MDPI - Publisher of Open Access Journals

29 pages, 618 KB

Open AccessSystematic Review

Early Detection of Glottic Cancer Through Machine Learning and Acoustic Voice Analysis: A Systematic Review

by Himanshu Verma, Roshani Mishra, Banumathy Nagamani, Sourabha Kumar Patro, Anurag Snehi Ramavat, Jaimanti Bakshi, Padmavati Khandnor, Sudesh Rani and Trilok Chand

Med. Sci. 2026, 14(5), 581; https://doi.org/10.3390/medsci14050581 (registering DOI) - 17 Sep 2026

Abstract

Purpose: Early detection of glottic cancer is essential for better outcomes, but current diagnostic methods remain largely invasive, highlighting the need for reliable non-invasive alternatives. Acoustic voice signals offer a non-invasive screening input, but their clinical value depends on whether signal-processing features [...] Read more.

Purpose: Early detection of glottic cancer is essential for better outcomes, but current diagnostic methods remain largely invasive, highlighting the need for reliable non-invasive alternatives. Acoustic voice signals offer a non-invasive screening input, but their clinical value depends on whether signal-processing features and learned models can distinguish malignancy from acoustically similar benign lesions rather than merely separate pathological from healthy voices. Despite growing research on acoustic analysis combined with machine learning (ML) techniques, no systematic synthesis of this evidence currently exists. Therefore, the present review aimed to identify acoustic features that differentiate early glottic malignancies from both benign vocal fold lesions and normal vocal function using various ML techniques. Method: Following PRISMA 2020 guidelines, a comprehensive literature search was conducted across Scopus, EBSCO, Ovid (Embase), and PubMed databases through November 2025. Eighteen studies met inclusion criteria, and PROBAST was used for quality appraisal of included studies. Data extraction focused on acoustic feature categories, ML techniques, classification performance metrics, and validation strategies. Results: Nine acoustic feature categories emerged, with cepstral coefficients (particularly MFCCs) most prevalent across 55.6% of studies. Binary pathological-versus-normal classification achieved consistently high accuracy (96–98.3%) across both traditional machine learning and deep learning approaches. However, malignant-versus-benign discrimination demonstrated substantially lower performance (81–87.88% accuracy, AUC 0.631–0.91), with voice-only models proving insufficient. Multimodal models incorporating clinical variables or laryngoscopic images achieved higher performance, but their results cannot be attributed to voice features alone. All 17 prediction studies were judged at high overall risk of bias, predominantly because of small effective sample sizes, model-selection optimism, possible data leakage, and limited independent validation. Conclusions: ML can detect broad voice pathology, but current evidence is insufficient to support stand-alone acoustic screening for early glottic cancer. Future studies require clearly defined cancer-specific targets, patient-level analysis, standardized acquisition, nested model development, calibration, and independent multicentervalidation. Full article

(This article belongs to the Section Cancer and Cancer-Related Research)

28 pages, 758 KB

Open AccessReview

Bioactive Peptides from Common Beans: A Review

by Cinthia Edith Sariñana-Núñez, Jose Alberto Gallegos-Infante, Martha Rocio Moreno-Jiménez, Nuria Elizabeth Rocha-Guzmán, Maria Cristina Añón and Alejandro Marangoni

Nutraceuticals 2026, 6(3), 62; https://doi.org/10.3390/nutraceuticals6030062 (registering DOI) - 17 Sep 2026

Abstract

Bioactive peptides derived from Phaseolus vulgaris represent a promising source for the development of functional ingredients because of the multiple biological activities associated with bean proteins and their hydrolysis products. In this review, a structured literature search was conducted in Scopus, Web of [...] Read more.

Bioactive peptides derived from Phaseolus vulgaris represent a promising source for the development of functional ingredients because of the multiple biological activities associated with bean proteins and their hydrolysis products. In this review, a structured literature search was conducted in Scopus, Web of Science, PubMed, and Google Scholar, considering publications from 2011 to 2026 on proteins, hydrolysates, peptide fractions, and peptides derived from P. vulgaris. A comprehensive examination of the methods for production, identification, purification, and characterization was conducted, along with a thorough analysis of the available evidence regarding their antioxidant, antihypertensive, antidiabetic, antimicrobial, and anti-inflammatory properties. Additionally, the potential applications of these substances in functional foods and nutraceuticals were investigated. Hydrolysates and peptide fractions have demonstrated antioxidant capacity and the ability to inhibit enzymes such as angiotensin-converting enzyme, DPP-IV, α-amylase, and α-glucosidase. In addition, studies using diverse models, including enzymatic and cellular assays, and animal models have demonstrated antimicrobial and anti-inflammatory properties. However, the available evidence varies significantly, as numerous studies have been conducted using hydrolysates, peptide mixtures, in vitro assays, or in silico predictions. Additionally, the validation of individual peptides and the available clinical evidence remain limited. Questions also remain regarding the gastrointestinal stability, bioaccessibility, absorption, safety, and behavior of these compounds in different food matrices. In summary, P. vulgaris demonstrates considerable potential as a source for the production of bioactive peptides. However, further research is necessary to validate these peptides individually and assess their stability, safety, dose–response relationships, and in vivo and clinical efficacy. Full article

(This article belongs to the Special Issue Feature Review Papers in Nutraceuticals)

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29 pages, 14054 KB

Open AccessArticle

TDA-ACT: Temporal-Derivative-Encoded Adaptive Action Chunking with Transformer for Flight Maneuver Generation

by Xiangyang Deng, Hongji Zhu, Limin Zhang, Yupeng Fu and Shandong Wang

AI 2026, 7(9), 373; https://doi.org/10.3390/ai7090373 (registering DOI) - 17 Sep 2026

Abstract

Traditional imitation learning is prone to distribution shift and trajectory divergence in highly dynamic, strongly time-varying flight tasks. To address this, we propose a temporally adaptive action-chunking framework built on temporal-derivative encoding, termed Temporal-Derivative-Encoded Adaptive Action Chunking with Transformer (TDA-ACT). First, using state [...] Read more.

Traditional imitation learning is prone to distribution shift and trajectory divergence in highly dynamic, strongly time-varying flight tasks. To address this, we propose a temporally adaptive action-chunking framework built on temporal-derivative encoding, termed Temporal-Derivative-Encoded Adaptive Action Chunking with Transformer (TDA-ACT). First, using state temporal-derivative features as the core representation, we construct a confidence-estimation mechanism that also incorporates the latent-variable variance of the maneuver-mode representation and the action-prediction variance produced by the decoder. Second, we develop a confidence-guided adaptive temporal-ensembling strategy that uses this confidence metric to jointly adjust the fusion scope and the fusion weights of historical predictions, enabling a dynamic trade-off between long-horizon smoothing under stable conditions and high-frequency responsiveness during aggressive maneuvers. On both the Loop and AileronRoll maneuvers in JSBSim, TDA-ACT reduces action jerk and suppresses trajectory divergence relative to ACT and other imitation-learning baselines. Full article

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17 pages, 875 KB

Open AccessHypothesis

PRRSV Fetal Infection in Pigs as a Risk Factor for the Emergence of More Efficient Zoonotic Hosts for Swine-Origin Influenza Virus

by Uladzimir Karniychuk

Vet. Sci. 2026, 13(9), 983; https://doi.org/10.3390/vetsci13090983 (registering DOI) - 17 Sep 2026

Abstract

Domestic pigs are susceptible to avian, swine, and human influenza A viruses (IAVs). This facilitates co-infections of different IAVs that result in genetic reassortment. In combination with husbandry practices such as high-density farming and frequent human–pig interactions, pigs serve as efficient zoonotic hosts [...] Read more.

Domestic pigs are susceptible to avian, swine, and human influenza A viruses (IAVs). This facilitates co-infections of different IAVs that result in genetic reassortment. In combination with husbandry practices such as high-density farming and frequent human–pig interactions, pigs serve as efficient zoonotic hosts for IAV. Despite significance in zoonotic transmission, factors influencing IAV pathogenesis, evolution, and transmission in pigs remain poorly studied. One factor that may alter IAV dynamics in pigs is co-infection with endemic swine viruses such as porcine reproductive and respiratory syndrome virus (PRRSV; Betaarterivirus; Nidovirales) that causes widespread disease in pigs on farms globally. During initial outbreaks, PRRSV triggers transplacental infections and massive fetal loss in naïve herds. Once herd immunity or vaccination is established, PRRSV may persist in affected herds, resulting in transplacental infections and the birth of piglets that appear normal or weak. These piglets are concerning from a zoonotic perspective because they may be immunocompromised and potentially serve as more efficient hosts for IAV, characterized by prolonged IAV shedding, enhanced viral replication, impaired seroconversion, and consequently extended co-infection windows that favor reassortment. Here, I summarize studies supporting the hypothesis that fetal exposure to PRRSV can alter IAV pathogenesis in surviving piglets, potentially enhancing IAV pathogenesis and transmission. I also highlight key experiments that need to be conducted to validate or invalidate a causal relationship between fetal PRRSV infection, persistent immunopathology in surviving piglets, and the resulting permissive environment for enhanced IAV evolution and transmission. Addressing this knowledge gap is essential for advancing our understanding of PRRSV and IAV biology in its zoonotic pig host and for developing effective strategies to mitigate the risk of IAV spillovers to humans. Full article

(This article belongs to the Special Issue Diagnosis, Epidemiology, and Vaccine Development of Swine Viral Diseases—3rd Edition)

22 pages, 3962 KB

Open AccessArticle

A Novel Protein Recovery Method via Gel Separation and Silica Columns Capable of Rapid Antigen Purification and Deep Proteomic Identification

by Dan Wang, Jianhong Wu, Xingmei Zheng, Ziquan Fan, Zhexuan Li, Cunzhi Peng, Bingqiang Xu and Zheng Tong

Molecules 2026, 31(18), 3307; https://doi.org/10.3390/molecules31183307 (registering DOI) - 17 Sep 2026

Abstract

Gel electrophoresis is widely used for protein and nucleic acid analysis. Nucleic acid recovery from agarose gels is convenient and efficient, but protein recovery is not. This study aimed to develop and validate a novel method for recovering proteins from gels. Methods: After [...] Read more.

Gel electrophoresis is widely used for protein and nucleic acid analysis. Nucleic acid recovery from agarose gels is convenient and efficient, but protein recovery is not. This study aimed to develop and validate a novel method for recovering proteins from gels. Methods: After protein separation on gels, excised gel slices containing target proteins are processed using the same silica-column workflow as that used for nucleic acid purification, but with buffers specifically adapted for protein recovery. This approach only requires brief centrifugation steps and avoids laborious extraction and specialized equipment. Results: Proteome-wide recovery showed a slight preference of the method for low-molecular-mass and acidic proteins, while individual protein recovery efficiencies ranged from 69.9% to 86.7% and showed no correlation with intrinsic protein properties. The method effectively supported antigen purification. A banana (Musa acuminata AAA group ‘Brazilian’) proteome library constructed from recovered fractions contained over 18,000 protein groups and 27,000 individual proteins, which significantly enhanced protein identification in library-based data-independent acquisition (DIA) compared to directDIA analysis of single samples. Conclusions: This method bridges gel-based protein separation- and column-based purification, making protein purification as simple, fast, and scalable as nucleic acid purification. It offers a practical alternative for proteomic sample preparation, antigen purification, and DIA workflows. Full article

(This article belongs to the Special Issue Advances in the Mass Spectrometry of Chemical and Biological Samples, 2nd Edition)

17 pages, 524 KB

Open AccessArticle

Depressive Symptoms and Self-Harming Behavior in Adolescents: Examining the Moderating Roles of Age and Gender

by Slavka Demuthova and Andrej Demuth

Adolescents 2026, 6(5), 80; https://doi.org/10.3390/adolescents6050080 (registering DOI) - 17 Sep 2026

Abstract

Self-harm and depressive symptoms are important mental health concerns during adolescence, yet the factors shaping their association remain insufficiently understood. This exploratory cross-sectional study examined the association between depressive symptoms and self-harming behavior and tested whether age and gender moderated this relationship. A [...] Read more.

Self-harm and depressive symptoms are important mental health concerns during adolescence, yet the factors shaping their association remain insufficiently understood. This exploratory cross-sectional study examined the association between depressive symptoms and self-harming behavior and tested whether age and gender moderated this relationship. A total of 1116 Slovak adolescents aged 11–19 years completed the Self-Harm Inventory and Children’s Depression Inventory. Spearman’s correlation, Mann–Whitney U test, linear regression, and moderation analyses using PROCESS were conducted. Depressive symptoms were moderately positively associated with self-harming behavior (ρ = 0.526, p < 0.001). Adolescents reporting repeated self-harm had significantly higher depressive symptom levels than the reference group, with a moderate-to-large group difference (r = 0.45). Depressive symptoms explained 32.3% of the variance in self-harm scores. Gender significantly moderated this association in the primary analysis, with stronger associations among women than men; however, the interaction explained only an additional 0.7% of variance (ΔR² = 0.007). Age did not significantly moderate the association. These findings indicate that depressive symptoms are an important correlate of adolescent self-harm, while the modestly stronger association observed among women suggests that gender may add nuance to this relationship, although this difference was not consistently observed across sensitivity analyses. Full article

(This article belongs to the Special Issue Developmental Risk and Protective Factors for Anxiety and Depression in Adolescence)

24 pages, 2086 KB

Open AccessArticle

Topology Optimization of Brake Disc Inner Carrier and Development of a Parametric Predictive Model Using Machine Learning

by Alexandros Karvounis and Alexandros Arailopoulos

Dynamics 2026, 6(3), 40; https://doi.org/10.3390/dynamics6030040 (registering DOI) - 17 Sep 2026

Abstract

Reducing unsprung mass in high-performance braking systems is critical for vehicle dynamics, but applying topology optimization (TO) to conventional solid discs under combined thermo-mechanical loading often causes “thermal entrapment” and structural failure. This study addresses this limitation by proposing a floating disc architecture [...] Read more.

Reducing unsprung mass in high-performance braking systems is critical for vehicle dynamics, but applying topology optimization (TO) to conventional solid discs under combined thermo-mechanical loading often causes “thermal entrapment” and structural failure. This study addresses this limitation by proposing a floating disc architecture and a two-stage computational framework. First, TO via the SIMP algorithm was applied to the Aluminum 7075-T6 inner carrier strictly under mechanical loads, decoupling artificial thermal stresses and yielding a fixed, optimized geometry. Results show the TO achieved a drastic 53% mass reduction (from 0.218 kg to 0.102 kg) specifically for the inner carrier component. Second, a high-fidelity Surrogate Model (Digital Twin) of this new geometry was developed to bypass the immense computational cost of multi-parameter, non-linear thermo-mechanical Finite Element Analysis (FEA). Utilizing Latin Hypercube Sampling (LHS) across 15 design scenarios and the Genetic Aggregation algorithm, the surrogate model was trained to predict real-time responses. Subsequently, the Digital Twin predicted stress and temperature fields with near-perfect accuracy (R² ≈ 0.9998), rapidly identifying the limit braking scenario. Fatigue analysis confirmed the final component safely withstands 10⁶ extreme braking cycles (safety factor 1.65). Full article

(This article belongs to the Topic Dynamics Modeling, Chaos Theories and Nonlinear Control of Complex Systems: Complexity and AI-Driven to Hybrid and Distributed Computing Approaches)

29 pages, 5896 KB

Open AccessArticle

Numerical Analysis of the Effects of Enclosure Geometry and Opening Sizes on the Aerodynamic Performance of Positive-Pressure Ventilators

by Piotr Kaczmarzyk, Daniel Małozięć, Paweł Janik, Bartosz Ziegler, Tomasz Krakowski and Łukasz Warguła

Appl. Sci. 2026, 16(18), 9256; https://doi.org/10.3390/app16189256 (registering DOI) - 17 Sep 2026

Abstract

The efficiency of positive-pressure ventilation (PPV) in multi-story buildings is determined not only by the technical parameters of the mobile ventilators but also by the geometry of the gas exchange path. This paper presents the results of a computational fluid dynamics (CFD) analysis [...] Read more.

The efficiency of positive-pressure ventilation (PPV) in multi-story buildings is determined not only by the technical parameters of the mobile ventilators but also by the geometry of the gas exchange path. This paper presents the results of a computational fluid dynamics (CFD) analysis conducted using the Large Eddy Simulation (LES) approach to evaluate the impact of varying ceiling and outlet window opening areas on tactical ventilation effectiveness. The numerical model was validated against full-scale experimental data, yielding high convergence for the incoming flow parameters—with flow rate and mean pressure deviations of merely 0.4% and 0.6%, respectively—thereby confirming that the Fire Dynamics Simulator (FDS) is a reliable research tool. The simulations evaluated variations in the opening sizes of ceilings (size coefficients: 1.0, 1.25, and 1.5) and windows (size coefficients: 1.0, 1.5, and 2.25). The volumetric flow rate varied widely, ranging from 13,729 m³/h to 19,148 m³/h, while the pressure drop coefficient ranged between 0.09 and 0.55. The findings demonstrate that enlarging the opening cross-sections along the entire gas exchange path reduces local resistance coefficients, consequently enhancing the total flow rate. Conversely, intentional throttling of the outlet opening enables the effective establishment of an overpressure barrier within the ventilated volume. This study confirms that LES modeling facilitates accurate forecasting of flow variables and optimization of tactical rescue operations without requiring costly full-scale field experiments on physical building structures. The data obtained aid incident commanders in selecting optimal opening configurations depending on the operational priority: dynamic smoke clearance or pressure stabilization within the protected volume. Full article

26 pages, 892 KB

Open AccessArticle

Identity-Private P2P Energy Trading for Virtual Power Plants

by Yuxuan Li, Ali Anaissi, Jie Hua and Weidong Huang

Smart Cities 2026, 9(9), 155; https://doi.org/10.3390/smartcities9090155 (registering DOI) - 17 Sep 2026

Abstract

The energy conservation, emission reduction, and electricity peak-load regulation requirements of smart cities have driven the establishment of virtual power plants (VPPs). Peer-to-peer (P2P) trading is applicable to distributed clean energy resources in VPPs and affects the transformation of the energy trading paradigm. [...] Read more.

The energy conservation, emission reduction, and electricity peak-load regulation requirements of smart cities have driven the establishment of virtual power plants (VPPs). Peer-to-peer (P2P) trading is applicable to distributed clean energy resources in VPPs and affects the transformation of the energy trading paradigm. To address the privacy protection and robustness issues of P2P trading, this paper presents a unified framework for point-to-point energy trading in VPPs. We comprehensively consider the multiple stages of verification and consensus in transactions and propose a complete framework. The proposed system can effectively protect participants’ private information and achieve identity authentication. Furthermore, we design a progressive settlement mechanism to ensure time-slot-level transaction parallelism. To verify the effectiveness of the method, we implemented the proposed system on IEEE bus benchmarks. The experiments covered the complete stages of authentication, consensus, and clearing. The overhead measurements showed that the overhead of the cryptographic components was reasonable and that the final signature adaptation introduced only a small computational overhead. Full article

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22 pages, 672 KB

Open AccessArticle

CNN Architecture Optimization for Multiplierless Inference

by Ivan Al Khayat, John Reuben and Dietmar Fey

Information 2026, 17(9), 913; https://doi.org/10.3390/info17090913 (registering DOI) - 17 Sep 2026

Abstract

Many CNN architectures are primarily optimized for classification accuracy and software-level metrics, but they do not necessarily account for resource-constrained integer inference. This work addresses this gap by optimizing CNN architectures with subsequent In-Memory Computing (IMC) implementation in mind, using an analytical resource–cost [...] Read more.

Many CNN architectures are primarily optimized for classification accuracy and software-level metrics, but they do not necessarily account for resource-constrained integer inference. This work addresses this gap by optimizing CNN architectures with subsequent In-Memory Computing (IMC) implementation in mind, using an analytical resource–cost model for multiplierless integer inference. Motivated by the need to reduce data movement and avoid explicit multipliers, the proposed methodology constrains candidate CNN architectures toward integer computations that can be expressed through memory look-ups, additions, and shifts, rather than conventional multiply–accumulate operations. Distributed Arithmetic provides the computational basis for this multiplierless formulation, while the proposed HWCost model is used together with validation performance and validation efficiency to rank and select candidate architectures. Candidate architectures are generated by combining six redesign techniques: Global Average Pooling (GAP) to reduce classifier complexity, Quantization-Aware Training (QAT) to optimize weight precision, reduction in convolution filter size, selection of the downsampling strategy, power-of-two constraints on the feature map size before GAP, and training oriented toward integer-only inference. We evaluate the combined effect of these techniques on MNIST, FashionMNIST, CIFAR-10, and PneumoniaMNIST. The results show that, across MNIST and FashionMNIST, the selected compact models reduce the estimated HWCost by up to

2.52 \times

with approximately one percentage point or less degradation in test accuracy. On CIFAR-10, the lowest-cost candidate reduces the estimated HWCost by

3.94 \times

, relative to the highest-accuracy candidate, at the cost of a larger accuracy reduction. On PneumoniaMNIST, the efficiency-oriented candidate achieves comparable independent-test-balanced accuracy to the highest-validation-balanced accuracy candidate while requiring substantially lower estimated HWCost. Full article

(This article belongs to the Special Issue Deep Learning for Image, Video and Signal Processing, 2nd Edition)

45 pages, 10032 KB

Open AccessReview

Expanding Synthetic Lethality in DNA Damage Response-Defective Cancers Through Stress Phenotype-Guided Kinase Targeting

by Mirco Masi, Giulia Varignani, Andrea Cavalli and Stefania Girotto

Int. J. Mol. Sci. 2026, 27(18), 8301; https://doi.org/10.3390/ijms27188301 (registering DOI) - 17 Sep 2026

Abstract

Synthetic lethality has reshaped oncology, particularly in tumours with defects in DNA damage response (DDR) pathways, yet therapeutic strategies centred on canonical DDR targets, including poly(ADP-ribose) polymerase (PARP), ataxia telangiectasia and Rad3-related protein (ATR), checkpoint kinase 1 (CHK1) and Wee1 G2 checkpoint kinase [...] Read more.

Synthetic lethality has reshaped oncology, particularly in tumours with defects in DNA damage response (DDR) pathways, yet therapeutic strategies centred on canonical DDR targets, including poly(ADP-ribose) polymerase (PARP), ataxia telangiectasia and Rad3-related protein (ATR), checkpoint kinase 1 (CHK1) and Wee1 G2 checkpoint kinase (WEE1), remain constrained by resistance, toxicity and biological heterogeneity of DDR alterations. Emerging evidence indicates that DDR deficiency extends beyond impaired DNA repair to generate interconnected stress phenotypes involving replication fork instability, chromosomal instability, transcriptional and cell-cycle dysregulation, oxidative/proteotoxic stress and metabolic imbalance. These states may increase tumour-cell reliance on kinases that are not canonical DNA repair enzymes or proximal DDR sensors, here referred to as non-canonical DDR-associated kinases. In this review, we examine the mechanistic rationale and translational potential of targeting kinases that regulate mitosis, transcriptional adaptation, checkpoint signalling, stress responses and metabolic homeostasis in DDR-defective tumours. We distinguish kinase dependencies supported by direct DDR-context-specific vulnerability or PARP inhibitor sensitisation from those whose relevance remains primarily mechanistic or hypothesis-generating and propose a shift from genotype-based patient selection toward functional stress phenotyping that integrates DNA repair capacity with replication stress, chromosomal instability, transcriptional conflict and the metabolic state. Finally, we evaluate pharmacological strategies, including rational combinations, allosteric modulation, polypharmacology and targeted protein degradation, and highlight the need for biomarker-guided clinical translation. Full article

(This article belongs to the Special Issue Synthetic Lethality Strikes: Outsmarting Cancer with Precision Medicine)

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20 pages, 890 KB

Open AccessReview

Vitamin D Deficiency in Hip Fracture Patients: Outcome-Specific Associations and Post-Fracture Management—A Narrative Review

by Hannah Lee, Jaehee Lee, Yejun Lee and Suk-Kyoon Song

Medicina 2026, 62(9), 1794; https://doi.org/10.3390/medicina62091794 (registering DOI) - 17 Sep 2026

Abstract

Background and Objectives: Vitamin D deficiency is common in older adults with hip fracture and has been associated with adverse postoperative outcomes. However, heterogeneity in deficiency thresholds, outcome definitions, and patient populations has complicated the interpretation and clinical application of existing evidence. This [...] Read more.

Background and Objectives: Vitamin D deficiency is common in older adults with hip fracture and has been associated with adverse postoperative outcomes. However, heterogeneity in deficiency thresholds, outcome definitions, and patient populations has complicated the interpretation and clinical application of existing evidence. This narrative review aimed to summarize current evidence regarding perioperative vitamin D status, its associations with postoperative complications, mortality, functional recovery, and secondary fracture, and the role of vitamin D supplementation after hip fracture. Materials and Methods: Relevant studies were identified through PubMed searches and manual screening of reference lists. Cohort studies, randomized controlled trials, systematic reviews, meta-analyses, and clinical guidelines addressing vitamin D status, supplementation, hip fracture outcomes, fracture prevention, or postoperative recovery in older adults were narratively synthesized. Results: Low serum 25-hydroxyvitamin D was associated with selected early medical complications, mortality, impaired functional recovery, and secondary hip fracture, although these associations varied across outcomes. The strongest prognostic associations with mobility were observed in patients with severe deficiency (approximately ≤10–12 ng/mL), whereas mild insufficiency showed less consistent associations. Heterogeneity among studies reflected differences in deficiency thresholds, sampling timing, outcome definitions, follow-up duration, study populations, and adjustment for frailty and comorbidity. Vitamin D supplementation consistently increased serum 25-hydroxyvitamin D concentrations but did not consistently improve gait, postoperative complications, mortality, or recurrent fracture. Favorable outcomes reported with exercise- and nutrition-based multimodal interventions could not be attributed to vitamin D supplementation alone. Conclusions: Vitamin D deficiency should be interpreted within the broader context of frailty, nutritional status, muscle function, and skeletal health after hip fracture. Vitamin D assessment and correction should be integrated into comprehensive post-fracture care alongside osteoporosis treatment, adequate calcium and protein intake, rehabilitation, and fall prevention. However, clinical benefits of supplementation beyond correction of deficiency remain uncertain, and future studies should focus on patients with severe deficiency and clinically meaningful, patient-centered outcomes. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Treatment of Osteoporosis and Fractures)

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12 pages, 268 KB

Open AccessArticle

Assessing the Correlation Between Inter-Leg Ankle–Brachial Index Asymmetry and Peripheral Artery Disease Outcomes

by Ben Li, Mariam Zakaria, Mo’ath Bani Ali, Ola Kassem, Houssam Younes, Abdelrahman Zamzam, Nadya Al Matrooshi, Rawand Abdin and Mohammad Qadura

J. Cardiovasc. Dev. Dis. 2026, 13(9), 470; https://doi.org/10.3390/jcdd13090470 (registering DOI) - 17 Sep 2026

Abstract

Background/Objectives: Peripheral artery disease (PAD) remains underdiagnosed and suboptimally treated, with limited disease awareness and underutilization of available diagnostic strategies representing important contributing factors. The ankle–brachial index (ABI) is the gold-standard screening test for PAD and has been shown to correlate with limb [...] Read more.

Background/Objectives: Peripheral artery disease (PAD) remains underdiagnosed and suboptimally treated, with limited disease awareness and underutilization of available diagnostic strategies representing important contributing factors. The ankle–brachial index (ABI) is the gold-standard screening test for PAD and has been shown to correlate with limb outcomes. However, the current interpretation of ABIs does not account for clinically significant differences between legs, which may reflect asymmetric disease burden and have an impact on limb outcomes. The association between inter-leg ABI asymmetry and PAD outcomes is unclear and requires further study. Thus, we assessed the prognostic importance of a clinically significant difference in left and right ABI values (≥0.15) on limb outcomes in patients with PAD. Methods: A total of 3313 patients with PAD who received outpatient vascular care at a single institution were retrospectively analyzed. At baseline, ABIs were measured in a certified vascular laboratory by dividing the higher of the dorsalis pedis or posterior tibial artery systolic pressures in each leg by the higher brachial systolic pressure. Inter-leg ABI asymmetry was defined by an absolute difference between left and right ABI values ≥ 0.15, which has been shown to be clinically significant. The primary outcome was major adverse limb event (MALE) over 2 years of follow-up. MALE was defined as the need for vascular intervention (either open or endovascular lower extremity revascularization) or major lower extremity amputation above the ankle. The association between inter-leg ABI asymmetry and 2-year MALE was evaluated using univariable and multivariable logistic regression models adjusted for age, sex, body mass index (BMI), and ABI-defined hemodynamic severity. Results: The mean participant age was 58.4 years (SD 12.9), 966 (29.2%) participants were female, and the mean BMI was 28.8 kg/m² (SD 5.7). There were 666 (20.1%) patients who had inter-leg ABI asymmetry. The mean inter-leg ABI difference was 0.38 (SD 0.29) in the inter-leg ABI asymmetry group and 0.04 (SD 0.02) in the no inter-leg ABI asymmetry group (p < 0.001). Patients with inter-leg ABI asymmetry were more likely to have moderate PAD (36.0% vs. 6.5%, p < 0.001) and severe PAD (6.2% vs. 0.7%, p < 0.001), and less likely to have mild PAD (57.8% vs. 92.8%, p < 0.001), compared to patients with no inter-leg ABI asymmetry. Over the median follow-up period of 2 years, 304 (9.2%) participants experienced MALE. The 2-year MALE rate was significantly higher in patients with inter-leg ABI asymmetry compared to those without (26.0% vs. 4.9%, p < 0.001). Similarly, patients with inter-leg ABI asymmetry had a higher rate of the need for revascularization (21.5% vs. 4.1%, p < 0.001) and major amputation (10.2% vs. 1.8%, p < 0.001). Multivariable logistic regression controlling for age, sex, BMI, and ABI-defined hemodynamic severity showed that inter-leg ABI asymmetry was independently associated with 2-year MALE (adjusted OR 3.70, 95% CI 2.80–4.91, p < 0.001). Conclusions: In this study, over 20% of patients with PAD had clinically significant inter-leg ABI asymmetry, which was independently associated with a nearly four times higher odds of 2-year MALE, including the need for revascularization and major amputation. Our results suggest that inter-leg ABI asymmetry may represent a readily available prognostic marker of adverse limb outcomes in patients with PAD. Further external validation and prospective studies are needed to determine whether incorporating inter-leg ABI asymmetry into clinical assessment improves risk stratification or clinical outcomes. Full article

(This article belongs to the Special Issue Management and Challenges in Peripheral Arterial Disease)

20 pages, 3992 KB

Open AccessArticle

Payload-Free Epitope Imprinted Polymer Nanoparticles Selectively Targeting IL-13Rα2 and Inhibition of Diffuse Midline Glioma Cells

by Damla Ulker, Adem Ozleyen, Dmitry Pshezhetskiy, Elena Piletska, Salvador Macip, Nikolai A. Barlev and Sergey Piletsky

Cancers 2026, 18(18), 3028; https://doi.org/10.3390/cancers18183028 (registering DOI) - 17 Sep 2026

Abstract

Background/ Objectives: Diffuse midline gliomas (DMGs), including diffuse intrinsic pontine glioma (DIPG), present a significant medical challenge due to their aggressive nature and poor prognosis. Widespread overexpression of the interleukin-13 receptor subunit alpha-2 (IL-13Rα2) across gliomas makes it a promising therapeutic target. Method: [...] Read more.

Background/ Objectives: Diffuse midline gliomas (DMGs), including diffuse intrinsic pontine glioma (DIPG), present a significant medical challenge due to their aggressive nature and poor prognosis. Widespread overexpression of the interleukin-13 receptor subunit alpha-2 (IL-13Rα2) across gliomas makes it a promising therapeutic target. Method: Using epitope mapping through a molecular imprinting (EMMI) technique, we developed nanosized molecularly imprinted polymers (nanoMIPs) that specifically recognize different IL-13Rα2 domains. Results: Functional assays showed that nanoMIPs binding to the surface of IL-13Rα2 reduced glioma cell viability, while sparing non-tumor cells. Consistent with receptor-mediated interactions, these nanoMIPs were selectively accumulated onto glioma cells, a specificity validated using a reverse-epitope nanoMIP negative control (nanoMIP-1*). IL-13Rα2-specific nanoMIPs suppressed phosphorylation of ERK1/2, AKT, and STAT3, disrupting major survival pathways. Moreover, these nanoMIPs activated the pro-apoptotic caspase-3/7 pathway, confirming apoptosis induction. Conclusions: Our findings demonstrate that IL-13Rα2-specific nanoMIPs, without a pharmacological payload, exert strong anti-proliferative and pro-apoptotic effects on DMG cells. Collectively, nanoMIPs represent a robust, reproducible synthetic antibody nanoplatform for targeted therapies in cancer and other diseases characterized by cell-surface protein dysregulation. Full article

(This article belongs to the Section Methods and Technologies Development)

28 pages, 36427 KB

Open AccessArticle

A Comparative Study of Fracture Evolution and Failure Characteristics of Coal Specimens Under Different Mining-Induced Stress Paths Using True Triaxial Tests and Acoustic Emission Monitoring

by Xiaobei Shang, Ze Xia, Xuehua Li and Xiaozhao Li

Appl. Sci. 2026, 16(18), 9252; https://doi.org/10.3390/app16189252 (registering DOI) - 17 Sep 2026

Abstract

To investigate the fracture evolution and failure mechanisms of coal specimens under different mining-induced stress paths, true triaxial tests were conducted along six paths grouped into three categories: bidirectional loading–unloading, unidirectional double-face unloading, and unidirectional single-face unloading. Acoustic emission (AE) monitoring was used [...] Read more.

To investigate the fracture evolution and failure mechanisms of coal specimens under different mining-induced stress paths, true triaxial tests were conducted along six paths grouped into three categories: bidirectional loading–unloading, unidirectional double-face unloading, and unidirectional single-face unloading. Acoustic emission (AE) monitoring was used to analyze specimen failure and the corresponding AE responses. The results show that brittle shear failure dominated under the σ₁–σ₂ loading–unloading path, whereas ductile failure was more pronounced under the σ₁–σ₃ loading–unloading path. Under unidirectional double-face unloading of σ₂ or σ₃, tensile–shear cracking became more pronounced, and the failure mode shifted from shear-dominated failure to tensile–shear composite failure. Under unidirectional single-face unloading, the specimens unloaded along σ₂ exhibited better stability than those unloaded along σ₃. Fractures were mainly concentrated in the half region adjacent to the unloading face and were dominated by tensile cracks and their associated secondary fractures. AE activity under all testing conditions showed clear stage-dependent characteristics. In particular, high-intensity AE activity appeared earlier and was more pronounced when σ₂ was unloaded. The RA–AF distributions indicate the coexistence of tensile- and shear-type cracking. This interpretation is consistent with the macroscopic failure patterns associated with the intermediate principal stress effect. These findings provide a reference for early warning and stability control of surrounding rock in underground coal mining engineering. Full article

(This article belongs to the Topic Advances in Mining and Geotechnical Engineering)

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23 pages, 877 KB

Open AccessPerspective

From Entities to States: A Dynamic Interpretation of Humic Substances

by Pellegrino Conte

Appl. Sci. 2026, 16(18), 9255; https://doi.org/10.3390/app16189255 (registering DOI) - 17 Sep 2026

Abstract

Humic substances have long been interpreted as high molecular weight macromolecules, yet this view largely reflects the translation of instrumental responses into ontological claims. Size exclusion chromatography measures hydrodynamic behavior relative to calibration standards, not molecular architecture; nuclear magnetic resonance reports chemical environments [...] Read more.

Humic substances have long been interpreted as high molecular weight macromolecules, yet this view largely reflects the translation of instrumental responses into ontological claims. Size exclusion chromatography measures hydrodynamic behavior relative to calibration standards, not molecular architecture; nuclear magnetic resonance reports chemical environments and dynamic regimes, not polymeric identity; fractal scaling describes morphology, not bonding. Conflating these levels of description has sustained artificial dichotomies and obscured the role of interaction-driven organization. Here, humic substances are reinterpreted as operationally defined, interaction-dominated states of organic matter that emerge under specific boundary conditions of pH, ionic strength and hydration, recognizable through measurable dynamic signatures (accessibility, confinement, hysteresis, relaxation) rather than inferred molecular architecture. The State Resilience Index (SRI) is proposed as a quantitative descriptor of how strongly a humic-like state resists, or recovers from, controlled perturbations, expressing “humic behavior” as an observable property of system response rather than a presumed molecular identity. Reframing humic substances from entities to states resolves long-standing conceptual tensions without discarding their practical utility, provided operational clarity, functional focus, and contextual limitation are explicitly maintained. The future of humic-substances research is not to resolve a molecular identity for humic fractions, but to quantify when and why organic matter behaves humic-like. Full article

(This article belongs to the Section Environmental Sciences)

33 pages, 8996 KB

Open AccessArticle

CREB1 and GSK3 Isoforms as Potential Adaptive Signaling Nodes in PI3K/Akt/mTOR Inhibitor Treated Philadelphia Chromosome-Positive B-ALL

by Himanshu Dhanda, Shamsuz Zaman, Sandeep Kumar Swain, Neetu Kushwaha, Raj Kamal, Manpreet Kaur, Bhavika Rishi, Pranay Tanwar, Sufian Zaheer, Amitabh Singh, Sumita Chaudhry, Fouzia Siraj and Aroonima Misra

Int. J. Mol. Sci. 2026, 27(18), 8300; https://doi.org/10.3390/ijms27188300 (registering DOI) - 17 Sep 2026

Abstract

Philadelphia chromosome-positive (Ph+) B-cell acute lymphoblastic leukemia (ALL), driven by the BCR-ABL1 fusion, remains highly aggressive, with poor prognosis despite tyrosine kinase inhibitor (TKI) therapy. Aberrant PI3K/Akt/mTOR pathway activation contributes to resistance, warranting identification of predictive kinase biomarkers. To identify and validate critical [...] Read more.

Philadelphia chromosome-positive (Ph+) B-cell acute lymphoblastic leukemia (ALL), driven by the BCR-ABL1 fusion, remains highly aggressive, with poor prognosis despite tyrosine kinase inhibitor (TKI) therapy. Aberrant PI3K/Akt/mTOR pathway activation contributes to resistance, warranting identification of predictive kinase biomarkers. To identify and validate critical phospho-kinase markers within the PI3K/Akt/mTOR axis as candidate adaptive signaling nodes and exploratory prognostic markers in Ph+ B-ALL. Network pharmacology using STRING and Cytoscape mapped the protein–protein interactions, identifying high-centrality nodes. Functional enrichment analyses (GO/KEGG) were then performed via ShinyGO. Experimentally, phospho-kinase arrays profiled 39 kinase phosphorylation sites in Ph+ B-ALL cells (SUPB-15) treated with PI3K/Akt/mTOR inhibitors (Rapamycin, GDC-0941, GSK690693, Perifosine). Gene expression was validated by RT-qPCR in 100 Ph+ B-ALL patients and protein validation employed Western blot in 50 patient samples with 15 and five healthy controls, respectively. Network analysis identified CREB1 and GSK3 isoforms as central hub regulators. Phospho-kinase profiling revealed p-CREB (Ser133) phosphorylation upregulation following Perifosine, GDC-0941, and Rapamycin treatment, with no statistically significant change after GSK690693. p-GSK3α/β (Ser21/9) phosphorylation showed a statistically significant increase after Perifosine, with non-significant trends after GDC-0941, and a significant reduction following Rapamycin. Hierarchical clustering then divided proteins into four distinct clusters positioning CREB1 in cluster 3 and GSK3α/β in cluster 2 as candidate adaptive response markers based on their phosphorylation profiles. RT-qPCR demonstrated marked downregulation of GSK3α (approximately 71%), GSK3β (63%), and CREB1 (65%) transcripts in patients versus controls, with even greater suppression seen in cell lines. Conversely, Western blot revealed a significant 2.49 fold elevated p-CREB (Ser133) (β = 1.317, p = 0.000347) and a phospho-GSK3α/β (Ser21/9) level that did not differ significantly between patients and controls (β = 0.467, p = 0.466), revealing mRNA–protein discordance indicative of compensatory post-transcriptional and post-translational regulation. These findings represent treatment-associated and disease-state associations between altered phosphorylation states and the Ph+ B-ALL context; functional validation remains an essential next step. mRNA–protein discordance with transcriptional downregulation (63–71%) contrasting with elevated p-CREB levels (2.49-fold, p = 0.000347) suggests post-translational compensatory mechanisms under therapeutic pressure. CREB1 and GSK3 isoforms emerge as central network nodes that might potentially mediate adaptive resistance, although functional validation is required. It should be noted that the evidence presented is associative rather than causal and a direct link between the observed phosphorylation changes and clinical drug resistance has not been established in this study. Sustained CREB phosphorylation despite PI3K/Akt/mTOR inhibition implicates alternative kinase pathways (MAPK/ERK, CaMK), supporting rational combination therapy strategies. These findings position p-CREB and p-GSK-3α/β as candidate biomarkers, highlighting the value of phospho-proteomics over transcriptomics alone in capturing pathway activation. Multi-omics integration may prove essential for overcoming adaptive resistance in ALL patients. Full article

(This article belongs to the Special Issue Acute Leukemia: From Basic Research to Clinical Application, Second Edition)

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23 pages, 10468 KB

Open AccessArticle

Proteome-Scale Discovery and Multilevel Validation of Antioxidant Short Peptides from Apostichopus japonicus: Keap1 Interactions and Cellular Antioxidant Responses

by Jingxian Zheng, Yijia Tang, Shu Xing and Weiwei Han

Antioxidants 2026, 15(9), 1188; https://doi.org/10.3390/antiox15091188 (registering DOI) - 17 Sep 2026

Abstract

Antioxidant peptides from marine proteins are promising bioactive compounds, yet efficient discovery and multilevel validation remain challenging. Here, we established a proteome-scale workflow integrating virtual enzymatic hydrolysis, dual-model antioxidant prediction, consensus ranking, toxicity screening, sequence-diversity-informed selection, experimental validation, and molecular simulation to identify [...] Read more.

Antioxidant peptides from marine proteins are promising bioactive compounds, yet efficient discovery and multilevel validation remain challenging. Here, we established a proteome-scale workflow integrating virtual enzymatic hydrolysis, dual-model antioxidant prediction, consensus ranking, toxicity screening, sequence-diversity-informed selection, experimental validation, and molecular simulation to identify antioxidant short peptides from Apostichopus japonicus. Five newly identified antioxidant short peptides (DHE, HDHE, DDHN, EHED, and QHDE) were synthesized for experimental validation. All showed DPPH and ABTS radical-scavenging activity, good cytocompatibility, and protection against D-galactose-induced loss of HepG2 cell viability. HDHE showed the highest DPPH activity and QHDE showed the highest ABTS activity at higher concentrations, whereas EHED produced the greatest recovery of cell viability. Molecular docking and 100 ns molecular dynamics simulations indicated sequence-dependent Keap1 interaction patterns and preserved global receptor stability, but these computational features did not parallel cytoprotection. Western blotting further showed differential regulation of Keap1, Nrf2, and HO-1, with DDHN, EHED, and QHDE significantly increasing HO-1 expression. Across the workflow, predicted activity, chemical radical scavenging, Keap1 interaction characteristics, and cellular protection did not converge on the same peptide. These findings establish a proteome-scale discovery strategy and show that multilevel validation is essential because computational, chemical, molecular-interaction, and cellular readouts represent complementary rather than interchangeable dimensions of antioxidant peptide performance. Full article

(This article belongs to the Special Issue Antioxidants from the Sea and Their Application)

15 pages, 3899 KB

Open AccessArticle

Multimodal Analysis and Heterologous Expression Strategies Reveal the Crucial Role of the Lac2 Gene from Lentinus sajor-caju in Lignin Degradation

by Changlong Gou, Lilong Luo, Liang Zhang, Liming Chen, Yangci Liao and Yuqiong Wang

J. Fungi 2026, 12(9), 698; https://doi.org/10.3390/jof12090698 (registering DOI) - 17 Sep 2026

Abstract

The complex chemical structure of plant lignin limits roughage utilization. Biological modification is commonly used to enhance lignin properties. Lentinus sajor-caju (L. sajor-caju) is a potent white-rot fungus for lignocellulose pretreatment in animal roughage. However, the key lignin-degrading enzyme genes remain [...] Read more.

The complex chemical structure of plant lignin limits roughage utilization. Biological modification is commonly used to enhance lignin properties. Lentinus sajor-caju (L. sajor-caju) is a potent white-rot fungus for lignocellulose pretreatment in animal roughage. However, the key lignin-degrading enzyme genes remain unclear. This study evaluated the key enzyme genes involved in lignin degradation and their efficiency in decomposing alkaline lignin. Transcriptome and proteome comparative analyses of L. sajor-caju cultured in media with glucose and alkaline lignin as carbon sources revealed that the AA1 laccase aids lignin decomposition in L. sajor-caju. Additionally, a laccase heterologously expressing strain in Pichia pastoris X-33 was constructed. Compared with the wild-type L. sajor-caju strain W-2, Lac2 laccase activity increased by 67.35%. Electron microscopy showed that Lac2 degraded alkaline lignin, forming irregular pores and surface fusion. These findings indicate that Lac2 laccase has potential application value. In the future, it may be applied in agriculture, the chemical industry, and the energy sector to efficiently convert lignin into feed additives or energy products. Full article

(This article belongs to the Special Issue Molecular Biology of Mushroom, 2nd Edition)

28 pages, 730 KB

Open AccessArticle

Motivation Dynamics and Resilience Construction Among Chinese University Learners of German as a Third Language: A Grounded Theory Study

by Jie Wang

Systems 2026, 14(9), 1165; https://doi.org/10.3390/systems14091165 (registering DOI) - 17 Sep 2026

Abstract

While the motivational dynamics of second language (L2) learning have been extensively theorized, the nonlinear, cyclical nature of third language (L3) motivation remains empirically underexplored. This study aims to develop a process-oriented model that captures the nonlinear dynamics and resilience mechanisms enabling re-engagement [...] Read more.

While the motivational dynamics of second language (L2) learning have been extensively theorized, the nonlinear, cyclical nature of third language (L3) motivation remains empirically underexplored. This study aims to develop a process-oriented model that captures the nonlinear dynamics and resilience mechanisms enabling re-engagement after interruption. Drawing upon Complex Dynamic Systems Theory, this study adopts a qualitative approach informed by constructivist grounded theory principles, rather than a strict constructivist grounded theory design, to investigate motivational dynamics and resilience construction among 30 Chinese university learners of German as a third language (L3), using in-depth narrative accounts and semi-structured interviews with five representative cases. The findings reveal a recurrent nonlinear cycle of engagement, interruption, suspension, re-engagement, and recovery. Interruptions fall into four types: external pressure-induced, internal psychological, passive structural, and rational strategic interruption, the last of which suggests that active withdrawal may itself serve as a form of resilience. Re-engagement relies on the synergy of teacher affective triggers, peer support, external pressure, and meaning restoration, unfolding predominantly as gradual affective accumulation rather than instantaneous insight. Resilience construction emerges from the interplay of five resources: teacher affective guardianship, peer emotional support, meaning reconstruction, small-step accumulation, and pressure-driven persistence. Across repeated cycles, learners may undergo a progressive meaning reconstruction, shifting from utilitarian motives to intrinsic identification. The proposed “Interruption-re-engagement” model offers a process-oriented framework for understanding the phased decline and conditional recovery of L3 motivation, addressing the explanatory gap in mainstream motivation theories regarding nonlinear motivational processes. Full article

(This article belongs to the Section Systems Practice in Social Science)

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28 pages, 675 KB

Open AccessArticle

Curved-Stern Internal Waves with Applied Pressure in a Finite-Depth Two-Layer Fluid

by Osama Ogilat

Mathematics 2026, 14(18), 3388; https://doi.org/10.3390/math14183388 (registering DOI) - 17 Sep 2026

Abstract

The wave train generated by a moving vessel remains a persistent challenge in ship hydrodynamics, particularly in stratified oceans where internal waves contribute significantly to drag. This research investigates steady interfacial wave generation by flow past a semi-infinite curved plate in a two-layer [...] Read more.

The wave train generated by a moving vessel remains a persistent challenge in ship hydrodynamics, particularly in stratified oceans where internal waves contribute significantly to drag. This research investigates steady interfacial wave generation by flow past a semi-infinite curved plate in a two-layer fluid where both layers are of finite depth. Previous studies were limited by flat-plate geometries and infinite-depth approximations, neglecting the critical role of applied pressure as a design variable. We address these limitations to facilitate the engineering goal of wave drag reduction through optimal hull and pressure configurations. Using a scalar Wiener–Hopf formulation, we construct an analytical solution where the kernel is factorized via Cauchy-type integrals, bypassing the technical constraints of traditional infinite-product expansions. We derive a closed-form far-field amplitude and a wave-free condition,

M (μ) = 0

. This condition is a single complex equation, i.e., two independent real constraints. A one-parameter hull design can therefore generally only minimise the downstream wave amplitude; exact cancellation at linear order generally requires a second, independent real design freedom, such as a jointly optimised applied pressure. We quantify both regimes explicitly. Our findings demonstrate that physical stern flow patterns exhibit spatial relaxation and advection scales essential for energy transfer. This result provides a mathematically sharp framework for wave drag minimisation, quantifying the explicit performance trade-off between hull curvature and dynamic pressure control in stratified environments, and we are careful throughout to distinguish the formal linear theory cancellation from what is achievable with a single physically realisable (real-valued) design parameter. Full article

(This article belongs to the Section E: Applied Mathematics)

27 pages, 3413 KB

Open AccessArticle

Multi-Tier Validation of a Single-Lead Wearable ECG Signal-Processing Pipeline: Clinical Comparison and Algorithmic Benchmarking on Public Expert-Annotated Databases

by Josip Vrdoljak and Dora Aletta Racz

Sensors 2026, 26(18), 5905; https://doi.org/10.3390/s26185905 (registering DOI) - 17 Sep 2026

Abstract

Wearable single-lead electrocardiogram (ECG) devices are increasingly used for out-of-clinic rhythm monitoring, but the rigour with which their signal-processing pipelines are validated varies widely across the literature, with most published reports relying on either a single clinical comparison or a single algorithmic benchmark. [...] Read more.

Wearable single-lead electrocardiogram (ECG) devices are increasingly used for out-of-clinic rhythm monitoring, but the rigour with which their signal-processing pipelines are validated varies widely across the literature, with most published reports relying on either a single clinical comparison or a single algorithmic benchmark. We propose and apply a multi-tier validation methodology—combining clinical reference comparison, expert-annotated database benchmarking, and a deliberate morphological stress-test—and demonstrate it on the SmartGuard single-lead wearable ECG device and its signal-processing pipeline. The three tiers comprise (i) a within-subject clinical comparison in 31 healthy adult volunteers against a Bionet Cardio 7 limb-lead Lead I reference with cardiologist-confirmed measurements (a two-electrode limb configuration approximating Lead I, not a full diagnostic 12-lead ECG), (ii) algorithmic benchmarking on the Lobachevsky University ECG Database (LUDB, 200 records, expert annotations), and (iii) a robustness stress-test on the QT Database (QTDB, 103 records, hybrid expert annotations). The pipeline integrates discrete wavelet transform-based PQRST delineation with a derivative-based QRS-width refinement, a tangent-method T-wave end estimator, and median-absolute-deviation robust averaging. In the clinical tier, mean within-subject biases were negligible for heart rate, QT, QTc and RR (all p > 0.6) and borderline for QRS duration (+7.3 ms, p = 0.066), with a systematic R-wave amplitude underestimation (−0.15 mV, p < 0.0001). On LUDB, heart-rate and RR-interval agreement were excellent (Pearson r > 0.95) and QRS duration good (r = 0.73, MAE 13.8 ms). On QTDB, performance degraded in line with the increased morphological heterogeneity of the dataset, particularly for QT-related metrics. Despite this minimal mean bias at the population level, individual-record QT and QTc errors showed high dispersion, precluding accurate clinical QT interpretation from single wearable traces in individual patients. Moreover, the resting, healthy-adult design of the clinical tier means its findings cannot be extrapolated to arrhythmic conditions or exercising states. The protocol is described in sufficient detail to serve as a template for evaluating other wearable single-lead ECG devices. Full article

(This article belongs to the Special Issue Advances in Wearable Sensors for Healthcare Applications)

12 pages, 1373 KB

Open AccessCase Report

Non-Oliguric IRIS Grade V Acute Kidney Injury Associated with Suspected Leptospirosis in an Urban Dog Unvaccinated Against Leptospirosis from the Republic of Korea: A Case Report

by Taehyun Roh and Kunho Song

Vet. Sci. 2026, 13(9), 982; https://doi.org/10.3390/vetsci13090982 (registering DOI) - 17 Sep 2026

Abstract

Leptospirosis is a zoonotic disease that can cause severe acute kidney injury (AKI) in dogs. A three-year-old intact male Border Collie, unvaccinated against leptospirosis, with a history of exposure to urban stagnant water presented with acute vomiting, diarrhea, and moderate dehydration. Initial evaluation [...] Read more.

Leptospirosis is a zoonotic disease that can cause severe acute kidney injury (AKI) in dogs. A three-year-old intact male Border Collie, unvaccinated against leptospirosis, with a history of exposure to urban stagnant water presented with acute vomiting, diarrhea, and moderate dehydration. Initial evaluation revealed extreme azotemia (blood urea nitrogen, 175.8 mg/dL; creatinine, 11.10 mg/dL) and hyperphosphatemia (13.6 mg/dL), consistent with International Renal Interest Society (IRIS) AKI Grade V; urine output remained within the non-oliguric range (2.15–3.0 mL/kg/h) throughout the catheterized period (Day 0–4). Clinical and imaging findings supported acute intrinsic renal injury over chronic kidney disease. A multiplex real-time PCR targeting the Leptospira LipL32 gene was positive in urine (Ct 31.10), providing molecular evidence supporting active infection or shedding of pathogenic Leptospira spp., without identifying the infecting serovar. Empirical antimicrobial therapy targeting suspected leptospirosis, together with intravenous fluid therapy, was initiated on clinical suspicion prior to the PCR result. Renal and inflammatory biomarkers improved progressively over 22 days without extracorporeal kidney support; the patient’s non-oliguric status, hemodynamic stability, and objective clinical improvement supported this management approach. This report documents, in detail, the clinicopathological recovery trajectory of a dog with non-oliguric IRIS Grade V AKI associated with suspected leptospirosis, information that may assist clinicians in recognizing and managing similarly severe presentations without assuming that dialysis is always required. Full article

(This article belongs to the Topic Advances in Infectious and Parasitic Diseases of Animals)

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24 pages, 1269 KB

Open AccessArticle

Predictive Modeling of Basalt-Fiber-Reinforced Bentonite Strength Using Gaussian Process Regression

by Zülfü Gürocak, Zeynep Bala Duranay, Yasemin Aslan Topçuoğlu and Hanifi Güldemir

Minerals 2026, 16(9), 951; https://doi.org/10.3390/min16090951 (registering DOI) - 17 Sep 2026

Abstract

This study proposes a Gaussian Process Regression (GPR) method for estimating the compressive strength of soil mixtures containing bentonite and basalt fibers. GPR is a preferred probabilistic machine learning approach, especially for limited datasets, due to its high generalization ability and its ability [...] Read more.

This study proposes a Gaussian Process Regression (GPR) method for estimating the compressive strength of soil mixtures containing bentonite and basalt fibers. GPR is a preferred probabilistic machine learning approach, especially for limited datasets, due to its high generalization ability and its ability to directly calculate prediction uncertainty. In this study, experimentally obtained bentonite and basalt fiber ratio values were used as input parameters of the model, and unconfined compressive strength (q_u) was determined as the output variable. Model performance was evaluated using the Leave-One-Out Cross-Validation (LOOCV) method. The performance of the proposed GPR model was evaluated with various metrics. Accordingly, the MAE and RMSE values of the model were calculated as 3.667 kPa and 4.756 kPa, respectively, while the R² value was 0.945. The results show that the GPR model provides high prediction accuracy and is a reliable prediction tool for small datasets. Furthermore, the prediction surfaces and uncertainty analyses obtained by the model contributed to a better understanding of the effect of mixture parameters on compressive strength. Full article

(This article belongs to the Special Issue Microstructure and Reinforcement Mechanisms of Fiber-Reinforced Clay)

27 pages, 5772 KB

Open AccessArticle

Selected Energy-Related Emissions and Indicative Forest Carbon Uptake: An IPCC-Based Screening Assessment

by Merve Erol, Meral Korkmaz and Alban Kuriqi

Earth 2026, 7(5), 154; https://doi.org/10.3390/earth7050154 (registering DOI) - 17 Sep 2026

Abstract

Carbon-accounting studies of small, lightly industrialized provinces remain underrepresented despite their relevance to regional climate policy. This study quantifies energy-related CO₂ emissions from selected sources in Tunceli Province, Eastern Türkiye, for 2022 using the IPCC Tier 1 methodology, with an activity-based bottom-up [...] Read more.

Carbon-accounting studies of small, lightly industrialized provinces remain underrepresented despite their relevance to regional climate policy. This study quantifies energy-related CO₂ emissions from selected sources in Tunceli Province, Eastern Türkiye, for 2022 using the IPCC Tier 1 methodology, with an activity-based bottom-up road-transport estimate as a sensitivity analysis. Because the official grid factor is published on a CO₂-equivalent basis, we report the aggregate in Gg CO₂-eq yr⁻¹. Under the adopted activity-data assumptions, the selected sources were estimated to produce 288.47 Gg CO₂-eq yr⁻¹. The fuel-based road-transport series reaches a minimum in 2020, although observed vehicle-activity data are lacking. As an illustrative scenario conditional on the assumed coefficients, applying a literature-derived gross-uptake coefficient range of 2–5 t CO₂ ha⁻¹ yr⁻¹, whose local applicability could not be established, to 137,718 ha of productive closed-canopy forest gives an indicative gross sequestration potential of 275.44–688.59 Gg CO₂ yr⁻¹; the upper bound exceeds the compiled emissions, and the lower bound does not. So the comparison shows only that forest uptake capacity is of the same order of magnitude as emissions, not an observed net balance or an operating sink. Under ceteris paribus assumptions, a 75% reduction in residential coal use would avoid about 97.85 Gg CO₂ yr⁻¹ (33.9% of the baseline), roughly 42% of which would be reintroduced by natural-gas substitution. Residential heating decarbonization, building efficiency, and forest conservation emerge as mitigation priorities for small forest-rich provinces. Full article

(This article belongs to the Special Issue Climate-Sensitive Urban Design for Heatwave Mitigation)

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17 pages, 2131 KB

Open AccessReview

The Post-Stress Epigenome: Mechanisms of Recovery and Persistence

by Sirithip Chuaijit, Suhardi Suhardi and Jirapan Thongsroy

Stresses 2026, 6(3), 68; https://doi.org/10.3390/stresses6030068 (registering DOI) - 17 Sep 2026

Abstract

Stress can reshape the epigenome through changes in DNA methylation, histone modifications, chromatin accessibility, and non-coding RNA regulation. Much is known about how these changes arise during stress, yet their fate once the initiating stimulus has subsided is less clear. Some alterations are [...] Read more.

Stress can reshape the epigenome through changes in DNA methylation, histone modifications, chromatin accessibility, and non-coding RNA regulation. Much is known about how these changes arise during stress, yet their fate once the initiating stimulus has subsided is less clear. Some alterations are rapidly reversed, whereas others recover only partially or at selected loci, and a subset persists long after the acute response has ended. This review examines the mechanisms and contextual factors that shape post-stress recovery and persistence. We consider how stress interacts with cell identity, chromatin context, metabolic state, DNA damage and repair, and the machinery responsible for rebuilding epigenetic organization. We use epigenetic recovery capacity as a conceptual framework describing the extent and rate at which altered epigenetic features return toward a defined pre-stress or homeostatic state. We propose that this capacity, together with stress burden and locus susceptibility, may shape post-stress fate. Persistence itself does not necessarily constitute epigenetic memory. Some persistent states may remain functionally neutral, whereas others may be engaged during adaptive or maladaptive responses. We further outline an evidence framework that distinguishes epigenetic persistence from functional and causal epigenetic memory and discuss the potential for redirecting maladaptive post-stress trajectories. Full article

(This article belongs to the Section Animal and Human Stresses)

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25 pages, 1529 KB

Open AccessSystematic Review

Economic Empowerment Interventions on Mental Health Outcomes Among People Living with HIV in Low and Middle-Income Countries: A Systematic Literature Review

by Peter Onchuru Mokaya, Evans Kasmai Kiptulon, Dahabo Adi Galgalo, Mohammed Elmadani and Gabriella Hideg-Fehér

Behav. Sci. 2026, 16(9), 1680; https://doi.org/10.3390/bs16091680 (registering DOI) - 17 Sep 2026

Abstract

There is strong evidence of the correlation between economic hardship and poor mental health outcomes among people living with HIV (PLHIV). However, the causal efficacy and mechanisms of specific economic interventions through which they contribute to mental health improvement among PLHIV remain fragmented [...] Read more.

There is strong evidence of the correlation between economic hardship and poor mental health outcomes among people living with HIV (PLHIV). However, the causal efficacy and mechanisms of specific economic interventions through which they contribute to mental health improvement among PLHIV remain fragmented and inconsistent. This systematic review aims to collate and synthesize existing evidence on the effect of economic empowerment interventions on mental health symptoms among PLHIV in low- and middle-income countries (LMICs). We conducted a comprehensive literature review that adhered to the PRISMA guidelines for methodological rigor and transparency. Comprehensive searches were conducted in PubMed, Web of Science, Embase, CINAHL, Scopus, and MEDLINE. We conducted a narrative synthesis of 11 studies: two cohorts, two qualitative, one intervention (non-randomized), and six randomized clinical trials. We registered this review with PROSPERO (CRD420251152471). The process theory served as an analytical framework. Evidence suggests that multi-component economic empowerment interventions (e.g., combined savings, skills training, and psychological support) may be associated with improved mental health among PLHIV in LMICs. Qualitative evidence from other studies suggested that reduced financial stress and strengthened psychological resources may contribute to improved mental health. The effectiveness of the intervention depends not only on simple cash transfers but also on a theoretically sound integrated approach. Interventions were more effective among lower-income groups. Integration of multi-component economic and psychosocial interventions into standard HIV care could improve mental health outcomes among PLHIV in LMICs and is hereby recommended by this study. Full article

(This article belongs to the Section Health Psychology)

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