Integrated landscape of plasma metabolism and proteome of patients with post-traumatic deep vein thrombosis.

Deep vein thrombosis (DVT) is a leading cause of morbidity and mortality after trauma. Here, we integrate plasma metabolomics and proteomics to evaluate the metabolic alterations and their function in up to 680 individuals with and without DVT after trauma (pt-DVT). We identify 28 metabolites and 2 clinical parameter clusters associated with pt-DVT. Then, we develop a panel of 9 metabolites (hexadecanedioic acid, pyruvic acid, L-Carnitine, serotonin, PE(P-18:1(11Z)/18:2(9Z,12Z)), 3-Hydroxycapric acid, 5,6-DHET, 3-Methoxybenzenepropanoic acid and pentanenitrile) that can predict pt-DVT with high performance, which can be verified in an independent cohort. Furthermore, the integration analysis of metabolomics and proteomics data indicates that the upregulation of glycolysis/gluconeogenesis-TCA cycle may promote thrombosis by regulating ROS levels in red blood cells, suggesting that interfering with this process might be potential therapeutic strategies for pt-DVT. Together, our study comprehensively delineates the metabolic and hematological dysregulations for pt-DVT, and provides potential biomarkers for early detection.

Blood metabolites, neurocognition and psychiatric disorders: a Mendelian randomization analysis to investigate causal pathways.

BACKGROUND: Neurocognitive dysfunction is observationally associated with the risk of psychiatric disorders. Blood metabolites, which are readily accessible, may become highly promising biomarkers for brain disorders. However, the causal role of blood metabolites in neurocognitive function, and the biological pathways underlying their association with psychiatric disorders remain unclear. METHODS: To explore their putative causalities, we conducted bidirectional two-sample Mendelian randomization (MR) using genetic variants associated with 317 human blood metabolites (nmax = 215,551), g-Factor (an integrated index of multiple neurocognitive tests with nmax = 332,050), and 10 different psychiatric disorders (n = 9,725 to 807,553) from the large-scale genome-wide association studies of European ancestry. Mediation analysis was used to assess the potential causal pathway among the candidate metabolite, neurocognitive trait and corresponding psychiatric disorder. RESULTS: MR evidence indicated that genetically predicted acetylornithine was positively associated with g-Factor (0.035 standard deviation units increase in g-Factor per one standard deviation increase in acetylornithine level; 95% confidence interval, 0.021 to 0.049; P = 1.15 × 10-6). Genetically predicted butyrylcarnitine was negatively associated with g-Factor (0.028 standard deviation units decrease in g-Factor per one standard deviation increase in genetically proxied butyrylcarnitine; 95% confidence interval, -0.041 to -0.015; P = 1.31 × 10-5). There was no evidence of associations between genetically proxied g-Factor and metabolites. Furthermore, the mediation analysis via two-step MR revealed that the causal pathway from acetylornithine to bipolar disorder was partly mediated by g-Factor, with a mediated proportion of 37.1%. Besides, g-Factor mediated the causal pathway from butyrylcarnitine to schizophrenia, with a mediated proportion of 37.5%. Other neurocognitive traits from different sources provided consistent findings. CONCLUSION: Our results provide genetic evidence that acetylornithine protects against bipolar disorder through neurocognitive abilities, while butyrylcarnitine has an adverse effect on schizophrenia through neurocognition. These findings may provide insight into interventions at the metabolic level for risk of neurocognitive and related disorders.

Epigallocatechin-3-Gallate Inhibits Oxidative Stress Through the Keap1/Nrf2 Signaling Pathway to Improve Alzheimer Disease.

Alzheimer disease (AD) is a common neurodegenerative disease with an intricate pathophysiological mechanism. Oxidative stress has been shown in several investigations as a significant factor in AD progression. For instance, studies have confirmed that oxidative stress inhibition may considerably improve AD symptoms, with potent antioxidants being touted as a possible interventional strategy in the search for AD treatment. Epigallocatechin-3-gallate (EGCG) acts as a natural catechin that has antioxidant effect. It activates the kelch-like epichlorohydrin-associated proteins (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway to inhibit oxidative stress. The Keap1/Nrf2 signal pathway is not only an upstream signaling target for a variety of antioxidant enzymes, but also minimizes high levels of reactive oxygen species. This report analyzes the antioxidant effect of EGCG in AD, elaborates its specific mechanism of action, and provides a theoretical basis for its clinical application in AD.

A Predictive Model of Pressure Injury in Children Undergoing Living Donor Liver Transplantation Based on Machine Learning Algorithm.

AIMS: The aim of our study was to formulate and validate a prediction model using machine learning algorithms to forecast the risk of pressure injuries (PIs) in children undergoing living donor liver transplantation (LDLT). DESIGN: A retrospective cohort study. METHODS: The research was carried out at China's largest paediatric liver transplantation centre. A total of 438 children who underwent LDLT between June 2021 and December 2022 constituted the study cohort. The dataset was partitioned randomly into 70% for training datasets (306 cases) and 30% for testing datasets (132 cases). Utilising four machine learning algorithms-Decision Tree, Random Forest, Gradient Boosting Decision Tree and eXtreme Gradient Boosting-we identified risk factors and constructed predictive models. RESULTS: Out of 438 children, 42 developed PIs, yielding an incidence rate of 9.6%. Notably, 94% of these cases were categorised as Stage 1, and 54% were localised on the occiput. Upon evaluating the four prediction models, the Decision Tree model emerged as the most effective. The primary contributors to pressure injury in the Decision Tree model were identified as operation time, intraoperative corticosteroid administration, preoperative skin protection measures and preoperative skin conditions. A visualisation elucidating the logical inference process for the 10 variables within the Decision Tree model was presented. Ultimately, based on the Decision Tree model, a predictive system was developed. CONCLUSION: Machine learning algorithms facilitate the identification of crucial factors, enabling the creation of an effective Decision Tree model to forecast pressure injury development in children undergoing LDLT. IMPACT: With this predictive model at their disposal, nurses can assess the pressure injury risk level in children more intuitively. Subsequently, they can implement tailored preventive strategies to mitigate the occurrence of PIs. PATIENT OR PUBLIC CONTRIBUTION: Paediatric patients contributed electronic health records datasets.

A model based on C-TIRADS combined with SWE for predicting Bethesda I thyroid nodules.

Objectives: This study aimed to explore the performance of a model based on Chinese Thyroid Imaging Reporting and Data Systems (C-TIRADS), clinical characteristics, and shear wave elastography (SWE) for the prediction of Bethesda I thyroid nodules before fine needle aspiration (FNA). Materials and methods: A total of 267 thyroid nodules from 267 patients were enrolled. Ultrasound and SWE were performed for all nodules before FNA. The nodules were scored according to the 2020 C-TIRADS, and the ultrasound and SWE characteristics of Bethesda I and non-I thyroid nodules were compared. The independent predictors were determined by univariate analysis and multivariate logistic regression analysis. A predictive model was established based on independent predictors, and the sensitivity, specificity, and area under the curve (AUC) of the independent predictors were compared with that of the model. Results: Our study found that the maximum diameter of nodules that ranged from 15 to 20 mm, the C-TIRADS category <4C, and E max <52.5 kPa were independent predictors for Bethesda I thyroid nodules. Based on multiple logistic regression, a predictive model was established: Logit (p) = -3.491 + 1.630 × maximum diameter + 1.719 × C-TIRADS category + 1.046 × E max (kPa). The AUC of the model was 0.769 (95% CI: 0.700-0.838), which was significantly higher than that of the independent predictors alone. Conclusion: We developed a predictive model for predicting Bethesda I thyroid nodules. It might be beneficial to the clinical optimization of FNA strategy in advance and to improve the accurate diagnostic rate of the first FNA, reducing repeated FNA.

Bifunctional ArsI Dioxygenase from Acidovorax sp. ST3 with Both Methylarsenite [MAs(III)] Demethylation and MAs(III) Oxidation Activities.

Methylated arsenicals, including highly toxic species, such as methylarsenite [MAs(III)], are pervasive in the environment. Certain microorganisms possess the ability to detoxify MAs(III) by ArsI-catalyzed demethylation. Here, we characterize a bifunctional enzyme encoded by the arsI gene from Acidovorax sp. ST3, which can detoxify MAs(III) through both the demethylation and oxidation pathways. Deletion of the 22 C-terminal amino acids of ArsI increased its demethylation activity while reducing the oxidation activity. Further deletion of 44 C-terminal residues enhanced the MAs(III) demethylation activity. ArsI has four vicinal cysteine pairs, with the first pair being necessary for MAs(III) demethylation, while at least one of the other three pairs contributes to MAs(III) oxidation. Molecular modeling and site-directed mutagenesis indicated that one of the C-terminal vicinal cysteine pairs is involved in modulating the switch between oxidase and demethylase activity. These findings underscore the critical role of the C-terminal region in modulating the enzymatic activities of ArsI, particularly in MAs(III) demethylation. This research reveals the structure-function relationship of the ArsI enzyme and advances our understanding of the MAs(III) metabolism in bacteria.

Association of polygenic risk scores with Alzheimer's disease and plasma biomarkers among Chinese older adults: A community-based study.

INTRODUCTION: We examined the associations of polygenic risk score (PRS) with Alzheimer's disease (AD) and plasma biomarkers in the Chinese population. METHODS: This population-based study used baseline data from MIND-China (2018; n = 4873) and follow-up data from dementia-free individuals (2014-2018; n = 2117). We measured AD-related plasma biomarkers in a subsample (n = 1256). Data were analyzed using logistic and Cox regression models. RESULTS: We developed PRS with (PRSAPOE) and without (PRSnon- APOE) apolipoprotein E (APOE) gene. In the longitudinal analysis, PRSAPOE was associated with a multivariable-adjusted hazards ratio of 1.91 (95% CI = 1.13-3.23) for AD. PRSAPOE in combination with demographics yielded discriminative (area under the curve [AUC]) and predictive(C-statistic) accuracy of 0.80 (95% confidence interval [CI] = 0.77-0.84) and 0.80 (0.77-0.82), respectively. PRSnon- APOE showed an association with AD risk similar to PRSAPOE. PRSAPOE, but not PRSnon- APOE, was associated with reduced plasma Aß42/Aß40 ratio and increased Neurofilament light chain (NfL) (p < 0.05). DISCUSSION: The PRS with and without APOE gene, in combination with demographics, shows good discriminative and predictive ability for AD. The AD-related pathologies underlie AD risk associated with PRSAPOE. HIGHLIGHTS: The PRSAPOE and PRSnon- APOE were associated with AD risk in the Chinese population. The PRSAPOE and PRSnon- APOE, in combination with demographics, showed good discriminative and predictive ability for AD. The AD-related pathologies underlie the AD risk associated with PRSAPOE but not PRSnon- APOE.

Synergistic associations of CD33 variants and hypertension with brain and cognitive aging among dementia-free older adults: A population-based study.

INTRODUCTION: CD33 rs3865444 and hypertension (HTN) are related to cognitive impairment, individually. However, little is known about their combined effects on cognitive function in older adults. METHODS: This population-based study included 4368 dementia-free participants (age ≥65 years) in the Multimodal Interventions to Delay Dementia and Disability in Rural China (MIND-China), with data available in 1044 persons for gray matter volume and 85 persons for cerebral blood flow (CBF). We used general linear regression and mediation models to examine the associations of rs3865444 and HTN with cognition, brain atrophy, and CBF. RESULTS: Among rs3865444 CC carriers, HTN and late-life HTN were significantly associated with impaired cognition. Midlife and late-life HTN were correlated with brain atrophy. CD33 rs3865444 CC moderated the mediation effect of gray matter volume on the association between HTN and global cognition. HTN was correlated with low CBF in rs3865444 CC carriers. DISCUSSION: There are synergistic associations of CD33 rs3865444 and HTN with brain and cognitive aging in dementia-free older adults.

A dual-signal mode electrochemical aptasensor based on tetrahedral DNA nanostructures for sensitive detection of citrinin in food using PtPdCo mesoporous nanozymes.

Citrinin (CIT) is a mycotoxin with nephrotoxicity and hepatotoxicity, presenting a significant threat to human health that is often overlooked. Therefore, a dual-signal mode (DPV and SWV) aptasensor for citrinin (CIT) detection was constructed based on tetrahedral DNA nanostructures (TDN) in this study. Furthermore, PtPdCo mesoporous nanozymes exhibit catalase-like catalytic functions, generating significant electrochemical signals through a Fenton-like reaction. Meanwhile their excellent Methylene Blue (MB) loading capability ensures independent dual signal outputs. The RecJf exonuclease-assisted (RecJf Exo-assisted) process can expand the linear detection range, enabling further amplification of the signal. Under optimized conditions, the constructed aptaensor exhibited excellent detection performance with limits of detection (LODs) of 7.67 × 10-3 ng·mL-1 (DPV mode) and 1.57 × 10-3 ng·mL-1 (SWV mode). Due to its multiple signal amplification and highly accurate dual-signal mode detection capability, this aptasensor shows promising potential for the in situ detection.

Enhancement and Predictable Guidance of Coalescence-Induced Droplet Jumping on V-Shaped Superhydrophobic Surfaces with a Ridge.

Coalescence-induced droplet jumping has attracted significant attention in recent years. However, achieving a high jumping velocity while predictably regulating the jumping direction of the merged droplets by simple superhydrophobic structures remains a challenge. In this work, a novel V-shaped superhydrophobic surface with a ridge is conceived for enhanced and predictably guided coalescence-induced droplet jumping. By conducting experiments and lattice Boltzmann simulations, it is found that the presence of a ridge in the V-shaped superhydrophobic surface can modify the fluid dynamics during the droplet coalescence process, resulting in a much higher droplet jumping velocity than that achieved by the V-shaped superhydrophobic surface without a ridge. The enhancement of the droplet jumping velocity is mainly attributed to the combined effect of the earlier and more sufficient impingement between the liquid bridge and the ridge, as well as the accelerated droplet contraction by redirecting the internal liquid flow toward the jumping direction. A high normalized jumping velocity of Vj*≈0.71 is achieved by the newly designed surface, with a 930% increase in the energy conversion efficiency in comparison with that on a flat surface. Moreover, adjusting the opening direction of the V-groove at different groove angles is found to be an effective method to regulate the droplet jumping direction and expand the range of the jumping angle. Particularly, the droplet jumping angle can be well predicted based on the rotational angle (ω) and the groove angle (α), i.e., θj,p ≈ 90° - 0.5α - ω.

Associations of 24-hour movement behaviors with depressive symptoms in rural-dwelling older adults: a compositional data analysis.

BACKGROUND: We aimed to explore the association of sleep duration with depressive symptoms among rural-dwelling older adults in China, and to estimate the impact of substituting sleep with sedentary behavior (SB) and physical activity (PA) on the association with depressive symptoms. METHODS: This population-based cross-sectional study included 2001 rural-dwelling older adults (age ≥ 60 years, 59.2% female). Sleep duration was assessed using the Pittsburgh Sleep Quality Index. We used accelerometers to assess SB and PA, and the 15-item Geriatric Depression Scale to assess depressive symptoms. Data were analyzed using restricted cubic splines, compositional logistic regression, and isotemporal substitution models. RESULTS: Restricted cubic spline curves showed a U-shaped association between daily sleep duration and the likelihood of depressive symptoms (P-nonlinear < 0.001). Among older adults with sleep duration < 7 h/day, reallocating 60 min/day spent on SB and PA to sleep were associated with multivariable-adjusted odds ratio (OR) of 0.81 (95% confidence interval [CI] = 0.78-0.84) and 0.79 (0.76-0.82), respectively, for depressive symptoms. Among older adults with sleep duration ≥ 7 h/day, reallocating 60 min/day spent in sleep to SB and PA, and reallocating 60 min/day spent on SB to PA were associated with multivariable-adjusted OR of 0.78 (0.74-0.84), 0.73 (0.69-0.78), and 0.94 (0.92-0.96), respectively, for depressive symptoms. CONCLUSIONS: Our study reveals a U-shaped association of sleep duration with depressive symptoms in rural older adults and further shows that replacing SB and PA with sleep or vice versa is associated with reduced likelihoods of depressive symptoms depending on sleep duration.

1H-Pyrrole-2,5-dicarboxylic acid, a quorum sensing inhibitor from one endophytic fungus in Areca catechu L., acts as antibiotic accelerant against Pseudomonas aeruginosa.

Pseudomonas aeruginosa has already been stipulated as a "critical" pathogen, emphasizing the urgent need for researching and developing novel antibacterial agents due to multidrug resistance. Bacterial biofilm formation facilitates cystic fibrosis development and restricts the antibacterial potential of many current antibiotics. The capacity of P. aeruginosa to form biofilms and resist antibiotics is closely correlated with quorum sensing (QS). Bacterial QS is being contemplated as a promising target for developing novel antibacterial agents. QS inhibitors are a promising strategy for treating chronic infections. This study reported that the active compound PT22 (1H-pyrrole-2,5-dicarboxylic acid) isolated from Perenniporia tephropora FF2, one endophytic fungus from Areca catechu L., presents QS inhibitory activity against P. aeruginosa. Combined with gentamycin or piperacillin, PT22 functions as a novel antibiotic accelerant against P. aeruginosa. PT22 (0.50 mg/mL, 0.75 mg/mL, and 1.00 mg/mL) reduces the production of QS-related virulence factors, such as pyocyanin and rhamnolipid, and inhibits biofilm formation of P. aeruginosa PAO1 instead of affecting its growth. The architectural disruption of the biofilms was confirmed by visualization through scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Real-time quantitative PCR (RT-qPCR) indicated that PT22 significantly attenuated the expression of QS-related genes followed by docking analysis of molecules against QS activator proteins. PT22 dramatically increased the survival rate of Galleria mellonella. PT22 combined with gentamycin or piperacillin presents significant inhibition of biofilm formation and eradication of mature biofilm compared to monotherapy, which was also confirmed by visualization through SEM and CLSM. After being treated with PT22 combined with gentamycin or piperacillin, the survival rates of G. mellonella were significantly increased compared to those of monotherapy. PT22 significantly enhanced the susceptibility of gentamycin and piperacillin against P. aeruginosa PAO1. Our results suggest that PT22 from P. tephropora FF2 as a potent QS inhibitor is a candidate antibiotic accelerant to combat the antibiotic resistance of P. aeruginosa.

Carbon Dots: A Review with Focus on Sustainability.

Carbon dots (CDs) are an emerging class of nanomaterials with attractive optical properties, which promise to enable a variety of applications. An important and timely question is whether CDs can become a functional and sustainable alternative to incumbent optical nanomaterials, notably inorganic quantum dots. Herein, the current CD literature is comprehensively reviewed as regards to their synthesis and function, with a focus on sustainability aspects. The study quantifies why it is attractive that CDs can be synthesized with biomass as the sole starting material and be free from toxic and precious metals and critical raw materials. It further describes and analyzes employed pretreatment, chemical-conversion, purification, and processing procedures, and highlights current issues with the usage of solvents, the energy and material efficiency, and the safety and waste management. It is specially shown that many reported synthesis and processing methods are concerningly wasteful with the utilization of non-sustainable solvents and energy. It is finally recommended that future studies should explicitly consider and discuss the environmental influence of the selected starting material, solvents, and generated byproducts, and that quantitative information on the required amounts of solvents, consumables, and energy should be provided to enable an evaluation of the presented methods in an upscaled sustainability context.

Corrigendum: Disease spectrum, prevalence, genetic characteristics of inborn errors of metabolism in 21,840 hospitalized infants in Chongqing, China, 2017-2022.

[This corrects the article DOI: 10.3389/fgene.2024.1395988.].

Dual orexin receptor antagonist ameliorates sleep deprivation-induced learning and memory impairment in APP/PS1 mice.

Sleep is considered closely related to cognitive function, and cognitive impairment is the main clinical manifestation of Alzheimer's disease (AD). Sleep disturbance in AD patients is more severe than that in healthy elderly individuals. Additionally, sleep deprivation reportedly increases the activity of the hypothalamic orexin system and the risk of AD. To investigate whether intervention with the orexin system can improve sleep disturbance in AD and its impact on AD pathology. In this study, six-month-old amyloid precursor protein/presenilin 1 mice were subjected to six weeks of chronic sleep deprivation and injected intraperitoneally with almorexant, a dual orexin receptor antagonist (DORA), to investigate the effects and mechanisms of sleep deprivation and almorexant intervention on learning and memory in mice with AD. We found that sleep deprivation aggravated learning and memory impairment and increased brain ß-amyloid (Aß) deposition in mice with AD. The application of almorexant can increase the total sleep time of sleep-deprived mice and reduce cognitive impairment and Aß deposition, which is related to the improvement in Aquaporin-4 polarity. Thus, DORA may be an effective strategy for delaying the progression of AD patients by improving the sleep disturbances.

Clinical biomarker-based biological aging and risk of benign prostatic hyperplasia: A large prospective cohort study.

Objective: Chronological age (CAge), biological age (BAge), and accelerated age (AAge) are all important for aging-related diseases. CAge is a known risk factor for benign prostatic hyperplasia (BPH); However, the evidence of association of BAge and AAge with BPH is limited. This study aimed to evaluate the association of CAge, Bage, and AAge with BPH in a large prospective cohort. Method: A total of 135,933 males without BPH at enrolment were extracted from the UK biobank. We calculated three BAge measures (Klemera-Doubal method, KDM; PhenoAge; homeostatic dysregulation, HD) based on 16 biomarkers. Additionally, we calculated KDM-BAge and PhenoAge-BAge measures based on the Levine method. The KDM-AAge and PhenoAge-AAge were assessed by the difference between CAge and BAge and were standardized (mean = 0 and standard deviation [SD] = 1). Cox proportional hazard models were applied to assess the associations of CAge, Bage, and AAge with incident BPH risk. Results: During a median follow-up of 13.150 years, 11,811 (8.690%) incident BPH were identified. Advanced CAge and BAge measures were associated with an increased risk of BPH, showing threshold effects at a later age (all P for nonlinearity <0.001). Nonlinear relationships between AAge measures and risk of BPH were also found for KDM-AAge (P = 0.041) and PhenoAge-AAge (P = 0.020). Compared to the balance comparison group (-1 SD < AAge < 1 SD), the accelerated aging group (AAge > 2 SD) had a significantly elevated BPH risk with hazard ratio (HR) of 1.115 (95% CI, 1.000-1.223) for KDM-AAge and 1.180 (95% CI, 1.068-1.303) for PhenoAge-AAge, respectively. For PhenoAge-AAge, subgroup analysis of the accelerated aging group showed an increased HR of 1.904 (95% CI, 1.374-2.639) in males with CAge <50 years and 1.233 (95% CI, 1.088-1.397) in those having testosterone levels <12 nmol/L. Moreover, AAge-associated risk of BPH was independent of and additive to genetic risk. Conclusions: Biological aging is an independent and modifiable risk factor for BPH. We suggest performing active health interventions to slow biological aging, which will help mitigate the progression of prostate aging and further reduce the burden of BPH.

Cardiometabolic multimorbidity, peripheral biomarkers, and dementia in rural older adults: The MIND-China study.

INTRODUCTION: Evidence has emerged that cardiometabolic multimorbidity (CMM) is associated with dementia, but the underlying mechanisms are poorly understood. METHODS: This population-based study included 5704 older adults. Of these, data were available in 1439 persons for plasma amyloid-ß (Aß), total tau, and neurofilament light chain (NfL) and in 1809 persons for serum cytokines. We defined CMM following two common definitions used in previous studies. Data were analyzed using general linear, logistic, and mediation models. RESULTS: The presence of CMM was significantly associated with an increased likelihood of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) (p < 0.05). CMM was significantly associated with increased plasma Aß40, Aß42, and NfL, whereas CMM that included visceral obesity was associated with increased serum cytokines. The mediation analysis suggested that plasma NfL significantly mediated the association of CMM with AD. DISCUSSION: CMM is associated with dementia, AD, and VaD in older adults. The neurodegenerative pathway is involved in the association of CMM with AD. HIGHLIGHTS: The presence of CMM was associated with increased likelihoods of dementia, AD, and VaD in older adults. CMM was associated with increased AD-related plasma biomarkers and serum inflammatory cytokines. Neurodegenerative pathway was partly involved in the association of CMM with AD.

Population coding for figure-ground texture segregation in macaque V1 and V4.

Object recognition often involves the brain segregating objects from their surroundings. Neurophysiological studies of figure-ground texture segregation have yielded inconsistent results, particularly on whether V1 neurons can perform figure-ground texture segregation or just detect texture borders. To address this issue from a population perspective, we utilized two-photon calcium imaging to simultaneously record the responses of large samples of V1 and V4 neurons to figure-ground texture stimuli in awake, fixating macaques. The average response changes indicate that V1 neurons mainly detect texture borders, while V4 neurons are involved in figure-ground segregation. However, population analysis (SVM decoding of PCA-transformed neuronal responses) reveal that V1 neurons not only detect figure-ground borders, but also contribute to figure-ground texture segregation, although requiring substantially more principal components than V4 neurons to reach a 75 % decoding accuracy. Individually, V1/V4 neurons showing larger (negative/positive) figure-ground response differences contribute more to figure-ground segregation. But for V1 neurons, the contribution becomes significant only when many principal components are considered. We conclude that V1 neurons participate in figure-ground segregation primarily by defining the figure borders, and the poorly structured figure-ground information V1 neurons carry could be further utilized by V4 neurons to accomplish figure-ground segregation.

Visuospatial dysfunction predicts dementia-first phenoconversion in isolated REM sleep behaviour disorder.

OBJECTIVE: While isolated rapid eye movement sleep behaviour disorder (iRBD) is known as a prodrome of α-synucleinopathies, the prediction for its future phenoconversion to parkinsonism-first or dementia-first subtype remains a challenge. This study aimed to investigate whether visuospatial dysfunction predicts dementia-first phenoconversion in iRBD. METHODS: Patients with iRBD and control subjects were enrolled in this prospective cohort study. Baseline neuropsychological assessment included the Unified Parkinson's Disease Rating Scale part III, Montreal Cognitive Assessment (MoCA), Rey-Osterrieth complex figure (ROCF), Colour Trails test (CTT), Farnsworth-Munsell 100-hue test and Digit Span test. The anterior and posterior subscores of MoCA as well as their modified versions were explored. A composite score derived from ROCF and CTT was also explored. Regular follow-up was conducted to determine the phenoconversion status of iRBD patients. RESULTS: The study included 175 iRBD patients and 98 controls. During a mean follow-up of 5.1 years, 25.7% of patients experienced phenoconversion. Most of the neuropsychological tests could differentiate dementia-first but not parkinsonism-first convertors from non-convertors. The modified posterior subscore of MoCA, by integrating the Alternating Trail Making and Clock Drawing components into original the posterior subscore, which mainly reflects visuospatial function, was the strongest predictor for dementia-first phenoconversion (adjusted HR 5.48, 95% CI 1.67 to 17.98). CONCLUSION: Visuospatial dysfunction, as reflected mainly by the modified posterior subscore of MoCA, is a predictive factor for dementia-first phenoconversion in iRBD, suggesting its potential for being a biomarker for clinical prognostic prediction and potential neuroprotective trials aiming to delay or prevent dementia.

Prognostic implications of preoperative, postoperative, and dynamic changes of alpha-fetoprotein and des-gamma (γ)-carboxy prothrombin expression pattern for hepatocellular carcinoma after hepatic resection: a multicenter observational study.

Background: The utility of pre- and post-operative alpha-fetoprotein (AFP) and des-gamma (γ)-carboxy prothrombin (DCP) expression patterns and their dynamic changes as predictors of the outcome of hepatic resection for hepatocellular carcinoma (HCC) has yet to be well elucidated. Methods: From a multicenter database, AFP and DCP data during the week prior to surgery and the first post-discharge outpatient visit (within 1-2 months after surgery) were collected from patients with HCC who underwent hepatectomy. AFP-DCP expression patterns were categorized according to the number of positive tumor markers (AFP ≥ 20ng/mL, DCP ≥ 40mAU/mL), including double-negative, single-positive, and double-positive. Changes in the AFP-DCP expression patterns were delineated based on variations in the number of positive tumor markers when comparing pre- and post-operative patterns. Results: Preoperatively, 53 patients (8.3%), 337 patients (52.8%), and 248 patients (38.9%) exhibited double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Postoperatively, 463 patients (72.6%), 130 patients (20.4%), and 45 patients (7.0%) showed double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Survival analysis showed a progressive decrease in recurrence-free (RFS) and overall survival (OS) as the number of postoperative positive tumor markers increased (both P < 0.001). Multivariate analysis showed that postoperative AFP-DCP expression pattern, but not preoperative AFP-DCP expression pattern, was an independent risk factor for RFS and OS. Further analysis showed that for patients with positive preoperative markers, prognosis gradually improves as positive markers decrease postoperatively. In particular, when all postoperative markers turned negative, the prognosis was consistent with that of preoperative double-negative patients, regardless of the initial number of positive markers. Conclusions: AFP-DCP expression patterns, particularly postoperative patterns, serve as vital sources of information for prognostic evaluation following hepatectomy for HCC. Moreover, changes in AFP-DCP expression patterns from pre- to post-operation enable dynamic prognostic risk stratification postoperatively, aiding the development of individualized follow-up strategies.