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20 pages, 2673 KB  
Article
Dynamics of Tilapia Lake Virus in Recirculating Aquaculture Systems and the Impact of Vaccination on Outbreak Control
by Montakarn Sresung, Jidapa Yamkasem, Supitchaya Theplhar, Piyathip Setthawong, Surapong Rattanakul, Skorn Mongkolsuk, Kwanrawee Sirikanchana, Win Surachetpong and Tuchakorn Lertwanakarn
Viruses 2026, 18(1), 96; https://doi.org/10.3390/v18010096 (registering DOI) - 9 Jan 2026
Abstract
Tilapia lake virus (TiLV) is a highly virulent pathogen that has caused substantial mortality in tilapia farms, particularly those with open-water systems. However, TiLV can also emerge and persist in closed environments, such as recirculating aquaculture systems (RAS), where environmental accumulation and repeated [...] Read more.
Tilapia lake virus (TiLV) is a highly virulent pathogen that has caused substantial mortality in tilapia farms, particularly those with open-water systems. However, TiLV can also emerge and persist in closed environments, such as recirculating aquaculture systems (RAS), where environmental accumulation and repeated exposure may intensify infection and sustain outbreaks. In this case study, we conducted three field experiments to better understand TiLV dynamics among Nile tilapia in RAS. In experiment I, we quantified the TiLV levels in the fish, water, and sediment to compare outbreak and no-outbreak conditions and found that the TiLV concentrations in liver samples and the water were significantly higher in the outbreak ponds and positively correlated with increased fish mortality. In experiment II, we used a side-by-side field trial to evaluate the protective efficacy of a TiLV vaccine and its effects on the viral loads in the fish and aquatic environment during outbreaks. The vaccinated fish showed substantially lower cumulative mortality (16.7%) than the unvaccinated controls (37.7%), with a relative percent survival of 55.6%. Additionally, the TiLV concentrations in the pond water of the vaccinated group were significantly lower. In experiment III, we compared the TiLV patterns between RAS and non-RAS operations to determine how water recirculation influences viral accumulation and outbreak severity. The results revealed limited viral accumulation and shorter disease outbreak duration in the non-RAS. Overall, our findings showed that the TiLV levels in the rearing water were closely linked with disease severity in the RAS-based tilapia hatcheries. Continuous water recirculation allowed the virus to build up in the system, which led to more prolonged outbreaks, while the non-RAS conditions with regular water discharge showed lower viral loads and faster recovery. The vaccinated fish had better survival rates and released less virus into the water, which helped reduce infection pressure across the ponds. Together, these results suggest that combining vaccination with good water management and molecular monitoring can provide a practical, noninvasive way to detect and control TiLV outbreaks in intensive farming systems. Full article
(This article belongs to the Special Issue Viral Pathogenesis and Novel Vaccines for Fish Viruses)
27 pages, 1121 KB  
Article
Effect of Organic Soil Amendments and Vineyard Topographic Position on the Chemical Composition of Syrah, Trincadeira, Alicante Bouschet, and Antão Vaz Grapes (Vitis vinifera L.) in the Alentejo Wine Region
by Matteo Pierini, Shrika G. Harjivan, Nicolò Sieli, Maria João Cabrita, Sérgio Prats, Sofia Catarino and Jorge M. Ricardo-da-Silva
Environments 2026, 13(1), 44; https://doi.org/10.3390/environments13010044 - 9 Jan 2026
Abstract
Climate change and unsustainable agricultural practices are triggering land degradation in semi-arid Mediterranean regions. Organic amendments, such as mulching materials, have shown promising potential to mitigate these impacts by improving soil chemical, physical, and biological properties, while enhancing grapevine growth and productivity. This [...] Read more.
Climate change and unsustainable agricultural practices are triggering land degradation in semi-arid Mediterranean regions. Organic amendments, such as mulching materials, have shown promising potential to mitigate these impacts by improving soil chemical, physical, and biological properties, while enhancing grapevine growth and productivity. This study evaluated the effects of wheat straw mulch (M) and wheat straw combined with biochar (MB), together with vineyard topography (bottom vs. top), on grape chemical and phenolic composition in four Vitis vinifera L. cultivars (Syrah, Trincadeira, Alicante Bouschet, and Antão Vaz) grown in the Alentejo wine region. Grapes were sampled separately at top and bottom topographic positions, and classical and phenolic parameters were analyzed. The application of M and MB significantly modified must composition, mainly through changes in nitrogen and sugar levels across topographic positions. Only MB exhibited stronger effects, enhancing must quality, while MB and M reduced bottom–top variability. Similar patterns and positional effects were observed for phenolic and color parameters. Both organic treatments lowered total monomeric anthocyanin concentrations, although positional differences with wheat straw mulch were found. The results highlight that combining soil management with topography and variety response can optimize grape phenolic composition and promote sustainable viticulture through targeted, site-specific mulching strategies. Full article
15 pages, 3468 KB  
Article
Comparative Study of Cytokine Measurements in Blood Plasma and Serum, and Saliva of Juvenile Pigs During Experimentally Induced Acute Inflammation
by Pernille Aagaard Madsen, Kevin Jerez-Bogotá, Darya Vodolazska and Charlotte Lauridsen
Vet. Sci. 2026, 13(1), 68; https://doi.org/10.3390/vetsci13010068 - 9 Jan 2026
Abstract
This study aimed to assess cytokine levels in blood plasma and serum, and saliva of juvenile pigs in response to acute systemic inflammation. The objectives were to: (1) validate an analytical method for quantifying cytokines in serum; (2) assess the reliability of serum [...] Read more.
This study aimed to assess cytokine levels in blood plasma and serum, and saliva of juvenile pigs in response to acute systemic inflammation. The objectives were to: (1) validate an analytical method for quantifying cytokines in serum; (2) assess the reliability of serum compared to plasma for cytokine quantification; and (3) explore the potential of saliva as a non-invasive alternative for cytokine measurement. Changes in 13 cytokines (IFN-γ, TNF-α, IL-1α, IL-1β, IL-1ra, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18 and GM-CSF) were analyzed in serum and saliva samples collected over a 72 h period following lipopolysaccharide (LPS) infusion to induce an acute inflammatory response in 10 juvenile pigs (~28 kg BW). EDTA plasma was collected over the same time period, and a subset of four cytokines (IL-1β, IL-6, IL-10 and IFN-γ) was analyzed to assess correlations with serum concentrations. A strong positive correlation was observed between serum and EDTA plasma levels of IL-1β, IL-6, IL-10 and IFN-γ (r = 0.91–1.00, p < 0.001), indicating that both serum and EDTA plasma can be used to obtain reliable measurements of cytokine concentrations in blood of juvenile pigs. Among the 13 analyzed cytokines in serum, TNF-α and IL-6 appeared as the most reliable cytokines during acute inflammation, peaking at 1 h and between 2 and 3 h post LPS infusion, respectively. In general, saliva did not correlate with serum for most cytokines, suggesting limited application of such a non-invasive matrix for systemic cytokine monitoring. However, IL-1α was detected at higher concentrations in saliva than in serum, suggesting that saliva may be useful for monitoring specific cytokines under certain inflammatory conditions. Further research is needed to clarify the origin and physiological role of salivary cytokines following LPS stimulation. Serum and plasma were suitable for cytokine analysis; however, serum may offer practical advantages by facilitating blood sample handling. Saliva may be useful for monitoring specific cytokines under certain inflammatory conditions. Full article
(This article belongs to the Section Veterinary Biomedical Sciences)
28 pages, 766 KB  
Article
The Rebirth of Industrial Heritage: How the Regeneration of Historical Spaces Impacts People’s Mental and Physical Health Through Restorative Perception
by Yinghang Fu and Mengchang Yang
Buildings 2026, 16(2), 290; https://doi.org/10.3390/buildings16020290 - 9 Jan 2026
Abstract
This study aims to explore how industrial heritage regeneration spaces influence employees’ physical and psychological health through restorative perception. With the rapid urbanization and increasing emphasis on sustainable development, the adaptive reuse of industrial heritage sites has become a vital strategy in urban [...] Read more.
This study aims to explore how industrial heritage regeneration spaces influence employees’ physical and psychological health through restorative perception. With the rapid urbanization and increasing emphasis on sustainable development, the adaptive reuse of industrial heritage sites has become a vital strategy in urban renewal. However, the impact of such spaces on people’s health remains underexplored, especially in terms of how the work environment and restorative psychological mechanisms interact. Using a cross-sectional survey design, data from 486 employees in adaptive reuse projects across major cities in China were analyzed through Structural Equation Modeling (SEM). Employees were chosen as the target population because they represent a group with stable, repeated, and long-term exposure to the regenerated environment during daily routines. Compared with visitors, whose exposure duration, activity purposes, and spatial routes are highly variable, employees provide a more consistent context to test the proposed restorative mechanisms. The results revealed that industrial heritage attribute perception (IHAP), including scale, materiality, historical presence, and functional transformation, significantly predicted restorative perception (β = 0.546, p < 0.001), which in turn positively influenced both psychological health (β = −0.647, p < 0.001) and physical health (β = 0.688, p < 0.001). Instrumental variable analysis using “building age” and “green coverage rate” confirmed the robustness of these findings, showing that restorative perception still significantly improved mental (β = −2.295, p < 0.001) and physical health (β = 0.528, p < 0.001) after addressing endogeneity issues. Furthermore, individual differences such as work tenure (β = 0.239, p < 0.001) and environmental sensitivity (β = 0.054, p > 0.05) moderated these effects. This study extends Attention Restoration Theory (ART) by applying it to historical industrial environments, offering both theoretical insights and practical guidance for designing adaptive reuse spaces that promote employee well-being. Full article
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20 pages, 497 KB  
Article
Synthesis and Antibacterial Evaluation of 5-Aminosalicylic Acid Derivatives
by Kazimieras Anusevičius, Jūratė Šiugždaitė, Birutė Sapijanskaitė-Banevič, Valentas Špiliauskas, Birutė Grybaitė, Livija Tubytė and Vytautas Mickevičius
Appl. Sci. 2026, 16(2), 703; https://doi.org/10.3390/app16020703 - 9 Jan 2026
Abstract
The anti-inflammatory scaffold 5-aminosalicylic acid, which is widely used in therapeutic applications, was chosen for the synthesis of N-[3-(hydrazinecarbonyl)-4-hydroxyphenyl]acetamide (1) to enhance its antibacterial properties. The condensation of hydrazide 1 with aromatic aldehydes provided hydrazone derivatives 2af, [...] Read more.
The anti-inflammatory scaffold 5-aminosalicylic acid, which is widely used in therapeutic applications, was chosen for the synthesis of N-[3-(hydrazinecarbonyl)-4-hydroxyphenyl]acetamide (1) to enhance its antibacterial properties. The condensation of hydrazide 1 with aromatic aldehydes provided hydrazone derivatives 2af, whereas cyclocondensation reactions and other related transformations afforded five-membered heterocycles, including pyrrole 3, pyrazole 4, pyrrolidinone 7, oxadiazoles 9, 10, thiadiazole 14, and triazole 15. Additional modifications yielded acetylhydrazine derivative 11, which was O-alkylated to analogue 12. Antibacterial evaluation showed stronger activity against Gram-positive bacteria such as S. aureus and MRSA than against Gram-negative strains of E. coli and S. Enteritidis, consistent with differences in cell membrane permeability. Notably, derivatives containing pyrrolidinone 7, thiosemicarbazide 13, and 1,3,4-thiadiazole 14 exhibited potent bactericidal activity against S. aureus and MRSA, while hydrazones 2b, 2c, 2f, pyrrole 3, and pyrrolidinone 7 exhibited activity against E. coli. These results provide a practical strategy for the discovery of heterocyclic compounds and emphasise the potential of functionalised 5-aminosalicylic acid derivatives as prime candidates for the development of broad-spectrum antibacterial agents. Full article
(This article belongs to the Special Issue Heterocyclic Compounds: Discovery, Synthesis and Applications)
30 pages, 1019 KB  
Article
The Impact of Artificial Intelligence on Corporate Green Value Co-Creation: Empirical Evidence from China’s Manufacturing Industry
by Xiaolin Sun and Wenxin Pi
Sustainability 2026, 18(2), 698; https://doi.org/10.3390/su18020698 - 9 Jan 2026
Abstract
Against the dual demands of green transformation and digital integration in the manufacturing industry, green value co-creation has become a core pathway for enterprises to achieve sustainable development. However, the role of artificial intelligence (AI) in driving green value co-creation remains under explored, [...] Read more.
Against the dual demands of green transformation and digital integration in the manufacturing industry, green value co-creation has become a core pathway for enterprises to achieve sustainable development. However, the role of artificial intelligence (AI) in driving green value co-creation remains under explored, especially in the context of Chinese manufacturing. To enrich this research, this study aims to investigate the impact of AI development on corporate green value co-creation and its intrinsic mechanism. This study draws on panel data of listed manufacturing enterprises listed on China’s Shanghai and Shenzhen A share markets spanning the period 2015–2024, and employs multiple regression and negative binomial regression as research methodologies to empirically examine the impact of AI development on corporate green value co-creation and its underlying mechanisms. The results demonstrate that: AI development exerts a significantly positive effect on manufacturing enterprises’ green value co-creation, which is achieved by enhancing firms’ technological spillover capacity and total factor productivity (TFP); financing constraints negatively moderate the aforementioned relationship, while corporate influence plays a positive moderating role; heterogeneity analysis reveals that this impact is more pronounced for enterprises under voluntary regulation, state-owned enterprises (SOEs), and high-pollution enterprises. This study elucidates AI’s role and mechanism in corporate green development at the micro level, provides empirical evidence for related research, and offers practical insights to promote enterprise AI advancement and green value co-creation. Full article
18 pages, 1446 KB  
Article
Unveiling the Impact of Mandatory IP Location Disclosure on Social Media Users’ Shared Emotions: A Regression Discontinuity Analysis Based on Weibo Data
by Heng Zhang, Aiping Gao, Zhuyu Chen and Xinyuan Lu
Information 2026, 17(1), 63; https://doi.org/10.3390/info17010063 - 9 Jan 2026
Abstract
Social media serves as a vital channel for emotional expression, yet mandatory IP location disclosure raises concerns about how reducing anonymity affects users’ shared emotions, particularly in privacy-sensitive contexts such as mental health discussions. In 2022, all Chinese social media platforms implemented this [...] Read more.
Social media serves as a vital channel for emotional expression, yet mandatory IP location disclosure raises concerns about how reducing anonymity affects users’ shared emotions, particularly in privacy-sensitive contexts such as mental health discussions. In 2022, all Chinese social media platforms implemented this disclosure feature. This study examines the emotional and behavioral consequences of Sina Weibo’s mandatory IP location disclosure policy, which took effect on 28 April 2022. We collected 193,761 Weibo posts published under the topic of depression from 1 March to 30 June 2022, and applied sentiment analysis combined with regression discontinuity in time (RDiT) to estimate causal effects around the policy threshold. Results indicate that the policy significantly intensified negative emotional expression: the estimated discontinuity is −1.3506 (p < 0.01), meaning posts became more negative immediately after implementation. In contrast, the effect on positive sentiment was comparatively weak and mostly statistically insignificant. Behavioral changes were also observed: both average daily posting volume and average text length are declined. These findings demonstrate that mandatory disclosure can suppress self-disclosure and amplify negative emotional tone in privacy-sensitive settings, offering practical guidance for users, platform designers, and policymakers on implementing transparency features responsibly. Full article
(This article belongs to the Special Issue Machine Learning and Data Mining for User Classification, 2nd Edition)
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13 pages, 297 KB  
Article
Follicular Klotho in the Ovarian Microenvironment: Exploring Its Role in IVF Outcome Prediction
by Mehmet Alican Sapmaz, Sait Erbey, Murat Polat, Selin Yıldız, İnci Kahyaoğlu, Ömer Osman Eroğlu, Emine Utlu Özen and Ayfer Bakır
Medicina 2026, 62(1), 139; https://doi.org/10.3390/medicina62010139 - 9 Jan 2026
Abstract
Background and Objectives: Klotho (KL) is a multifunctional protein involved in reproductive physiology; however, its precise role in ovarian reserve and in vitro fertilization (IVF) outcomes remains unclear. This study aimed to evaluate the relationship between follicular fluid KL levels, ovarian reserve markers, [...] Read more.
Background and Objectives: Klotho (KL) is a multifunctional protein involved in reproductive physiology; however, its precise role in ovarian reserve and in vitro fertilization (IVF) outcomes remains unclear. This study aimed to evaluate the relationship between follicular fluid KL levels, ovarian reserve markers, and key IVF success parameters. Materials and Methods: This prospective study included a total of 150 women undergoing IVF, of whom 82 had diminished ovarian reserve (DOR) and 68 had normal ovarian reserve (NOR). All participants underwent controlled ovarian stimulation using a standard antagonist protocol. During oocyte pick-up (OPU), the first aspirated follicular fluid sample was collected, processed, and analyzed for KL concentrations using a Human Klotho ELISA kit. Hormonal profiles, ovarian reserve markers, and IVF outcomes were compared between groups. Results: Follicular fluid KL levels were significantly lower in the DOR group compared with the NOR group (117.07 ± 28.88 pg/mL vs. 266.13 ± 58.29 pg/mL; p < 0.001). Anti-Müllerian hormone (AMH) levels were reduced, whereas follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels were significantly higher in the DOR group (all p < 0.001). Implantation and clinical pregnancy rates were also significantly lower in the DOR group compared with the NOR group (p < 0.001 and p = 0.003, respectively). KL levels showed a strong positive correlation with the number of fertilized oocytes in both groups (DOR: r = 0.690; NOR: r = 0.552). Each one-unit increase in KL was associated with a 3.7% increase in implantation probability and a 3.2% increase in clinical pregnancy probability in the DOR group, and with corresponding increases of 4.4% and 1.2% in the NOR group (all p < 0.05). Conclusions: This study demonstrates significant associations between follicular fluid KL levels and fertilization, implantation, and clinical pregnancy outcomes. These associations appear to be more pronounced than those observed with traditional ovarian reserve markers such as AMH and antral follicle count. Reduced KL levels are associated with fewer fertilized oocytes, whereas higher KL concentrations correspond to increased implantation and clinical pregnancy probabilities. Nevertheless, similar to other non-invasive biomarkers, current evidence is insufficient to support routine clinical use of KL. Large-scale, well-designed, multicenter studies are therefore required to validate its clinical relevance and to determine whether KL can serve as a reliable and practical predictor of IVF success. Full article
(This article belongs to the Special Issue Advances in Reproductive Health)
36 pages, 1404 KB  
Article
Influence of Changing the Support Points, Within a Fixed Cross-Section, on the Static Response of a Double-Layer Beam
by Piotr Ruta, Katarzyna Misiurek, Olga Szyłko-Bigus and Monika Podwórna
Appl. Sci. 2026, 16(2), 701; https://doi.org/10.3390/app16020701 - 9 Jan 2026
Abstract
The paper presents the analysis of the influence of the location and characteristics of supports on the static response of two-layer beams. The possibility of tangential movement at the supports was considered. Multilayer beams, which combine the advantages of different materials, are widely [...] Read more.
The paper presents the analysis of the influence of the location and characteristics of supports on the static response of two-layer beams. The possibility of tangential movement at the supports was considered. Multilayer beams, which combine the advantages of different materials, are widely used in construction. The authors’ previous research showed that the stiffness of the connection between layers significantly affects the behaviour of the system. This paper demonstrates that the supports’ position is another crucial factor that influences the beams’ response, which is an issue that has not been previously considered in the literature. A two-layer system was modelled using the Euler–Bernoulli beam theory. Consistent normal displacements and tangential forces at the layer interface, which were proportional to the relative slip, were assumed. From the equilibrium equations and considered assumptions, three coupled displacement equations were derived and then solved using finite Fourier transforms. They were applied to solve beams, the two ends of which cannot move in the direction perpendicular to the beam’s axis, with at least one of the beam ends being a pinned support. To verify the method’s accuracy, several numerical examples were analysed. It was shown that both the support position and the possibility of tangential displacement at the supports have a significant impact on the static response. Additionally, the crucial role of the stiffness of the interlayer connection was confirmed. The developed approach provides a practical tool for assessing two-layer beam systems and highlights the importance of considering support conditions in the design and analysis of such structures. Full article
(This article belongs to the Section Civil Engineering)
18 pages, 3196 KB  
Article
GreenKSA: A Theory-Based Gamified Application to Foster Pro-Environmental Behavior in Saudi Arabia
by Aeshah Alturkistani and Mayda Alrige
Sustainability 2026, 18(2), 692; https://doi.org/10.3390/su18020692 - 9 Jan 2026
Abstract
Individual actions play a pivotal role in climate change, one of the most urgent global challenges, as daily behaviors generate substantial greenhouse gas emissions. Saudi Arabia, in particular, demonstrates its strong commitment to environmental sustainability through the Saudi Green Initiative and Middle East [...] Read more.
Individual actions play a pivotal role in climate change, one of the most urgent global challenges, as daily behaviors generate substantial greenhouse gas emissions. Saudi Arabia, in particular, demonstrates its strong commitment to environmental sustainability through the Saudi Green Initiative and Middle East Green Initiative, aiming for net-zero emissions by 2060 and advancing reforestation, land conservation, and renewable energy under Vision 2030. However, many Saudi individuals remain unaware of the environmental consequences of their choices, including transportation, energy consumption, and lifestyle habits. To address this gap, this study developed GreenKSA, the first Arabic-supported gamified mobile application designed to promote pro-environmental behavior within the Saudi culture. The app integrates gamification elements grounded in Self-Determination Theory (SDT) and Trans-Theoretical Model (TTM) in an attempt to bridge the gap between theory and practice. GreenKSA delivers multimedia content—short videos and infographics—demonstrating sustainable routines in households, workplaces, and mobility. The design and user experience of GreenKSA were evaluated in a pilot study of 10 participants. The results indicated high usability (SUS = 91.25) and a positive overall user experience. By combining theory-driven design with culturally relevant gamification elements, this study contributes to digital sustainability interventions and aligns with the global Sustainable Development Goals SDG 12: Responsible Consumption and Production, and SDG 13: Climate Action. Full article
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21 pages, 880 KB  
Review
Addressing Unmet Needs in Heart Failure with Preserved Ejection Fraction: Multi-Omics Approaches to Therapeutic Discovery
by Taemin Kim, Michael Sheen, Daniel Ryan and Jacob Joseph
Int. J. Mol. Sci. 2026, 27(2), 673; https://doi.org/10.3390/ijms27020673 - 9 Jan 2026
Abstract
Heart failure with preserved ejection fraction (HFpEF) accounts for about half of heart failure cases and is linked to aging, obesity, diabetes, and multimorbidity, yet disease-modifying therapies remain limited. A major barrier is heterogeneity: HFpEF comprises overlapping inflammatory, fibrotic, cardiometabolic, and hemodynamic/vascular endophenotypes [...] Read more.
Heart failure with preserved ejection fraction (HFpEF) accounts for about half of heart failure cases and is linked to aging, obesity, diabetes, and multimorbidity, yet disease-modifying therapies remain limited. A major barrier is heterogeneity: HFpEF comprises overlapping inflammatory, fibrotic, cardiometabolic, and hemodynamic/vascular endophenotypes embedded within systemic cardiorenal and cardiohepatic cross-talk, which conventional metrics such as left ventricular ejection fraction (LVEF), natriuretic peptides (NPs), and standard imaging capture incompletely. In this narrative review, we synthesize clinical, mechanistic, and trial data to describe HFpEF endophenotypes and their multi-organ interactions; critically appraise why traditional diagnostic and enrollment strategies contributed to neutral outcomes in landmark trials; and survey emerging cardiovascular multi-omics studies. We then outline an integrative systems-biology framework that applies (i) within-layer analyses and cross-layer integration, (ii) network-based driver nomination and biomarker discovery, and (iii) target nomination to link molecular programs with circulating markers and candidate therapies. Finally, we discuss practical challenges in implementing multi-omics HFpEF research and highlight future directions such as artificial intelligence (AI)-enabled multi-omics integration, cross-organ profiling, and biomarker-guided, endotype-enriched platform trials. Collectively, these advances position HFpEF as a proving ground for precision cardiology, in which therapies are matched to molecularly defined disease programs rather than ejection-fraction cutoffs alone. Full article
(This article belongs to the Special Issue Cardiovascular Research: From Molecular Mechanisms to Novel Therapies)
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25 pages, 4020 KB  
Article
Utility of a Digital PCR-Based Gene Expression Panel for Detection of Leukemic Cells in Pediatric Acute Lymphoblastic Leukemia
by Jesús García-Gómez, Dalia Ramírez-Ramírez, Rosana Pelayo, Octavio Martínez-Villegas, Lauro Fabián Amador-Medina, Juan Ramón González-García, Augusto Sarralde-Delgado, Luis Felipe Jave-Suárez and Adriana Aguilar-Lemarroy
Int. J. Mol. Sci. 2026, 27(2), 674; https://doi.org/10.3390/ijms27020674 - 9 Jan 2026
Abstract
Acute lymphoblastic leukemia (ALL) is a genetically heterogeneous disease where current clinical practice guidelines remain focused on traditional cytogenetic markers. Despite recent advances demonstrating excellent diagnostic accuracy for gene expression signatures, a discontinuity exists between biomarker validation and clinical implementation. This study aimed [...] Read more.
Acute lymphoblastic leukemia (ALL) is a genetically heterogeneous disease where current clinical practice guidelines remain focused on traditional cytogenetic markers. Despite recent advances demonstrating excellent diagnostic accuracy for gene expression signatures, a discontinuity exists between biomarker validation and clinical implementation. This study aimed to develop and validate a multiparametric gene expression signature using digital PCR (dPCR) to accurately diagnose pediatric ALL, with potential utility for monitoring measurable residual disease (MRD). We analyzed 130 bone marrow aspirates from pediatric patients from four clinical groups: non-leukemia, MRD-negative, MRD-positive and leukemia characterized by immunophenotype. Gene expression of an 8-gene panel (JUP, MYC, NT5C3B, GATA3, PTK7, CNP, ICOSLG, and SNAI1) was quantified by dPCR. The diagnostic performance of individual markers was assessed, and a Random Forest machine learning model was trained to classify active disease. The model was validated using a 5-fold stratified cross-validation approach. Individual markers, particularly JUP, MYC, and NT5C3B, showed good diagnostic accuracy for distinguishing leukemia from non-leukemia. However, integrating all eight markers into a multivariate Random Forest model significantly enhanced performance. The model achieved a mean cross-validated area under the curve (AUC) of 0.908 (±0.041) on receiver operator characteristic (ROC) analysis and 0.961 (±0.019) on Precision–Recall (PR) analysis, demonstrating high reliability and a favorable balance between sensitivity and precision. The integrated model achieved high sensitivity (88.9%) for detecting active disease, particularly at initial diagnosis. Although specificity was moderate (65.0%), the high positive predictive value (PPV 85.1%) and accuracy (81.5%) confirm the clinical utility of a positive result. While the panel showed promising performance for distinguishing MRD-positive from MRD-negative samples, the limited MRD-positive cohort size (n = 11) indicates that validation in larger MRD-focused studies is required before clinical implementation for treatment monitoring. This dPCR-based platform provides accessible, quantitative detection without requiring knowledge of clonal shifts or specific genomic landscape, offering potential advantages for resource-limited settings such as those represented in our Mexican pediatric cohort. Full article
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10 pages, 221 KB  
Article
Office-Based LA-BET Without Sedation or Nerve Block: Prospective Evaluation of a Simplified Local Anesthesia Protocol
by Cheng-Yu Hsieh, Yi-Fan Chou and Chuan-Jen Hsu
J. Clin. Med. 2026, 15(2), 543; https://doi.org/10.3390/jcm15020543 - 9 Jan 2026
Abstract
Background/Objectives: Balloon eustachian tuboplasty (BET) is an effective surgical option for obstructive eustachian tube dysfunction (OETD). However, the feasibility of performing BET under local anesthesia (LA) using simplified analgesic protocols remains underexplored. We examined the feasibility of a streamlined LA-BET protocol. Methods [...] Read more.
Background/Objectives: Balloon eustachian tuboplasty (BET) is an effective surgical option for obstructive eustachian tube dysfunction (OETD). However, the feasibility of performing BET under local anesthesia (LA) using simplified analgesic protocols remains underexplored. We examined the feasibility of a streamlined LA-BET protocol. Methods: Fifty patients (sixty-four ears) diagnosed with primary OETD between March 2024 and December 2025 were enrolled. All patients underwent BET under LA using intramuscular ketorolac and topical lidocaine gel without sedation or nerve blocks. Pain scores, blood pressure changes, and patient acceptance were analyzed for each patient; Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7) scores, tympanogram types, and Valsalva results were analyzed for each ear. All outcome measures were assessed 3 months postoperatively. Results: The mean ETDQ-7 score significantly improved from 24.9 ± 7.4 to 11.9 ± 5.4 (p < 0.001). The minimal clinically important difference (MCID ≥ 3.7) was achieved in 90.6% of ears, and normalization (ETDQ-7 ≤ 14.5) in 75.0%. The proportion of ears with positive Valsalva maneuvers increased from 39.1 to 76.6% (p < 0.01), and type A tympanograms improved from 64.1 to 84.4% (p = 0.018). Mean pain scores were 3.5 during insertion, 2.1 during balloon inflation, and 0.6 after deflation. All patients completed the procedure, and 96% would undergo LA again. Conclusions: LA-BET performed using intramuscular ketorolac and topical lidocaine gel is safe, tolerable, and effective. This protocol provides symptom relief and functional improvement without sedation or nerve block and offers a practical outpatient alternative for chronic OETD management. Full article
41 pages, 1895 KB  
Review
Mitochondrial Redox Vulnerabilities in Triple-Negative Breast Cancer: Integrative Perspectives and Emerging Therapeutic Strategies
by Alfredo Cruz-Gregorio
Metabolites 2026, 16(1), 60; https://doi.org/10.3390/metabo16010060 - 9 Jan 2026
Abstract
Breast cancer is a significant public health concern, with triple-negative breast cancer (TNBC) being the most aggressive subtype characterized by considerable heterogeneity and the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Currently, there [...] Read more.
Breast cancer is a significant public health concern, with triple-negative breast cancer (TNBC) being the most aggressive subtype characterized by considerable heterogeneity and the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Currently, there are no practical alternatives to chemotherapy, which is associated with a poor prognosis. Therefore, developing new treatments for TNBC is an urgent need. Reactive oxygen species (ROS) and redox adaptation play central roles in TNBC biology. Targeting the redox state has emerged as a promising therapeutic approach, as it is vital to the survival of tumors, including TNBC. Although TNBC does not produce high levels of ROS compared to ER- or PR-positive breast cancers, it relies on mitochondria and oxidative phosphorylation (OXPHOS) to sustain ROS production and create an environment conducive to tumor progression. As a result, novel treatments that can modulate redox balance and target organelles essential for redox homeostasis, such as mitochondria, could be promising for TNBC—an area not yet reviewed in the current scientific literature, thus representing a critical gap. This review addresses that gap by synthesizing current evidence on TNBC biology and its connections to redox state and mitochondrial metabolism, with a focus on innovative strategies such as metal-based compounds (e.g., copper, gold), redox nanoparticles that facilitate anticancer drug delivery, mitochondrial-targeted therapies, and immunomodulatory peptides like GK-1. By integrating mechanistic insights into the redox state with emerging therapeutic approaches, I aim to highlight new redox-centered opportunities to improve TNBC treatments. Moreover, this review uniquely integrates mitochondrial metabolism, redox imbalance, and emerging regulated cell-death pathways, including ferroptosis, cuproptosis, and disulfidptosis, within the context of TNBC metabolic heterogeneity, highlighting translational vulnerabilities and subtype-specific therapeutic opportunities. Full article
(This article belongs to the Special Issue Mitochondrial Metabolism, Redox State and Immunology in Cancer)
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17 pages, 2421 KB  
Article
SEM-Based Evaluation and Quantitative Validation of ICON Resin Infiltration in Sound Enamel: A Microinvasive Preventive Strategy in Orthodontics
by Alexandra Ecaterina Saveanu, Catalina Iulia Saveanu, Oana Dragos, Maria Sophia Saveanu and Daniela Anistoroaei
Prosthesis 2026, 8(1), 8; https://doi.org/10.3390/prosthesis8010008 - 9 Jan 2026
Abstract
Background: Resin infiltration has emerged as a micro-invasive strategy for managing enamel porosities, offering both therapeutic and aesthetic benefits. ICON® (DMG, Hamburg, Germany) is the most widely used system; however, evidence on its penetration behavior in sound enamel remains limited. Objectives: This [...] Read more.
Background: Resin infiltration has emerged as a micro-invasive strategy for managing enamel porosities, offering both therapeutic and aesthetic benefits. ICON® (DMG, Hamburg, Germany) is the most widely used system; however, evidence on its penetration behavior in sound enamel remains limited. Objectives: This in vitro study aimed to evaluate the penetration depth and morphological pattern of ICON resin infiltration in sound human enamel, using quantitative morphometric analysis and scanning electron microscopy (SEM). Methods: Fourteen freshly extracted, caries-free anterior teeth were sectioned longitudinally. ICON® resin infiltrate was applied to the buccal enamel surfaces according to the manufacturer’s protocol, while the lingual/palatal surfaces served as internal controls. Penetration depth was measured quantitatively on both mesial (surface A) and distal (surface B) halves, and SEM was used to assess resin–enamel interface morphology. Statistical analysis included the Shapiro–Wilk test, paired t-test, Pearson correlation, and percentage difference calculation. Results: The mean difference in penetration depth between surfaces A and B was −21.29 µm (p = 0.525), indicating no statistically significant variation. A strong positive correlation was observed between surfaces (r = 0.783, p = 0.001). The mean percentage difference was −3.57% (SD = 18.61%), suggesting minimal directional bias. SEM images confirmed continuous and homogeneous resin infiltration within enamel prisms. Post-hoc power analysis indicated 15.2% power, reflecting the impact of the limited sample size typical for SEM-based exploratory studies. Conclusions: Within the limitations of this in vitro investigation, ICON resin infiltration demonstrated uniform and consistent penetration in sound enamel, supported by both quantitative and SEM analyses. These findings validate its potential as a reliable preventive and micro-invasive biomaterial in dental practice, particularly for protecting enamel surfaces prior to orthodontic bracket bonding. Further clinical research with larger cohorts is recommended to confirm its long-term stability and prophylactic performance. Full article
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