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12 pages, 8504 KiB

Open AccessArticle

Altered Lactylation Myocardial Tissue May Contribute to a More Severe Energy-Deprived State of the Tissue and Left Ventricular Outflow Tract Obstruction in HOCM

by Ruoxuan Li, Jing Wang, Jia Zhao, Jiao Liu, Yuze Qin, Yue Wang, Yiming Yuan, Nan Kang, Lu Yao, Fan Yang, Ke Feng, Lanlan Zhang, Shengjun Ta, Bo Wang and Liwen Liu

Bioengineering 2025, 12(4), 379; https://doi.org/10.3390/bioengineering12040379 (registering DOI) - 3 Apr 2025

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiovascular disease. In general, obstructive hypertrophic cardiomyopathy (HOCM) is more closely related to severe clinical symptoms and adverse clinical outcomes. Therefore, it is necessary to explore the possible causes of HOCM, which may help physicians [...] Read more.

Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiovascular disease. In general, obstructive hypertrophic cardiomyopathy (HOCM) is more closely related to severe clinical symptoms and adverse clinical outcomes. Therefore, it is necessary to explore the possible causes of HOCM, which may help physicians better understand the disease and effectively control and manage the progression of the disease. In recent years, the discovery of lactylation has provided scholars with a new direction to explore the occurrence of diseases. In cardiovascular diseases, this post-translational modification can exacerbate cardiac dysfunction, and it can also promote the cardiac repair process after myocardial infarction. In this study, we used the myocardial tissue of mice carrying the Myh7 V878A gene mutation site for protein lactylation detection. Through a further analysis of the enriched pathways using KEGG enrichment, GO enrichment, and Wiki Pathways enrichment, we found that the enriched pathways with lactylation modifications in the HOCM mice mainly included the fatty acid oxidation pathway, the tricarboxylic acid cycle pathway, the adrenergic signaling pathway in cardiomyocytes, and the cardiomyocyte hypertrophy pathway. Among the above pathways, significant changes in lactylation occurred in proteins including Acads, Acaa2, Mdh2, Myl2, and Myl3. We used the COIP experiment to verify the omics results and the ELISA assay to verify the function of the enzymes. We found that a decrease in lactylation modifications also led to a decrease in enzyme function. The abnormalities of these proteins not only lead to abnormalities in energy metabolism in the myocardial tissue of HOCM but also may affect myocardial contractility, resulting in the impaired contractile function of HOCM. The results of this study lay a preliminary theoretical foundation for further exploring the pathogenesis of HOCM. Full article

(This article belongs to the Section Cellular and Molecular Bioengineering)

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11 pages, 269 KiB

Open AccessArticle

A Fractional Dirac System with Eigenparameter-Dependent and Transmission Conditions

by Abdullah Kablan and Fulya Şahantürk

Fractal Fract. 2025, 9(4), 227; https://doi.org/10.3390/fractalfract9040227 (registering DOI) - 3 Apr 2025

Abstract

This work investigates the fractional Dirac system that has transmission conditions, and its boundary condition contains an eigenparameter. Defining a convenient inner product space and a new operator that has the same eigenvalues as the considered problem, we demonstrate that the fractional Dirac [...] Read more.

This work investigates the fractional Dirac system that has transmission conditions, and its boundary condition contains an eigenparameter. Defining a convenient inner product space and a new operator that has the same eigenvalues as the considered problem, we demonstrate that the fractional Dirac system is symmetric in this space. Thus, we have reached some remarkable results for the spectral characteristics of the operator. Furthermore, in the next section of the study, the existence of solutions was examined. Full article

(This article belongs to the Special Issue Advances in Fractional Initial and Boundary Value Problems)

20 pages, 1878 KiB

Open AccessArticle

“I Want to Be Born with That Pronunciation”: Metalinguistic Comments About K-Pop Idols’ Inner Circle Accents

by Jihye Kim and Luoxiangyu Zhang

Languages 2025, 10(4), 75; https://doi.org/10.3390/languages10040075 (registering DOI) - 3 Apr 2025

Abstract

The Korean popular music (K-pop) industry, with its global popularity and increasing multilingual orientation, serves as a suitable context for exploring language perceptions. This research examines the metalinguistic commentary on K-pop idols’ English accents on YouTube. Specifically, we investigate how online users evaluate [...] Read more.

The Korean popular music (K-pop) industry, with its global popularity and increasing multilingual orientation, serves as a suitable context for exploring language perceptions. This research examines the metalinguistic commentary on K-pop idols’ English accents on YouTube. Specifically, we investigate how online users evaluate the idols’ English accents and how their metalinguistic comments communicate linguistic ideologies that favor a “native” way of speaking. Our dataset consists of 602 metalinguistic comments drawn from four popular YouTube videos featuring the evaluation of K-pop idols’ accents. We employ content analysis to first categorize comments into positive, negative, and neutral evaluations, then focus on aspects being evaluated in the users’ comments (e.g., social attractiveness and (non-)nativeness). The results indicate that a vast majority of comments (88.1%) convey positive evaluations, largely associating the idols’ accents with social appeal and native-like accents. Although a few neutral and negative evaluations exist, our result shows a dominant preference for inner circle accents and complex attitudes toward accented speech in digital spaces. We conclude by highlighting the influence of digital platforms in shaping language perceptions and the implications for linguistic stereotyping in the context of K-pop culture. Full article

(This article belongs to the Special Issue L2 Speech Perception and Production in the Globalized World)

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16 pages, 1118 KiB

Open AccessArticle

Amygdala EFP Neurofeedback Effects on PTSD Symptom Clusters and Emotional Regulation Processes

by Nadav Goldental, Raz Gross, Daniela Amital, Eiran V. Harel, Talma Hendler, Aron Tendler, Liora Levi, Dmitri Lavro, Tal Harmelech, Shulamit Grinapol, Nitsa Nacasch and Eyal Fruchter

J. Clin. Med. 2025, 14(7), 2421; https://doi.org/10.3390/jcm14072421 - 2 Apr 2025

Abstract

Background: Post-traumatic stress disorder (PTSD) manifests through distinct symptom clusters that can respond differently to treatments. Neurofeedback guided by the Amygdala-derived-EEG-fMRI-Pattern (Amyg-EFP-NF) has been utilized to train PTSD patients to regulate amygdala-related activity and decrease symptoms. Methods: We conducted a combined analysis of [...] Read more.

Background: Post-traumatic stress disorder (PTSD) manifests through distinct symptom clusters that can respond differently to treatments. Neurofeedback guided by the Amygdala-derived-EEG-fMRI-Pattern (Amyg-EFP-NF) has been utilized to train PTSD patients to regulate amygdala-related activity and decrease symptoms. Methods: We conducted a combined analysis of 128 PTSD patients from three clinical trials of Amyg-EFP-NF to evaluate effects across symptom clusters (as assessed by CAPS-5 subscales) and on emotion regulation processing (evaluated by the ERQ). Results: Amyg-EFP-NF significantly reduced severity across all PTSD symptom clusters immediately post-treatment, with improvements maintained at three-month follow-up. The arousal and reactivity cluster showed continued significant improvement during follow-up. Combined effect sizes were large (η²_p = 0.23–0.35) across all symptom clusters. Regression analysis revealed that emotion regulation processes significantly explained 17% of the variance in symptom improvement during the follow-up period. Conclusions: Reduction of PTSD symptoms following Amyg-EFP-NF occurs across all symptom clusters, with emotional regulation processes potentially serving as an underlying mechanism of action. These results support Amyg-EFP-NF as a comprehensive treatment approach for PTSD that continues to show benefits after treatment completion. Full article

(This article belongs to the Section Mental Health)

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17 pages, 2157 KiB

Open AccessArticle

Different Effects of Riociguat and Vericiguat on Pulmonary Vessels and Airways

by Katharina Nubbemeyer, Julia Krabbe, Svenja Böll, Anna Michely, Sebastian Kalverkamp, Jan Spillner and Christian Martin

Biomedicines 2025, 13(4), 856; https://doi.org/10.3390/biomedicines13040856 (registering DOI) - 2 Apr 2025

Abstract

Background/Objectives: Pulmonary hypertension is a progressive disease leading to right heart failure. One treatment strategy is to induce vasodilation via the nitric oxide–soluble guanylate cyclase–cyclic guanosine monophosphate (NO–sGC–cGMP) signaling pathway. There are currently two soluble guanylate cyclase stimulators on the market: Riociguat [...] Read more.

Background/Objectives: Pulmonary hypertension is a progressive disease leading to right heart failure. One treatment strategy is to induce vasodilation via the nitric oxide–soluble guanylate cyclase–cyclic guanosine monophosphate (NO–sGC–cGMP) signaling pathway. There are currently two soluble guanylate cyclase stimulators on the market: Riociguat and vericiguat, with vericiguat having a longer half-life and needing to be taken only once a day. This study investigated whether the pharmacological differences between the drugs affect pulmonary vessels and airways. Methods: The effects of vericiguat and riociguat on pulmonary arteries, veins, and airways were studied using rat precision-cut lung slices (PCLS). Vessels were pretreated with endothelin-1 and airways with serotonin. In isolated perfused lungs (IPL), the effects of sGC stimulation on pulmonary artery pressure (PAP), airway resistance, inflammatory cytokine, and chemokine release were quantified. Results: Riociguat and vericiguat caused pulmonary artery dilation in PCLS. During IPL, riociguat was more effective than vericiguat in reducing PAP with a statistically significant reduction of 10%. Both drugs were potent bronchodilators in preconstricted airways (p < 0.001). Only vericiguat reduced airway resistance during IPL, as shown here for the first time. Both drugs significantly reduced IL-6 and IL-1ß levels, while riociguat also reduced VEGF-A and KC-GRO levels. Conclusions: Riociguat and vericiguat had three main effects in the two rat ex-vivo models: They dilated the pulmonary arteries, induced bronchodilation, and reduced inflammation. These properties could make sGC stimulators useful for treating diseases associated with endothelial dysfunction. In the future, vericiguat may provide an alternative treatment to induce bronchodilation in respiratory diseases. Full article

(This article belongs to the Special Issue Cardiovascular Diseases: From Pathophysiology to Novel Therapeutic Approaches)

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19 pages, 1670 KiB

Open AccessReview

Bioelectric Membrane Potential and Breast Cancer: Advances in Neuroreceptor Pharmacology for Targeted Therapeutic Strategies

by Chitaranjan Mahapatra, Jineetkumar Gawad, Chandrakant Bonde and Mahesh B. Palkar

Receptors 2025, 4(2), 9; https://doi.org/10.3390/receptors4020009 - 2 Apr 2025

Abstract

Bioelectric membrane potentials regulate cellular growth, differentiation, and movement. Disruptions in bioelectric signaling are strongly linked to cancer development, as abnormal membrane potentials and ion channel activity can drive tumor progression. In breast cancer, ion channel dysfunction and neuroreceptor-related pathways play significant roles [...] Read more.

Bioelectric membrane potentials regulate cellular growth, differentiation, and movement. Disruptions in bioelectric signaling are strongly linked to cancer development, as abnormal membrane potentials and ion channel activity can drive tumor progression. In breast cancer, ion channel dysfunction and neuroreceptor-related pathways play significant roles in the cell cycle, epithelial–mesenchymal transition, angiogenesis, inflammation, the tumor microenvironment, and tumor progression. Neuroreceptors are critical not only in initiating and advancing cancer but also in conferring resistance to treatments. Neuroreceptors also play a key role, with dopamine receptor D2 activation reducing breast tumor growth by 40% in preclinical models, while serotonin signaling has been shown to promote epithelial–mesenchymal transition (EMT), increasing invasiveness. Advances in understanding these biological mechanisms could lead to more cost-effective and less invasive therapeutic strategies to treat tumors. This review explores the expanding evidence connecting bioelectric activity to breast cancer, focusing on neuroreceptor pharmacology as a transformative therapeutic approach. Examining the modulation of bioelectricity through neuroreceptor pharmacology to influence breast cancer progression and integrating these insights into therapeutic development offers a promising path for addressing treatment challenges and improving precision in managing aggressive cancer subtypes. Full article

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16 pages, 1885 KiB

Open AccessArticle

Administration of Polyphenol-Rich Sugarcane Extract Alleviates Deficits Induced by Amyloid-Beta_1–42 (Aβ_1–42) in Transgenic C. elegans

by Deniz Heydarian, Matthew Flavel, Mihiri Munasinghe, Markandeya Jois and Jency Thomas

J. Ageing Longev. 2025, 5(2), 12; https://doi.org/10.3390/jal5020012 - 2 Apr 2025

Abstract

Polyphenol-Rich Sugarcane Extract (PRSE), derived from Saccharum officinarum, demonstrates significant neuroprotective effects against amyloid-beta (Aβ_1–42)-induced deficits associated with Alzheimer’s disease (AD). This study utilized transgenic C. elegans expressing Aβ_1–42 to investigate PRSE’s impact on lifespan, sensory behavior, learning, memory, [...] Read more.

Polyphenol-Rich Sugarcane Extract (PRSE), derived from Saccharum officinarum, demonstrates significant neuroprotective effects against amyloid-beta (Aβ_1–42)-induced deficits associated with Alzheimer’s disease (AD). This study utilized transgenic C. elegans expressing Aβ_1–42 to investigate PRSE’s impact on lifespan, sensory behavior, learning, memory, and amyloid fibril accumulation. Supplementation with 5 mg/mL of PRSE extended the mean lifespan of Aβ_1–42 worms by 11% (17.78 ± 0.36 days) and reduced amyloid fibril levels by 34% in aged worms compared to untreated worms. PRSE also improved sensory behavior, with a 27% increase in naïve chemotaxis at day 8. Memory deficits were mitigated, with PRSE-treated worms showing 21% and 30% reductions in short-term associative memory loss after 1 h intervals on days 8 and 12, respectively. These improvements can be associated with the polyphenolic compounds in PRSE, which aid in reducing amyloid aggregation. The findings highlight PRSE’s potential as a dietary supplement to address AD-related symptoms and pathologies. Further studies are needed to understand its mechanisms and confirm its effectiveness in mammals, supporting its potential use as a natural preventative supplement for Alzheimer’s and related neurodegenerative diseases. Full article

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19 pages, 530 KiB

Open AccessReview

Essential Amino Acids and Fatty Acids in Novel Foods: Emerging Nutritional Sources and Implications

by Lucia Maddaloni, Lorenzo Maria Donini, Laura Gobbi, Luca Muzzioli and Giuliana Vinci

Dietetics 2025, 4(2), 14; https://doi.org/10.3390/dietetics4020014 - 2 Apr 2025

Abstract

Essential amino acids and essential fatty acids are vital nutrients that must be obtained from the diet. However, traditional sources face limitations amid increasing global food security and sustainability challenges. This study aims to evaluate the nutritional potential of novel foods, including microalgae [...] Read more.

Essential amino acids and essential fatty acids are vital nutrients that must be obtained from the diet. However, traditional sources face limitations amid increasing global food security and sustainability challenges. This study aims to evaluate the nutritional potential of novel foods, including microalgae (e.g., spirulina and chlorella), fungi (e.g., oyster and shiitake mushrooms), edible insects (e.g., mealworms and migratory locusts), and unconventional plants (e.g., water lentils and canihua). The study will compare their amino acid and fatty acid profiles with those of conventional animal and plant sources. The comparative analysis conducted in this study reveals that these innovative foods offer balanced and high-quality protein and lipid profiles, and contribute essential nutrients needed to prevent deficiencies and support metabolic health. Significantly, the integration of these novel foods into established dietary patterns, such as the Mediterranean diet, has the potential to enhance nutritional quality while promoting environmental sustainability. In conclusion, the adoption of these innovative food sources provides a viable strategy to meet nutritional demands and address global health and ecological challenges, paving the way toward a more resilient and sustainable food system. Full article

14 pages, 1829 KiB

Open AccessArticle

Nickel, Cu, Fe, Zn, and Se Accumulation, and the Antioxidant Status of Mushrooms Grown in the Arctic Under Ni/Cu Pollution and in Unpolluted Areas

by Nadezhda Golubkina, Uliana Plotnikova, Andrew Koshevarov, Evgeniya Sosna, Olga Hlebosolova, Natalia Polikarpova, Otilia Cristina Murariu, Alessio Vincenzo Tallarita and Gianluca Caruso

Stresses 2025, 5(2), 25; https://doi.org/10.3390/stresses5020025 - 2 Apr 2025

Abstract

Mushrooms play an important role in ecosystem sustainability and are highly valued in medicine and human nutrition. Using AAS and biochemical methods of analysis, the antioxidant status and mineral composition of seven mushroom species (Armillaria mellea, Xeromocus illudens, Leccinum aurantiacum [...] Read more.

Mushrooms play an important role in ecosystem sustainability and are highly valued in medicine and human nutrition. Using AAS and biochemical methods of analysis, the antioxidant status and mineral composition of seven mushroom species (Armillaria mellea, Xeromocus illudens, Leccinum aurantiacum, Leccinum scrabum, Lactarium pubescens, Rusula vesca, and Lycoperpon molle Pers.) gathered near the Pechenganikel smelting plant in the Pasvik Nature Reserve of the Murmansk region were evaluated. The concentrations of Ni and Cu in the fruiting bodies of mushrooms were in the ranges of 0.43–39.7 and 7.9–45.9 mg kg⁻¹ d.w., respectively. An unusually high biological concentration factor (BCF) for Ni, Cu, and Zn levels in mushrooms grown in soils with a low amount of these elements indicates the low suitability of the mentioned parameter for mushroom characteristics in territories with an uneven distribution of elements in soil. On the other hand, selenium (Se) showed high BCF levels, exceeding 1, for all mushrooms tested, with the highest values associated with L. saccatum (5.17) and the lowest values with A. mellea (1.36). A significant excess (3.4) of the Recommended Daily Allowance (RDA) level per 30 g of dry mushrooms was recorded for Ni in Russula vesca gathered 6 km from the Ni/Cu smelting plant, and 1.3 excess of the RDA was recorded in L. scrabum grown in the vicinity of the Shuonyoka waterfall. No RDA excess was revealed for Cu. Positive correlations between Se, polyphenol content, and total antioxidant activity (AOA) (r = 0.915–0.926; p < 0.001) and a negative correlation between Cu–Se and Cu–AOA in Leccinum species indicate the important role of antioxidant defense and Se, particularly in Arctic mushroom growth and survival, providing a specific protection of mushrooms against Cu toxicity. Full article

(This article belongs to the Collection Feature Papers in Plant and Photoautotrophic Stresses)

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11 pages, 1186 KiB

Open AccessArticle

Synthesis of Indole-Based Derivatives Containing Ammonium Salts, Diamines and Aminoureas for Organocatalysis

by Marcello Casertano, Brian G. Kelly, Malachi W. Gillick-Healy, Paolo Grieco and Mauro F. A. Adamo

Organics 2025, 6(2), 15; https://doi.org/10.3390/org6020015 - 2 Apr 2025

Abstract

Indole heterocycles have an established reactivity, and these compounds are H-bond donors via a peculiar non-basic NH. However, the indole core has been scarcely employed in organocatalysis, with only a few examples relevant to electrophilic halogenation reported. To expand the range of potential [...] Read more.

Indole heterocycles have an established reactivity, and these compounds are H-bond donors via a peculiar non-basic NH. However, the indole core has been scarcely employed in organocatalysis, with only a few examples relevant to electrophilic halogenation reported. To expand the range of potential transformations achievable via indole catalysis, we have designed a set of new organic species incorporating an indole core, alongside three privelaged chiral moieties found in many known organocatalysts, namely a quaternary ammonium salt, a diamine and an amino-urea. Herein, we report an optimised synthetic route for the preparation of these potential catalytic species in an enantiomerically pure form. The syntheses are conceived to be modular and therefore will allow each of the three single organic catalysts to be expanded into families without alteration of the synthetic layout, therefore leading to a fast optimisation of new asymmetric procedures. Full article

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13 pages, 393 KiB

Open AccessArticle

Explaining the Link Between Alcohol and Homicides: Insights from the Analysis of Legal Cases in Lithuania

by Laura Miščikienė, Justina Trišauskė, Mindaugas Štelemėkas and Kristina Astromskė

Medicina 2025, 61(4), 657; https://doi.org/10.3390/medicina61040657 - 2 Apr 2025

Abstract

Background and Objectives: Alcohol consumption has been a longstanding public health concern and known link to violence. The aims of this study were to analyze alcohol-related homicide cases in Lithuania, focusing on the prevalence of binge drinking among perpetrators and victims, the [...] Read more.

Background and Objectives: Alcohol consumption has been a longstanding public health concern and known link to violence. The aims of this study were to analyze alcohol-related homicide cases in Lithuania, focusing on the prevalence of binge drinking among perpetrators and victims, the situational and behavioral patterns leading to violence, and the legal outcomes of these cases. Materials and Methods: This study employed a retrospective analysis of court case law of criminal cases of the year 2019. The analysis was conducted by combining qualitative and quantitative analytical approaches. Results: The findings revealed that 84.6% of homicides occurred during binge drinking events. Alcohol intoxication was prevalent among both perpetrators (92.3%) and victims (86.5%), emphasizing the dual role of alcohol in homicide cases. Interpersonal violence was the primary pattern of homicide (78.8%), while planned homicides accounted for 21.2%. Thematic content analysis of the cases revealed that Lithuanian courts consistently regard alcohol consumption as an aggravating factor that contributes to the commission of violent crimes and influences the severity of criminal punishment. This reflects a judicial position that voluntary intoxication does not lessen legal responsibility, despite its effects on impairing judgment, heightening aggression and impulsivity, and escalating conflicts into deadly violence. Conclusions: Our findings revealed that the majority of alcohol-involved homicides occurred during binge drinking events, in a domestic environment, and because of unplanned acts of interpersonal violence. Targeted public health interventions should focus on strengthening alcohol control policies and enforcing stricter regulations to discourage binge drinking environments. Full article

(This article belongs to the Special Issue Advances in Health, Lifestyle and Environmental Risk Factors Monitoring)

19 pages, 1018 KiB

Open AccessArticle

Mode Decomposition Bi-Directional Long Short-Term Memory (BiLSTM) Attention Mechanism and Transformer (AMT) Model for Ozone (O₃) Prediction in Johannesburg, South Africa

by Israel Edem Agbehadji and Ibidun Christiana Obagbuwa

Forecasting 2025, 7(2), 15; https://doi.org/10.3390/forecast7020015 - 2 Apr 2025

Abstract

This paper presents a model that combines mode decomposition approaches with a bi-directional long short-term memory (BiLSTM) attention mechanism and a transformer (AMT) to predict the concentration level of ozone (O₃) in Johannesburg, South Africa. Johannesburg is a densely populated city [...] Read more.

This paper presents a model that combines mode decomposition approaches with a bi-directional long short-term memory (BiLSTM) attention mechanism and a transformer (AMT) to predict the concentration level of ozone (O₃) in Johannesburg, South Africa. Johannesburg is a densely populated city and the industrial and economic hub of South Africa. Being the industrial hub, air pollution is a major concern as it affects human health. Using air pollutants and meteorological datasets, a model was proposed that uses a mode decomposition approach to address the nonlinear nature of O₃concentration. This nonlinearity is one of the most challenging issues in air quality prediction, and this study proposed a model to decompose input data and identify the most relevant features and leverage attention mechanisms to produce weighted parameters that can enhance the model’s performance. The model’s performance enhancement approach was aimed at ensuring an effective model that easily adapts to frequently changing pollutant data in air quality prediction. The performance was evaluated statistically with root mean squared error (RMSE), mean absolute error (MAE), and mean square error (MSE). The proposed EEMD-CEEMDAN-BiLSTM-AMT model produced the most optimal result with MSE (4.80 × 10⁻⁶), RMSE (0.002), and MAE (0.001). When compared with the other similar models, the proposed model was best in terms of MSE value. Future work seeks to enhance the proposed model to fine-tune its performance on different air pollutant concentrations in South Africa. Full article

(This article belongs to the Section Environmental Forecasting)

20 pages, 4739 KiB

Open AccessPerspective

LLM Fine-Tuning: Concepts, Opportunities, and Challenges

by Xiao-Kun Wu, Min Chen, Wanyi Li, Rui Wang, Limeng Lu, Jia Liu, Kai Hwang, Yixue Hao, Yanru Pan, Qingguo Meng, Kaibin Huang, Long Hu, Mohsen Guizani, Naipeng Chao, Giancarlo Fortino, Fei Lin, Yonglin Tian, Dusit Niyato and Fei-Yue Wang

Big Data Cogn. Comput. 2025, 9(4), 87; https://doi.org/10.3390/bdcc9040087 - 2 Apr 2025

Abstract

As a foundation of large language models, fine-tuning drives rapid progress, broad applicability, and profound impacts on human–AI collaboration, surpassing earlier technological advancements. This paper provides a comprehensive overview of large language model (LLM) fine-tuning by integrating hermeneutic theories of human comprehension, with [...] Read more.

As a foundation of large language models, fine-tuning drives rapid progress, broad applicability, and profound impacts on human–AI collaboration, surpassing earlier technological advancements. This paper provides a comprehensive overview of large language model (LLM) fine-tuning by integrating hermeneutic theories of human comprehension, with a focus on the essential cognitive conditions that underpin this process. Drawing on Gadamer’s concepts of Vorverständnis, Distanciation, and the Hermeneutic Circle, the paper explores how LLM fine-tuning evolves from initial learning to deeper comprehension, ultimately advancing toward self-awareness. It examines the core principles, development, and applications of fine-tuning techniques, emphasizing its growing significance across diverse field and industries. The paper introduces a new term, “Tutorial Fine-Tuning (TFT)”, which annotates a process of intensive tuition given by a “tutor” to a small number of “students”, to define the latest round of LLM fine-tuning advancements. By addressing key challenges associated with fine-tuning, including ensuring adaptability, precision, credibility and reliability, this paper explores potential future directions for the co-evolution of humans and AI. By bridging theoretical perspectives with practical implications, this work provides valuable insights into the ongoing development of LLMs, emphasizing their potential to achieve higher levels of cognitive and operational intelligence. Full article

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22 pages, 1424 KiB

Open AccessGuidelines

Cystic Fibrosis Newborn Screening: A Systematic Review-Driven Consensus Guideline from the United States Cystic Fibrosis Foundation

by Meghan E. McGarry, Karen S. Raraigh, Philip Farrell, Faith Shropshire, Karey Padding, Cambrey White, M. Christine Dorley, Steven Hicks, Clement L. Ren, Kathryn Tullis, Debra Freedenberg, Q. Eileen Wafford, Sarah E. Hempstead, Marissa A. Taylor, Albert Faro, Marci K. Sontag and Susanna A. McColley

Int. J. Neonatal Screen. 2025, 11(2), 24; https://doi.org/10.3390/ijns11020024 - 2 Apr 2025

Abstract

Newborn screening for cystic fibrosis (CF) has been universal in the US since 2010; however, there is significant variation among newborn screening algorithms. Systematic reviews were used to develop seven recommendations for newborn screening program practices to improve timeliness, sensitivity, and equity in [...] Read more.

Newborn screening for cystic fibrosis (CF) has been universal in the US since 2010; however, there is significant variation among newborn screening algorithms. Systematic reviews were used to develop seven recommendations for newborn screening program practices to improve timeliness, sensitivity, and equity in diagnosing infants with CF: (1) The CF Foundation recommends the use of a floating immunoreactive trypsinogen (IRT) cutoff over a fixed IRT cutoff; (2) The CF Foundation recommends using a very high IRT referral strategy in CF newborn screening programs whose variant panel does not include all CF-causing variants in CFTR2 or does not have a variant panel that achieves at least 95% sensitivity in all ancestral groups within the state; (3) The CF Foundation recommends that CF newborn screening algorithms should not limit CFTR variant detection to the F508del variant or variants included in the American College of Medical Genetics-23 panel; (4) The CF Foundation recommends that CF newborn screening programs screen for all CF-causing CFTR variants in CFTR2; (5) The CF Foundation recommends conducting CFTR variant screening twice weekly or more frequently as resources allow; (6) The CF Foundation recommends the inclusion of a CFTR sequencing tier following IRT and CFTR variant panel testing to improve the specificity and positive predictive value of CF newborn screening; (7) The CF Foundation recommends that both the primary care provider and the CF specialist be notified of abnormal newborn screening results. Through implementation, it is anticipated that these recommendations will result in improved sensitivity, equity, and timeliness of CF newborn screening, leading to improved health outcomes for all individuals diagnosed with CF following newborn screening and a decreased burden on families. Full article

(This article belongs to the Special Issue Advances in Cystic Fibrosis Newborn Screening: From Laboratory Testing to Diagnosis)

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21 pages, 3233 KiB

Open AccessArticle

Mitigating Settlement and Enhancing Bearing Capacity of Adjacent Strip Footings Using Sheet Pile Walls: An Experimental Approach

by Ali M. Basha, Ahmed Yousry Akal and Mohamed H. Zakaria

Infrastructures 2025, 10(4), 83; https://doi.org/10.3390/infrastructures10040083 - 2 Apr 2025

Abstract

In construction, closely spaced footings cause stress interactions that impact bearing capacity, settlement, and stability. This study experimentally evaluates the role of sheet pile walls (SPWs) in improving the performance of two adjacent strip footings—an existing footing and a newly placed footing—on sandy [...] Read more.

In construction, closely spaced footings cause stress interactions that impact bearing capacity, settlement, and stability. This study experimentally evaluates the role of sheet pile walls (SPWs) in improving the performance of two adjacent strip footings—an existing footing and a newly placed footing—on sandy soil. The influence of SPW penetration depth (L_s) and center-to-center spacing between footings (X) on settlement and bearing resistance under vertical loads was investigated. Experiments were conducted in a large-scale soil tank (330 × 30 cm, depth 210 cm), with X ranging from 300 mm to 1000 mm and SPW lengths varying from 0 mm to 1500 mm. The results show that SPWs significantly enhance foundation performance by reducing settlement and increasing bearing capacity. When L_s/B = 6, the settlement of the new footing (F₁) decreases by 48%, while the existing footing (F₂) sees reductions of 47%, 67%, and 77% at L_s/B = 3, 4, and 5, respectively, under 500 kN/m² stress. The bearing capacity of F1 increases by 53% when X = 300 mm, demonstrating strong interference effects. Conversely, the F₂ settlement increases as X decreases, with a 96% rise at X = 300 mm, but it stabilizes at L_s/B = 5. SPWs also shift failure from general shear to punching shear, modifying soil–structure interaction. These findings highlight the effectiveness of SPWs in mitigating settlement, enhancing load-bearing capacity, and optimizing foundation design in closely spaced footing systems. The results suggest that an SPW length-to-footing width ratio (L_s/B) between 4 and 5 is optimal for minimizing settlement and improving stability, with only a slight difference in effectiveness between these two ratios. Full article

(This article belongs to the Section Infrastructures and Structural Engineering)

12 pages, 1604 KiB

Open AccessArticle

Trends in Bicycle Accidents and Injury Analysis in Poland: Insights from 2016 to 2023

by Sebastian Glowinski, Szymon Rzepczyk and Maciej Obst

Safety 2025, 11(2), 32; https://doi.org/10.3390/safety11020032 - 2 Apr 2025

Abstract

Bicycle safety remains a critical concern as cycling gains popularity, especially in urban areas where traffic conditions pose significant risks. The increasing presence of bicycles and derivatives of them further complicates traffic dynamics, raising the potential for accidents and injuries. This study examines [...] Read more.

Bicycle safety remains a critical concern as cycling gains popularity, especially in urban areas where traffic conditions pose significant risks. The increasing presence of bicycles and derivatives of them further complicates traffic dynamics, raising the potential for accidents and injuries. This study examines bicycle accident trends in Poland from 2016 to 2023 using data provided by the Polish Police, supplemented with medical insights on injury mechanisms. The analysis highlights key patterns, such as the higher incidence of accidents during summer, fewer accidents on weekends compared to weekdays, and the disproportionate fatality rate among cyclists over 60. Failure to yield the right of way emerges as a leading cause of accidents. These findings underscore the need for a multifaceted approach to improving cyclist safety, including infrastructural enhancements, public education, stricter enforcement of traffic laws, and advancements in medical response and protective gear. Addressing these factors can contribute to a safer environment that supports the continued growth of sustainable and active transportation. Full article

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14 pages, 648 KiB

Open AccessArticle

Study on Decomposition Characteristics of Early Spring Ephemeral Plant Litter in Various Forest Types

by Qiang Liu, Jinping Zheng and Chunnan Fan

Horticulturae 2025, 11(4), 382; https://doi.org/10.3390/horticulturae11040382 - 2 Apr 2025

Abstract

In terrestrial ecosystems, the decomposition of early spring ephemeral plant litter (ESPL for short) is one of the important processes in the carbon and nutrient cycles during the early spring stage. The current study focused on four typical spring ephemeral plant species in [...] Read more.

In terrestrial ecosystems, the decomposition of early spring ephemeral plant litter (ESPL for short) is one of the important processes in the carbon and nutrient cycles during the early spring stage. The current study focused on four typical spring ephemeral plant species in three forest types of Northeast China and investigated the decomposition characteristics of herb litters, using litterbag decomposition experiments. The study results indicate that the mass loss rate of ESPL decomposition after 50 days can be as high as 73.15% to 80.44%. Throughout the entire decomposition period, there is a significant correlation between the decomposition of ESPL and time, with initial decomposition relatively fast and later decomposition slowing down. Overall, Hylomecon japonicum exhibits slightly faster decomposition, and Cardamine leucantha decomposes relatively slowly, while Cardamine leucantha shows the highest mass loss rate in the first 10 days, reaching 38.71%. The mass loss rates of the four types of ESPL are significantly correlated with the litter nutrient conditions, as are the stage-specific mass loss rates. Furthermore, there are distinct differences in the nutrient composition affecting the decomposition of different types of ESPL. Across different forest stands, influenced by different decomposition environments, such as soil conditions, the decomposition of ESPL is fastest in the deciduous broad-leaved forest, with decomposition reaching 50% and 95% in only 15–18 days and 63–88 days, respectively. In the broad-leaved forest, it takes 18–23 days and 78–110 days, while, in the birch forest, it takes 22–32 days and 99–136 days. Full article

(This article belongs to the Section Floriculture, Nursery and Landscape, and Turf)

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4 pages, 1202 KiB

Open AccessEditorial

Biological Attachment Systems and Biomimetics—In Memory of William Jon P. Barnes

by Thies H. Büscher and Stanislav N. Gorb

Biomimetics 2025, 10(4), 220; https://doi.org/10.3390/biomimetics10040220 - 2 Apr 2025

Abstract

Any system preventing the separation of two surfaces may be defined as an attachment system [...] Full article

(This article belongs to the Special Issue Biological Attachment Systems and Biomimetics)

20 pages, 2119 KiB

Open AccessArticle

Experimental Investigations of Capillary Flow in Three-Dimensional-Printed Microchannels

by Behrouz Pirouz, Seyed Navid Naghib, Diamante Chirillo, Hana Javadi Nejad and Patrizia Piro

Fluids 2025, 10(4), 91; https://doi.org/10.3390/fluids10040091 - 2 Apr 2025

Abstract

In recent years, the application of microfluidic devices has increased, and three-dimensional (3D) printers for fabricating microdevices could be considered a suitable technique but, in some cases, may confront some issues. The main issues include channel roughness values, print orientation due to the [...] Read more.

In recent years, the application of microfluidic devices has increased, and three-dimensional (3D) printers for fabricating microdevices could be considered a suitable technique but, in some cases, may confront some issues. The main issues include channel roughness values, print orientation due to the 3D printer’s setup, filament materials, nozzle specifications, and condition. This study aims to analyze the capillary-driven flow in microdevices produced by 3D printers. Therefore, four 3D printer-based microchannels were investigated, and the capillary-driven flow of five liquids with different viscosities and contact angles was evaluated experimentally. The experimental results were compared with theoretical calculations using the Lucas−Washburn equation, and the impact of the width, length, and closed and open microchannel on flow behaviors was explored. The experimental results showed that the peak velocity for open and closed microchannels decreases with the length. Moreover, there were differences in flow behavior between open and closed microchannels. For the former, the maximum average velocity appeared in the microchannel with a width of 400 μm, while for the latter, it was for a width of 1000 μm. In addition, the flow velocity decreased when the viscosity increased, regardless of microchannel width. The decrease was more pronounced for the lower-viscosity liquids (ethanol and water) and smaller for the higher-viscosity ones (coffee and olive oil). Finally, the advantages and challenges of 3D printer-based microdevices are presented. Full article

12 pages, 753 KiB

Open AccessArticle

A Laboratory-Developed Assay for the Simultaneous Detection of Aspergillus fumigatus and Pneumocystis jirovecii Pulmonary Pathogens

by Margherita Cacaci, Debora Talamonti, Giulia Menchinelli, Damiano Squitieri, Riccardo Torelli, Elena De Carolis, Giulia De Angelis, Maurizio Sanguinetti and Brunella Posteraro

J. Fungi 2025, 11(4), 280; https://doi.org/10.3390/jof11040280 - 2 Apr 2025

Abstract

Invasive fungal diseases are a significant threat in immunocompromised patients, underscoring the need for rapid and accurate diagnostics. This study describes the development and validation of a real-time PCR-based laboratory-developed assay (LDA) on the Panther Fusion system for the simultaneous detection of Aspergillus [...] Read more.

Invasive fungal diseases are a significant threat in immunocompromised patients, underscoring the need for rapid and accurate diagnostics. This study describes the development and validation of a real-time PCR-based laboratory-developed assay (LDA) on the Panther Fusion system for the simultaneous detection of Aspergillus fumigatus (AF) and Pneumocystis jirovecii (PJ) in bronchoalveolar lavage fluid (BALF) samples. The assay was evaluated using 239 clinical BALF samples, including cases confirmed positive for AF or PJ by reference mycological methods. Rigorous optimization ensured compatibility with the automated workflow of the Panther Fusion system, which addresses challenges such as BALF viscosity and fungal DNA recovery. No cross-reactivity with non-target fungal species was observed, and the assay demonstrated high analytical sensitivity and specificity. Only two false-negative results were reported, which could plausibly be reclassified as true negatives when interpreted alongside the serum beta-d-glucan and galactomannan assay results. For PJ detection, the assay showed excellent concordance with the OLM PneumID assay, supporting its reliability in clinical settings. The dual-target approach facilitates the simultaneous detection of both pathogens within a single workflow, improving diagnostic efficiency. The AF/PJ LDA represents a robust and scalable alternative to existing molecular assays, with the potential to enhance routine diagnostics for pulmonary fungal infections. Full article

(This article belongs to the Special Issue Diagnosis of Human Pathogenic Fungi)

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12 pages, 2093 KiB

Open AccessArticle

Subtraction CT Angiography for the Evaluation of Lower Extremity Artery Disease with Severe Arterial Calcification

by Ryoichi Tanaka and Kunihiro Yoshioka

J. Cardiovasc. Dev. Dis. 2025, 12(4), 131; https://doi.org/10.3390/jcdd12040131 - 2 Apr 2025

Abstract

(1) Background: Peripheral arterial CT angiography (CTA) is an alternative to conventional angiography for diagnosing lower extremity artery disease (LEAD). However, severe arterial calcifications often hinder accurate assessment of arterial stenosis. This study evaluated the diagnostic performance of subtraction CTA with volume position [...] Read more.

(1) Background: Peripheral arterial CT angiography (CTA) is an alternative to conventional angiography for diagnosing lower extremity artery disease (LEAD). However, severe arterial calcifications often hinder accurate assessment of arterial stenosis. This study evaluated the diagnostic performance of subtraction CTA with volume position matching compared to conventional CTA, using invasive digital subtraction angiography (DSA) as the gold standard. (2) Methods: Thirty-two patients with LEAD (mean age: 69.6 ± 10.8 years; M/F = 28:4) underwent subtraction CTA and DSA. The arterial tree was divided into 20 segments per patient, excluding segments with a history of bypass surgery. Subtraction was performed separately for each limb using volume position matching. Maximum intensity projections were reconstructed from both conventional and subtraction CTA data. Percent stenosis per arterial segment was measured using calipers and compared with DSA. Segments were classified as stenotic (> 50% luminal narrowing) or not, with heavily calcified or stented segments assigned as incorrect. (3) Results: Of 640 segments, 636 were analyzed. Subtraction CTA and conventional CTA left 13 (2.0%) and 160 (25.2%) segments uninterpretable, respectively. Diagnostic accuracies (accuracy, precision, recall, macro F1 score) for subtraction CTA were 0.885, 0.884, 0.936, and 0.909, compared to 0.657, 0.744, 0.675, and 0.708 for conventional CTA. (4) Conclusions: Subtraction CTA with volume position matching is feasible and achieves high diagnostic accuracy in patients with severe calcific sclerosis. Full article

(This article belongs to the Special Issue Clinical Applications of Cardiovascular Computed Tomography (CT))

11 pages, 569 KiB

Open AccessReview

Cerebral and Spinal Cord Protection Strategies in Aortic Arch Surgery

by Andrea Myers, Ciprian Nita and Guillermo Martinez

J. Cardiovasc. Dev. Dis. 2025, 12(4), 130; https://doi.org/10.3390/jcdd12040130 - 2 Apr 2025

Abstract

Perioperative management of patients undergoing surgeries of the aortic arch is challenging. This cohort of patients has a high risk of poor neurological outcomes both as a consequence of the disease process as well as the methods employed during surgical management. Many strategies [...] Read more.

Perioperative management of patients undergoing surgeries of the aortic arch is challenging. This cohort of patients has a high risk of poor neurological outcomes both as a consequence of the disease process as well as the methods employed during surgical management. Many strategies have been put forward to ameliorate these complications; however, maintaining cerebral and spinal cord perfusion and reducing metabolic oxygen demand is the core principle of these strategies. Moderate hypothermia and selective ante-grade perfusion are the most promising methods that provide the best conditions for the competing requirements of both the brain and spinal cord. Intraoperative and postoperative monitoring is essential for early detection and intervention in delayed spinal cord ischaemia and stroke. In this article we aim to discuss the current methods of neuroprotection and spinal cord protection in aortic arch surgery and stenting. Full article

(This article belongs to the Special Issue Current Status and Future Challenges of Aortic Arch Surgery)

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11 pages, 2248 KiB

Open AccessArticle

Pathology of Free-Living Loggerhead Turtle (Caretta caretta) Embryos on the Island of Linosa (Italy)

by Frine Eleonora Scaglione, Matteo Cuccato, Erica Longato, Paola Pregel, Daniele Zucca, Stefano Nannarelli, Alessandra De Lucia, Marco Pilia, Elisabetta Manuali, Marco Gobbi, Enrico Bollo and Simonetta Appino

Vet. Sci. 2025, 12(4), 328; https://doi.org/10.3390/vetsci12040328 - 2 Apr 2025

Abstract

On the beach of Linosa Island (Italy), 43 loggerhead sea turtle (Caretta caretta) unhatched eggs were recovered from nests, formalin-fixed and necropsied. The tissue samples were stained with hematoxylin-eosin (HE), Grocott, von Kossa, periodic acid-Schiff (PAS), and Movat pentachrome stains. Histologically, [...] Read more.

On the beach of Linosa Island (Italy), 43 loggerhead sea turtle (Caretta caretta) unhatched eggs were recovered from nests, formalin-fixed and necropsied. The tissue samples were stained with hematoxylin-eosin (HE), Grocott, von Kossa, periodic acid-Schiff (PAS), and Movat pentachrome stains. Histologically, vacuolar degeneration (100.0%) and increased numbers of melanomacrophages (18.6%) in the liver, and edema (14.0%) in the lungs were observed. Twenty-five kidneys (58.1%) showed deposition of blue amorphous material with HE staining, which also appeared PAS-positive and black with von Kossa staining, allowing a diagnosis of calcium oxalate, confirmed by transmission electron microscopy (TEM). The hepatic lesions may be indicative of toxicosis, infection, or a defense mechanism. A statistically significant association between the nest position and renal oxalosis (renal calcium oxalate deposition) was observed. Renal oxalosis was probably due to the exceptionally high summer temperatures, which were statistically higher compared to the temperatures recorded in the previous two years. Full article

(This article belongs to the Section Anatomy, Histology and Pathology)

16 pages, 2506 KiB

Open AccessArticle

Development of Multiple Real-Time Fluorescent Quantitative PCR for Vibrio Pathogen Detection in Aquaculture

by Binzhe Zhang, Yulie Qiu, Chenxi Shi and Jian Zhang

Vet. Sci. 2025, 12(4), 327; https://doi.org/10.3390/vetsci12040327 - 2 Apr 2025

Abstract

The Vibrio genus represents a critical group of bacterial pathogens in the marine environment globally, leading to massive mortality in the aquaculture industry. Diagnosing vibriosis, an infection caused by Vibrio species, in clinical samples poses challenges due to its non-specific clinical manifestations. In [...] Read more.

The Vibrio genus represents a critical group of bacterial pathogens in the marine environment globally, leading to massive mortality in the aquaculture industry. Diagnosing vibriosis, an infection caused by Vibrio species, in clinical samples poses challenges due to its non-specific clinical manifestations. In this study, we developed a TaqMan probe-based multiplex real-time PCR method for the simultaneous detection and quantification of four Vibrio pathogens: Vibrio anguillarum (Va), Vibrio alginolyticus (Val), Vibrio harveyi (Vh), and Vibrio scophthalmi (Vsc). The assay targets conserved intra-species regions and specific inter-species regions using specific primers and TaqMan probes to ensure specificity. Sensitivity analysis demonstrated that the multiplex real-time PCR assay could simultaneously detect the four different bacteria, with detection limits of 26–60 copies per reaction, making it 100 times more sensitive than conventional PCR assays. Additionally, the assay exhibited high reproducibility, with intra- and inter-group coefficients of variation below 1.4%. A total of 63 clinical samples was analyzed using this established assay, which successfully detected both single and mixed infections. These results demonstrate that the multiplex quantitative PCR assay is a rapid, specific, and sensitive diagnostic tool for the detection of Va, Val, Vh, and Vsc, making it suitable for monitoring these bacteria in both single- and co-infected clinical samples. Full article

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19 pages, 2733 KiB

Open AccessArticle

Evaluating the Potential of Roof Water Harvesting System for Drinking Water Supplies During Emergencies Under the Impacts of Climate Change: ‘A Case Study of Swat District, Pakistan’

by Shamaima Wafa Qammar, Fayaz Ahmad Khan and Rashid Rehan

Standards 2025, 5(2), 11; https://doi.org/10.3390/standards5020011 - 2 Apr 2025

Abstract

It is well understood that climate change is a major cause of the environmental shifts that are significantly impacting human lives. The floods caused by climate change are not only occurring more frequently each year, but they also bring up the problem of [...] Read more.

It is well understood that climate change is a major cause of the environmental shifts that are significantly impacting human lives. The floods caused by climate change are not only occurring more frequently each year, but they also bring up the problem of access to clean water for drinking and other daily usage for the affected communities. The Swat district of the Khyber Pakhtunkhwa province in Pakistan is one of the impacted regions and the growing concern for clean water access is yet to be resolved. This study aims to propose a sustainable solution to water access during the emergencies, particularly in flood and drought situations. While the roof water harvesting system (RWHS) is well established and functional in many developed regions, its potential remains underexplored in Pakistan. This research study analyzed the climate change projection data for the Saidu Sharif region of Swat. The regional climate data are gathered from the Shared Socio-economic Pathways (SSPs) for the period from 2015 to 2045. Five general circulation models (GCMs) were selected based on their performance in South Asian climate simulations. Analysis of the regional forecasted climate data indicates that almost all of the five climate models have predicted the periods of excessive rainfall to occur in the months of July, August, and September, while prolonged dry seasons may last between 271 and 325 days annually. Hydrological modeling was used to estimate RWHS performance, which incorporated the key parameters such as catchment area, runoff coefficient, and rainfall intensity. The findings suggest that the proposed RWHS could meet basic drinking water needs during the floods and even during the drought periods near around 100% satisfaction of water demand under certain conditions. For example, for an average drought period of 273 days, a household of seven people with a per capita daily water demand of 17 L requires a storage capacity of 33

m^{3}

. On the other hand, for a maximum drought duration of 325 days, the required storage volume increases to 39

m^{3}

. Demand satisfaction calculations are also used to evaluate the effectiveness of the proposed model. This research contributes to addressing the growing water scarcity challenge posed by climate change in the Swat region and offers a sustainable and practical solution. Full article

(This article belongs to the Special Issue Sustainable Development Standards)

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