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13 pages, 1614 KB  
Article
Mitral Annular Disjunction Assessed Using Cardiac MR Imaging in Pediatric Patients
by Şükriye Yılmaz, Berna Ucan, Hasan Bulut, Senem Özgür, Tamer Yoldaş and Pelin Altınbezer
Diagnostics 2025, 15(22), 2857; https://doi.org/10.3390/diagnostics15222857 (registering DOI) - 12 Nov 2025
Abstract
Background/Objectives: Mitral annular disorders constitute a heterogeneous group of structural abnormalities that can significantly influence morbidity and mortality in both adult and pediatric populations. Advances in cardiac magnetic resonance (CMR) imaging have refined the ability to characterize these disorders with high spatial [...] Read more.
Background/Objectives: Mitral annular disorders constitute a heterogeneous group of structural abnormalities that can significantly influence morbidity and mortality in both adult and pediatric populations. Advances in cardiac magnetic resonance (CMR) imaging have refined the ability to characterize these disorders with high spatial resolution and reproducibility. Among them, mitral annular disjunction (MAD) and mitral valve prolapse (MVP) have emerged as interrelated entities implicated in valvular dysfunction, arrhythmogenesis, and myocardial remodeling. This study aimed to determine the prevalence of MAD in a pediatric cohort, explore its association with MVP, and delineate related CMR findings, including myocardial fibrosis. Methods: A retrospective review was conducted in 295 pediatric patients who underwent clinically indicated CMR between September 2022 and June 2025. Echocardiographic and CMR data were systematically compared for the detection of MAD, MVP, and mitral regurgitation (MR). MAD length and mitral annular measurements were obtained from two-chamber and left ventricular outflow tract (LVOT) cine sequences. Late gadolinium enhancement (LGE) was evaluated to identify myocardial fibrosis. Results: MAD was detected more frequently by means of CMR than echocardiography (23.2% vs. 9.3%), as was MVP (34.2% vs. 22.4%), whereas MR was more often observed on echocardiography (31.2% vs. 15.2%). Inter-modality agreement was moderate for MAD, moderate-to-substantial for MVP, and fair for MR. LGE was identified only in patients with concomitant MAD and MVP, suggesting limited myocardial involvement in isolated MAD. Conclusions: CMR demonstrates superior sensitivity in detecting MAD and MVP compared with echocardiography and allows for early recognition of systolic–diastolic annular dissociation before advanced myocardial remodeling occurs. These findings underscore the clinical utility of CMR as a complementary modality for comprehensive assessment, risk stratification, and follow-up of pediatric patients with suspected mitral annular abnormalities. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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11 pages, 1474 KB  
Article
ARROW: Allele-Specific Recombined gRNA Design for Reduced Off-Target with Enhanced Specificity
by Taegeun Bae, Kyung Wook Been, Seunghun Kang, Sumin Hong, Junho K. Hur and Woochang Hwang
Bioengineering 2025, 12(11), 1237; https://doi.org/10.3390/bioengineering12111237 (registering DOI) - 12 Nov 2025
Abstract
Background/Objectives: Allele-specific genome editing using the CRISPR–Cas9 system is crucial for achieving precise therapeutic interventions in dominant inherited diseases that are otherwise difficult to treat with conventional approaches. However, Cas9–guide RNA (gRNA) complexes often tolerate single-base mismatches in target sequences, making it challenging [...] Read more.
Background/Objectives: Allele-specific genome editing using the CRISPR–Cas9 system is crucial for achieving precise therapeutic interventions in dominant inherited diseases that are otherwise difficult to treat with conventional approaches. However, Cas9–guide RNA (gRNA) complexes often tolerate single-base mismatches in target sequences, making it challenging to discriminate between wild-type and mutant alleles differing by only one nucleotide. Although previous studies have attempted to improve specificity by introducing mismatches into gRNAs, none has systematically investigated the impact of different mismatch types and positions on editing outcomes. In this study, we developed an effective strategy to enhance specificity and minimize off-target effects by deliberately introducing mismatches into gRNAs and comprehensively evaluating their editing performance. Results: We established an efficient strategy for the selective editing of mutant alleles that reduces Cas9 sequence tolerance and enhances specificity through the intentional introduction of mismatches into gRNAs. The efficacy of this approach was demonstrated by successful allele-specific editing of cancer-associated heterozygous point mutations in EGFR L858R and KRAS G12V, while minimizing editing of the corresponding wild-type alleles. Conclusion: Compared with perfectly matched gRNAs, the strategic incorporation of mismatches into gRNAs enhanced editing specificity for single-base mutant alleles. Our findings substantially improve the precision and safety of CRISPR-based genome editing for cancer therapy, particularly in cases involving mutant alleles. Full article
(This article belongs to the Section Cellular and Molecular Bioengineering)
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24 pages, 11969 KB  
Article
Regulation of TGF-β and BMP Signaling by Natural Triterpene Compounds in Pulmonary Arterial Hypertension (PAH)
by Sila Ozlem Sener, Sabita Shaha, Saltan Gülçin İşcan, Ufuk Ozgen, Merve Yuzbasioglu Baran, Aleyna Nalcaoğlu and Md Talat Nasim
Curr. Issues Mol. Biol. 2025, 47(11), 939; https://doi.org/10.3390/cimb47110939 (registering DOI) - 12 Nov 2025
Abstract
Pulmonary arterial hypertension (PAH) is a devastating cardiovascular disorder caused by right heart failure leading to premature death. The TGFBR2 and BMPR-II receptors, which are members of the TGF-β receptor family, are considered promising targets for developing novel drugs in PAH. Lupeol and [...] Read more.
Pulmonary arterial hypertension (PAH) is a devastating cardiovascular disorder caused by right heart failure leading to premature death. The TGFBR2 and BMPR-II receptors, which are members of the TGF-β receptor family, are considered promising targets for developing novel drugs in PAH. Lupeol and ψ-taraxasterol, naturally occurring triterpene molecules with proven anti-inflammatory, anti-cancer, and cardioprotective activities, hold considerable potential in the treatment of PAH. Hence, the present study aimed to evaluate the impacts of lupeol and ψ-taraxasterol isolated from Cirsium sintenisii Freyn on the TGF-β and BMP pathways, aiming to determine their therapeutic values in PAH. The effects of the compounds were extensively investigated using both in silico and wet lab experiments, including reporter assays, RT-PCR/QPCR, Western blots, and cell proliferations assays. Both lupeol and ψ-taraxasterol demonstrated interactions with the majority of components of these signaling pathways, including the TGFBR2 and BMPR-II receptors, suggesting that both compounds were capable of modulating the BMP and TGF-β pathways. Data derived from reporter assays, RT-PCR/QPCR, and Western blots demonstrated that lupeol and ψ-taraxasterol inhibited the TGF-β signaling pathway by reducing the phosphorylation of the SMAD3 protein and the expression of pai-1 transcripts. Additionally, ψ-taraxasterol enhanced BMP signaling via regulating the phosphorylation of SMAD1/5 proteins and upregulated the expression of id-1 transcripts. Finally, lupeol and ψ-taraxasterol inhibited abnormal proliferation of mutant-type (bmpr2R899X+/-) PAMSCs stimulated with the TGF-β1 ligand with no discernible effects on wild-type cells. This is the first comprehensive report outlining the potential therapeutic effects of lupeol and ψ-taraxasterol in PAH, which may have immediate experimental and clinical applications not only in PAH but also other BMP- and TGF-β-associated disorders. Full article
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16 pages, 2594 KB  
Article
The Potential Roles of Prophages in the Pathogenicity of Klebsiella pneumoniae Strains from Kenya
by Julie K. Akhwale, Ivy J. Mutai and Janet Y. Nale
Antibiotics 2025, 14(11), 1145; https://doi.org/10.3390/antibiotics14111145 (registering DOI) - 12 Nov 2025
Abstract
Background/Objectives: Antimicrobial resistance (AMR) in Klebsiella pneumoniae poses a serious threat to healthcare, especially in sub-Saharan Africa (SSA). To complement AMR infection control in Kenya, here, clinical and environmental genomes were investigated to determine the potential roles prophages play in K. pneumoniae pathogenicity. [...] Read more.
Background/Objectives: Antimicrobial resistance (AMR) in Klebsiella pneumoniae poses a serious threat to healthcare, especially in sub-Saharan Africa (SSA). To complement AMR infection control in Kenya, here, clinical and environmental genomes were investigated to determine the potential roles prophages play in K. pneumoniae pathogenicity. Methods: Prophages were extracted from 89 Kenyan K. pneumoniae genomes. The intact prophages were examined for virulence genes carriage, and their phylogenetic relationships were established. Results: Eighty-eight (~99%) of the genomes encode at least a single prophage, and there is an average of four prophages and 2.8% contributory genomes per bacterial strain. From the 364 prophages identified, 250 (68.7%) were intact, while 58 (15.9%) and 57 (15.7%) were questionable and incomplete, respectively. Approximately, 30% of the intact prophages encode 38 virulence genes that are linked to iron uptake (8), regulation (6), adherence (5), secretion system (4), antiphagocytosis (4), autotransporter (4), immune modulation (3), invasion (2), toxin (1) and cell surface/capsule (1). Phylogenetic analyses revealed three distinct clades of the intact prophages irrespective of their hosts, sources and locations, which support the plasticity of the genomes and potential to mediate horizontal gene transfer. Conclusions: This study provides first evidence showing the diverse prophages that are encoded in K. pneumoniae from SSA with particular focus on Kenyan strains. This also shows the potential roles these prophages play in the pathogenicity and success of K. pneumoniae and could improve knowledge and complement control strategies in the region and across the globe. Further work is needed to show the expression of these genes through lysogenisation. Full article
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23 pages, 1366 KB  
Article
Work Engagement, Job Crafting, and Their Effects on Green Work Outcomes
by Ksenia Gurcham, Osman M. Karatepe, Elisa Rescalvo-Martin and Turgay Avci
Sustainability 2025, 17(22), 10090; https://doi.org/10.3390/su172210090 (registering DOI) - 12 Nov 2025
Abstract
The present study examines the effect of work engagement (WENG) on task-related pro-environmental behavior (TPEB) and green creativity, with job crafting as a mediator. Based on data collected from 187 customer-contact hotel and restaurant employees in the United Kingdom, we employed structural equation [...] Read more.
The present study examines the effect of work engagement (WENG) on task-related pro-environmental behavior (TPEB) and green creativity, with job crafting as a mediator. Based on data collected from 187 customer-contact hotel and restaurant employees in the United Kingdom, we employed structural equation modeling to test our hypotheses. The findings from a time-lagged survey study denote that WENG fosters employees’ job crafting, while job crafting boosts their TPEBs and green creativity. Our findings shed light on the relationship between WENG and green outcomes (TPEB and green creativity) through the mediating role of employees’ job crafting. The findings highlight that employees high in WENG use their job crafting behaviors that in turn enable them to display TPEBs and green creativity. This empirical piece contributes to the existing knowledge, since there is little research regarding the effects of non-green organizational factors on green work outcomes. The practical and theoretical implications of the findings are subsequently discussed. Full article
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21 pages, 1931 KB  
Review
Microfluidic Field-Deployable Systems for Colorimetric-Based Monitoring of Nitrogen Species in Environmental Waterbodies: Past, Present, and Future
by Jelena Milinovic, James Lunn, Sherif Attia and Gregory Slavik
Environments 2025, 12(11), 434; https://doi.org/10.3390/environments12110434 (registering DOI) - 12 Nov 2025
Abstract
The biogeochemical cycling of nitrogen (N) in natural waterbodies, ranging from freshwaters to estuaries and seawater, is fundamental to the health of aquatic ecosystems. Anthropogenic pressures (agricultural runoff, atmospheric deposition, and wastewater discharge) have profound effects on these cycles, leading to widespread problems, [...] Read more.
The biogeochemical cycling of nitrogen (N) in natural waterbodies, ranging from freshwaters to estuaries and seawater, is fundamental to the health of aquatic ecosystems. Anthropogenic pressures (agricultural runoff, atmospheric deposition, and wastewater discharge) have profound effects on these cycles, leading to widespread problems, such as eutrophication, harmful algal blooms, and contamination of drinking water sources. Monitoring of different N-species—ammonium (NH4+), nitrite (NO2), nitrate (NO3) ions, dissolved organic nitrogen (DON), and total nitrogen (TN)—is of crucial importance to protect and mitigate environmental harm. Traditional analytical methodologies, while providing accurate laboratory data, are hampered by logistical complexity, high cost, and the inability to capture transient environmental events in near-real time. In response to this demand, miniaturised microfluidic technologies offer the opportunity for rapid, on-site measurements with significantly reduced reagent/sample consumption and the development of portable sensors. Here, we review and critically evaluate the principles, state-of-the-art applications, inherent advantages, and ongoing challenges associated with the use of microfluidic colorimetry for N-species in a variety of environmental waterbodies. We explore adaptations of classical colorimetric chemistry to microfluidic-based formats, examine strategies to mitigate complex matrix interferences, and consider future trajectories with autonomous platforms and smart sensor networks for simultaneous multiplexed N-species determination. Full article
(This article belongs to the Special Issue Monitoring of Contaminated Water and Soil)
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24 pages, 53871 KB  
Article
Hyperspectral Object Tracking via Band and Context Refinement Network
by Jingyan Zhang, Zhizhong Zheng, Kang Ni, Nan Huang, Qichao Liu and Pengfei Liu
Remote Sens. 2025, 17(22), 3689; https://doi.org/10.3390/rs17223689 - 12 Nov 2025
Abstract
The scarcity of labeled hyperspectral video samples has motivated existing methods to leverage RGB-pretrained networks; however, many existing methods of hyperspectral object tracking (HOT) select only three representative spectral bands from hyperspectral images, leading to spectral information loss and weakened target discrimination. To [...] Read more.
The scarcity of labeled hyperspectral video samples has motivated existing methods to leverage RGB-pretrained networks; however, many existing methods of hyperspectral object tracking (HOT) select only three representative spectral bands from hyperspectral images, leading to spectral information loss and weakened target discrimination. To address this issue, we propose the Band and Context Refinement Network (BCR-Net) for HOT. Firstly, we design a band importance learning module to partition hyperspectral images into multiple false-color images for pre-trained backbone network. Specifically, each hyperspectral band is expressed as a non-negative linear combination of other bands to form a correlation matrix. This correlation matrix is used to guide an importance ranking of the bands, enabling the grouping of bands into false-color images that supply informative spectral features for the multi-branch tracking framework. Furthermore, to exploit spectral–spatial relationships and contextual information, we design a Contextual Feature Refinement Module, which integrates multi-scale fusion and context-aware optimization to improve feature discrimination. Finally, to adaptively fuse multi-branch features according to band importance, we employ a correlation matrix-guided fusion strategy. Extensive experiments on two public hyperspectral video datasets show that BCR-Net achieves competitive performance compared with existing classical tracking methods. Full article
(This article belongs to the Special Issue SAR and Multisource Remote Sensing: Challenges and Innovations)
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13 pages, 554 KB  
Article
Association of Chromosome 3p21.32 Haplotype Blocks Introgressed from Neanderthals with Critical COVID-19 in a Spanish Cohort
by Daniel Vázquez-Coto, Marta García-Clemente, Tamara Hermida-Valverde, Guillermo M. Albaiceta, Laura Amado, Lorena M. Vega-Prado, Claudia García-Lago, Pablo Herrero-Puente, Jesús Martínez-Borra, Rebeca Lorca, Juan Gómez and Eliecer Coto
Life 2025, 15(11), 1733; https://doi.org/10.3390/life15111733 (registering DOI) - 12 Nov 2025
Abstract
Background: Human chromosome 3p21.31 variants introgressed from Neanderthals have been associated with a higher risk of developing a severe form of COVID-19. These Neanderthal DNA variants would regulate the expression of several genes, including LZTFL1 (implicated in the epithelial–mesenchymal transition) and proinflammatory chemokine [...] Read more.
Background: Human chromosome 3p21.31 variants introgressed from Neanderthals have been associated with a higher risk of developing a severe form of COVID-19. These Neanderthal DNA variants would regulate the expression of several genes, including LZTFL1 (implicated in the epithelial–mesenchymal transition) and proinflammatory chemokine receptors. Methods: We studied three introgressed haplotypes in patients who developed critical COVID-19 (N = 446; 82 deaths), less severe non-critical COVID-19 (N = 552), and population controls (N = 500) from the region of Asturias, Northern Spain. All the participants were genotyped for six single nucleotide polymorphisms that defined the three 3p21.31 haplotypes. Results: For the haplotype in the LZTFL1 gene, the total patients were significantly higher frequency carriers of the Neanderthal variant compared to controls (24% vs. 17%; p < 0.05, OR = 1.53, 95% CI = 1.16–2.01). Multiple logistic regression showed that critical COVID-19 was independently associated with male sex, hypertension, dyslipaemia, and the introgressed LZTFL1 haplotype (p = 0.006). The frequency of these introgressed genotypes did not differ between normotensives and normolipaemics in the two patient groups but was significantly increased among hypertensives (p = 0.003) and dyslipaemics (p = 0.001). Conclusions: In our population, the 3p21.31 haplotypes introgressed from Neanderthals were associated with increased risk of critical COVID-19, and the risk effect was higher among patients with hypertension and dyslipaemia. Full article
(This article belongs to the Section Genetics and Genomics)
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25 pages, 2486 KB  
Article
A Preliminary Mechanics-Informed Machine Learning Framework for Objective Assessment of Parkinson’s Disease and Rehabilitation Outcomes
by Amirali Hanifi, Roozbeh Abedini-Nassab and Mohammed N. Ashtiani
Diagnostics 2025, 15(22), 2855; https://doi.org/10.3390/diagnostics15222855 (registering DOI) - 12 Nov 2025
Abstract
Background/Objectives: Non-invasive methods for evaluating rehabilitation outcomes in Parkinson’s disease (PD) remain limited. This preliminary study proposes a mechanics-informed machine learning (ML) framework integrating force-plate data with dimensionality reduction, clustering, and statistical analysis to objectively assess motor control and the effects of a [...] Read more.
Background/Objectives: Non-invasive methods for evaluating rehabilitation outcomes in Parkinson’s disease (PD) remain limited. This preliminary study proposes a mechanics-informed machine learning (ML) framework integrating force-plate data with dimensionality reduction, clustering, and statistical analysis to objectively assess motor control and the effects of a targeted intervention. Methods: Twelve PD patients were randomly assigned to a PD control group performing standard exercises or an intervention group incorporating additional transverse-plane trunk motion exercises for 10 weeks. Ground reaction forces and center of pressure (COP) signals were recorded pre- and post-intervention using a force plate, alongside data from six healthy individuals as a benchmark. Features related to postural sway and COP dynamics were extracted and refined using Forward Feature Selection. Dimensionality reduction (t-SNE) and unsupervised clustering (K-means) identified group-level patterns. SHAP values and Cohen’s d quantified feature importance and effect size. Clustering robustness was assessed with bootstrapping, nested cross-validation, and permutation testing. Results: K-means clustering revealed clear pre/post-intervention separation in five of six intervention patients, with post-intervention states shifting toward the control cluster. Clustering showed strong performance (Silhouette 0.77–0.79; Calinski–Harabasz 100.8–184.9; Davies–Bouldin 0.29–0.45). The most predictive features (RMS-SML and PL-SAP) showed large effect sizes (Cohen’s d = –12.1 and –4.53, respectively) distinguishing PD patients from healthy controls. Traditional statistical tests (e.g., ANOVA) failed to detect within-group changes (p > 0.05), but ML-based methods captured subtle, nonlinear postural adaptations. Conclusions: This preliminary mechanics-informed ML framework detects PD-related motor deficits and rehabilitation-induced improvements using force-plate data, warranting validation in larger cohorts. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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5 pages, 160 KB  
Editorial
Editorial: Physical Examination and Rehabilitation of Fasciae and Muscles in Sports Injuries
by Carmelo Pirri and Nathaly Gaudreault
Bioengineering 2025, 12(11), 1238; https://doi.org/10.3390/bioengineering12111238 (registering DOI) - 12 Nov 2025
Abstract
Sport injuries remain one of the most pervasive challenges in sport medicine, affecting athletes across disciplines and levels of performance [...] Full article
12 pages, 698 KB  
Article
Direction of Change in Cardiorespiratory Fitness in School-Age Children: A Longitudinal Single-Centre Study
by Maria Zadarko-Domaradzka, Marek Sobolewski and Emilian Zadarko
Healthcare 2025, 13(22), 2871; https://doi.org/10.3390/healthcare13222871 (registering DOI) - 12 Nov 2025
Abstract
Background/Objectives: Cardiorespiratory fitness (CRF) is currently a topic of widespread interest in the field of public health, considered as the basic marker for health status assessment. Better CRF is generally accepted to be beneficial in cardiovascular and metabolic disease prevention, both in [...] Read more.
Background/Objectives: Cardiorespiratory fitness (CRF) is currently a topic of widespread interest in the field of public health, considered as the basic marker for health status assessment. Better CRF is generally accepted to be beneficial in cardiovascular and metabolic disease prevention, both in children and in adults. The aim of this study was to present the direction of change in the cardiorespiratory fitness of Polish children aged 9 to 13 in a longitudinal study. Methods: Three series of cardiorespiratory fitness measurements were performed on school-aged children at one-year intervals. CRF was assessed based on the number of laps run in the 20 m shuttle run test (20mSRT). In order to check the level of cardiorespiratory fitness in consecutive years, the 20mSRT results were compared to the international percentile norms, considering the children’s sex and age. Results: The number of completed laps shows great diversity with reference to age. Together with age, the advantage of boys in terms of the number of completed laps becomes visible. The distribution of percentile classification results in subsequent tests across the whole study population shows that a low percentage of children who were qualified for the study had their CRF below the 20th percentile, and a relatively high percentage was above the 80th percentile. Conclusions: For the whole test group, the results of the percentile classification did not change significantly in subsequent tests. It is worth noting, though, that together with age, CRF changes evolved towards higher values in the tested group, as a vast majority was at the level of the 50th percentile. However, still a significant group of the tested children remained within the low percentile values of CRF. Full article
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12 pages, 1193 KB  
Article
First-Principles Study of Rare-Earth Doping Effects on Nitrogen Adsorption and Diffusion in Chromium
by Shuhui Chen, Bao Chen, Min Liu, Ji Liu, Gen Li and Ying Jin
Corros. Mater. Degrad. 2025, 6(4), 57; https://doi.org/10.3390/cmd6040057 (registering DOI) - 12 Nov 2025
Abstract
To address the premature corrosion failure of chromium-based coatings in harsh environments (e.g., high temperatures, chloride-containing solutions), this work systematically investigates how rare-earth (RE, i.e., Ce and La) elements regulate nitrogen (N) adsorption and diffusion behavior in Cr during the early stages of [...] Read more.
To address the premature corrosion failure of chromium-based coatings in harsh environments (e.g., high temperatures, chloride-containing solutions), this work systematically investigates how rare-earth (RE, i.e., Ce and La) elements regulate nitrogen (N) adsorption and diffusion behavior in Cr during the early stages of nitriding, a critical corrosion protection strategy, using first-principles density functional theory (DFT). Results show that RE preferentially occupies Cr substitutional site, increasing the Young’s modulus from 293.5 GPa (pristine Cr) to 344.9 GPa (Ce-doped) and 348.7 GPa (La-doped). Surface RE doping on Cr(110) significantly enhances N adsorption energy from −3.23 eV to −3.559/−3.645 eV (Ce-/La-doped), whereas subsurface doping slightly weakens the adsorption. Moreover, the energy barrier for N penetration into subsurface is reduced from 2.11 eV to 2.03/1.91 eV (Ce-/La-doped), thereby facilitating nitridation. Notably, RE is found to strongly trap vacancies and N atoms, leading to increased migration barriers and thus hindering their long-range transport. These findings demonstrate that RE exhibits a dual role during nitriding: promoting N incorporation at the surface while restricting its deep diffusion into the bulk. The study provides theoretical insights into the atomistic mechanisms by which RE elements modulate nitriding efficiency in Cr-based alloys, offering guidance for the design of RE-doped surface-modified coatings with improved corrosion resistance. Full article
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15 pages, 1741 KB  
Article
Multidrug-Resistant Enterococcus faecalis from Yak Feces: Isolation, Genomic Characterization and Functional Insights
by Jiayan Huang, Zixuan Li, Zhanchun Bai and Sizhu Suolang
Vet. Sci. 2025, 12(11), 1077; https://doi.org/10.3390/vetsci12111077 (registering DOI) - 12 Nov 2025
Abstract
Enterococcus faecalis (E. faecalis) is a significant zoonotic pathogen, primarily causing opportunistic infections in humans while often existing as a commensal in animal reservoirs, facilitating its dissemination. Current understanding of the resistance profiles, virulence mechanisms, and host–pathogen interactions of E. faecalis [...] Read more.
Enterococcus faecalis (E. faecalis) is a significant zoonotic pathogen, primarily causing opportunistic infections in humans while often existing as a commensal in animal reservoirs, facilitating its dissemination. Current understanding of the resistance profiles, virulence mechanisms, and host–pathogen interactions of E. faecalis from ruminants, particularly unique species such as the plateau yak, remains limited. This knowledge gap hinders the accurate assessment of their transmission risk and the development of effective control strategies. This study presents a comprehensive analysis of a multidrug-resistant E. faecalis isolate from yak feces, integrating whole-genome sequencing (WGS), an animal challenge model, and transcriptomic profiling. Antimicrobial susceptibility testing revealed resistance to β-lactams, aminoglycosides, glycopeptides, tetracyclines, and fluoroquinolones. WGS identified numerous resistance genes (e.g., parC, gyrA, rpoB) and virulence-associated genes (e.g., prgB/asc10, cpsA/uppS). Phylogenetic analysis indicated a close relationship with a human urinary tract isolate (ASM3679337v1). Mouse challenge experiments demonstrated that this strain induced significant intestinal histopathological damage. A subsequent transcriptomic analysis of infected tissues identified the differential activation of key signaling pathways, including NF-κB and MAPK. Our findings provide crucial insights into the resistance and pathogenic mechanisms of ruminant-derived E. faecalis and establish an experimental foundation for optimizing clinical antimicrobial therapy against such strains. Full article
(This article belongs to the Section Veterinary Food Safety and Zoonosis)
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10 pages, 857 KB  
Article
Estimating the Utility of Using Structured and Unstructured Data for Extracting Incidents of External Hospitalizations from Patient Documents
by Michael Davenport, Robert Hall, Saraswathi Kappala, Trevor Michelson, Robert Mitchell, David Winski, Cynthia Hau, Sarah Leatherman and Frank Meng
Information 2025, 16(11), 978; https://doi.org/10.3390/info16110978 (registering DOI) - 12 Nov 2025
Abstract
Patients within the US Department of Veterans Affairs (VA) healthcare system have the option of receiving care at facilities external to the VA network. This work presents a method for identifying external hospitalizations among the VA’s patient population by utilizing data stored in [...] Read more.
Patients within the US Department of Veterans Affairs (VA) healthcare system have the option of receiving care at facilities external to the VA network. This work presents a method for identifying external hospitalizations among the VA’s patient population by utilizing data stored in patient records. The process of extracting this information is complicated by the fact that indicators of external hospitalizations come from two sources: well-defined structured data and free-form unstructured text. Though natural language processing (NLP) leveraging Large Language Models (LLMs) has advanced capabilities to automate information extraction from free text, deploying these systems remains complex and costly. Using structured data is low-cost, but its utility must be determined in order to optimally allocate resources. We describe a method for estimating the utility of using structured and unstructured data and show that if specific conditions are met, the level of effort to perform this estimate can be greatly reduced. For external hospitalizations in the VA, our analysis showed that 44.4% of cases identified using unstructured data could not be found using structured data alone. Full article
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12 pages, 4715 KB  
Article
Nitrogen-Doped Carbon Coated Zn0.17Co0.83P as a Highly Active and Stable Electrocatalyst for Hydrogen Evolution
by Guo-Ping Shen, Xiao-Mei Men, Si-Jia Guo, Na Xu and Bin Dong
Catalysts 2025, 15(11), 1071; https://doi.org/10.3390/catal15111071 (registering DOI) - 12 Nov 2025
Abstract
Zeolitic imidazolate frameworks (ZIFs) can provide fascinating stereo morphology and tunable metal active sites, which plays an important role in the synthesis of various catalytic materials. However, it is still a problem to make use of these advantages to design efficient hydrogen evolution [...] Read more.
Zeolitic imidazolate frameworks (ZIFs) can provide fascinating stereo morphology and tunable metal active sites, which plays an important role in the synthesis of various catalytic materials. However, it is still a problem to make use of these advantages to design efficient hydrogen evolution reaction (HER) catalysts. Herein, we use covalent coordination strategy to synthesize bimetallic CoxZn1−x(2-MeIM)2 precursors with regular dodecahedral structures for providing uniform active sites and stable carbon skeleton. Furthermore, the ratio of Co and Zn atoms was optimized to balance the electron density and give full play to the synergistic catalytic effect. And then, the subsequent high temperature annealing process is used to construct the amorphous carbon layer, which can improve the overall stability of the material. The gas phase phosphating process realizes the transformation from ZIF material to metal phosphide resulting in enhanced hydrogen evolution activity. Finally, the optimized amorphous nitrogen-doped carbon (NC)-coated Zinc-doped cobalt phosphide (Zn0.17Co0.83P@NC) requires only 237.60 mV to reach the current density of 10 mA cm−2 in alkaline medium, which is 223.22 mV lower than that of CoP, and has a stability of up to 18 h. This work provides a reference for the rational design of efficient and stable compound electrocatalysts for alkaline hydrogen evolution based on the bimetallic ZIF as a precursor. Full article
(This article belongs to the Special Issue Non-Noble Metal Electrocatalytic Materials for Clean Energy)
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27 pages, 382 KB  
Article
Profitability and Capital Intensity: Moderating Role of Debt Financing
by Abdulazeez Y. H. Saif-Alyousfi, Abdullah Alsadan and Hassan Alalmaee
Economies 2025, 13(11), 324; https://doi.org/10.3390/economies13110324 (registering DOI) - 12 Nov 2025
Abstract
This study investigates the relationship between capital intensity, debt financing, and profitability in non-financial firms in Oman over the period 2012–2022. Using a robust panel dataset of 76 firms, the research explores how capital structure dynamics influence firm performance across different firm sizes [...] Read more.
This study investigates the relationship between capital intensity, debt financing, and profitability in non-financial firms in Oman over the period 2012–2022. Using a robust panel dataset of 76 firms, the research explores how capital structure dynamics influence firm performance across different firm sizes and industries. The findings reveal that capital intensity significantly enhances profitability, and debt financing further strengthens this effect, with variations observed across firm size and sector. The analysis also identifies a non-linear (concave) relationship between capital intensity and profitability, indicating that while moderate capital investment improves firm performance, excessive capital accumulation may lead to diminishing returns. Larger firms, with better access to financial resources, exhibit a stronger positive relationship between debt financing and profitability, while smaller firms face more challenges due to limited access to capital. Industry-specific results indicate that capital-intensive sectors, such as Energy and Industrials, demonstrate a more pronounced effect of capital intensity on profitability compared to less capital-intensive sectors. The study also incorporates the effects of the COVID-19 pandemic, showing its significant influence on firm performance, particularly in sectors with high debt exposure. By integrating non-linear effects, firm size, industry heterogeneity, and pandemic shocks, this study provides novel insights into capital structure management in emerging economies, offering implications for both corporate decision-makers and policymakers aiming to enhance financial access and optimize debt strategies across sectors. Full article
(This article belongs to the Section Macroeconomics, Monetary Economics, and Financial Markets)
5 pages, 146 KB  
Editorial
Novel Insights and Advances in Steels and Cast Irons
by Annalisa Fortini and Chiara Soffritti
Metals 2025, 15(11), 1240; https://doi.org/10.3390/met15111240 (registering DOI) - 12 Nov 2025
Abstract
The manufacturing sector relies extensively on ferrous alloys, with steels and cast irons serving as essential materials for structural and functional components across a wide range of industries, including automotive, energy generation, and civil engineering [...] Full article
(This article belongs to the Special Issue Novel Insights and Advances in Steels and Cast Irons)
12 pages, 691 KB  
Systematic Review
The Diagnostic Accuracy of Magnetic Resonance Imaging Versus Transvaginal Ultrasound in Deep Infiltrating Endometriosis and Their Impact on Surgical Decision-Making: A Systematic Review
by Michael O’Leary, Conor Neary and Edward Lawrence
Diagnostics 2025, 15(22), 2856; https://doi.org/10.3390/diagnostics15222856 (registering DOI) - 12 Nov 2025
Abstract
Objectives: This study aimed to systematically compare the diagnostic accuracy of magnetic resonance imaging (MRI) and transvaginal ultrasound (TVUS) for deep infiltrating endometriosis (DIE) and to evaluate their impact on surgical decision-making. Methods: We carried out a systematic review of studies (2015–2025) comparing [...] Read more.
Objectives: This study aimed to systematically compare the diagnostic accuracy of magnetic resonance imaging (MRI) and transvaginal ultrasound (TVUS) for deep infiltrating endometriosis (DIE) and to evaluate their impact on surgical decision-making. Methods: We carried out a systematic review of studies (2015–2025) comparing MRI and TVUS for DIE in the same patients, with surgical/histological confirmation used as the reference standard. The primary outcomes were sensitivity and specificity by lesion site; the secondary outcomes included the reported impact on surgical decision-making and treatment planning. Results: Nine studies met the inclusion criteria. For rectosigmoid lesions, the sensitivity was 79–94% for TVUS and 86–94% for MRI, with a high specificity for both (84–95%). TVUS demonstrated strong diagnostic accuracy for posterior compartment disease, but its sensitivity was notably lower for uterosacral ligament and bladder lesions (25–83%). MRI showed higher sensitivity for anterior and multi-compartmental lesions (75–94%), reflecting its superior anatomical coverage. Imaging informed surgical planning, ensuring the inclusion of subspecialists such as colorectal or urological surgeons. It also guided the extent of resection and need for radical versus conservative procedures. Conclusions: TVUS and MRI are complementary imaging modalities in the diagnosis and staging of DIE. TVUS offers high specificity and remains particularly effective for posterior compartment disease, whereas MRI provides broader anatomical coverage and higher sensitivity for anterior and multi-compartmental involvement. Importantly, integrating imaging into preoperative planning improves multidisciplinary coordination, optimises preparedness, and guides resection. This is the first review to systematically compare MRI and TVUS for DIE with an emphasis on lesion-level accuracy and the impact on surgical decision-making. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Management of Endometrial Diseases)
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17 pages, 3002 KB  
Article
The Adaptation of Cancer Cells to Serum Deprivation Is Mediated by mTOR-Dependent Cholesterol Synthesis
by Bayansulu Ilyassova, Nargiz Rakhimgerey, Saule Rakhimova, Nazerke Satvaldina, Asset Daniyarov, Ainur Akilzhanova, Ulykbek Kairov, Dinara Begimbetova and Dos D. Sarbassov
Int. J. Mol. Sci. 2025, 26(22), 10932; https://doi.org/10.3390/ijms262210932 (registering DOI) - 12 Nov 2025
Abstract
Cancer cells can sustain survival independently of exogenous growth factors. To investigate their adaptation to serum deprivation, we analyzed transcriptomic responses in two cancer cell lines. Transcriptome analysis revealed upregulation of mRNAs encoding cholesterol biosynthesis enzymes. This was a critical adaptive response, as [...] Read more.
Cancer cells can sustain survival independently of exogenous growth factors. To investigate their adaptation to serum deprivation, we analyzed transcriptomic responses in two cancer cell lines. Transcriptome analysis revealed upregulation of mRNAs encoding cholesterol biosynthesis enzymes. This was a critical adaptive response, as a pharmacological inhibition of the pathway with statin triggered a robust apoptotic cell death accompanied by generation of a mitochondrial reactive oxygen species. The mechanistic target of rapamycin complex 1 (mTORC1), a master regulator of cell growth, is known to be engaged in controlling lipid biosynthesis. We detected the high polysomal and preribosomal peaks not only in serum-containing medium but also under serum deprivation, indicating a high rate of protein synthesis and ribosomal biogenesis independent of serum. In addition, the inhibition of mTOR kinase activity substantially reduced polysome abundance, with a more pronounced effect in serum-deprived cancer cells. Notably, the mTOR kinase inhibition also prevented the upregulation of the cholesterol synthesis enzyme that established a direct link between mTOR activity, protein synthesis, and cholesterol biosynthesis. Together, our results show that cancer cells adapt to serum withdrawal by activating the cholesterol synthesis pathway through mTOR-dependent regulation of gene expression and protein synthesis, underscoring a critical mechanism of survival under serum withdrawal. Full article
(This article belongs to the Special Issue Programmed Cell Death and Oxidative Stress: 3rd Edition)
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23 pages, 5447 KB  
Article
3D-Printed Alginate–Chitosan Hydrogel Loaded with Cannabidiol as a Platform for Drug Delivery: Design and Mechanistic Characterization
by Hernan Santiago Garzon, Camilo Alfonso-Rodríguez, João G. S. Souza, Lina J. Suárez and Daniel R. Suárez
J. Funct. Biomater. 2025, 16(11), 422; https://doi.org/10.3390/jfb16110422 (registering DOI) - 12 Nov 2025
Abstract
Alginate and chitosan (Ag/Cs) combined form an effective platform to develop biocompatible hydrogels with customizable properties for controlled drug release. Cannabidiol (CBD), a hydrophobic compound with anti-inflammatory and antibacterial effects, represents a powerful strategy to enhance their therapeutic performance. A/Cs hydrogels were produced [...] Read more.
Alginate and chitosan (Ag/Cs) combined form an effective platform to develop biocompatible hydrogels with customizable properties for controlled drug release. Cannabidiol (CBD), a hydrophobic compound with anti-inflammatory and antibacterial effects, represents a powerful strategy to enhance their therapeutic performance. A/Cs hydrogels were produced using the CELLINK® printer with 12 and 24 mg/mL of CBD. SEM and FTIR were assessed. Viscoelasticity was assessed using oscillatory rheology. Structural strength was evaluated via uniaxial compression. Swelling and absorption were measured gravimetrically under physiological conditions. CBD was successfully incorporated into the 3D-printed A/Cs hydrogel. Increasing the CBD concentration led to mechanical changes such as a dose-dependent decrease in G′ and a slight reduction in the linearity threshold (typically 10–30% from medium loads), while still maintaining G′ > G″. FTIR showed shifts in O–H/N–H and C=O, indicating hydrogen bonding without new reactive bands. Microscopic images revealed moderate pore compaction and increased tortuosity with dose. At higher CBD concentrations, the hydrogel resisted compression but could deform further before failure. Equilibrium swelling and absorption kinetics decreased with increasing dose, resulting in a reduced initial burst and lower water uptake capacity. The CBD-loaded hydrogel provides a mechanically suitable and molecularly stable platform for local drug release in the oral cavity. Full article
(This article belongs to the Special Issue Biomaterials and Bioengineering in Dentistry (2nd Edition))
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4 pages, 154 KB  
Editorial
Advances in the Performance of Ships and Offshore Structures
by Bai-Qiao Chen, Sheng Xu and Emre Uzunoglu
J. Mar. Sci. Eng. 2025, 13(11), 2133; https://doi.org/10.3390/jmse13112133 (registering DOI) - 12 Nov 2025
Abstract
The domain of maritime engineering is continually evolving with a focus on optimizing the performance and safety of ships and offshore structures [...] Full article
(This article belongs to the Special Issue Advances in the Performance of Ships and Offshore Structures)
30 pages, 2068 KB  
Article
Ethical AI in Healthcare: Integrating Zero-Knowledge Proofs and Smart Contracts for Transparent Data Governance
by Mohamed Ezz, Alaa S. Alaerjan and Ayman Mohamed Mostafa
Bioengineering 2025, 12(11), 1236; https://doi.org/10.3390/bioengineering12111236 (registering DOI) - 12 Nov 2025
Abstract
In today’s rapidly advancing healthcare landscape, integrating Artificial Intelligence (AI) and Machine Learning (ML) has the potential to significantly improve patient care and streamline medical processes. The utilization of confidential patient data to train and develop these technologies, however, raises significant concerns regarding [...] Read more.
In today’s rapidly advancing healthcare landscape, integrating Artificial Intelligence (AI) and Machine Learning (ML) has the potential to significantly improve patient care and streamline medical processes. The utilization of confidential patient data to train and develop these technologies, however, raises significant concerns regarding authenticity, security, and privacy. In this study, we introduce MediChainAI, a safe and practical framework that allows patients full ownership over their own health data by integrating Self-Sovereign Identity (SSI), Blockchain, and sophisticated cryptography techniques. By clearly outlining the goals and parameters of this access, MediChainAI allows patients to safely and selectively share data with healthcare providers and researchers. While SSI guarantees that patients have ownership of their data, the framework uses Blockchain technology to keep things transparent and secure. Further, MediChainAI makes use of Merkle trees, which provide verified access to subsets of data without jeopardizing the privacy of the whole dataset. The encryption mechanism, which is based on smart contracts, is a distinctive feature of the framework that allows researchers and medical practitioners controlled and secure access to patient data. In order to improve the accuracy and reliability of medical diagnoses and treatment, this strategy makes sure that only confirmed, legitimate data is utilized to train medical models. A significant step toward safer and more personalized healthcare, MediChainAI encourages ethical and patient-focused innovation by effectively resolving essential issues regarding data security and patient privacy. Full article
(This article belongs to the Section Biosignal Processing)
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14 pages, 396 KB  
Article
Primary vs. Rescue Medium Vessel Occlusions: Comparative Clinical Outcomes in Patients with Acute Ischemic Stroke
by Gokhan Ozdemir, Alper Eren, Nazim Kizildag, Omer Lutfi Gundogdu, Ayse Nur Ersoy, Muslu Kazim Korez, Leyla Ozturk Sonmez, Gozde Ongun, Nursen Unal and Uygar Utku
J. Clin. Med. 2025, 14(22), 8008; https://doi.org/10.3390/jcm14228008 (registering DOI) - 12 Nov 2025
Abstract
Background: Medium vessel occlusions (MeVOs) are an increasingly recognized but heterogeneous target for endovascular therapy (EVT). This study aims to compare primary MeVO, rescue MeVO, and large vessel occlusion (LVO) thrombectomy cases to identify which MeVO subtypes derive a meaningful benefit from EVT [...] Read more.
Background: Medium vessel occlusions (MeVOs) are an increasingly recognized but heterogeneous target for endovascular therapy (EVT). This study aims to compare primary MeVO, rescue MeVO, and large vessel occlusion (LVO) thrombectomy cases to identify which MeVO subtypes derive a meaningful benefit from EVT under appropriate safety conditions. Methods: We retrospectively analyzed a multicenter registry of patients undergoing EVT for acute ischemic stroke. MeVO was defined as the occlusion of the A1-A3, M2-M3, P1-P3, fetal PCA, or PICA segments and classified as primary or rescue. Clinical outcomes were assessed by NIHSS score at baseline, discharge, and 90 days; functional outcome by the modified Rankin scale (mRS); and reperfusion by modified thrombolysis in cerebral infarction (mTICI). Safety endpoints included intracranial hemorrhage and mortality. Results: Among 603 EVT patients, 202 (33.5%) had MeVO. Compared to LVO, MeVO patients were older and had more prior strokes but achieved similar reperfusion and safety outcomes. At 90 days, mRS distribution differed, with MeVO showing more mRS 2 and LVO more mRS 1, while higher-disability strata were comparable. Within MeVO, 119 (58.9%) were primary and 83 (41.1%) rescue occlusions. Rescue MeVO patients presented with higher baseline severity (NIHSS score of 19 vs. 18) and, despite similar reperfusion, experienced worse 90-day outcomes and higher mortality (21.7% vs. 0.8%). Conclusions: EVT for primary MeVO is feasible, effective, and safe, whereas rescue MeVO is associated with poor functional outcomes and markedly higher mortality. These findings highlight rescue MeVO as a distinct phenotype and support a selective approach prioritizing disabling syndromes, proximal/dominant branch occlusions, and IVT non-response. Full article
(This article belongs to the Section Vascular Medicine)
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10 pages, 1057 KB  
Article
The Role of Cadence and Torque in Fatigue-Related Power Output Decline in Cycling’s Grand Monuments
by Alejandro Javaloyes-Torres, Jose Luis Sánchez-Jiménez, Iván Peña-González, Manuel Moya-Ramón and Manuel Mateo-March
Sports 2025, 13(11), 406; https://doi.org/10.3390/sports13110406 (registering DOI) - 12 Nov 2025
Abstract
This study examined the effects of cadence and torque on fatigue-related power output (PO) decline in professional cyclists during the Five Monuments, comparing top-5 finishers with cyclists ranked from 6th to 30th. Retrospective data from 64 male cyclists (top-5 n = 14, top-30 [...] Read more.
This study examined the effects of cadence and torque on fatigue-related power output (PO) decline in professional cyclists during the Five Monuments, comparing top-5 finishers with cyclists ranked from 6th to 30th. Retrospective data from 64 male cyclists (top-5 n = 14, top-30 n = 42) in the 2021–2023 Five Monuments were analyzed. PO, cadence, and torque profiles were constructed for 10 s, 1 min, 5 min, and 20 min maximal mean power efforts and after 30–60 kJ·kg−1 workloads. Repeated-measures ANOVA assessed group differences, and Pearson correlations evaluated variable relationships under fatigue. Top-5 finishers exhibited higher PO (e.g., 20 min: p = 0.003; 60 kJ·kg−1: p < 0.001) and torque (e.g., 20 min at 60 kJ·kg−1: p < 0.001) compared to cyclists ranked 6th to 30th. They also displayed lower cadence during 10 s efforts at 50–60 kJ·kg−1 (p = 0.008). Top-5 cyclists maintained stable PO and torque beyond 60 kJ·kg−1, whereas the top-30 group showed significant declines (p < 0.001). Torque was strongly correlated with PO (r = 0.6–0.9, p < 0.001), while cadence showed a weaker correlation (r = 0.1–0.5). Top-5 cyclists show greater durability, sustaining higher torque and power output during prolonged efforts with minimal cadence changes. These biomechanical traits distinguish elite performers in the Five Monuments and underscore the value of training for torque sustainability and fatigue resistance. Full article
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10 pages, 1510 KB  
Article
Enhanced Gettering of Multicrystalline Silicon Using Nanowires for Solar Cell Applications
by Achref Mannai, Karim Choubani, Wissem Dimassi and Mohamed Ben Rabha
Inorganics 2025, 13(11), 374; https://doi.org/10.3390/inorganics13110374 (registering DOI) - 12 Nov 2025
Abstract
In this work, we present a gettering technique for multicrystalline silicon (mc-Si) by combining a nanowire structure with thermal treatment under nitrogen in an infrared lamp furnace. The silicon nanowires were elaborated using the Silver Nanoparticles Chemical Etching (Ag-NPsCE) technique. The optimal conditions [...] Read more.
In this work, we present a gettering technique for multicrystalline silicon (mc-Si) by combining a nanowire structure with thermal treatment under nitrogen in an infrared lamp furnace. The silicon nanowires were elaborated using the Silver Nanoparticles Chemical Etching (Ag-NPsCE) technique. The optimal conditions for achieving effective gettering were determined based on the minority carrier lifetime (τeff) measurements. The results show τeff as a function of the gettering temperature and etching time, both before and after the removal of Ag nanoparticles using HNO3. In both cases, the surface was identically treated with a 10% HF dip immediately prior to the carrier lifetime measurements. The highest τeff value, prior to Ag removal, was obtained after an etching duration of 3 min and was 6 µs at an excess carrier density Δn = 1 × 1014 cm−3. Moreover, τeff improves after silver removal. Therefore, removing Ag atoms using an aqueous HNO3 solution is necessary to prevent this issue. Following Ag nanoparticle removal, τeff further increases, reaching 19 µs at a gettering temperature of 850 °C. Similarly, the electrical conductivity (ρ) and carrier mobility (μ) improve significantly after gettering, where the resistivity increases from 5.5 Ω·cm for the reference mc-Si to 1.9 Ω·cm, and the mobility rises from 122 cm2·V−1·s−1 to 253 cm2·V−1·s−1 after nanowire-based gettering at 850 °C. Overall, this method provides a scalable, practical, and cost-effective route to optimize mc-Si for high-performance photovoltaic applications. Full article
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12 pages, 2307 KB  
Article
Application of Droplet-Array Sandwiching Technology to Click Reactions for High-Throughput Screening
by Yoshinori Miyata, Shoma Nishimura, Sora Kawakami, Yuriko Higuchi and Satoshi Konishi
Micromachines 2025, 16(11), 1270; https://doi.org/10.3390/mi16111270 (registering DOI) - 12 Nov 2025
Abstract
High-throughput screening (HTS) is an essential process in drug discovery, requiring platforms that ensure reagent economy, high efficiency, and resistance to cross-contamination. Click chemistry is well suited for HTS because of its biocompatibility, high selectivity, and quantitative fluorescent readout. We focus on droplet-array [...] Read more.
High-throughput screening (HTS) is an essential process in drug discovery, requiring platforms that ensure reagent economy, high efficiency, and resistance to cross-contamination. Click chemistry is well suited for HTS because of its biocompatibility, high selectivity, and quantitative fluorescent readout. We focus on droplet-array sandwiching technology (DAST), in which two droplet microarrays (DMAs) are vertically opposed to achieve solute transport and reagent mixing by controlled contact and separation. Herein, we integrate click chemistry with DAST and evaluate its feasibility as a HTS platform. In DAST, DMAs are formed on wettability-patterned (WP; hydrophilic/hydrophobic) substrates, preserving resistance to cross-contamination. First, we immobilized dibenzocyclooctyne (DBCO) on a WP substrate and verified the occurrence of DBCO–azide reaction using an azide-functional fluorescent dye. The fluorescence intensity increased with concentration and reached a plateau at higher concentrations, indicating saturation behavior in the DBCO–azide click reaction. Second, acoustic mixing with repeated droplet contact–separation was applied to generate concentration gradients on a single substrate while maintaining droplet independence. Third, we qualitatively reproduced the expected concentration dependence of manual handling by combining DAST-based gradient formation with click reaction fluorescence readout. These results reveal that DAST enables a reagent-efficient, cross-contamination-resistant, and low-instrument-dependent HTS foundation for click-chemistry-based assays. Full article
(This article belongs to the Special Issue Advanced Developments in Droplet Microfluidics)
12 pages, 8211 KB  
Article
Novel Visual Grade and Hounsfield Unit Predict Adequate Bone Strength for Cementless Total Knee Arthroplasty
by Dong Hwan Lee, Dai-Soon Kwak, Sheen-Woo Lee, Yong Deok Kim, Nicole Cho and In Jun Koh
Medicina 2025, 61(11), 2018; https://doi.org/10.3390/medicina61112018 (registering DOI) - 12 Nov 2025
Abstract
Background and Objectives: The use of cementless total knee arthroplasty (TKA) is increasing, but established methods for assessing bone quality to prevent early failure remain undefined. Current preoperative assessments using central bone mineral density (BMD) do not accurately reflect peripheral bone quality, [...] Read more.
Background and Objectives: The use of cementless total knee arthroplasty (TKA) is increasing, but established methods for assessing bone quality to prevent early failure remain undefined. Current preoperative assessments using central bone mineral density (BMD) do not accurately reflect peripheral bone quality, and intraoperative evaluation is subjective. This study aimed to establish objective assessment methods by analyzing the correlations between a novel visual grading system, CT Hounsfield units (HU), and actual bone strength. Materials and Methods: This prospective study included 131 patients undergoing posterior-stabilized TKA. We developed a novel visual grading system (Excellent, Good, Fair, Poor) based on femoral cutting surface characteristics. CT HUs were measured preoperatively by an assisting surgeon in the box bone area. Femoral box specimens underwent indentation testing to determine their actual bone strength. Minimum Required Strength (MRS) was defined at 2.5-fold the patient’s body weight, and Estimated Withstanding Strength (EWS) was determined by scaling first failure load using area ratios. Patients were classified as “cementless suitable” (EWS > MRS) or “cemented mandatory” (EWS < MRS). Correlations were assessed using Spearman’s rank correlation for visual grade and Pearson correlation for Hounsfield units. ROC curve analysis determined diagnostic accuracy. Results: Visual grade exhibited an exceptionally robust relationship to bone strength (Spearman ρ = 0.903, p < 0.01), whereas HU showed substantial correlation (Pearson r = 0.660, p < 0.01, R2 = 0.435). Visual grading achieved excellent diagnostic accuracy (AUC = 0.974, sensitivity 95.1%, specificity 95.9%) using “Good” grade as cutoff. HU demonstrated AUC of 0.938 with 92.7% sensitivity and 81.6% specificity at a cutoff value of 65.2. Conclusions: Our novel visual grading system and CT HU demonstrated excellent correlations with actual distal femoral bone strength and outstanding diagnostic performance for identifying cementless TKA candidates. Unlike traditional subjective intraoperative assessments such as the “thumb test”, this system provides objective visual criteria directly correlated with actual bone strength. Preoperative HU screening with intraoperative visual grading can help prevent early failure. Full article
(This article belongs to the Special Issue Advances in Knee Surgery: From Diagnosis to Recovery)
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