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Non-toroidal-shaped primary pass-through protection current transformers (CTs) are used to measure high currents. Their design provides them with a big airgap that allow the passing of several cables per phase though them, which is the main advantage versus toroidal types, as the number of CTs required to measure the whole phase current is drastically reduced. The cables passed through the transformer window can be in several positions. As the isolines of the magnetic field generated by the primary currents are centered in the cables, if these cables are not centered in the transformer window, then the magnetic field will be non-uniform along the transformer core. Consequently, local saturations can appear if the cables are not properly disposed, causing the malfunction of the CT. In this paper, the performance of a non-toroidal-shaped protection CT is studied. This research is focused on the influence of the cable position on possible partial saturations of the CT when it is operating near to its accuracy limit. Depending on the cable position, the ratio of the primary and secondary currents can depart from the assigned ratio. The validation of this phenomenon was carried out via finite element analysis (FEA), showing that partial transformer core saturations appear in areas of the magnetic core close to the cable. By applying FEA, the admissible accuracy region for cable positioning inside the CT is also delimited. Finally, the simulation results are ratified with experimental tests performed in non-toroidal protection CTs, varying the primary cables' positions, which are subjected to currents up to 5 kA, achieving satisfactory results. From this analysis, installation recommendations are given.

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Introduction: In post-COVID survivors, transforming growth factor-beta-1 (TGF-ß1) might mediate fibroblast activation, resulting in persistent fibrosis. Methods: In this study, 82 survivors of COVID-19-associated ARDS were examined at 6- and 24-months post-ICU discharge. At 6-months, quantitative CT analysis of lung attenuation was performed and active TGF-ß1 was measured in blood and exhaled breath condensate (EBC). Results: At 6-months of ICU-discharge, patients with reduced DmCO/alveolar volume ratio exhibited higher plasma and EBC levels of active TGF-ß1. Plasma TGF-ß1 levels were elevated in dyspneic survivors and directly related to the high-attenuation lung volume. In vitro, plasma and EBC from survivors induced profibrotic changes in human primary fibroblasts in a TGF-ß receptor-dependent manner. Finally, at 6-months, plasma and EBC active TGF-ß1 levels discriminated patients who, 24-months post-ICU-discharge, developed gas exchange impairment. Discussion: TGF-ß1 pathway plays a pivotal role in the early-phase fibrotic abnormalities in COVID-19-induced ARDS survivors, with significant implications for long-term functional impairment.

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To date, studies of the impacts of climate warming on individuals and populations have mostly focused on mortality and thermal tolerance. In contrast, much less is known about the consequences of sublethal effects, which are more challenging to detect, particularly in wild species with cryptic life histories. This necessitates the development of molecular tools to identify their signatures. In a split-clutch field experiment, we relocated clutches of wild, nesting loggerhead sea turtles (Caretta caretta) to an in situ hatchery. Eggs were then split into two sub-clutches and incubated under shallow or deep conditions, with those in the shallow treatment experiencing significantly higher temperatures in otherwise natural conditions. Although no difference in hatching success was observed between treatments, hatchlings from the shallow, warmer treatment had different length-mass relationships and were weaker at locomotion tests than their siblings incubated in the deep, cooler treatment. To characterise the molecular signatures of these thermal effects, we performed whole genome bisulfite sequencing on blood samples collected upon emergence. We identified 287 differentially methylated sites between hatchlings from different treatments, including on genes with neurodevelopmental, cytoskeletal, and lipid metabolism functions. Taken together, our results show that higher incubation temperatures induce sublethal effects in hatchlings, which are reflected in their DNA methylation status at identified sites. These sites could be used as biomarkers of thermal stress, especially if they are retained across life stages. Overall, this study suggests that global warming reduces hatchling fitness, which has implications for dispersal capacity and ultimately a population's adaptive potential. Conservation efforts for these endangered species and similar climate-threatened taxa will therefore benefit from strategies for monitoring and mitigating exposure to temperatures that induce sublethal effects.

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Despite their potential relevance as molecular models for industrial and biological catalysis, well-defined mononuclear iron carbide complexes are unknown, in part due to the limited number of appropriate C1 synthons. Here, we show the ability of the cyaphide anion (C≡P-) to serve as a C1 source. The high spin (S = 2) cyaphide complex PhB(tBuIm)3Fe-C≡P (PhB(tBuIm)3- = phenyl(tris(3-tert-butylimidazol-2-ylidene)borate) is readily accessed using the new cyaphide transfer reagent [Mg(DippNacNac)(CP)]2 (DippNacNac = CH{C(CH3)N(Dipp)}2 and Dipp = 2,6-di(iso-propyl)phenyl). Phosphorus atom abstraction is effected by the three-coordinate Mo(III) complex Mo(NtBuAr)3 (Ar = 3,5-Me2C6H3), which produces the known phosphide (tBuArN)3Mo≡P along with a transient iron carbide complex PhB(tBuIm)3Fe≡C. Electronic structure calculations reveal that PhB(tBuIm)3Fe≡C adopts a doublet ground state with nonzero spin density on the carbide ligand. While isolation of this complex is thwarted by rapid dimerization to afford the corresponding diiron ethynediyl complex, the carbide can be intercepted by styrene to provide an iron alkylidene.

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BACKGROUND: Efficient recanalization of occluded cerebral arteries is crucial in the treatment of acute ischemic stroke. Double stent retrievers have shown the potential to enhance the rates of recanalization on the first pass. This study aims to evaluate the efficacy and safety of the double stent retriever technique and the predictors of achieving first-pass effect in patients with acute ischemic stroke. METHODS: This prospective multicenter study involved 209 patients from 16 comprehensive stroke centers in Spain. Patients with occlusions in the anterior circulation were treated using the Aperio Hybrid double stent retriever. The study examined various deployment techniques, including simultaneous and sequential deployment and stent configurations, comparing the Y-shaped and parallel configurations. RESULTS: The double stent retriever technique achieved a first-pass effect in 72.7% of cases and a final successful recanalization rate of 99.5%. The Y-shaped configuration was significantly associated with higher recanalization rates on the first pass (OR 2.59, 95% CI 1.18 to 5.68, P=0.02). Procedural complications were mild to moderate in 6.7% and severe in 1.5% of cases, with symptomatic intracranial hemorrhage occurring in 3.3% of patients. At 3 months follow-up, 57.2% of patients achieved a good clinical outcome, with a mortality rate of 15.1%. CONCLUSION: The findings support the efficacy of the double stent retriever technique, particularly the Y-shaped configuration, in achieving high recanalization rates on the first pass with an acceptable safety profile. This technique may offer clinical benefits for future acute ischemic stroke treatment protocols.

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A genomic database of all Earth's eukaryotic species could contribute to many scientific discoveries; however, only a tiny fraction of species have genomic information available. In 2018, scientists across the world united under the Earth BioGenome Project (EBP), aiming to produce a database of high-quality reference genomes containing all ~1.5 million recognized eukaryotic species. As the European node of the EBP, the European Reference Genome Atlas (ERGA) sought to implement a new decentralised, equitable and inclusive model for producing reference genomes. For this, ERGA launched a Pilot Project establishing the first distributed reference genome production infrastructure and testing it on 98 eukaryotic species from 33 European countries. Here we outline the infrastructure and explore its effectiveness for scaling high-quality reference genome production, whilst considering equity and inclusion. The outcomes and lessons learned provide a solid foundation for ERGA while offering key learnings to other transnational, national genomic resource projects and the EBP.

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To explore new compounds with antitumour activity, fifteen phenolic nor-tripterpenes isolated from Celastraceae species, Maytenus jelskii, Maytenus cuzcoina, and Celastrus vulcanicola, have been studied. Their chemical structures were elucidated through spectroscopic and spectrometric techniques, resulting in the identification of three novel chemical compounds. Evaluation on human tumour cell lines (A549 and SW1573, non-small cell lung; HBL-100 and T-47D, breast; HeLa, cervix, and WiDr, colon) revealed that three compounds, named 6-oxo-pristimerol, demethyl-zeylasteral, and zeylasteral, exhibited significant activity (GI50 ranging from 0.45 to 8.6 µM) on at least five of the cell lines tested. Continuous live cell imaging identified apoptosis as the mode of action of selective cell killing in HeLa cells. Furthermore, their effect on a drug-sensitive Saccharomyces cerevisiae strain has been investigated to deepen on their mechanism of action. In dose-response growth curves, zeylasteral and 7α-hydroxy-blepharodol were markedly active. Additionally, halo assays were conducted to assess the involvement of oxidative stress and/or mitochondrial function in the anticancer profile, ruling out these modes of action for the active compounds. Finally, we also delve into the structure-activity relationship, providing insights into how the molecular structure of these compounds influences their biological activity. This comprehensive analysis enhances our understanding of the therapeutic potential of this triterpene type and underscores its relevance for further research in this field.

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The electrochemical oxidation of anodic metals (M = nickel and palladium) in an acetonitrile solution of the thiosemicarbazone ligands (E)-2-(1-(4-methoxyphenyl)ethylidene)-N-methylhydrazine-1-carbothioamide (a), (E)-2-(1-(p-tolyl)ethylidene)hydrazine-1-carbothioamide (b), and (E)-N-phenyl-2-(1-(p-tolyl)ethylidene)hydrazine-1-carbothioamide (c) yielded the homoleptic complexes [ML2], 1a, 1b, 1c, and 2c and [M4L4], 2a as air-stable solids. The crystal structures for 1a, 1b, 1c, and 2c show the ligands in a transoid disposition with the [S,S] and [N,N] donor atom pairs occupying cis positions on the nearly square planar coordination plane of the metal. The structure for 2a of S4 symmetry comprises a tetranuclear palladacycle where the metalated ligands are arranged around a central Pd4S4 environment: a crown ring with alternating palladium and sulfur atoms. The latter complex is the first example of an electrochemical preparation of a cyclometalated palladium compound, marking a milestone in the chemistry of such species. The compounds have been fully characterized by elemental microanalysis, mass spectrometry, infrared (IR), and 1H nuclear magnetic resonance (NMR) spectra.

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We know that fruit production, especially in the Mediterranean, will need to adapt to climate change to ensure the sustainability of fruit tree-based agroecosystems. However, there is a lack of evidence on the long-term effects of this change on sustainability indicators. To fill this gap, we used a fruit tree model, QualiTree, to analyze the impacts ofclimate change on the ecosystem services provided by apple orchards in south-eastern France. To do this, a blooming model was parameterized to simulate blooming date on the basis of climate data, and QualiTree was supplemented with a model of nitrogen processes in the tree and a soil module describing resource input (irrigation, mineral and organic fertilization), transfer in the soil (water and nitrogen) and metabolic transformation-immobilization (mineralization, (de)nitrification). This type of extension makes it possible to simulate a wide array of ecosystem services, including C sequestration, nitrate leaching and nitrous oxide emissions. The model was compared with data from an apple orchard in southeastern France. The predicted daily mean and variability over time of fruit growth, composition and soil water content were consistent with observed data. QualiTree was then used to assess the potential impacts of climate change on the ecosystem services supplied by apple orchards. For this purpose, weather variables from 2020 to 2100 were generated for three contrasted greenhouse gas emission scenarios, and simulations were performed under two irrigation schemes (no restriction and restricted use of water). Model outputs indicated that, on average, marketable apple yields would increase until 2050 and then subsequently decrease. The fruit refractometric index, an indicator of fruit quality, was projected to sharply decrease with the intensity of climate change. Ecosystem services such as C sequestration by the orchard will decrease with climate change severity, mainly due to a higher mineralization of soil humus, whereas N2O emissions will increase with larger denitrification rates. Soil water availability, fertility, drainage and leaching were predicted to depend more on the irrigation strategy than on climate change severity. The new functions performed in QualiTree broadened its predictive capabilities and allowed for a better understanding of ecosystem service delivery in fruit orchards under varying climate conditions.

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Alpha-1 antitrypsin (AAT) is an acute-phase reactant with immunomodulatory properties that mainly inhibits neutrophil elastase. Low serum levels cause AAT deficiency (AATD), an underdiagnosed condition that predisposes to pulmonary and hepatic diseases. The SERPINA1 gene, which encodes AAT, contains more than 500 variants. PI*Z and PI*S alleles are the most diagnosed causes of AATD, but the role of the SERPINA1 haplotypes in AAT function remains unknown. SERPINA1 gene was PCR amplified from 94 asthma patients, using primers with tails for indexing. Sequencing libraries were loaded into a MinION-Mk1C, and MinKNOW was used for basecalling and demultiplexing. Nanofilt and Minimap2 were used for filtering and mapping/alignment. Variant calling/phasing were performed with PEPPER-Margin-DeepVariant. SERPINA1 gene was 100% covered for all samples, with a minimum sequencing depth of 500X. 75 single nucleotide variants and 4 indels were detected, with 45 and 2 of them highly polymorphic (MAF>0.1), respectively. Nine of the SNVs showed differences in allele frequencies when compared with the overall Spanish population. More than 90% of heterozygous SNVs were phased, yielding 91 and 58 different haplotypes for each SERPINA1 amplified region. Haplotype-based Linkage Disequilibrium (LD) analysis suggests that a recombination hotspot could generate variation in the SERPINA1 gene. The proposed workflow enables haplotype-aware genotyping of the SERPINA1 gene by nanopore sequencing, which will allow the development of novel AATD diagnostic strategies.

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INTRODUCTION: Medically refractory epilepsy (MRE) occurs in about 30 % of patients with epilepsy, and the treatment options available to them have evolved over time. The classic treatment for medial temporal lobe epilepsy (mTLE) is anterior temporal lobectomy (ATL), but an initiative to find less invasive options has resulted in treatments such as neuromodulation, ablative procedures, and stereotactic radiosurgery (SRS). SRS has been an appealing non-invasive option and has developed an increasing presence in the literature over the last few decades. This article provides an overview of SRS for MRE with two example cases, and we discuss the optimal technique as well as the advantages, alternatives, and risks of this therapeutic option. CASES: We present two example cases of patients with MRE, who were poor candidates for invasive surgical treatment options and underwent SRS. The first case is a 65-year-old female with multiple medical comorbidities, whose seizure focus was localized to the left temporal lobe, and the second case is a 19-year-old male with Protein C deficiency and medial temporal lobe sclerosis. Both patients underwent SRS to targets within the medial temporal lobe, and both achieve significant improvements in seizure frequency and severity. DISCUSSION: SRS has generally been shown to be inferior to ATL for seizure reduction in medically refractory mTLE. However, there are patients with epilepsy for which SRS can be considered, such as patients with medical comorbidities that make surgery high risk, patients with epileptogenic foci in eloquent cortex, patients who have failed to respond to surgical management, patients who choose not to undergo surgery, and patients with geographic constraints to epilepsy centers. Patients and their physicians should be aware that SRS is not risk-free. Patients should be counseled on the latency period and monitored for risks such as delayed cerebral edema, visual field deficits, and radiation necrosis.

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In an attempt to address the large inequities faced by the plant biology communities from the Global South (i.e. countries located around the tropics and the Southern Hemisphere) at international conferences, this Viewpoint is the reflexive thinking arising from the concurrent session titled 'Arabidopsis and its translational research in the Global South' organized at the International Conference of Arabidopsis Research 2023 (ICAR 2023) in Chiba, Japan in June 2023. Here, we highlight the main obstacles plant biology communities in the Global South face in terms of knowledge production, as measured by the unequal production and citation of publications, investigating and advancing local plant genomics and biodiversity, combating disparities in gender and diversity, and current initiatives to break isolation of scientists.

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The tumor microenvironment (TME) is characterized by a network of cancer cells, recruited immune cells, and extracellular matrix (ECM). However, the specific role of neutrophils during tumor development, and their interactions with other immune cells is still not well understood. Here, we use both standard well plate culture and an under oil microfluidic (UOM) assay with an integrated ECM bridge to elucidate how naive primary neutrophils respond to tumor cells. Our data demonstrated that tumor cells trigger cluster formation in neutrophils accompanied with the generation of reactive oxygen species (ROS) and neutrophil extracellular trap (NET) release. Using label-free optical metabolic imaging (OMI), we observed changes in the metabolic activities of primary neutrophils during the different clustering phases when challenged with tumor cells. Finally, our data demonstrates that neutrophils in direct contact, or in close proximity, with tumor cells exhibit greater metabolic activities compared to non-contact neutrophils.

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Individuals of Pacific ancestry suffer some of the highest rates of health disparities yet remain vastly underrepresented in genomic research, including currently available linear and pangenome references. To begin addressing this, we developed the first Pacific ancestry pangenome reference using 23 individuals with diverse Pacific ancestry. We assembled 46 haploid genomes from these 23 individuals, resulting in highly accurate and contiguous genome assemblies with an average quality value of 55.0 and an average N50 of 40.7 Mb, marking the first de novo assembly of highly accurate Pacific ancestry genomes. We combined these assemblies to create a pangenome reference, which added 30.6 Mb of novel sequence missing from the Human Pangenome Reference Consortium (HPRC) reference. Mapping short reads to this pangenome reduced variant call errors and yielded more true-positive variants compared to the HPRC and T2T-CHM13 references. This Pacific ancestry pangenome reference serves as a resource to enhance genetic analyses for this underserved population.

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OBJECTIVE: Glucagon has long been proposed as a component of multi-agonist obesity therapeutics due to its ability to induce energy expenditure and cause weight loss. However, chronic glucagon-receptor agonism has been associated with a reduction in circulating amino acids and loss of lean mass. Importantly, it is currently not known whether the metabolic benefits of glucagon can be maintained under contexts that allow the defence of lean mass. METHODS: We investigate the metabolic effects of the long-acting glucagon receptor agonist, G108, when administered to obese mice at low-doses, and with dietary protein supplementation. RESULTS: Dietary protein supplementation can only fully defend lean mass at a low dose of G108 that is sub-anorectic and does not reduce fat mass. However, in this context, G108 is still highly effective at improving glucose tolerance and reducing liver fat in obese mice. Mechanistically, liver RNA-Seq analysis reveals that dietary protein supplementation defends anabolic processes in low-dose G108-treated mice, and its effects on treatment-relevant glucose and lipid pathways are preserved. CONCLUSION: Glucagon-mediated energy expenditure and weight loss may be mechanistically coupled to hypoaminocidemia and lean mass loss. However, our data suggest that glucagon can treat MAFLD at doses which allow full defence of lean mass given sufficient dietary protein intake. Therefore, proportionate glucagon therapy may be safe and effective in targeting hepatocytes and improving in glycaemia and liver fat.

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Herein, we demonstrate mechanically stable large-area thin films with a purely real refractive index (n) close to 1 in the optical range. At specific wavelengths, it can reach values as small as n = 1.02, the lowest reported for thin solid slabs. These are made of a random network of interwoven spherical silica shells, created by chemical vapour deposition of a thin layer of silica on the surface of randomly packed monodisperse polymer nanoparticles that form a film. Thermal processing of the composites results in highly porous silica-based transparent thin films. We demonstrate the potential of this approach by making novel photonic materials such as strong optical diffusers, built by integrating scattering centers within the ultralow n transparent films, or highly efficient light-emitting slabs, in which losses by total internal reflection are practically absent as a result of the almost null optical impedance at the film-air interface.

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Plasmonic nanoparticles (NPs) have played a significant role in the evolution of modern nanoscience and nanotechnology in terms of colloidal synthesis, general understanding of nanocrystal growth mechanisms, and their impact in a wide range of applications. They exhibit strong visible colors due to localized surface plasmon resonance (LSPR) that depends on their size, shape, composition, and the surrounding dielectric environment. Under resonant excitation, the LSPR of plasmonic NPs leads to a strong field enhancement near their surfaces and thus enhances various light-matter interactions. These unique optical properties of plasmonic NPs have been used to design chemical and biological sensors. Over the last few decades, colloidal plasmonic NPs have been greatly exploited in sensing applications through LSPR shifts (colorimetry), surface-enhanced Raman scattering, surface-enhanced fluorescence, and chiroptical activity. Although colloidal plasmonic NPs have emerged at the forefront of nanobiosensors, there are still several important challenges to be addressed for the realization of plasmonic NP-based sensor kits for routine use in daily life. In this comprehensive review, researchers of different disciplines (colloidal and analytical chemistry, biology, physics, and medicine) have joined together to summarize the past, present, and future of plasmonic NP-based sensors in terms of different sensing platforms, understanding of the sensing mechanisms, different chemical and biological analytes, and the expected future technologies. This review is expected to guide the researchers currently working in this field and inspire future generations of scientists to join this compelling research field and its branches.