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Search Results (3,466)

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Keywords = activity recognition (AR)

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20 pages, 853 KB  
Article
Transition from Paediatric to Adult Care in Congenital Heart Disease: A Call for Action
by Fabiola Boccuto, Rosaria Barracano, Giulia Guglielmi, Anamaria Mihailescu, Martina Avesani, Elettra Pomiato, Pierfrancesco Montanaro, Gabriele De Palma, Berardo Sarubbi, Antonella Bruna Cutrì, Jolanda Sabatino, Massimo Chessa, Gianfranco Butera and Claudia Montanaro
J. Clin. Med. 2025, 14(24), 8869; https://doi.org/10.3390/jcm14248869 - 15 Dec 2025
Abstract
Background: Transition from paediatric to adult care in congenital heart disease (CHD) represents a pivotal and vulnerable phase that critically influences long-term survival, morbidity, and quality of life. Advances in paediatric cardiology and surgery have generated a rapidly growing population of adults with [...] Read more.
Background: Transition from paediatric to adult care in congenital heart disease (CHD) represents a pivotal and vulnerable phase that critically influences long-term survival, morbidity, and quality of life. Advances in paediatric cardiology and surgery have generated a rapidly growing population of adults with congenital heart disease who exhibit complex, lifelong, and multidisciplinary needs. However, survival does not equate to cure, and discontinuity of care during adolescence remains a major predictor of adverse outcomes. Despite widespread recognition of their importance, transition programmes are heterogeneous worldwide, and standardised, evidence-based protocols are missing. Objective: This review calls for action acknowledging the urgent need for structured and standardised transition programmes in CHD care, integrating the key elements that should be addressed in any programme to optimise outcomes. Content: Transition should be understood as a multidisciplinary, longitudinal process integrating medical management, patient and family education, psychological preparation, and societal inclusion. Core domains include tailored physical activity, nutritional counselling, cardiovascular risk factor management, infective endocarditis prevention, reproductive health, psychosocial support, and engagement of primary care providers, educators, and employers. Evidence demonstrates that structured transition programmes enhance health literacy, adherence, and self-management, while reducing loss to follow-up. The active involvement of primary care providers, psychologists, educators, and employers is essential to sustain holistic and equitable care. Conclusions: Transition should be reframed as an essential, lifelong component of CHD care. The development and implementation of standardised, multidisciplinary, evidence-based transition protocols are urgently required to ensure continuity, empower patients, and optimise long-term clinical and psychosocial outcomes for adults with CHD. Full article
(This article belongs to the Special Issue Clinical Management of Pediatric Heart Diseases)
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21 pages, 3233 KB  
Review
Synthetic Pentatricopeptide Repeat Proteins: Building a Toolkit for Precise RNA Control
by Jose M. Lombana, Maureen R. Hanson and Stephane Bentolila
Int. J. Mol. Sci. 2025, 26(24), 12033; https://doi.org/10.3390/ijms262412033 - 14 Dec 2025
Viewed by 43
Abstract
In plants, cytidine-to-uridine (C-to-U) and uridine-to-cytidine (U-to-C) editing events are directed by pentatricopeptide repeat (PPR) proteins, modular RNA-binding factors that recognize their RNA targets through a predictable amino acid–nucleotide recognition code. Deciphering this code has enabled the rational design of synthetic PPR (synPPR) [...] Read more.
In plants, cytidine-to-uridine (C-to-U) and uridine-to-cytidine (U-to-C) editing events are directed by pentatricopeptide repeat (PPR) proteins, modular RNA-binding factors that recognize their RNA targets through a predictable amino acid–nucleotide recognition code. Deciphering this code has enabled the rational design of synthetic PPR (synPPR) proteins with programmable RNA-binding specificity and robust stability in heterologous systems. Recent advances have extended these synthetic scaffolds to active RNA editors by fusing them to catalytically competent DYW deaminase domains, generating customizable enzymes capable of precise base conversion in bacteria, plants, and even human cells. This review summarizes current understanding of the structural and mechanistic principles underlying PPR-mediated RNA editing and highlights recent progress in the design and application of synPPR proteins. We discuss how synthetic PPR proteins have been used as programmable RNA stabilizers, translational regulators, and targeted C-to-U or U-to-C editors, as well as their emerging therapeutic potential in RNA-mediated diseases. The development of compact, cofactor-independent editors derived from early-diverging plant lineages further expands the versatility of this platform. Together, these efforts establish synthetic PPR proteins as a powerful and flexible class of RNA engineering tools with applications spanning basic research, biotechnology, and biomedicine. Continued refinement of targeting specificity, catalytic efficiency, and effector modularity will propel PPR-based editors toward broader use in synthetic biology and therapeutic RNA modulation. Full article
(This article belongs to the Section Molecular Biology)
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16 pages, 5703 KB  
Article
Genome-Wide Identification of PGRP Gene Family and Its Role in Dendrolimus kikuchii Immune Response Against Bacillus thuringiensis Infection
by Yanjiao Tang, Zizhu Wang, Qiang Guo, Xue Fu, Ning Zhao, Bin Yang and Jielong Zhou
Biology 2025, 14(12), 1783; https://doi.org/10.3390/biology14121783 - 13 Dec 2025
Viewed by 129
Abstract
Peptidoglycan recognition proteins (PGRPs) are conserved pattern recognition receptors (PRRs) that play key roles in insect innate immunity by binding bacterial peptidoglycan (PGN) and activating downstream signaling pathways. The Dendrolimus kikuchii, a major defoliator of coniferous forests in southern China, has incompletely [...] Read more.
Peptidoglycan recognition proteins (PGRPs) are conserved pattern recognition receptors (PRRs) that play key roles in insect innate immunity by binding bacterial peptidoglycan (PGN) and activating downstream signaling pathways. The Dendrolimus kikuchii, a major defoliator of coniferous forests in southern China, has incompletely characterized immune defenses. This study systematically identified the PGRP gene family in D. kikuchii based on genome-wide data, identifying 10 PGRP genes with typical PGRP/Amidase_2 conserved domains, including 6 PGRP-S proteins and 4 PGRP-L proteins. Additionally, to further investigate the evolutionary relationships of these PGRP genes, a maximum likelihood (ML) phylogenetic tree was constructed using PGRP amino acid sequences from 6 different insect species, along with the 10 PGRP amino acid sequences from D. kikuchii. Phylogenetic analysis revealed that the DkikPGRP genes of D. kikuchii are distributed across distinct evolutionary branches and share high homology with PGRP genes from other insects, suggesting a close evolutionary relationship between the PGRP genes of D. kikuchii and those of other insect species. Transcriptome profiling revealed that DkikPGRP-S1, -S2, -S3, -S4, and -S5 were upregulated in the midgut, fat body, and hemolymph after Bt infection, showing tissue- and time-specific immune responses. Functional assays using siRNA knockdown demonstrated distinct roles of DkikPGRP-S4 and DkikPGRP-S5: DkikPGRP-S5 mainly promoted antimicrobial peptide (AMP) expression, including attacin, lebocin, lysozyme, and cecropin, whereas DkikPGRP-S4 showed a complex regulatory pattern, enhancing lebocin and lysozyme but suppressing attacin without affecting gloverin or cecropin. Silencing either gene significantly increased larval mortality upon Bt challenge. These results highlight the specialized immune regulatory functions of PGRPs in D. kikuchii, provide new insights into host–pathogen interactions, and suggest potential molecular targets for sustainable pest management strategies. Full article
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15 pages, 6758 KB  
Article
Dynamic Changes and Sediment Reduction Effect of Terraces on the Loess Plateau
by Chenfeng Wang, Xiaoping Wang, Xudong Fu, Xiaoming Zhang and Yunqi Wang
Remote Sens. 2025, 17(24), 4021; https://doi.org/10.3390/rs17244021 - 13 Dec 2025
Viewed by 82
Abstract
Terraces are the main engineering of soil erosion control on the Loess Plateau, offering measures for sediment reduction and water conservation, as well as the potential for increasing agricultural productivity. Over the years, large-scale terrace construction has been undertaken; however, the management has [...] Read more.
Terraces are the main engineering of soil erosion control on the Loess Plateau, offering measures for sediment reduction and water conservation, as well as the potential for increasing agricultural productivity. Over the years, large-scale terrace construction has been undertaken; however, the management has been inadequate, especially in terms of long-term monitoring and mapping. Moreover, the sediment reduction effect of terrace construction is not yet fully understood. Therefore, this study utilizes Landsat series data, integrating remote sensing imaging principles with machine learning techniques to achieve long–term temporal sequence mapping of terraces at a 30 m spatial resolution on the Loess Plateau. The sediment reduction effect brought about by terrace construction on the Loess Plateau is quantified using a sediment reduction formula. The results show that Elevation (Ele.), red band (R), Normalized Difference Vegetation Index (NDVI), Enhanced Vegetation Index (EVI), and Near-infrared Reflectance of Vegetation (NIRv) are key parameters for remote sensing identification of terraces. These five remote sensing variables explain 88% of the terrace recognition variance. Coupling the Random Forest classification model with the LandTrendr algorithm allows for rapid time-series mapping of terrace spatial distribution characteristics on the Loess Plateau. The producer’s accuracy of terrace identification is 93.49%, the user’s accuracy is 93.81%, the overall accuracy is 88.61%, and the Kappa coefficient is 0.87. The LandTrendr algorithm effectively removes terraces affected by human activities. Terraces are mainly distributed in the southeastern Loess areas, including provinces such as Gansu, Shaanxi, and Ningxia. Over the past 30 years, the terrace area on the Loess Plateau has increased from 0.9790 million hectares in 1990 to 9.8981 million hectares in 2020. The sediment reduction effect is particularly notable, with an average reduction of 49.75% in soil erosion across the region. This indicates that terraces are a key measure for soil erosion control in the region and a critical strategy for improving farmland productivity. The data from this study provides scientific evidence for soil erosion control on the Loess Plateau and enhances the precision of terrace management. Full article
(This article belongs to the Section Remote Sensing in Geology, Geomorphology and Hydrology)
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14 pages, 639 KB  
Article
Recognising Emotions from the Voice: A tDCS and fNIRS Double-Blind Study on the Role of the Cerebellum in Emotional Prosody
by Sharon Mara Luciano, Laura Sagliano, Alessia Salzillo, Luigi Trojano and Francesco Panico
Brain Sci. 2025, 15(12), 1327; https://doi.org/10.3390/brainsci15121327 - 13 Dec 2025
Viewed by 191
Abstract
Background: Emotional prosody refers to the variations in pitch, pause, melody, rhythm, and stress of pronunciation conveying emotional meaning during speech. Although several studies demonstrated that the cerebellum is involved in the network subserving recognition of emotional facial expressions, there is only [...] Read more.
Background: Emotional prosody refers to the variations in pitch, pause, melody, rhythm, and stress of pronunciation conveying emotional meaning during speech. Although several studies demonstrated that the cerebellum is involved in the network subserving recognition of emotional facial expressions, there is only preliminary evidence suggesting its possible contribution to recognising emotional prosody by modulating the activity of cerebello-prefrontal circuits. The present study aims to further explore the role of the left and right cerebellum in the recognition of emotional prosody in a sample of healthy individuals who were required to identify emotions (happiness, anger, sadness, surprise, disgust, and neutral) from vocal stimuli selected from a validated database (EMOVO corpus). Methods: Anodal transcranial Direct Current Stimulation (tDCS) was used in offline mode to modulate cerebellar activity before the emotional prosody recognition task, and functional near-infrared spectroscopy (fNIRS) was used to monitor stimulation-related changes in oxy- and deoxy- haemoglobin (O2HB and HHB) in prefrontal areas (PFC). Results: Right cerebellar stimulation reduced reaction times in the recognition of all emotions (except neutral and disgust) as compared to both the sham and left cerebellar stimulation, while accuracy was not affected by the stimulation. Haemodynamic data revealed that right cerebellar stimulation reduced O2HB and increased HHB in the PFC bilaterally relative to the other stimulation conditions. Conclusions: These findings are consistent with the involvement of the right cerebellum in modulating emotional processing and in regulating cerebello-prefrontal circuits. Full article
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29 pages, 3722 KB  
Review
Glial Cells in the Early Stages of Neurodegeneration: Pathogenesis and Therapeutic Targets
by Eugenia Ahremenko, Alexander Andreev, Danila Apushkin and Eduard Korkotian
Int. J. Mol. Sci. 2025, 26(24), 11995; https://doi.org/10.3390/ijms262411995 - 12 Dec 2025
Viewed by 278
Abstract
Astrocytes and microglia constitute nearly half of all central nervous system cells and are indispensable for its proper function. Both exhibit striking morphological and functional heterogeneity, adopting either neuroprotective (A2, M2) or proinflammatory (A1, M1) phenotypes in response to cytokines, pathogen-associated molecular patterns [...] Read more.
Astrocytes and microglia constitute nearly half of all central nervous system cells and are indispensable for its proper function. Both exhibit striking morphological and functional heterogeneity, adopting either neuroprotective (A2, M2) or proinflammatory (A1, M1) phenotypes in response to cytokines, pathogen-associated molecular patterns (PAMPs)/damage-associated molecular patterns (DAMPs), toll-like receptor 4 (TLR4) activation, and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling. Crucially, many of these phenotypic transitions arise during the earliest stages of neurodegeneration, when glial dysfunction precedes overt neuronal loss and may act as a primary driver of disease onset. This review critically examines glial-centered hypotheses of neurodegeneration, with emphasis on their roles in early disease phases: (i) microglial polarization from an M2 neuroprotective state to an M1 proinflammatory state; (ii) NLRP3 inflammasome assembly via P2X purinergic receptor 7 (P2X7R)-mediated K+ efflux; (iii) a self-amplifying astrocyte–microglia–neuron inflammatory feedback loop; (iv) impaired microglial phagocytosis and extracellular-vesicle–mediated propagation of β-amyloid (Aβ) and tau; (v) astrocytic scar formation driven by aquaporin-4 (AQP4), matrix metalloproteinase-9 (MMP-9), glial fibrillary acidic protein (GFAP)/vimentin, connexins, and janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling; (vi) cellular reprogramming of astrocytes and NG2 glia into functional neurons; and (vii) mitochondrial dysfunction in glia, including Dynamin-related protein 1/Mitochondrial fission protein 1 (Drp1/Fis1) fission imbalance and dysregulation of the sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Sirt1/PGC-1α) axis. Promising therapeutic strategies target pattern-recognition receptors (TLR4, NLRP3/caspase-1), cytokine modulators (interleukin-4 (IL-4), interleukin-10 (IL-10)), signaling cascades (JAK2–STAT, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphoinositide 3-kinase–protein kinase B (PI3K–AKT), adenosine monophosphate-activated protein kinase (AMPK)), microglial receptors (triggering receptor expressed on myeloid cells 2 (TREM2)/spleen tyrosine kinase (SYK)/ DNAX-activating protein 10 (DAP10), siglec-3 (CD33), chemokine C-X3-C motif ligand 1/ CX3C motif chemokine receptor 1 (CX3CL1/CX3CR1), Cluster of Differentiation 200/ Cluster of Differentiation 200 receptor 1 (CD200/CD200R), P2X7R), and mitochondrial biogenesis pathways, with a focus on normalizing glial phenotypes rather than simply suppressing pathology. Interventions that restore neuroglial homeostasis at the earliest stages of disease may hold the greatest potential to delay or prevent progression. Given the complexity of glial phenotypes and molecular isoform diversity, a comprehensive, multitargeted approach is essential for mitigating Alzheimer’s disease and related neurodegenerative disorders. This review not only synthesizes pathogenesis but also highlights therapeutic opportunities, offering what we believe to be the first concise overview of the principal hypotheses implicating glial cells in neurodegeneration. Rather than focusing on isolated mechanisms, our goal is a holistic perspective—integrating diverse glial processes to enable comparison across interconnected pathological conditions. Full article
(This article belongs to the Special Issue Early Molecular Markers of Neurodegeneration)
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32 pages, 5708 KB  
Article
Affordable Audio Hardware and Artificial Intelligence Can Transform the Dementia Care Pipeline
by Ilyas Potamitis
Algorithms 2025, 18(12), 787; https://doi.org/10.3390/a18120787 - 12 Dec 2025
Viewed by 198
Abstract
Population aging is increasing dementia care demand. We present an audio-driven monitoring pipeline that operates either on mobile phones, microcontroller nodes, or smart television sets. The system combines audio signal processing with AI tools for structured interpretation. Preprocessing includes voice activity detection, speaker [...] Read more.
Population aging is increasing dementia care demand. We present an audio-driven monitoring pipeline that operates either on mobile phones, microcontroller nodes, or smart television sets. The system combines audio signal processing with AI tools for structured interpretation. Preprocessing includes voice activity detection, speaker diarization, automatic speech recognition for dialogs, and speech-emotion recognition. An audio classifier detects home-care–relevant events (cough, cane taps, thuds, knocks, and speech). A large language model integrates transcripts, acoustic features, and a consented household knowledge base to produce a daily caregiver report covering orientation/disorientation (person, place, and time), delusion themes, agitation events, health proxies, and safety flags (e.g., exit seeking and falling). The pipeline targets real-time monitoring in homes and facilities, and it is an adjunct to caregiving, not a diagnostic device. Evaluation focuses on human-in-the-loop review, various audio/speech modalities, and the ability of AI to integrate information and reason. Intended users are low-income households in remote settings where in-person caregiving cannot be secured, enabling remote monitoring support for older adults with dementia. Full article
(This article belongs to the Special Issue AI-Assisted Medical Diagnostics)
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11 pages, 2591 KB  
Article
Synthesis of Novel Anion Recognition Molecules as Quinazoline Precursors
by Gábor Krajsovszky, László Piros, Dóra Bogdán, Eszter Kalydi, Tamás Gáti, Pál Szabó, Péter Horváth and István M. Mándity
Int. J. Mol. Sci. 2025, 26(24), 11975; https://doi.org/10.3390/ijms262411975 - 12 Dec 2025
Viewed by 155
Abstract
Thiourea and structurally related urea derivatives are widely recognised for their ability to transport anions through hydrogen bonding interactions. The strength of these interactions correlates with the electronegativity of the ligand and the acidity of the NH hydrogens involved. Thiourea, being more acidic [...] Read more.
Thiourea and structurally related urea derivatives are widely recognised for their ability to transport anions through hydrogen bonding interactions. The strength of these interactions correlates with the electronegativity of the ligand and the acidity of the NH hydrogens involved. Thiourea, being more acidic than urea, exhibits partial deprotonation in the presence of certain anions such as organic carboxylates, fluoride, and bromide, while remaining resistant to deprotonation by chloride. This behaviour suggests a degree of selectivity toward chloride ions. Additionally, while carbamide-containing molecules tend to aggregate—potentially reducing their ion-binding efficiency—thiourea derivatives show reduced aggregation, preserving their binding capabilities. In this study, we report the synthesis and characterisation of 21 novel thiourea derivatives obtained by reacting 2-aminobenzoylamino acid esters with various substituted phenyl isothiocyanates. Seven similar thiourea-containing molecules were made as a comparison—without the amino acids—by reacting aniline with the different phenyl isothiocyanates. The reaction kinetics were found to be influenced primarily by the electronic nature of the substituents on the phenyl ring. Electron-withdrawing groups (EWGs), such as para-nitro, 3,5-bis(trifluoromethyl), and fluorine, accelerated the reaction, while electron-donating groups (EDGs), such as para-methoxy, slowed it down. Interestingly, the nature of the amino acid precursors had no significant impact on reaction time; however, reactions with aniline proceeded the fastest. Solvent choice also played a role: reactions in N,N-dimethylformamide (DMF) proceeded faster than in acetone, although with reduced yields. Consequently, reaction conditions were optimised to balance time efficiency and product yield. To evaluate the chloride ion-binding properties of the synthesised compounds, 1H NMR titration experiments were conducted in deuterated dimethyl sulfoxide (DMSO-d6). The association constants (Ka) derived from these studies revealed a clear correlation with the electronic nature of the substituents. Compounds bearing EWGs exhibited enhanced chloride binding, while those with EDGs showed diminished binding affinity. Surprisingly, the presence of amino acid moieties led to a decrease in Ka values, despite the electron-withdrawing nature of the amide groups. This suggests that steric or conformational factors may play a role in modulating binding strength. Overall, the synthesised thiourea derivatives demonstrate mild, reversible chloride ion-binding behaviour, making them promising candidates for further development as selective anion receptors. The insights gained from this study contribute to a deeper understanding of structure–activity relationships in anion-binding systems and may inform the design of future supramolecular architectures with tailored ion recognition properties. Full article
(This article belongs to the Special Issue Techniques and Strategies in Drug Design and Discovery, 3rd Edition)
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18 pages, 4970 KB  
Article
Generation of a scFv Derived from an IgM-Producing Hybridoma for the Detection of REST Expression in Premalignant Lesions and Invasive Squamous Cell Carcinoma
by Cynthia Rodríguez-Nava, Karen Cortés-Sarabia, Lidia Riaño-Umbarila, Baltazar Becerril-Luján, Yolanda Medina-Flores, Olga Mata-Ruíz, Lourdes Lloret-Sánchez, Berenice Illades-Aguiar, Luz del Carmen Alarcón-Romero and Carlos Ortuño-Pineda
Int. J. Mol. Sci. 2025, 26(24), 11946; https://doi.org/10.3390/ijms262411946 - 11 Dec 2025
Viewed by 78
Abstract
Cervical cancer (CC) can be prevented through continuous screening and the timely detection of cervical intraepithelial neoplasia (CIN) using immunohistochemistry techniques to identify biomarker expressions. In a previous study, we proposed nuclear REST loss as a biomarker in precancerous lesions and CC; however, [...] Read more.
Cervical cancer (CC) can be prevented through continuous screening and the timely detection of cervical intraepithelial neoplasia (CIN) using immunohistochemistry techniques to identify biomarker expressions. In a previous study, we proposed nuclear REST loss as a biomarker in precancerous lesions and CC; however, no validated antibodies are available for detecting REST in cytology or cervical tissues. Although we have developed an IgM-type anti-REST monoclonal antibody capable of detecting REST in liquid-based cytology cells, it was not useful for the detection of REST in cervical tissues by immunohistochemistry. The main objective of this study is to generate single-chain variable fragments (scFvs) for the clinical evaluation of REST in cervical tissues from women with CIN and CC. Using RNA from an IgM-producing hybridoma anti-REST, we conducted RT-PCR and PCR to obtain the coding sequences for the variable regions of the heavy and light chains. These sequences were joined with a linker to create a single-chain antibody. The scFv was then cloned into the pSyn1 vector, expressed in E. coli TG1, and purified through chromatography. Subsequently, it was characterized using immunological methods to assess its biological activity and employed to evaluate REST expression in cytological samples and cervical tissues. The anti-REST scFv represents an innovative detection tool that retains the antigen recognition of the parental IgM while overcoming its size limitation, enabling tissue penetration and detection of REST in cervical samples. Its application facilitates the identification of REST in cervical samples, reinforcing REST’s potential as a diagnostic biomarker for CC and CIN. Full article
(This article belongs to the Special Issue Recent Advances in New Biomarkers for Cancers)
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23 pages, 1185 KB  
Review
The Current Landscape of Modular CAR T Cells
by Alexander Haide Joechner, Melanie Mach and Ziduo Li
Int. J. Mol. Sci. 2025, 26(24), 11898; https://doi.org/10.3390/ijms262411898 - 10 Dec 2025
Viewed by 268
Abstract
Despite the groundbreaking impact of currently approved CAR T-cell therapies, substantial unmet clinical needs remain. This highlights the need for CAR T treatments that are easier to tune, combine, and program with logic rules, in oncology and autoimmunity. Modular CAR T cells use [...] Read more.
Despite the groundbreaking impact of currently approved CAR T-cell therapies, substantial unmet clinical needs remain. This highlights the need for CAR T treatments that are easier to tune, combine, and program with logic rules, in oncology and autoimmunity. Modular CAR T cells use a two-part system: the CAR on the T cell binds an adaptor molecule (AM), and that adaptor binds the tumour-associated antigen (TAA). This design separates recognition of the target antigen and activation of the T cells, resulting in a cellular therapy concept with better control, flexibility, and safety compared to established direct-targeting CAR T-cell systems. The key advantage of the system is the adaptor molecule, often an antibody-based reagent, that targets the TAA. Adaptors can be swapped or combined without re-engineering the T cells, enabling straightforward multiplexing and logic-gated control. The CAR itself is designed to recognise the AM via a unique tag on the adaptor. Only when the CAR, AM, and antigen-positive target cell assemble correctly is T-cell effector function activated, leading to cancer cell lysis. This two-component system has several features that need to be considered when designing a modular CAR: First, the architecture of the CAR, i.e., how the binding domain and the backbone are designed, can influence tonic signalling and activation/exhaustion parameters. Second, the affinity of CAR–AM and AM–TAA will mostly define the engagement kinetics of the system. Third, the valency of the AM has an impact on exhaustion and non-specific activation of CAR T cells. And lastly, the architecture of the AM, especially the size, defines the pharmacokinetics and, consequently, the dosing scheme of the AM. The research conducted on direct-targeting CAR T cells have generated in-depth knowledge of the advantages and disadvantages of the technology in its current form, with remarkable clinical success in relapsed/refractory disease and long-term survival in otherwise difficult-to-treat patient populations. On the other hand, CAR T-cell therapy poses the risk of severe adverse events and antigen loss coupled with antigen-negative relapse which remains the main reason for failed therapies. Addressing these issues in the traditional setting of one CAR targeting one antigen will always be difficult due to the heterogeneous nature of most oncologic diseases, but the flexibility to change target antigens and the modulation of CAR T response by dosing the AM in a modular CAR system might be pivotal to mitigate these hurdles of direct CAR T cells. Since the first conception of modular CARs in 2012, there have been more than 30 constructs published, and some of those have been translated into phase I/II clinical trials with early signs of success, but whether these will progress into a late-stage clinical trial and gain regulatory approval remains to be seen. Full article
(This article belongs to the Special Issue Adapter CAR T Cells: From the Idea to the Clinic)
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24 pages, 450 KB  
Article
Late Fusion Model for Emotion Recognition from Facial Expressions and Biosignals in a Dataset of Children with Autism Spectrum Disorder
by Dominika Kiejdo, Monika Depka Prądzinska and Teresa Zawadzka
Sensors 2025, 25(24), 7485; https://doi.org/10.3390/s25247485 - 9 Dec 2025
Viewed by 337
Abstract
Children with autism spectrum disorder (ASD) often display atypical emotional expressions and physiological responses, making emotion recognition challenging. This study proposes a multimodal recognition model employing a late fusion framework combining facial expression with physiological measures: electrodermal activity (EDA), temperature (TEMP), and heart [...] Read more.
Children with autism spectrum disorder (ASD) often display atypical emotional expressions and physiological responses, making emotion recognition challenging. This study proposes a multimodal recognition model employing a late fusion framework combining facial expression with physiological measures: electrodermal activity (EDA), temperature (TEMP), and heart rate (HR). Emotional states are annotated using two complementary schemes derived from a shared set of labels. Three annotators provide one categorical Ekman emotion for each timestamp. From these annotations, a majority-vote label identifies the dominant emotion, while a proportional distribution reflects the likelihood of each emotion based on the relative frequency of the annotators’ selections. Separate machine learning models are trained for each modality and for each annotation scheme, and their outputs are integrated through decision-level fusion. A distinct decision-level fusion model is constructed for each annotation scheme, ensuring that both the categorical and likelihood-based representations are optimally combined. The experiments on the EMBOA dataset, collected within the project “Affective loop in Socially Assistive Robotics as an intervention tool for children with autism”, show that the late fusion model achieves higher accuracy and robustness than unimodal baselines. The system attains an accuracy of 68% for categorical emotion classification and 78% under the likelihood-estimation scheme. The results obtained, although lower than those reported in other studies, suggest that further research into emotion recognition in autistic children using other fusions is warranted, even in the case of datasets with a significant number of missing values and low sample representation for certain emotions. Full article
(This article belongs to the Section Biomedical Sensors)
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21 pages, 3243 KB  
Article
A Multimodal Agent Framework for Construction Scenarios: Accurate Perception, Dynamic Retrieval, and Explainable Hazard Reasoning
by Sihan Cheng, Yujun Qi, Rui Wu and Yangyang Guan
Buildings 2025, 15(24), 4439; https://doi.org/10.3390/buildings15244439 - 9 Dec 2025
Viewed by 227
Abstract
Construction sites are complex environments where traditional safety monitoring methods often suffer from low detection accuracy and limited interpretability. To address these challenges, this study proposes a modular multimodal agent framework that integrates computer vision, knowledge representation, and large language model (LLM)–based reasoning. [...] Read more.
Construction sites are complex environments where traditional safety monitoring methods often suffer from low detection accuracy and limited interpretability. To address these challenges, this study proposes a modular multimodal agent framework that integrates computer vision, knowledge representation, and large language model (LLM)–based reasoning. First, the CLIP model fine-tuned with Low-Rank Adaptation (LoRA) is combined with YOLOv10 to achieve precise recognition of construction activities and personal protective equipment (PPE). Second, a construction safety knowledge graph integrating Retrieval-Augmented Generation (RAG) is constructed to provide structured domain knowledge and enhance contextual understanding. Third, the FusedChain prompting strategy is designed to guide large language models (LLMs) to perform step-by-step safety risk reasoning. Experimental results show that the proposed approach achieves 97.35% accuracy in activity recognition, an average F1-score of 0.84 in PPE detection, and significantly higher performance than existing methods in hazard reasoning. The modular design also facilitates scalable integration with more advanced foundation models, indicating strong potential for real-world deployment in intelligent construction safety management. Full article
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24 pages, 8154 KB  
Article
Sex-Specific Electrocortical Interactions in a Color Recognition Task in Men and Women with Opioid Use Disorder
by Jo Ann Petrie, Abhishek Trikha, Hope L. Lundberg, Kyle B. Bills, Preston K. Manwaring, J. Daniel Obray, Daniel N. Adams, Bruce L. Brown, Donovan E. Fleming and Scott C. Steffensen
Biomedicines 2025, 13(12), 3002; https://doi.org/10.3390/biomedicines13123002 - 8 Dec 2025
Viewed by 368
Abstract
Background: Opioid use disorder (OUD) and associated overdose deaths have reached epidemic proportions worldwide over the past two decades, with death rates for men consistently reported at twice the rate for women. We have recently reported sex-specific differences in electrocortical activity in [...] Read more.
Background: Opioid use disorder (OUD) and associated overdose deaths have reached epidemic proportions worldwide over the past two decades, with death rates for men consistently reported at twice the rate for women. We have recently reported sex-specific differences in electrocortical activity in persons with OUD in a visual object recognition task. The mesolimbic dopamine (DA) system is implicated in OUD but also plays a critical role in some disorders of visual attention and a modulatory role in the processing of visual stimuli in the blue cone pathway of the retina. We hypothesized that electrocortical responses to color stimuli would be affected differentially in men and women with OUD. Methods: Using a controlled, cross-sectional, age-matched (18–56 years) design, we evaluated color processing in male and female subjects recruited from a community-based, high-intensity residential substance abuse and detoxification treatment program. We evaluated electroencephalogram (EEG) event-related potentials (ERPs) and reaction time (RT), in male and female participants with OUD (n = 38) vs. sex- and age-matched non-OUD control participants (n = 37) in a simple color recognition Go/No-Go task, as well as perceptual and behavioral responses in physiological and neuropsychological tests. Results: N200, P300, and late potential (LP) Relevant stimulus-induced ERPs were evoked by the task and were well-differentiated from Irrelevant distractor stimuli. P300 amplitudes were significantly greater and N200 and LP latencies were significantly shorter in male vs. female non-OUD controls in this task. There were significant sex differences in N200, P300, and LP amplitudes and latencies between male vs. female non-OUD subjects and OUD differences with blue color as the Relevant stimulus. In the Binocular Rivalry Test, there were shorter dwell times for perceiving a blue stimulus in male OUD subjects and there were significant sex and OUD differences in neuropsychological tests including Finger Tapping, Trails A/B, and Symbol Digit Modalities Test. Conclusions: These findings suggest that there are significant sex-related physiological, perceptual, and cognitive differences in color processing that may result from deficits in DA production in the retina that mirror deficits in mesolimbic DA transmission correlating with OUD, suggesting that blue color processing has the potential to be an effective biomarker for brain DA and for diagnosis and monitoring of treatment efficacy in substance use disorders. Full article
(This article belongs to the Special Issue Molecular Psychiatry and Antipsychotics)
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15 pages, 1182 KB  
Article
DVL, a Lectin from Dioclea violacea Seeds, Disturbs the Proteomic Profile of Candida krusei, Leading to Cell Death
by Romério R. S. Silva, Rayara J. P. Carvalho, Maria H. C. Santos, Ana L. E. Santos, Rômulo F. Carneiro, Celso S. Nagano, Pedro F. N. Souza and Claudener S. Teixeira
Antibiotics 2025, 14(12), 1228; https://doi.org/10.3390/antibiotics14121228 - 5 Dec 2025
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Abstract
Background/Objectives Plant lectins have emerged as potential antifungal molecules, where the carbohydrate recognition domain (CRD) is possibly the main mode of action of these proteins. Previously, we saw that the lectin extracted from the seeds of Dioclea violacea (DVL) has anti-candida activity against [...] Read more.
Background/Objectives Plant lectins have emerged as potential antifungal molecules, where the carbohydrate recognition domain (CRD) is possibly the main mode of action of these proteins. Previously, we saw that the lectin extracted from the seeds of Dioclea violacea (DVL) has anti-candida activity against Candida krusei cells by acting to inhibit ergosterol biosynthesis, cell wall deformation, and deregulation of the redox system. Methods We have now confirmed this anti-candida activity by proteomic analysis, with the expression of proteins that show us how C. krusei cells respond to this treatment. Results A total of 395 proteins were identified: 142 proteins exclusively found in untreated C. krusei cells and 245 proteins exclusive to DVL-treated cells. Eight proteins were detected in both conditions. Six displayed positive accumulation (fold change > 1.5), one exhibited negative accumulation (fold change < 0.5). We observed the expression of proteins related to cell wall remodeling; alteration of energy metabolism, suggesting a metabolic adaptation to stress; oxidative stress was responded to through the expression of proteins with antioxidant action, in addition to identifying multidrug transport proteins that are often involved in the process of antifungal resistance and sterol transport to the membrane. Conclusions Our results show the complexity of adaptive responses of C. krusei cells to treatment with DVL, elucidating new mechanisms of resistance and paving the way for the development of more effective and innovative antifungal therapies. Full article
(This article belongs to the Special Issue Antimicrobial Peptides (AMPs) Against Human Pathogens)
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18 pages, 2264 KB  
Article
Evaluation of the Ca37 Monoclonal Antibody Targeting Alcohol Dehydrogenase Against Candidozyma auris (Candida auris) In Vitro and In Vivo
by Oier Rodriguez-Erenaga, Maialen Areitio, Lucia Abio-Dorronsoro, Nahia Cazalis-Bereicua, Leire Aparicio-Fernandez, Leire Martin-Souto, Idoia Buldain, Beñat Zaldibar, Aitor Rementeria, Aitziber Antoran and Andoni Ramirez-Garcia
J. Fungi 2025, 11(12), 864; https://doi.org/10.3390/jof11120864 - 5 Dec 2025
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Abstract
Candidozyma auris (Candida auris) is an emerging pathogenic yeast of global concern due to its persistence on abiotic and biotic surfaces and the difficulty of treating the severe infections it causes, which are frequently associated with high mortality rates because of [...] Read more.
Candidozyma auris (Candida auris) is an emerging pathogenic yeast of global concern due to its persistence on abiotic and biotic surfaces and the difficulty of treating the severe infections it causes, which are frequently associated with high mortality rates because of its extensive antifungal resistance. Thus, new therapeutic strategies are urgently needed to complement or replace current antifungal drugs. In this study, we evaluated the efficacy of Ca37, a monoclonal antibody (mAb) targeting the alcohol dehydrogenase (Adh) protein of Candida albicans, against C. auris both in vitro and in vivo. Protein electrophoresis and Western Blot analyses demonstrated immunoreactivity of Ca37 mAb with C. auris total protein and cell wall-associated protein extracts, among which Adh was identified. In vitro, incubation with Ca37 mAb significantly reduced the growth of several C. auris strains and enhanced the phagocytic activity of RAW 264.7 murine macrophages. In vivo, Ca37 mAb treatment increased the survival of Galleria mellonella larvae. In a murine model of systemic infection, treated mice displayed improved clinical condition, along with a greater number and larger area of immune-associated foci in the kidneys, suggesting enhanced fungal recognition. These findings support the potential of Ca37 mAb as an antifungal immunotherapy, although further studies in murine models are necessary to establish optimal dosing, efficacy, and mechanisms of action. Full article
(This article belongs to the Special Issue Mycological Research in Spain)
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