Search Results (147)

Parkinson’s Disease (PD) is the fastest-growing neurological disorder, characterized by the degeneration of dopaminergic neurons. Treatments remain symptomatic, and objective biomarkers for therapeutic response are lacking. This review aims to evaluate the potential of Proton Magnetic Resonance Spectroscopy (¹H-MRS) to provide objective and reproducible biomarkers for monitoring treatment response in PD. This systematic review followed PRISMA guidelines. Articles were searched in PubMed, Web of Science, Scopus, and Embase, and studies employing ¹H-MRS to evaluate pharmacological treatments in PD were included, analyzing pre- and post-treatment changes. Six studies were included, investigating cannabinoids, dopamine agonists, monoamine oxidase B inhibitors, and levodopa. Key metabolites analyzed were N-acetylaspartate, Creatine, Choline, myo-Inositol, and Glx (glutamate+glutamine). Increases in NAA, a marker of neuronal integrity and mitochondrial function, suggested neuroprotective mechanisms of dopaminergic drugs, while stable Cho and mI levels, markers of membrane metabolism and inflammatory processes, suggested limited short-term responsiveness. This is the first systematic review evaluating ¹H-MRS for monitoring neurometabolic changes induced by pharmacological treatments in PD. Observed metabolite changes appear to reflect treatment mechanisms and potential neuroprotective properties. Findings suggest that ¹H-MRS may serve as an objective biomarker for assessing therapeutic efficacy and potential neuroprotective drug effects, although further studies are needed to confirm its clinical utility. Full article

Multi-view data, captured from various perspectives, is crucial for training view-invariant human action recognition models, yet its acquisition is hindered by spatio-temporal constraints and high costs. This study aims to develop the Pose Scene EveryWhere (PSEW) framework, which automatically generates temporally consistent, multi-view 3D human action data from a single monocular video. The proposed framework first predicts 3D human parameters from each video frame using a deep learning-based Human Mesh Recovery (HMR) model. Subsequently, it applies tracking, linear interpolation, and Kalman filtering to refine temporal consistency and produce naturalistic motion. The refined human meshes are then reconstructed into a virtual 3D scene by estimating a stable floor plane for alignment, and finally, novel-view videos are rendered using user-defined virtual cameras. As a result, the framework successfully generated multi-view data with realistic, jitter-free motion from a single video input. To assess fidelity to the original motion, we used Root Mean Square Error (RMSE) and Mean Per Joint Position Error (MPJPE) as metrics, achieving low average errors in both 2D (RMSE: 0.172; MPJPE: 0.202) and 3D (RMSE: 0.145; MPJPE: 0.206) space. PSEW provides an efficient, scalable, and low-cost solution that overcomes the limitations of traditional data collection methods, offering a remedy for the scarcity of training data for action recognition models. Full article

The growing demand for real-time human motion reconstruction in Virtual Reality (VR), Augmented Reality (AR), and the Metaverse requires high accuracy with minimal hardware. This paper presents SSR-HMR, a skeleton-aware, sparse node-based method for full-body motion reconstruction from limited inputs. The approach incorporates a lightweight spatiotemporal graph convolutional module, a torso pose refinement design to mitigate orientation drift, and kinematic tree-based optimization to enhance end-effector positioning accuracy. Smooth motion transitions are achieved via a multi-scale velocity loss. Experiments demonstrate that SSR-HMR achieves high-accuracy reconstruction, with mean joint and end-effector position errors of 1.06 cm and 0.52 cm, respectively, while operating at 267 FPS on a CPU. Full article

In this paper, we aimed to evaluate the efficacy and usefulness of three brief, easy-to-administer, and repeatable tests, namely SDMT, Digit Span Forward (DSF), and Digit Span Backward (DSB) in MS patients (MSp), and compared the results with those of healthy volunteers (CONs). We were hoping to identify the most sensitive test that could be used regularly in clinical practice. In addition, we tried to identify the metabolic background of the cognitive setting using the advanced radiological method, Mescher–Garwood (MEGA)-edited 1H Magnetic Resonance Spectroscopy (1H-MRS). A total of 22 relapsing MSp and 22 CONs were enrolled. The SDMT, DSF, and DSB tests were used on all participants. The patients also underwent a 1H-MRS brain examination. In addition to N-Acetyl-Aspartate (tNAA), Myoinositol (mIns), Choline (tCho), and Creatine (tCr) were also evaluated GABA and Glutamate–Glutamine (Glx) ratios. CONs were superior to MSp in the results of all neurocognitive tests. The DSB was found to be the most sensitive test for identifying MSp. The SDMT in MSp correlated with inflammatory and degenerative metabolites in the thalamus, hippocampus, and corpus callosum. A correlation between increased Glx- and GABA-ratios and SDMT was found. Unlike the SDMT, the DSF and DSB showed correlations with inflammatory metabolites in the caudate nucleus and hypothalamus. DSF correlated with GABA ratios in the hippocampus. Our study confirms the efficacy of DSF and DSB tests in evaluating working memory cognitive impairment in MSp, showing an association of the tests with specific brain metabolites. Full article

The study assesses the relationship between thalamic proton-MR spectroscopy (¹H-MRS) metabolites and thalamic ¹¹C-ER176 translocator-protein positron emission tomography (TSPO-PET) standardized uptake value ratios (SUVR) to advance our understanding of thalamic involvement in multiple sclerosis (MS)-associated neurodegeneration and disability. In this prospective cross-sectional study, patients with MS (pwMS) and controls underwent 3T-MRI, ¹H-MRS, and ¹¹C-ER176-PET targeting the thalamus. MRI-derived thalamic volume was normalized by intracranial volume. ¹H-MRS metabolites—N-acetylaspartate (NAA), glutamate (Glu), glutamine (Gln), total choline (tCho), and myo-inositol (mIns)—were normalized to total creatine (tCr). Clinical disability was evaluated using MS-specific tests of Expanded Disability Status Scale-EDSS and MS-functional composite-MSFC (including Paced Auditory Serial Addition Test-PASAT). Compared to controls (n = 30), pwMS (n = 21) exhibited smaller thalamic volume, higher thalamic ¹H-MRS mIns/tCr (putative gliosis marker), and higher thalamic ¹¹C-ER176-PET SUVR (glial density marker). In pwMS, higher thalamic mIns/tCr (r = −0.67) and tCho/tCr (r = −0.52) correlated with smaller thalamic volume. In pwMS, higher thalamic mIns/tCr correlated with higher thalamic ¹¹C-ER176-PET SUVR (r = 0.48) and decreased cognitive function (PASAT, rho = −0.48). In controls, decreased thalamic NAA/tCr correlated with increased thalamic ¹¹C-ER176-PET SUVR (r = −0.41). Thalamus, a core central nervous system relay, is affected early in MS disease course. Glial-mediated innate immune activation in the thalamus, evaluated by increased ¹H-MRS mIns/tCr and ¹¹C-ER176-PET SUVR, is associated with loss of thalamic volume and increased disability in pwMS. The multimodal imaging approach with ¹H-MRS mIns/tCr and ¹¹C-ER176-PET SUVR emerges as potential glial biomarkers, to better understand disease mechanisms and evaluate therapeutic interventions targeting glial activity in MS. Full article

Asthma is a heterogeneous chronic respiratory condition with distinct inflammatory phenotypes, including type 2-driven eosinophilic asthma. This randomized, double-blind, placebo-controlled exploratory trial investigated the effects of OmeGO^®, on respiratory outcomes in adults with type 2 asthma. Over a 20-week period, 66 participants received 6 g per day of either OmeGO^® (≥120 mg eicosapentaenoic acid (EPA), ≥180 mg docosahexaenoic acid (DHA)), or placebo. The key outcome was a composite score of moderate and severe exacerbation events. Asthma control was assessed using the Asthma Control Questionnaire-5-item (ACQ5) and the Global Initiative for Asthma (GINA) criteria. The median time to the first composite event was 37 days (95% CI 9–47) in the OmeGO group and 15 days (95% CI 12–33) in the placebo group (p = 0.347); 73% of the participants in the OmeGO experienced at least one exacerbation compared to 82% in the placebo group (p = 0.347). The weekly frequence of composite events was 0.36 per day in the OmeGO group and 0.32 in the placebo group (p = 0.777). Even though there are no differences in the exacerbation rates between groups, the time to first composite event should be further explored. Full article

Background: Addressing undernutrition and malnutrition requires a multi-pronged approach targeting different populations with appropriate interventions. Knowledge and perception (K&P) of Individuals and communities about nutrition to human health relationship/continuum is a prerequisite for addressing malnutrition in rural and mountain communities. Assessing K&P is essential for developing strategic interventions to up-scaling K&P of communities and achieving nutrition security. Homestead gardens are a proven intervention for achieving nutrition security for all family members of gardeners. Methods: This paper includes homestead gardeners from the Himalayan Mountain Region (HMR) as respondents. We developed a scale to assess the K&P of respondents, based on ratings from 20 judges. A total of 134 issues/items have been retained in the scale from macronutrients, micronutrients, minerals, and vitamins. A framework has also been developed and adopted for the study. A knowledge and perception index (KPI) has been developed based on the respondents’ responses. We have reviewed and analysed the national policy interventions for augmenting the K&P of the study community to achieve nutrition security. Results: The nutrition K&P of respondents are inadequate and far from the desirable level. Policy review and analysis indicate that the creation of K&P in the community to contribute to self and family nutrition security was previously highly neglected. Conclusions: The policy process of national, state, and county/district-level development sectors in developing countries under the HMR may take the initiative to ensure self-nutrition security by creating K&P of the community on nutrition issues. The designed scale is prudent requires testing and validation for measuring farmers’ K&P on nutrition, which may be adopted in future studies and policymaking not only nationally but also from an international perspective. Full article

Heart failure (HF) and left ventricular hypertrophy (LVH) are linked to fibroblast growth factor 23 (FGF23). This study aims to analyze whether FGF23 can predict postoperative outcomes in unselected left ventricular assist device (LVAD) candidates. Methods: We conducted a prospective observational study that included 27 patients (25 HeartMate3 and 2 HeartMateII) with a median follow-up of 30 months. We measured preoperative FGF23 plasma levels and computed the HeartMateII risk score (HMRS), the HeartMate3 risk score (HM3RS) and the EuroSCOREII with respect to postoperative mortality, as well as the Michigan right heart failure risk score (MRHFS), the Euromacs RHF risk score (EURORHFS), the CRITT score with respect to RHF prediction and the kidney failure risk equation (KFRE) with respect to kidney failure. Multivariate logistic regression and receiver operating characteristic (ROC) analyses were performed. Results: In the multivariate logistic regression, preoperative FGF23 level was found to be a predictor of postoperative RHF (OR: 1.37, 95-CI: 0.78–2.38; p = 0.031), mortality (OR: 1.10, 95%-CI: 0.90–1.60; p = 0.025) and the need for postoperative dialysis (OR: 1.09, 95%-CI: 0.91–1.44; p = 0.032). In the ROC analysis, FGF23 as a predictor of post-LVAD RHF had an area under the curve (AUC) of 0.81. Conclusions: FGF23 improves the prediction of clinically significant patient outcomes—such as need for dialysis, RHF and mortality—after HM3 and HMII implantation, as adding FGF23 to established risk scores increased their predictive value. Full article

T-cells constitute an essential component of the adaptive immune response, mount a protective response against foreign pathogens and are important regulators of anti-tumor immunotherapy. In this context, the activation of T-cells and chimeric antigen receptor (CAR)-expressing T-cells is orchestrated by various signaling pathways, involving the initiation of a protein tyrosine phosphorylation cascade. For T-cells, this involves initiation of the phosphorylation cascade via src-related protein-tyrosine kinase p56^lck, which we show to associate with the co-receptors CD4 and CD8 for the induction of a phosphorylation cascade needed for the activation of T-cells. Likewise, p56^lck phosphorylation of the antigen receptor immunoreceptor tyrosine-based activation motifs (ITAMs) and key CD28 tyrosine motifs ensures the functionality and the survival of CARs, while their phospho-targets are also inhibited by PD-1, a key component of the immune checkpoint blockade. This review covers historic and current elements of our knowledge of CD4/CD8–p56^lck-induced activation events and their importance to the development of CAR T-cell immunotherapies. Full article

Kernicterus spectrum disorder is the permanent and highly disabling neurologic sequel of neonatal exposure to hyperbilirubinemia, presenting, among other symptoms, variable and untreatable motor disabilities. To search for potential biomolecular explanations, we used a Gunn rat colony exhibiting spontaneous hyperbilirubinemia and a large variability of motor deficits on a beam-walking test. Histological and microscopic analyses confirmed worsening damage in the cerebellum (Cll; hypoplasia, increased death of neurons, and disrupted astroglial structures) and parietal motor cortex (hCtx; increased cell sufferance and astrogliosis). Clustering and network analyses of transcriptomic data reveal rearrangement of the physiological expression patterns and signaling pathways associated with bilirubin neurotoxicity. Bilirubin content among hyperbilirubinemic (jj) animals is overlapped, which suggests that the amount of bilirubin challenge does not fully explain the tissue, transcriptomic, proteomic, and neurobehavioral alterations. The expression of nine genes involved in key postnatal brain development processes is permanently altered in a phenotype-dependent manner. Among them, Grm1, a metabotropic glutamatergic receptor involved in glutamate neurotoxicity, is consistently downregulated in both brain regions both at the transcriptomic and proteomic levels. Our results support the role of Grm1 and glutamate as biomolecular markers of ongoing bilirubin neurotoxicity, suggesting the possibility to improve diagnosis by ¹H-MR spectroscopy. Full article

Background/Objectives: In the context of acute heart failure, proenkephalin A (penKid) has emerged as a prognostic marker for acute kidney injury (AKI), whereas bioactive adrenomedullin (bio-ADM) has been identified as a significant biomarker linked to shock and organ dysfunction. This raises the question of whether they can serve as predictors of postoperative complications in patients receiving left ventricular assist devices (LVADs). Methods: This observational study prospectively enrolled patients who had received LVAD implantation. Routine laboratory values as well as plasma levels of penKid and bio-ADM were assessed at four time intervals, spanning from preinduction of anesthesia to 48 h post surgery. Clinical data, the HeartMate 3-risk-score (HM3RS), HeartMateII-risk-score (HMRS), Michigan-right-heart-failure risk score (MRHFS), Euromacs-RHFS (EURORHFS), and kidney failure risk score (KFR) were calculated. Multivariate logistic regression and receiver operating characteristic (ROC) analysis were performed. We entered the biomarkers with the established risk scores into the models. Results: In 20 patients who had undergone LVAD implantation, preoperative penKid level was a predictor of postoperative AKI (OR: 1.05, 95%-CI: 1.0–1.09; p = 0.049) and 30-day mortality (OR: 1.01, 95%-CI: 1.0–1.02; p = 0.033). Bio-ADM was the only predictor of postoperative right heart failure (RHF) (OR: 1.11, 95%-CI: 1.01–1.23; p = 0.034) and rehospitalization (OR: 1.06, 95%-CI: 1.0–1.13; p = 0.047). In the ROC analysis, bio-ADM, as a predictor of post-LVAD RHF, had an area under the curve (AUC) of 0.88. When bio-ADM was added to the accepted clinical scores for post-LVAD RHF prediction (CRITT-score, MRHFS, and EURORHFS), the AUC reached 0.98. The AUC for preoperative penKid, as a predictor of postoperative AKI, was 0.95, and after adding its predictive value to the KFR score, the AUC reached 0.97. Conclusions: In the present study, the biomarkers penKid and bio-ADM predicted clinically significant patient outcomes after LVAD implantation such as AKI, RHF, and 30-day mortality. Adding biomarkers to well-established risk scores improved the AUC for prediction of postoperative complications. Full article

Lung adenocarcinoma (LUAD) is a leading cause of cancer-related mortality, with heme metabolism playing a critical role in tumor progression and treatment resistance. This study investigates the clinical implications of heme metabolism in LUAD, focusing on its link to ferroptosis and drug sensitivity. Using multi-omics data from TCGA-LUAD, GEO databases, and a single-cell RNA-seq cohort, we identified two molecular subtypes based on heme metabolism-related genes. We further developed a prognostic panel, termed the heme metabolism risk score (HMRS), using LASSO and multivariate Cox regression analyses. The HMRS panel effectively stratified patients into high- and low-risk groups, with high-risk patients showing enhanced tumor proliferation, suppressed ferroptosis, and resistance to chemotherapy. Single-cell analysis revealed elevated heme metabolism risk in epithelial cells correlated with tumor progression. Drug sensitivity predictions were validated in platinum-based chemotherapy cohorts, confirming HMRS as a robust prognostic tool. ABCC2 was identified as a key regulator of ferroptosis and cisplatin resistance, with in vitro experiments demonstrating that ABCC2 knockdown enhanced cisplatin-induced ferroptosis. These findings highlight HMRS as a critical tool for patient stratification and ABCC2 as a promising therapeutic target to overcome cisplatin resistance. Full article

Background: Transcranial photobiomodulation (t-PBM) is a promising non-invasive therapy for Major Depressive Disorder (MDD). MDD is associated with altered brain metabolism, including changes in N-acetylaspartate (NAA), choline (Cho), and creatine (Cr). This study assessed the effects of varying t-PBM doses on neurometabolite levels in the dorsolateral prefrontal cortex (dlPFC) and their correlations with clinical outcomes. Methods: In this randomized, sham-controlled, cross-over study, 33 adults with MDD received one session of t-PBM at low, medium, and high doses and a sham treatment. Proton magnetic resonance spectroscopy (1H-MRS) measured NAA, Cho, and Cr pre- and post-treatment. Clinical outcomes were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Symptoms of Depression Questionnaire (SDQ). Statistical analyses included paired t-tests or Wilcoxon signed-rank tests for neurometabolite changes, and linear mixed-effects regression models for t-PBM dose, neurometabolites, and time effects. Results: NAA levels increased significantly (7.52 ± 0.777 to 8.12 ± 1.05 mmol/L for one session; 7.36 ± 0.85 to 7.85 ± 0.68 mmol/L across all sessions); however, these changes were not associated with specific t-PBM doses or sham. No significant changes were observed for Cho and Cr levels. Positive correlations were found between Cho levels and MADRS scores (r = 0.59, p = 0.017), and negative correlations between Cr levels and SDQ scores at the medium dose (r = −0.91, p = 0.011). Conclusions: While NAA levels increased, and correlations between neurometabolites and clinical outcomes were observed, these findings do not suggest a specific effect of t-PBM. Larger randomized controlled trials with optimized dosing protocols, extended follow-up, and advanced spectroscopy are needed to clarify the neurometabolic therapeutic potential of t-PBM in MDD. Full article

The link between financial inclusion and financial stability is a central concern in public economic policymaking, particularly in emerging countries where access to financial services remains limited. While financial inclusion is widely regarded as a key driver of economic development, its impact on financial stability remains debated. Some studies highlight the stabilizing effect of financial inclusion, whereas others, like emphasize its potential risks. This study empirically investigates the relationship between financial inclusion and financial stability across the years 2011, 2014, 2017, and 2021 in 26 African and MENA countries. The hierarchical multiple regression (HMR) method is employed to assess the independent effect of financial inclusion, controlling for macroeconomic variables. The findings reveal that financial inclusion positively contributes to financial stability through channels such as digital payments and the number of bank branches. Conversely, savings, the number of ATMs, and the money supply exhibit a negative effect on financial stability. These results underscore the need for a regulatory framework that balances financial inclusion with financial stability. In particular, cybersecurity measures must be implemented to support the expansion of digital payments, and supervisory mechanisms should be reinforced to mitigate liquidity risks. Full article

As a cost-effective transitional strategy, the integrated utilization and transportation of hydrogen and natural gas have gained significant attention as a viable pathway toward carbon neutrality. However, hydrogen’s low density, viscosity, and calorific value cause upward migration and accumulation in pipelines, raising embrittlement risks. Its high diffusion and leakage rates also pose significant safety challenges. To address hydrogen–natural gas blending challenges, achieving uniform mixing is crucial. This study systematically examines hydrogen–methane mixing in T-junction pipelines via numerical simulations, analyzing hydrogen mixing ratios (HMR: 10–25%) and methane flow rates (4–10 m/s) to assess flow and mixing dynamics. The coefficient of variation (COV) quantifies mixing uniformity with spatial and temporal analyses, optimizing hydrogen injection for rapid, homogeneous mixing. The key findings are as follows: (1) The uniform mixing length (the minimum axial distance required for the first pipeline cross-section to achieve 95% mixing uniformity) decreases inversely with the HMR, from 100 D to 20.875 D (D represents the pipeline diameter) as the HMR rises from 10% to 25%. (2) Analysis of initial uniform mixing time (defined as the duration required for the first pipeline cross-section to achieve 95% mixing uniformity) shows significant reduction with increasing HMR. While methane flow rate has a less pronounced effect, it nevertheless contributes to reducing the outlet uniform mixing time (defined as the time required to attain 95% mixing uniformity at the pipeline outlet). (3) A fundamental trade-off in engineering applications is established: increasing the HMR reduces mixing length but extends overall mixing time (difference between outlet and initial mixing times), while higher methane flow rates shorten overall mixing time at the cost of increased mixing length. The primary objective of this research is to elucidate the fundamental fluid dynamics of hydrogen–methane mixtures in T-junction pipelines, providing scientific insights for the safe and efficient operation of hydrogen-blended natural gas pipeline systems. Full article