manon Lincker, Antonio Sessini and Alberto Carletti

Water 2024, 16(19), 2729; https://doi.org/10.3390/w16192729 (registering DOI) - 25 Sep 2024

Abstract

The Arborea plain in Sardinia (Italy) is classified as a nitrate-vulnerable zone (NVZ). In the present study, the individual work steps that are necessary to progress from the existing 3D hydrogeological model to a 3D numerical groundwater model using the interactive finite-element simulation system FEFLOW 7.4 are shown. The results of the transient flow model highlight the influence of the drainage network on the overall groundwater management: the total water volume drained by the ditches accounted for approximately 58% of the annual outflow volume. The numerical transport simulations conducted from 2012 to 2020 using hypothetical field-based nitrate input scenarios globally underestimated the high concentrations that were observed in the NVZ. However, as observed in the field, the computed nitrate concentrations in December 2020 still varied strongly in space, from several mg L⁻¹ to several hundreds of mg L⁻¹. The origin of these remaining local hotspots is not yet known. The modeling of rainfall fluctuations under the influence of climate change revealed a general long-term decline in the groundwater level of several tens of centimeters in the long term and, in conjunction with a zero-nitrate scenario, led to a significant decrease in nitrate pollution. Although hotspots were attenuated, the concentrations at several monitoring wells still exceeded the limit value of 50 mg L⁻¹. Full article

(This article belongs to the Special Issue Water-Related Geoenvironmental Issues, 2nd Edition)

24 pages, 14604 KiB

Open AccessReview

Imaging of Osteosarcoma: Presenting Findings, Metastatic Patterns, and Features Related to Prognosis

by Amandine Crombé, Mario Simonetti, Alessandra Longhi, Olivier Hauger, David Fadli and Paolo Spinnato

J. Clin. Med. 2024, 13(19), 5710; https://doi.org/10.3390/jcm13195710 (registering DOI) - 25 Sep 2024

Abstract

Background: Osteosarcomas are rare malignancies (<1% of all cancers) that produce an osteoid matrix. Osteosarcomas are the second most frequent type of primary bone tumor after multiple myeloma and the most prevalent primary bone tumor in children. The spectrum of imaging findings of these malignancies varies significantly, reflecting different histological subtypes. For instance, conventional osteosarcoma typically presents with a mixed radiological pattern (lytic and bone mineralization) or with a completely eburneous one; aggressive periosteal reactions such as sunburst, Codman triangle, and soft-tissue components are frequently displayed. On the other hand, telangiectatic osteosarcoma usually presents as a purely lytic lesion with multiple fluid–fluid levels on MRI fluid-sensitive sequences. Other typical and atypical radiological patterns of presentation in other subtypes of osteosarcomas are described in this review. In addition to the characteristics associated with osteosarcoma subtyping, this review article also focuses on imaging features that have been associated with patient outcomes, namely response to chemotherapy and event-free and overall survivals. This includes simple semantic radiological features (such as tumor dimensions, anatomical location with difficulty of radical surgery, occurrence of pathological fractures, and presence of distant metastases), but also quantitative imaging parameters from diffusion-weighted imaging, dynamic contrast-enhanced MRI, and 18F-FDG positron emission tomography and radiomics approaches. Other particular features are described in the text. Overall, this comprehensive literature review aims to be a practical tool for oncologists, pathologists, surgeons, and radiologists involved in these patients’ care. Full article

(This article belongs to the Section Nuclear Medicine & Radiology)

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27 pages, 3994 KiB

Open AccessFeature PaperArticle

From Weeds to Feeds: Exploring the Potential of Wild Plants in Horticulture from a Centuries-Long Journey to an AI-Driven Future

by Diego Rivera, Diego-José Rivera-Obón, José-Antonio Palazón and Concepción Obón

Horticulturae 2024, 10(10), 1021; https://doi.org/10.3390/horticulturae10101021 (registering DOI) - 25 Sep 2024

Abstract

Given the increasing food needs of humanity and the challenges cultivated species face in adapting to the climatic uncertainties we experience, it is urgent to cultivate new species. A highly relevant repertoire for this purpose is offered by the array of edible wild plants. We analyzed data from Murcia (Spain), involving 61 species and 59 informants, and the Global Database of Wild Food Plants, which includes 15,000 species, 500 localities, and nearly 700 references. Using local consensus, global distribution, and GBIF occurrence data, we built simple unimodal or bimodal models to explore their limitations. Our study highlights that approximately 15,000 wild or feral plant species are consumed as food, underlining the urgent need to support existing crops with new species due to current food crises and climate irregularities. We examined wild plant diversity from a horticultural perspective, considering their relationships with weeds and invasive species. Partial criteria, such as local consensus or global use, were found insufficient for selecting candidate species. We propose developing a specific artificial intelligence to integrate various factors—ecological, nutritional, toxicological, agronomic, biogeographical, ethnobotanical, economic, and physiological—to accurately model a species’ potential for domestication and cultivation. We propose the necessary tools and a protocol for developing this AI-based model. Full article

(This article belongs to the Collection Prospects of Using Wild Plant Species in Horticulture)

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15 pages, 347 KiB

Open AccessArticle

Stability Analysis and Stabilization of General Conformable Polynomial Fuzzy Models with Time Delay

by Imen Iben Ammar, Hamdi Gassara, Mohamed Rhaima, Lassaad Mchiri and Abdellatif Ben Makhlouf

Symmetry 2024, 16(10), 1259; https://doi.org/10.3390/sym16101259 (registering DOI) - 25 Sep 2024

Abstract

This paper introduces a sum-of-squares (S-O-S) approach to Stability Analysis and Stabilization (SAS) of nonlinear dynamical systems described by General Conformable Polynomial Fuzzy (GCPF) models with a time delay. First, we present GCPF models, which are more general compared to the widely recognized Takagi–Sugeno Fuzzy (T-SF) models. Then, we establish SAS conditions for these models using a Lyapunov–Krasovskii functional and the S-O-S approach, making the SAS conditions in this work less conservative than the Linear Matrix Inequalities (LMI)-based approach to the T-SF models. In addition, the SAS conditions are found by satisfying S-O-S conditions dependent on membership functions that are reliant on the polynomial fitting approximation algorithm. These S-O-S conditions can be solved numerically using the recently developed SOSTOOLS. To demonstrate the effectiveness and practicality of our approach, two numerical examples are provided to demonstrate the effectiveness and practicality of our approach. Full article

(This article belongs to the Special Issue Symmetry and Its Applications in Automation and Control Systems)

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17 pages, 440 KiB

Open AccessArticle

The Impact of Value-Added Intellectual Capital on Corporate Performance: Cross-Sector Evidence

by Darya Dancaková and Jozef Glova

Risks 2024, 12(10), 151; https://doi.org/10.3390/risks12100151 (registering DOI) - 25 Sep 2024

Abstract

This study explores the relationship between intellectual capital (IC) and the financial performance of 250 publicly traded companies in France, Germany, and Switzerland from 2009 to 2018, addressing the gaps in prior research regarding the differential impacts of IC components across countries and industries in Western and Central Europe. Using the Value-Added Intellectual Coefficient (VAIC™) approach, this study evaluates human capital efficiency (HCE), structural capital efficiency (SCE), and capital employed efficiency (CEE). Panel regression analyses at the country and industry levels were conducted to assess their effects on financial metrics, such as return on equity (ROE), return on assets (ROA), and asset turnover ratio (ATO). The findings reveal a significant positive association between SCE, CEE, and firm performance, with CEE showing the most substantial effect, while HCE had a relatively weaker impact. Additionally, the study uncovers a trade-off between the accumulation of patents and trademarks and short-term financial performance, raising new considerations for intellectual property management. This research contributes to the literature by providing a nuanced understanding of how IC components influence financial outcomes across different contexts and offers practical insights for firms aiming to optimize structural capital and capital-employed strategies for improved financial performance while acknowledging the limitations regarding the sample of publicly traded firms. Full article

(This article belongs to the Special Issue Corporate Finance and Intellectual Capital Management)

22 pages, 15918 KiB

Open AccessArticle

Exceptional Cluster of Simultaneous Shallow Landslides in Rwanda: Context, Triggering Factors, and Potential Warnings

by Fils-Vainqueur Byiringiro, Marc Jolivet, Olivier Dauteuil, Damien Arvor and Christine Hitimana Niyotwambaza

GeoHazards 2024, 5(4), 1018-1039; https://doi.org/10.3390/geohazards5040049 (registering DOI) - 25 Sep 2024

Abstract

Rwanda, in eastern tropical Africa, is a small, densely populated country where climatic disasters are often the cause of considerable damage and deaths. Landslides are among the most frequent hazards, linked to the country’s peculiar configuration including high relief with steep slopes, humid tropical climate with heavy rainfall, intense deforestation over the past 60 years, and extensive use of the soil for agriculture. The Karongi region, in the west-central part of the country, was affected by an exceptional cluster of more than 700 landslides during a single night (6–7 May 2018) over an area of 100 km². We analyse the causes of this spectacular event based on field geological and geomorphology investigation and CHIRPS and ERA5-Land climate data. We demonstrate that (1) the notably steep slopes favoured soil instability; (2) the layered soil and especially the gravelly, porous C horizon allowed water storage and served as a detachment level for the landslides; (3) relatively low intensity, almost continuous rainfall over the previous two months lead to soil water-logging; and (4) acoustic waves from thunder or mechanical shaking by strong wind destabilized the water-logged soil through thixotropy triggering the landslides. This analysis should serve as a guide for forecasting landslide-triggering conditions in Rwanda. Full article

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20 pages, 5990 KiB

Open AccessArticle

Design and Assessment of an Austenitic Stainless Alloy for Laser Powder Bed Additive Manufacturing

by Mariam Assi, Julien Favre, Marcin Brykala, Franck Tancret and Anna Fraczkiewicz

Appl. Sci. 2024, 14(19), 8649; https://doi.org/10.3390/app14198649 (registering DOI) - 25 Sep 2024

Abstract

Recent developments in metallic additive manufacturing (AM) processes for the production of high-performance industrial pieces have been hampered by the limited availability of reliably processable or printable alloys. To date, most of the alloys used in AM are commercial grades that have been previously optimized for different manufacturing techniques. This study aims to design new alloys specifically tailored for AM processes, to minimize defects in the final products and to optimize their properties. A computational approach is proposed to design novel and optimized austenitic alloy compositions. This method integrates a suite of predictive tools, including machine learning, calculation of phase diagrams (CALPHAD) and physical models, all piloted by a multi-objective genetic algorithm. Within this framework, several material-dependent criteria are examined and their impact on properties and on the occurrence of defects is identified. To validate our approach, experimental tests are performed on a selected alloy composition: powder is produced by gas atomization and samples are fabricated by laser powder bed fusion. The microstructure and mechanical properties of the alloys are evaluated and its printability is compared with a commercial 316L stainless steel taken as a reference. The optimized alloy performs similarly to 316L in terms of coefficient of thermal expansion, hardness and elongation, but has a 17% lower yield strength and ultimate tensile strength (UTS), indicating that further optimization is required. Full article

(This article belongs to the Special Issue Recent Advances of Additive Manufacturing in the Modern Industry)

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19 pages, 719 KiB

Open AccessArticle

Transitions between Localised Patterns with Different Spatial Symmetries in Non-Local Hyperbolic Models for Self-Organised Biological Aggregations

by Thanh Trung Le and Raluca Eftimie

Symmetry 2024, 16(10), 1257; https://doi.org/10.3390/sym16101257 (registering DOI) - 25 Sep 2024

Abstract

Pattern formation in biological aggregations is a topic of great interest, due to the complex spatial structure of various aggregations of cells/bacteria/animals that can be observed in nature. While many such aggregations look similar at the macroscopic level, they might differ in their microscopic spatial structure. However, the complexity of the non-linear and sometimes non-local interactions among individuals inside these aggregations makes it difficult to investigate these spatial structures. In this study, we investigate numerically the transitions between different spatial patterns of animal aggregations with various symmetries (even, odd or no symmetry) that characterise the microscopic distribution of individuals inside these aggregations. To this end, we construct a bifurcation diagram starting with perturbations of spatially homogeneous solutions with low, medium, and high amplitudes. For perturbations with low amplitudes, the bifurcating structures show transitions among even-symmetric, odd-symmetric, and non-symmetric solutions. For perturbations with large amplitudes, there are wide parameter regions with non-convergent solutions, characterised by oscillatory transitions between different relatively similar solutions. These numerical results emphasize: (i) the effect of nonlinear and non-local interactions on the microscopically different symmetric/non-symmetric structures of macroscopically similar ecological aggregations; (ii) the difficulty of developing continuation algorithms for this class of non-local models. Full article

(This article belongs to the Special Issue Mathematical Modeling in Biology and Life Sciences)

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19 pages, 5597 KiB

Open AccessArticle

Selective Co(II) and Ni(II) Separation Using the Trihexyl(tetradecyl)phosphonium Decanoate Ionic Liquid

by Anđela Kovačević, José Alejandro Ricardo García, Marilena Tolazzi, Andrea Melchior and Martina Sanadar

Molecules 2024, 29(19), 4545; https://doi.org/10.3390/molecules29194545 (registering DOI) - 25 Sep 2024

Abstract

The room temperature ionic liquid trihexyl(tetradecyl)phosphonium decanoate ([P₆₆₆₁₄][Dec]) was employed in the liquid-liquid extraction of Co(II) from hydrochloric acid solutions in the presence of Ni(II). The extraction performance in liquid-liquid separations showed a strong dependence on the acid content of the feed aqueous solution. The best performance in terms of extracted cobalt and selectivity was obtained when the feed contained a HCl concentration above 6 M On the contrary, when the experiment was performed in absence of HCl, a lower extraction and Co/Ni selectivity were obtained. This behavior has been rationalized by considering the protonation of the [Dec]⁻ anion and the different Co(II)/Ni(II) speciation in HCl media. Moreover, polymer inclusion membranes (PIMs) were prepared using PVC and [P₆₆₆₁₄][Dec] at different weight rations. Only the PIM formulated with a 30:70/PVC:[P₆₆₆₁₄][Dec] weight ratio demonstrated effective extraction of Co(II) from the HCl solution. The extraction efficiency and selectivity of the PIM was comparable to that from biphasic liquid experiments at 8 M HCl. The results of this study constitute a promising background for further practical developments of carboxylate-based ILs applied in Co/Ni separations. Full article

(This article belongs to the Special Issue From Molecules to Materials, Devices and Processes: The Chemical Basis of Novel Technologies)

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20 pages, 4839 KiB

Open AccessArticle

Critical Resolved Shear Stress and Work Hardening Determination in HCP Metals: Application to Zr Single Crystals

by Jean-Sébastien Lecomte, Jérôme Crépin and Pierre Barberis

Metals 2024, 14(10), 1101; https://doi.org/10.3390/met14101101 (registering DOI) - 25 Sep 2024

Abstract

Obtaining precise parameters of deformation modes remains a significant challenge in materials science research. Critical resolved shear stresses (CRSS) and work hardening, particularly in hexagonal metals, are crucial parameters for constitutive laws in crystal plasticity. This paper presents a novel approach to determine [...] Read more.

α

-Zr) at room temperature. In situ methods are employed to measure displacement fields using grids applied to the sample surface, while a comprehensive characterization of the activated deformation systems is performed via SEM and TEM. The CRSS for prismatic

⟨ a ⟩

, pyramidal

⟨ a ⟩

, and

\{10 \bar{1} 2\}

and

\{11 \bar{2} 1\}

twinning systems, as well as the self-hardening for prismatic slip and several work-hardening coefficients (for prismatic/prismatic and prismatic/pyramidal interactions), are reported in Zr single crystals. Finally, the results are compared with findings from the literature and atomistic simulations. Full article

(This article belongs to the Special Issue Metal Plastic Deformation and Forming)

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14 pages, 2850 KiB

Open AccessArticle

Dysfunction of Telomeric Cdc13-Stn1-Ten1 Simultaneously Activates DNA Damage and Spindle Checkpoints

by Nathalie Grandin and Michel Charbonneau

Cells 2024, 13(19), 1605; https://doi.org/10.3390/cells13191605 - 25 Sep 2024

Abstract

Telomeres, the ends of eukaryotic linear chromosomes, are composed of repeated DNA sequences and specialized proteins, with the conserved telomeric Cdc13/CTC1-Stn1-Ten1 (CST) complex providing chromosome stability via telomere end protection and the regulation of telomerase accessibility. In this study, SIZ1, coding for a SUMO E3 ligase, and TOP2 (a SUMO target for Siz1 and Siz2) were isolated as extragenic suppressors of Saccharomyces cerevisiae CST temperature-sensitive mutants. ten1-sz, stn1-sz and cdc13-sz mutants were isolated next due to being sensitive to intracellular Siz1 dosage. In parallel, strong negative genetic interactions between mutants of CST and septins were identified, with septins being noticeably sumoylated through the action of Siz1. The temperature-sensitive arrest in these new mutants of CST was dependent on the G2/M Mad2-mediated and Bub2-mediated spindle checkpoints as well as on the G2/M Mec1-mediated DNA damage checkpoint. Our data suggest the existence of yet unknown functions of the telomeric Cdc13-Stn1-Ten1 complex associated with mitotic spindle positioning and/or assembly that could be further elucidated by studying these new ten1-sz, stn1-sz and cdc13-sz mutants. Full article

(This article belongs to the Section Cell Proliferation and Division)

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12 pages, 313 KiB

Open AccessReview

Lactation in Primates: Understanding the Physiology of Lactation from an Evolutionary Perspective

by Michelle Pascale Hassler, Alexandre Fabre, Valérie Moulin, Lucie Faccin, Julie Gullstrand, Alexia Cermolacce and Pierre Frémondière

Humans 2024, 4(4), 298-309; https://doi.org/10.3390/humans4040019 (registering DOI) - 25 Sep 2024

Abstract

Lactation in humans is complex. Understanding the cultural and biological patterns of human breastfeeding requires a global evolutionary analysis that includes observations of other primates. Human breastfeeding may have several specificities, but some features could be shared with other non-human primates. The purpose of this work is to determine what makes human breastfeeding unique from an evolutionary perspective. We consider behavioral as well as biological variables. Human and non-human primates share behavioral characteristics, such as the need to learn breastfeeding skills, and they display an adaptation of the energy density of the milk according to the type of mothering. However, despite having slow-growing, secondarily altricial offspring and rather diluted milk, modern humans spend less time breastfeeding than the great apes, and consequently have shorter interbirth intervals. Milk composition in macro- and micro-constituents changes during lactation, demonstrating evolutionary and ecological adaptation. Among the great apes, the milk of modern humans contains a higher proportion of fats, an equivalent proportion of carbohydrates and proteins, and a greater variety of oligosaccharides involved in brain and immune system development. The microbiome of modern man is less diverse than those of non-human primates, but the presence of HMOs and immunoglobulin A suggests that human milk is particularly adapted to prevent neonatal infections. Full article

15 pages, 3971 KiB

Open AccessArticle

PLK1 Inhibitor Onvansertib Enhances the Efficacy of Alpelisib in PIK3CA-Mutated HR-Positive Breast Cancer Resistant to Palbociclib and Endocrine Therapy: Preclinical Insights

by Sreeja Sreekumar, Elodie Montaudon, Davis Klein, Migdalia E. Gonzalez, Pierre Painsec, Héloise Derrien, Laura Sourd, Tod Smeal, Elisabetta Marangoni and Maya Ridinger

Cancers 2024, 16(19), 3259; https://doi.org/10.3390/cancers16193259 - 25 Sep 2024

Viewed by 96

Abstract

Background: Endocrine therapy (ET) combined with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) is the preferred first-line treatment for hormone receptor-positive (HR+)/HER2- metastatic breast cancer. Although this is beneficial, acquired resistance leads to disease progression, and patients harboring PIK3CA mutations are treated with targeted therapies such as the PI3Kα inhibitor, alpelisib, alongside ET. Drug-associated resistance mechanisms limit the efficacy of alpelisib, highlighting the need for better combination therapies. This study aimed to evaluate the efficacy of combining alpelisib with a highly specific PLK1 inhibitor, onvansertib, in PIK3CA-mutant HR+ breast cancer preclinical models. Methods: We assessed the effect of the alpelisib and onvansertib combination on cell viability, PI3K signaling pathway, cell cycle phase distribution and apoptosis in PI3K-activated HR+ breast cancer cell lines. The antitumor activity of the combination was evaluated in three PIK3CA-mutant HR+ breast cancer patient-derived xenograft (PDX) models, resistant to ET and CDK4/6 inhibitor palbociclib. Pharmacodynamics studies were performed using immunohistochemistry and Simple Western analyses in tumor tissues. Results: The combination synergistically inhibited cell viability, suppressed PI3K signaling, induced G2/M arrest and apoptosis in PI3K-activated cell lines. In the three PDX models, the combination demonstrated superior anti-tumor activity compared to the single agents. Pharmacodynamic studies confirmed the inhibition of both PLK1 and PI3K activity and pronounced apoptosis in the combination-treated tumors. Conclusions: Our findings support that targeting PLK1 and PI3Kα with onvansertib and alpelisib, respectively, may be a promising strategy for patients with PIK3CA-mutant HR+ breast cancer failing ET + CDK4/6i therapies and warrant clinical evaluation. Full article

(This article belongs to the Section Cancer Therapy)

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21 pages, 15805 KiB

Open AccessArticle

Data-Driven Calibration of SWOT’s Systematic Errors: First In-Flight Assessment

by Clément Ubelmann, Gérald Dibarboure, Benjamin Flamant, Antoine Delepoulle, Maxime Vayre, Yannice Faugère, Pierre Prandi, Matthias Raynal, Frédéric Briol, Geoffroy Bracher and Emeline Cadier

Remote Sens. 2024, 16(19), 3558; https://doi.org/10.3390/rs16193558 - 25 Sep 2024

Viewed by 113

Abstract

The SWOT satellite, carrying the KaRIN first wide-swath onboard altimeter, was launched in December 2022, and has now delivered more than a year of surface water elevation data over the ocean and inland lakes/rivers. These data are affected by systematic errors which constitute the dominant part of the error budget at scales larger than a few thousands of kilometers. Some strategies for their estimation and calibration were explored during the pre-launch studies with performance estimations. Now, based on the real data, we propose in this study to assess the systematic error budget with statistical methods relying on spectral and co-spectral analysis. From this assessment, suggesting very low error levels (below requirements), we propose the implementation of the calibration algorithms at Level-2 and Level-3 with a few minor adjustments justified by the error spectra. The calibrated products are then validated with usual CalVal metrics. Full article

(This article belongs to the Section Satellite Missions for Earth and Planetary Exploration)

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