Search Results (70)

Background/Objectives: Routine liver biopsies play an important role in monitoring liver allografts but carry non-negligible risks. This pilot study assesses the feasibility of dynamic long-axial field-of-view (LAFOV) [¹⁸F]FDG PET/CT as a non-invasive alternative to biopsy. Methods: Liver transplant (LTx) recipients meeting the inclusion criteria of ≥10 months post-transplantation and scheduled routine biopsy were prospectively enrolled, along with healthy controls. All participants underwent dynamic LAFOV [¹⁸F]FDG PET/CT, followed by biopsy in LTx recipients, who were stratified by inflammatory severity using the BANFF score. Hepatic kinetic parameters (K1, k2, k3, k4) and SUVmean/SUVmax were compared using Mann–Whitney U tests. Correlations were assessed using Spearman’s rank correlation. A p-value < 0.05 was considered significant. Analyses were performed in RStudio (version 2024.12.10563). Results: Sixteen LTx recipients (mean age 48.6 years; seven female, nine male) and eight healthy controls (mean age 35.4 years; six female, two male) were included. Healthy controls had mean k3 and k4 values of 0.0037 min⁻¹ ± 0.0003 min⁻¹ and 0.0019 min⁻¹ ± 0.0011 min⁻¹, respectively. LTx recipients showed significantly higher k3 and k4 values, both when including and excluding patients with biopsy-confirmed inflammation. Descriptive comparisons between LTx recipients with and without significant inflammation (n = 3) showed no clear differences. Spearman analysis showed no significant correlations between the BANFF score and kinetic parameters. The strongest degree of correlation was found between BANFF score and k3, indicating a moderate positive but non-significant association (k3: rs = 0.396, p = 0.128). Conclusions: Elevated k3 and k4 values in LTx recipients were not explained by allograft inflammation, suggesting altered FDG kinetics post-transplant. These differences may confound [¹⁸F]FDG PET interpretation. Larger studies are needed to assess the clinical applicability of dynamic LAFOV [¹⁸F]FDG PET/CT. Full article

Background/Objectives: Early embryonic arrest during the cleavage stage (days 2–4) accounts for a substantial proportion of developmental failure in in vitro fertilization. This phenomenon remains poorly understood at the molecular level, even in chromosomally normal embryos identified by preimplantation genetic testing. This review aims to redefine cleavage-stage arrest from a passive energy deficit to a checkpoint-regulated endpoint caused by inadequate coordination among metabolism, transcriptome integrity, and stress-response pathways. Methods: We integrate evidence from long-read transcriptomics, metabolomics, epigenetics, and immunobiology relevant to pre-blastocyst development. These data are assembled into a unifying mechanistic framework and a clinically oriented stratification model, together with candidate multimodal readouts for early classification. Results: We propose a three-axis model linking: (i) metabolic–epigenetic insufficiency, including defective histone lactylation and impaired alpha-ketoglutarate-dependent DNA demethylation; (ii) isoform-level abnormalities, including intron retention and retrotransposon activation within a hidden transcriptomic landscape better resolved by long-read sequencing; and (iii) stress-related immune signaling, in which NLRP7 links alternative splicing and DNA-damage-response dysfunction with mitochondrial stress and p53-associated arrest. Within this framework, we distinguish three molecular arrest states: an early transition failure marked by defective maternal-to-embryonic reprogramming and severe splicing disruption; a metabolically quiescent state that may retain a limited rescue window; and a later stress-associated state characterized by senescence-like features, oxidative stress, and broad transcriptomic and genomic instability. Conclusions: Early embryo arrest should no longer be viewed as a nonspecific developmental failure, but as a mechanistically stratifiable condition with distinct metabolic, transcriptomic, and stress-associated trajectories. A diagnostic platform combining fluorescence lifetime imaging microscopy, long-read sequencing, and digital polymerase chain reaction may improve early mechanistic classification, help identify embryos with possible reversibility, and reduce uncertainty in embryo selection during in vitro fertilization. Full article

Background: Ultrasound imaging is an ideal tool for regular carotid plaque screening to identify individuals at high risk of stroke for clinical intervention. However, no existing study leverages multi-modal multi-view ultrasound imaging for AI-enabled auto-classification of carotid plaque vulnerability. This study aims to develop and validate an effective AI model for carotid plaque vulnerability classification through the applications of dual-modal (B-Mode and contrast-enhanced mode) dual-view (longitudinal and cross-sectional) settings to maximize the utility and potential of ultrasound imaging. Methods: Hybrid deep-learning (DL) and machine-learning (ML) methods were employed to balance between model discriminability and interpretability. B-Mode ultrasound (BMUS) and contrast-enhanced ultrasound (CEUS) images from 241 patients were retrospectively analyzed using the proposed hybrid-DL-ML variants. Results: Our findings suggest the hybrid VGG-RF model developed from a dual-modal dual-view setting outperforms those developed from other settings for identifying vulnerable carotid plaques. The VGG-RF model emerged as the best-performing model, achieving an optimal performance with an AUC of 0.908, precision of 0.765, recall of 0.929, specificity of 0.886, and F1 score of 0.839. The inherent interpretability of the VGG-RF model divulged that long-axis views of BMUS and CEUS images were the major contributing features for discriminating vulnerable carotid plaques against their counterparts. Conclusions: The present study underscored the effectiveness of AI models developed from dual-modal dual-view settings of ultrasound images. Notably, the hybrid VGG-RF model was benchmarked as the best-performing model among other studied hybrid DL-ML variants. Further studies on a larger cohort in a prospective setting are warranted to validate the findings of the current study. Full article

Background/Objectives: Automatic segmentation and identification of vertebrae in spinal CT are essential for assisting diagnosis of spinal disorders and for preoperative planning. The task is challenging due to the high structural similarity between adjacent vertebrae and the morphological variability of vertebrae. Most existing methods rely on fully supervised deep learning and, constrained by limited annotations, struggle to remain robust in complex scenarios. Methods: We propose a semi-supervised approach built on a dual-branch 3D U-Net. Mamba modules are inserted between the encoder and decoder to model long-range dependencies along the cranio–caudal axis. The identification branch employs a 3D convolutional block attention module (3D-CBAM) to enhance class discriminability. A unified semi-supervised objective is formulated via teacher–student consistency: for each unlabeled sample, weakly and strongly augmented views are generated, and cross-branch consistency is enforced, together with confidence-based filtering and class-frequency reweighting. In addition, a connected-component analysis is used to enforce anatomically plausible sequential continuity of vertebral indices in the outputs. Results: Experiments on VerSe 2019 and 2020 show that, on the public VerSe 2019 test set (with VerSe 2020 scans used as unlabeled training data), the supervised baseline achieved a Dice score of 89.8% and an identification accuracy of 92.3%. Incorporating unlabeled data improved performance to 91.6% Dice and 97.5% identification accuracy (relative gains of +1.8 and +5.2 percentage points). Compared with competing methods, the proposed semi-supervised model attains higher or comparable segmentation accuracy and the highest identification accuracy. Conclusions: Without additional annotation cost, the proposed method markedly improves the overall performance of vertebra segmentation and identification, offering more robust automated support for clinical workflows. Full article

River basins are not merely geographical spaces but also cultural-historical ecosystems, where the spatial patterns of Intangible Cultural Heritage (ICH) profoundly reflect the long-term interaction between human and environment, as well as contemporary transformations. While international research on ICH has evolved from conceptual clarification to interdisciplinary theory-building, and spatial quantitative methods have been widely applied to cultural heritage analysis, the spatial patterns, multi-scale structures, and “natural-human” driving mechanisms of ICH in continental arid river basins—particularly in the Tarim River Basin (TRB, China’s largest inland river and a key corridor of the Silk Road)—remain underexplored. To address this gap, this study takes 313 ICH items in the TRB as the research object. It uses ArcGIS 10.8.1 to visualize their spatial distribution and employs an integrated methodology—including global Moran’s I, kernel density estimation (KDE), DBSCAN spatial clustering, and geographical detector (Geodetector)—to systematically reveal their spatial characteristics and influencing factors. The findings indicate that: (1) The distribution of ICH exhibits a multi-scale feature of “global randomness with local clustering”: spatial autocorrelation is not significant at the county level, while at the micro-geographical scale, a dendritic structure characterized by “one axis, three cores, denser in the north and sparser in the south” emerges, which is highly coupled with the river network. DBSCAN clustering further identifies a “mainstem axis–tributary node” cluster system and a relatively high proportion of peripheral “noise” heritage points. (2) Agglomeration patterns vary significantly across different ICH categories, with traditional craftsmanship showing high clustering, while traditional sports, entertainment, and acrobatics display highly fragmented distributions. (3) The study reveals and validates a ternary “Water–Tourism–Urbanization” driving framework that predominantly shapes the spatial heterogeneity of ICH: water resources constitute a fundamental ecological threshold, whereas tourism development and urbanization have emerged as more explanatory social driving forces, with widespread nonlinear enhancement interactions between natural and human factors. This research moves beyond the traditional view of river basins as static cultural “containers,” providing empirical evidence for their dynamic nature as “cultural-ecological co-evolutionary systems.” The proposed ternary framework not only offers a new perspective for understanding the spatial resilience of ICH in arid regions and the potential risks of “spectacularization” and “spatial polarization” amid rapid changes, but also provides a scientific basis for spatial governance, culture-tourism integration, and the formulation of conservation strategies for ICH at the basin scale. Full article

Multi-channel common-aperture optical systems, which excel at simultaneous multi-spectral information acquisition, are widely used for image fusion. However, complex systems for long-distance multi-band detection suffer from difficulties in assembly and adjustment and light vignetting. To resolve this, the paper proposes a modular design method that splits the optical path into independent modules: the common-aperture optical path adopts an off-axis reflective beam-shrinking structure to extend the focal length and ensure 100% light input, compared with coaxial multi-channel common-aperture systems. The relay optical path of each spectral channel uses a continuous zoom design for smooth detection–recognition switching. Based on the method, a three-channel common-aperture system is developed integrating visible light (VIS), short-wave infrared (SWIR), and mid-wave infrared (MWIR). The modulation transfer function (MTF) and wavefront distribution of the common-aperture optical path approach the diffraction limit. After integration with the relay optical paths, the system, without global optimization, can achieve the following performance: the root mean square (RMS) across the full field of view (FOV) at different focal lengths for each channel is smaller than the detector pixel size (3.45 μm for VIS, 15 μm for SWIR/MWIR); the MTF exceeds 0.2 at the cutoff frequency. Subsequently, the results of the tolerance analysis verify the feasibility of the design for each module and the advantage of the modular layout in the assembly and adjustment of the system. Finally, the paper discusses the influence of parallel plates on the wavefront distortion of the system and proposes optimization thinking using freeform surfaces. The design results of the study validate the feasibility of the modular layout in simplifying the design and assembly of multi-channel common-aperture optical systems. Full article

Background/Objectives: Effective regurgitant orifice area (EROA) is a critical parameter in assessing mitral regurgitation (MR) severity. The Japanese Circulation Society recommends a volumetric method which uses mitral annular diameters from apical four-chamber (A4C) and two-chamber (A2C) views. However, given the elliptical shape of the mitral annulus, use of apical long-axis (A3C) and A2C views, which reflect the anatomical long and short axes, may improve measurement accuracy. This study aimed to determine the optimal echocardiographic view combination for precise EROA quantification in degenerative MR (DMR). Methods: We retrospectively analyzed 98 patients with DMR who underwent both transthoracic echocardiography (TTE) and three-dimensional transesophageal echocardiography (3D TEE) within three months between April 2018 and December 2023. EROA was calculated using volumetric methods based on two TTE view combinations, A4C-A2C (EROA 4/2) and A3C-A2C (EROA 3/2). These were compared with 3D TEE-derived vena contracta area (VCA), which served as reference standard. Results: Mean values of EROA were 0.57 ± 0.23 cm² for EROA 4/2, 0.50 ± 0.21 cm² for EROA 3/2, and 0.49 ± 0.18 cm² for 3D TEE VCA. EROA 4/2 was significantly larger than VCA (p < 0.01), whereas EROA 3/2 did not significantly differ from VCA (p = 0.41) and showed a stronger correlation with VCA than EROA 4/2 (r = 0.829 vs. r = 0.638, p < 0.01). Conclusions: Volumetric EROA assessment using A3C and A2C views provides more accurate quantification in DMR than the conventional A4C and A2C approach. Anatomically appropriate imaging planes should be prioritized to enhance the accuracy of MR severity evaluation. Full article

Background/Objectives: Epicardial fat thickness (EFT) is an echocardiographic marker of epicardial adipose tissue that has been linked to coronary atherosclerosis, but its relationship with both coronary artery disease (CAD) severity and myocardial ischemia remains incompletely assessed. This study evaluated the association between EFT, angiographic CAD severity, and stress-induced myocardial ischemia. Methods: In a prospective study, 125 consecutive patients with suspected stable angina underwent transthoracic echocardiography with EFT measurement, dobutamine stress echocardiography, and coronary angiography. EFT was measured at end-systole in the parasternal long-axis view. Significant CAD was defined as ≥50% stenosis in at least one major epicardial coronary artery. Myocardial ischemia was assessed using peak-stress wall motion score index (WMSI). Results: Significant CAD was present in 56% of patients. Mean EFT was significantly higher in patients with significant CAD compared with those without (7.8 ± 2.0 mm vs. 5.5 ± 1.5 mm; p < 0.001). EFT increased progressively with angiographic CAD severity (non-significant CAD: 5.5 ± 1.5 mm; one-vessel disease: 6.5 ± 1.8 mm; two-vessel disease: 7.5 ± 2.0 mm; three-vessel disease: 8.5 ± 1.9 mm; p < 0.001). Patients with EFT > 5 mm had a significantly higher prevalence of significant CAD (68.8% vs. 33.3%; p < 0.001) and were older, with higher body mass index and a greater prevalence of hypertension and obesity. Additionally, peak-stress WMSI was significantly higher in patients with elevated EFT (1.08 ± 0.07 vs. 1.04 ± 0.05; p = 0.005), indicating a greater ischemic burden. Conclusions: EFT is associated with both the anatomical severity of CAD and the extent of stress-induced myocardial ischemia, supporting its potential role in non-invasive risk stratification of patients with suspected CAD. Full article

Positron Emission Tomography (PET) is undergoing a profound transformation. Driven by the convergence of highly sensitive long-axial field-of-view (LAFOV) total-body PET systems and an expanding portfolio of targeted radiopharmaceuticals, PET is progressively evolving beyond its traditional role in oncologic diagnosis and staging. Ultra-sensitive scanners enable whole-body imaging with markedly reduced radiotracer doses, rapid acquisition times, and true dynamic multiparametric imaging across all organs simultaneously. In parallel, molecularly targeted radioligands support tumour phenotyping, theranostic applications, and personalized dosimetry. Together, these advances position PET as a systemic imaging platform capable of interrogating whole-body tumour biology, guiding precision therapies, and potentially enabling early detection or surveillance strategies in selected high-risk populations. This narrative review summarizes the technological foundations of total-body PET, reviews current clinical and translational applications, discusses opportunities and limitations for early detection and surveillance, and outlines a research and implementation roadmap to responsibly translate this paradigm into clinical oncology. Full article

Major depressive disorder (MDD) was long framed as a single clinical entity arising from a linear stress–monoamine–hypothalamic–pituitary–adrenal (HPA) axis cascade. This view was shaped by forced swim and learned helplessness tests in animals and by short-term symptom-based trials using scales such as the Hamilton Depression Rating Scale (HAM-D) and the Montgomery–Åsberg Depression Rating Scale (MADRS). This “unitary cascade” view has been dismantled by advances in neuroimaging, immune–metabolic profiling, sleep phenotyping, and plasticity markers, which reveal divergent circuit-level, inflammatory, and chronobiological patterns across anxiety-linked, pain-burdened, and cognitively weighted depressive presentations, all characterized by high rates of non-response and relapse. Translationally, face-valid rodent assays that equated immobility with despair have yielded limited bedside benefit, whereas cross-species bridges—electroencephalography (EEG) motifs, rapid eye movement (REM) architecture, effort-based reward tasks, and inflammatory/metabolic panels—are beginning to provide mechanistically grounded, clinically actionable readouts. In current practice, depression care is shifting toward systems psychiatry: inflammation-high and metabolic-high archetypes, anhedonia- and circadian-dominant subgroups, formal treatment-resistant depression (TRD) staging, connectivity-guided neuromodulation, esketamine, selected pharmacogenomic panels, and early digital phenotyping, as endpoints broaden to functioning and durability. A central gap is that heterogeneity is acknowledged but rarely built into trial design or implementation. This perspective advances a plasticity-centered systems psychiatry in which a testable prediction is that manipulating defined prefrontal–striatal and prefrontal–limbic circuits in sex-balanced, chronic-stress models will reproduce human network-defined biotypes and treatment response, and proposes hybrid effectiveness–implementation platforms that embed immune–metabolic and sleep panels, circuit-sensitive tasks, and digital monitoring under a shared, preregistered data standard. Full article

The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) play central roles in metabolic and cardiovascular regulation. GLP-1 receptor agonists (GLP-1RAs) are established therapies for type 2 diabetes mellitus (T2DM) and obesity because of their insulinotropic effects, weight reduction, and proven cardiovascular benefit in trial level. In contrast, GIP was historically overlooked due to reduced β-cell responsiveness in T2DM. The development of dual GIP/GLP-1 receptor agonists has reshaped this view. Tirzepatide, the first-in-class co-agonist, an antidiabetic medication to treat type 2 diabetes and for weight loss, provides superior glycemic control and weight loss compared with selective GLP-1RAs in clinical trials, demonstrating synergistic actions between the two incretin pathways. This review summarizes key physiology, pathophysiology, and therapeutic evidence in incretin biology. We describe secretion patterns, receptor distributions, and distinct actions of GIP and GLP-1, as well as alterations in incretin signaling in T2DM and obesity. Cardiovascular protective mechanisms are outlined, including improvements in lipid metabolism, reductions in blood pressure, enhanced endothelial nitric oxide activity, suppression of macrophage inflammation, decreased foam-cell formation, and stabilization of atherosclerotic plaques. At the therapeutic level, emerging directions—such as dual and triple agonists—and unresolved questions regarding long-term vascular effects of GIP and the potential for genotype-guided incretin therapy are also discussed. Collectively, these findings highlight an emerging shift toward integrated incretin-axis modulation as a therapeutic strategy for metabolic and cardiovascular disease. Full article

Phytoindication represents a long-established ecological approach; however, its conceptual basis remains contested, particularly concerning whether it is merely a surrogate for measuring environmental factors or a distinct method for assessing biotic system responses. In this study, we analysed vegetation communities of the sandy terrace in the Dnipro-Oril Nature Reserve (Ukraine) using ecological indicator values, naturalness, and hemeroby indices. The Dnipro-Oril Nature Reserve provides an ideal setting for this study, as it integrates strong natural gradients of soil moisture, nutrient availability, and topography with pronounced anthropogenic influences from the surrounding industrial landscape. This allows the assessment of both natural and human-driven components of ecological variability within a single system. A dataset of 1079 relevés was collected and classified into 24 associations. Multivariate analyses were applied to reveal different aspects of vegetation–environment relationships: MANOVA was used to assess whether plant associations differed significantly in their ecological indicator profiles, CCA to identify the main gradients of species composition constrained by environmental factors, and partial CCA to isolate the specific patterns of vegetation response attributable to individual predictors while controlling for covariates. We found that the indicator values were not independent but strongly intercorrelated, reflecting integrated biotic responses rather than methodological artefacts. This was confirmed by consistent ecological interpretation of the principal component structure and the concordance between ordination patterns and vegetation classification results. Two primary gradients were identified: a natural gradient, which combines soil moisture and nutrient availability with decreasing light, temperature, continentality, and soil pH; and an anthropogenic gradient, represented by the hemeroby–naturalness axis. The interplay of these gradients offers a comprehensive explanation for vegetation structure across various spatial scales, with natural factors shaping community types and anthropogenic influences exerting broader, less specific effects due to their diffuse impact across multiple plant associations. Our findings reveal a novel conceptual perspective, supporting the view that phytoindication is a unique ecological tool for assessing the integrated response of plant communities to environmental drivers, including both natural and anthropogenic gradients, rather than a simplified or less precise substitute for instrumental measurements. Nevertheless, the use of phytoindication does not eliminate the need for instrumental measurements in situations requiring precise quantification of specific physical or chemical environmental parameters. The correlated structure of indicator values revealed in this study demonstrates that phytoindication patterns are specific to each landscape. Therefore, comparative assessments across regions or time periods should be based on the correlation patterns of indicator values rather than their absolute scores. Full article

Bone immunity represents a dynamic interface where skeletal homeostasis intersects with systemic immune regulation. We synthesize emerging paradigms by contrasting two functionally distinct microenvironments: the marrow cavity, a hematopoietic and immune cell reservoir, and cancellous bone, a metabolically active hub orchestrating osteoimmune interactions. The marrow cavity not only generates innate and adaptive immune cells but also preserves long-term immune memory through stromal-derived chemokines and survival factors, while cancellous bone regulates bone remodeling via macrophage-osteoclast crosstalk and cytokine gradients. Breakthroughs in lymphatic vasculature identification challenge traditional views, revealing cortical and lymphatic networks in cancellous bone that mediate immune surveillance and pathological processes such as cancer metastasis. Central to bone immunity is the neuro–immune–endocrine axis, where sympathetic and parasympathetic signaling bidirectionally modulate osteoclastogenesis and macrophage polarization. Gut microbiota-derived metabolites, including short-chain fatty acids and polyamines, reshape bone immunity through epigenetic and receptor-mediated pathways, bridging systemic metabolism with local immune responses. In disease contexts, dysregulated immune dynamics drive osteoporosis via RANKL/IL-17 hyperactivity and promote leukemic evasion through microenvironmental immunosuppression. We further propose the “brain–gut–bone axis” as a systemic regulatory framework, wherein vagus nerve-mediated gut signaling enhances osteogenic pathways, while leptin and adipokine circuits link marrow adiposity to inflammatory bone loss. These insights redefine bone as a multidimensional immunometabolic organ, integrating neural, endocrine, and microbial inputs to maintain homeostasis. By elucidating the mechanisms of immune-driven bone pathologies, this work highlights therapeutic opportunities through biomaterial-mediated immunomodulation and microbiota-targeted interventions, paving the way for next-generation treatments in osteoimmune disorders. Full article

Visual representation of data can ease their understanding and interpretation, particularly when more variables are considered together. The ternary plot, based on a barycentric coordinate system and commonly used to represent compositional variables, may be difficult to interpret due to its structural complexity—stemming in part from the 60° axis projection and the need for indirect value estimation. This article presents its new alternative, the right-angled triangle plot, and compares the two plot types in the representation of a compositional variable of three components. According to a theoretical comparison, the right-angled plot has several technical advantages (e.g., larger plotting area, direct axis reading), resulting from its construction being based on the Cartesian coordinate system. To verify this hypothesis from an empirical point of view, a survey was conducted involving 441 researchers to assess the effectiveness in correctly interpreting the data presented on both plots. The bias was lower, and the precision was higher on the right-angled plot. Indeed, this study’s results, particularly the higher accuracy (more than 95% when a minimal tolerance was allowed) in determining the values of individual variables (X, Y, and Z), as well as the correctly identification of all three variables simultaneously in the right-angled plot compared with the ternary plot, suggest that the former may hold potential for improving the visualization of compositional data with three components. However, introducing this new type of plot would require familiarizing potential users with it, since the majority of respondents (63.2%) still considered the ternary plot easier to use, likely due to its long use and the novelty of the new plot type. Full article

Transcranial direct current stimulation (tDCS) can modulate cortical excitability in a polarity-specific manner, yet identical protocols often produce inconsistent outcomes across sessions or individuals. This narrative review proposes that much of this variability arises from the brain’s intrinsic temporal landscape. Integrating evidence from chronobiology, sleep research, and non-invasive brain stimulation, we argue that tDCS produces reliable, polarity-specific after-effects only within a circadian–homeostatic “window of efficacy”. On the circadian (Process C) axis, intrinsic alertness, membrane depolarisation, and glutamatergic gain rise in the late biological morning and early evening, whereas pre-dawn phases are marked by reduced excitability and heightened inhibition. On the homeostatic (Process S) axis, consolidated sleep renormalises synaptic weights, widening the capacity for further potentiation, whereas prolonged wakefulness saturates plasticity and can even reverse the usual anodal/cathodal polarity rules. Human stimulation studies mirror this two-process fingerprint: sleep deprivation abolishes anodal long-term-potentiation-like effects and converts cathodal inhibition into facilitation, while stimulating at each participant’s chronotype-aligned (phase-aligned) peak time amplifies and prolongs after-effects even under equal sleep pressure. From these observations we derive practical recommendations: (i) schedule excitatory tDCS after restorative sleep and near the individual wake-maintenance zone; (ii) avoid sessions at high sleep pressure or circadian troughs; (iii) log melatonin phase, chronotype, recent sleep and, where feasible, core temperature; and (iv) consider mild pre-heating or time-restricted feeding as physiological primers. By viewing Borbély’s two-process model and allied metabolic clocks as adjustable knobs for plasticity engineering, this review provides a conceptual scaffold for personalised, time-sensitive tDCS protocols that could improve reproducibility in research and therapeutic gain in the clinic. Full article