Wearable, Biocompatible, and Dual-Emission Ocular Multisensor Patch for Continuous Profiling of Fluoroquinolone Antibiotics in Tears.

The abuse or misuse of antibiotics in clinical and agricultural settings severely endangers human health and ecosystems, which has raised profound concerns for public health worldwide. Trace detection and reliable discrimination of commonly used fluoroquinolone (FQ) antibiotics and their analogues have consequently become urgent to guide the rational use of antibiotic medicines and deliver efficient treatments for associated diseases. Herein, we report a wearable eye patch integrated with a quadruplex nanosensor chip for noninvasive detection and discrimination of primary FQ antibiotics in tears during routine eyedrop treatment. A set of dual-mode fluorescent nanoprobes of red- or green-emitting CdTe quantum dots integrated with lanthanide ions and a sensitizer, adenosine monophosphate, were constructed to provide an enhanced fluorescence up to 45-fold and nanomolar sensitivity toward major FQs owing to the aggregation-regulated antenna effect. The aggregation-driven, CdTe-Ln(III)-based microfluidic sensor chip is highly specific to FQ antibiotics against other non-FQ counterparts or biomolecular interfering species and is able to accurately discriminate nine types of FQ or non-FQ eyedrop suspensions using linear discriminant analysis. The prototyped wearable sensing detector has proven to be biocompatible and nontoxic to human tissues, which integrates the entire optical imaging modules into a miniaturized, smartphone-based platform for field use and reduces the overall assay time to ∼5 min. The practicability of the wearable eye patch was demonstrated through accurate quantification of antibiotics in a bactericidal event and the continuous profiling of FQ residues in tears after using a typical prescription antibiotic eyedrop. This technology provides a useful supplement to the toolbox for on-site and real-time examination and regulation of inappropriate daily drug use that might potentially lead to long-term antibiotic abuse and has great implications in advancing personal healthcare techniques for the regulation of daily medication therapy.

Black phosphorus quantum dot-modified ADSCs as a novel therapeutic for periodontitis bone loss coupling of osteogenesis and osteoimmunomodulation.

Alveolar bone defect repair remains a persistent clinical challenge for periodontitis treatment. The use of peripheral functional seed cells is a hot topic in periodontitis. Herein, we explored the cellular behaviors and osteogenic ability of adipose-derived mesenchymal stem cells (ADSCs) treated with black phosphorus quantum dots (BPQDs). Additionally, macrophage polarization, osteogenic effects and angiogenesis were investigated through the paracrine pathway regulated by BPQD-modified ADSCs. Our results demonstrated that BPQDs showed good biocompatibility with ADSCs and BPQD-modified ADSCs could improve the bone repair in vivo inflammatory microenvironment by regulating osteogenesis and osteoimmunomodulation. The BPQDs increased the osteogenic differentiation of ADSCs via the Wnt/ß-catenin and BMP2/SMAD5/Runx2 signaling pathway. In addition, BPQD-modified ADSCs promoted the osteogenic effect of BMSCs and facilitated the polarization of macrophages from M1 towards M2 phenotype transformation through the paracrine pathway in the periodontitis microenvironment. This strategy provides a novel idea for treatment of alveolar bone defects for periodontitis in the foreseeable future.

Aquaporin mediated silicon-enhanced root hydraulic conductance is benefit to cadmium dilution in tobacco seedlings.

Numerous studies shown that silicon (Si) enhanced plants' resistance to cadmium (Cd). Most studies primarily focused on investigating the impact of Si on Cd accumulation. However, there is a lack of how Si enhanced Cd resistance through regulation of water balance. The study demonstrated that Si had a greater impact on increasing fresh weight compared to dry weight under Cd stress. This effect was mainly attributed to Si enhanced plant relative water content (RWC). Plant water content depends on the dynamic balance of water loss and water uptake. Our findings revealed that Si increased transpiration rate and stomatal conductance, leading to higher water loss. This, in turn, negatively impacted water content. The increased water content caused by Si could ascribe to improve root water uptake. The Si treatment significantly increased root hydraulic conductance (Lpr) by 131 % under Cd stress. This enhancement was attributed to Si upregulation genes expression of NtPIP1;1, NtPIP1;2, NtPIP1;3, and NtPIP2;1. Through meticulously designed scientific experiments, this study showed that Si enhanced AQP activity, leading to increased water content that diluted Cd concentration and ultimately improved plant Cd resistance. These findings offered fresh insights into the role of Si in bolstering plant resistance to Cd.

Increasing Multienzyme Cascade Efficiency and Stability of MOF via Partitioning Immobilization.

Enhancing the stability of multienzyme cascade reactions in metal-organic frameworks (MOFs) is a challenging task in the fields of biotechnology and chemistry. However, addressing this challenge could yield far-reaching benefits across the application range in the biomedical, food, and environmental sectors. In this study, multienzyme partitioning immobilization that sequentially immobilizes cascade enzymes with hierarchical MOFs is proposed to reduce substrate diffusion resistance. Conversion results of ginsenosides indicate that this strategy improves the cascade efficiency up to 1.26 times. The substrate diffusion model is used to investigate the dual-interenzyme mass transfer behavior of substrates in the restricted domain space and evaluate the substrate channeling effect under partitioning immobilization. Molecular docking and kinetic simulations reveal that the MOFs effectively limit the conformational changes of cascade enzymes at high temperatures and in organic solvents while maintaining a large pocket of active centers. This phenomenon increased efficient substrate docking to the enzyme molecules, further optimizing cascade efficiency. The results of the immobilization of GOX and horseradish peroxidase as model enzymes indicate that the partitioned MOF immobilization strategy could be used for universal adaptation of cascade enzymes.

Variety-dependent responses of common tobacco with differential cadmium resistance: Cadmium uptake and distribution, antioxidative activity, and gene expression.

Cadmium (Cd), which accumulates in tobacco leaves, enters the human body through inhalation of smoke, causing harmful effects on health. Therefore, identifying the pivotal factors that govern the absorption and resistance of Cd in tobacco is crucial for mitigating the harmful impact of Cd. In the present study, four different Cd-sensitive varieties, namely, ZhongChuan208 (ZC) with resistance, ZhongYan100 (ZY), K326 with moderate resistance, and YunYan87 (YY) with sensitivity, were cultivated in hydroponic with different Cd concentrations (20 µM, 40 µM, 60 µM and 80 µM). The results indicated that plant growth was significantly decreased by Cd. Irrespective of the Cd concentration, ZC exhibited the highest biomass, while YY had the lowest biomass; ZY and K326 showed intermediate levels. Enzymatic (APX, CAT, POD) and nonenzymatic antioxidant (Pro, GSH) systems showed notable variations among varieties. The multifactor analysis suggested that the ZC and ZY varieties, with higher levels of Pro and GSH content, contribute to a decrease in the levels of MDA and ROS. Among all the Cd concentrations, ZC exhibited the lowest Cd accumulation, while YY showed the highest. Additionally, there were significant differences observed in Cd distribution and translocation factors among the four different varieties. In terms of Cd distribution, cell wall Cd accounted for the highest proportion of total Cd, and organelles had the lowest proportion. Among the varieties, ZC showed lower Cd levels in the cell wall, soluble fraction, and organelles. Conversely, YY exhibited the highest Cd accumulation in all tissues; K326 and ZY had intermediate levels. Translocation factors (TF) varied among the varieties under Cd stress, with ZC and ZY showing lower TF compared to YY and K326. This phenomenon mainly attributed to regulation of the NtNramp3 and NtNramp5 genes, which are responsible for the absorption and transport of Cd. This study provides a theoretical foundation for the selection and breeding of tobacco varieties that are resistant to or accumulate less Cd.

Discovery of Antimicrobial Lysins from the "Dark Matter" of Uncharacterized Phages Using Artificial Intelligence.

The rapid rise of antibiotic resistance and slow discovery of new antibiotics have threatened global health. While novel phage lysins have emerged as potential antibacterial agents, experimental screening methods for novel lysins pose significant challenges due to the enormous workload. Here, the first unified software package, namely DeepLysin, is developed to employ artificial intelligence for mining the vast genome reservoirs ("dark matter") for novel antibacterial phage lysins. Putative lysins are computationally screened from uncharacterized Staphylococcus aureus phages and 17 novel lysins are randomly selected for experimental validation. Seven candidates exhibit excellent in vitro antibacterial activity, with LLysSA9 exceeding that of the best-in-class alternative. The efficacy of LLysSA9 is further demonstrated in mouse bloodstream and wound infection models. Therefore, this study demonstrates the potential of integrating computational and experimental approaches to expedite the discovery of new antibacterial proteins for combating increasing antimicrobial resistance.

Noninvasive imaging-guided ultrasonic neurostimulation with arbitrary 2D patterns and its application for high-quality vision restoration.

Retinal degeneration, a leading cause of irreversible low vision and blindness globally, can be partially addressed by retina prostheses which stimulate remaining neurons in the retina. However, existing electrode-based treatments are invasive, posing substantial risks to patients and healthcare providers. Here, we introduce a completely noninvasive ultrasonic retina prosthesis, featuring a customized ultrasound two-dimensional array which allows for simultaneous imaging and stimulation. With synchronous three-dimensional imaging guidance and auto-alignment technology, ultrasonic retina prosthesis can generate programmed ultrasound waves to dynamically and precisely form arbitrary wave patterns on the retina. Neuron responses in the brain's visual center mirrored these patterns, evidencing successful artificial vision creation, which was further corroborated in behavior experiments. Quantitative analysis of the spatial-temporal resolution and field of view demonstrated advanced performance of ultrasonic retina prosthesis and elucidated the biophysical mechanism of retinal stimulation. As a noninvasive blindness prosthesis, ultrasonic retina prosthesis could lead to a more effective, widely acceptable treatment for blind patients. Its real-time imaging-guided stimulation strategy with a single ultrasound array, could also benefit ultrasound neurostimulation in other diseases.

Projection Test for Mean Vector in High Dimensions.

This paper studies the projection test for high-dimensional mean vectors via optimal projection. The idea of projection test is to project high-dimensional data onto a space of low dimension such that traditional methods can be applied. We first propose a new estimation for the optimal projection direction by solving a constrained and regularized quadratic programming. Then two tests are constructed using the estimated optimal projection direction. The first one is based on a data-splitting procedure, which achieves an exact t-test under normality assumption. To mitigate the power loss due to data-splitting, we further propose an online framework, which iteratively updates the estimation of projection direction when new observations arrive. We show that this online-style projection test asymptotically converges to the standard normal distribution. Various simulation studies as well as a real data example show that the proposed online-style projection test retains the type I error rate well and is more powerful than other existing tests.

RANK-BASED INDICES FOR TESTING INDEPENDENCE BETWEEN TWO HIGH-DIMENSIONAL VECTORS.

To test independence between two high-dimensional random vectors, we propose three tests based on the rank-based indices derived from Hoeffding's D, Blum-Kiefer-Rosenblatt's R and Bergsma-Dassios-Yanagimoto's τ*. Under the null hypothesis of independence, we show that the distributions of the proposed test statistics converge to normal ones if the dimensions diverge arbitrarily with the sample size. We further derive an explicit rate of convergence. Thanks to the monotone transformation-invariant property, these distribution-free tests can be readily used to generally distributed random vectors including heavily tailed ones. We further study the local power of the proposed tests and compare their relative efficiencies with two classic distance covariance/correlation based tests in high dimensional settings. We establish explicit relationships between D,R,τ* and Pearson's correlation for bivariate normal random variables. The relationships serve as a basis for power comparison. Our theoretical results show that under a Gaussian equicorrelation alternative, (i) the proposed tests are superior to the two classic distance covariance/correlation based tests if the components of random vectors have very different scales; (ii) the asymptotic efficiency of the proposed tests based on D,τ* and R are sorted in a descending order.

Long, short, and medium terms wind speed prediction model based on LSTM optimized by improved moth flame optimization algorithm.

Time series prediction of wind speed has been widely used in wind power generation. The volatility and instability of wind speed have a large negative impact on wind turbines and power systems, which can lead to grid collapse in severe cases. Therefore, accurate wind speed prediction is crucial for wind power generation. In this paper, considering the influence of different parameters on algorithm training and prediction, an improved moth flame optimization algorithm is constructed to optimize the LSTM wind energy prediction system to obtain better performance. The system consists of three modules: data preprocessing, optimization, and prediction. The data preprocessing module uses fuzzy information granulation to blur the input data. On this basis, the combination of swarm intelligent optimization algorithm and prediction model can effectively predict wind speed time series. Taking the California wind farm as an example, the MAPE of the experiment in the short-term forecast is 3.15%, the MAPE of the medium-term forecast is 4.38%, and the MAPE of the long-term forecast is 18.28%. The experimental results show that the proposed model has obvious advantages over the previous model.

Lavender essential oil alleviates depressive-like behavior in alcohol-withdrawn rats: Insights from gut metabolites and hippocampal transcriptome analysis.

Lavender, an aromatic plant with a history dating back to ancient Egypt and Greece, is consumed because of its diverse pharmacological properties, including sedation, sleep aid, and antidepressant effects. However, the mechanisms underlying these antidepressant properties remain unclear. In this study, we explored the impact of lavender essential oil (LEO) inhalation on the diversity of gut microbiota, metabolites, and differential gene expression in the hippocampus of alcohol-withdrawn depressive rats. Additionally, we examined alterations in the hippocampal transient receptor potential (TRP) channel-mediated inflammatory regulation within the brain-gut axis of depressive rats. The results demonstrated a significant decrease in sucrose preference, diminished activity in the central zone of the open field test, and prolonged immobility time in the forced swim test in alcohol-withdrawn depressive rats, indicating the amelioration of depressive states following lavender essential oil inhalation. 16 S rDNA sequencing analysis revealed a significant reduction in Bacteroidota and Muribaculaceae in the gut of alcohol-withdrawn depressive rats, whereas lavender essential oil significantly increased the relative abundance of Muribaculaceae and other bacterial species. Metabolomic analysis identified 646 distinct metabolites as highly correlated biomarkers between the model and lavender essential oil groups. Furthermore, lavender essential oil inhalation significantly attenuated hippocampal inflammatory factors IL-2, IL-6, IL-1ß, and TNF-α. This study identified elevated expression of Trpv4 and Calml4 in the hippocampal region of alcohol-withdrawn depressed rats and showed that lavender essential oil inhalation regulated aberrantly expressed genes. Our research suggests that lavender essential oil downregulates Trpv4, modulates inflammatory factors, and alleviates depressive-like behavior in alcohol withdrawal rats.

The role and mechanism of PDZ binding kinase in hypobaric and hypoxic acute lung injury.

Background: Acute lung injury (ALI) caused by hypobaric hypoxia (HH) is frequently observed in high-altitude areas, and it is one of the leading causes of death in high-altitude-related diseases due to its rapid onset and progression. However, the pathogenesis of HH-related ALI (HHALI) remains unclear, and effective treatment approaches are currently lacking. Methods: A new mouse model of HHALI developed by our laboratory was used as the study subject (Chinese patent No. ZL 2021 1 1517241 X). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the messenger RNA (mRNA) expression levels of PDZ-binding kinase (PBK), sirtuin 1 (SIRT1), and PTEN-induced kinase 1 (PINK1) in mouse lung tissue. Hematoxylin and eosin staining was used to observe the main types of damage and damaged cells in lung tissue, and the lung injury score was used for quantification. The wet-dry (W/D) ratio was used to measure lung water content. Enzyme-linked immunosorbent assay was used to detect changes in inflammatory factors and oxidative stress markers in the lungs. Western blotting verified the expression of various mitochondrial autophagy-related proteins. The 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi-dazoylcarbocyanine iodide (JC-1) method was used determined the health status of mitochondria based on changes in mitochondrial membrane potential. Transmission electron microscopy was used to directly observe the morphology of mitochondria. Multicolor immunofluorescence was used to observe the levels of mitochondrial autophagy markers. Other signaling pathways and molecular mechanisms that may play a role in epithelial cells were analyzed via through RNA sequencing. Results: Low pressure and hypoxia caused pathological changes in mouse lung tissue, mainly ALI, leading to increased levels of inflammatory factors and intensified oxidative stress response in the lungs. Overexpression of PBK was found to alleviate HHALI, and activation of the p53 protein was shown to abrogate this therapeutic effect, while activation of SIRT1 protein reactivated this therapeutic effect. The therapeutic effect of PBK on HHALI is achieved via the activation of mitochondrial autophagy. Finally, RNA sequencing demonstrated that besides mitochondrial autophagy, PBK also exerts other functions in HHALI. Conclusions: Overexpression of PBK inhibits the expression of p53 and activates SIRT1-PINK1 axis mediated mitochondrial autophagy to alleviate HHALI.

The circMYBL2-encoded p185 protein suppresses colorectal cancer progression by inhibiting serine biosynthesis.

Circular RNAs (circRNAs) are a class of covalently closed single-stranded loop RNAs that have been implicated to play a functional role in almost all types of cancers. Previous studies have revealed that circMYBL2 acts as a tumor-promoting circRNA. Here, we found that circMYBL2 in colorectal cancer (CRC) encodes a 185-amino acid protein, p185. Functionally, circMYBL2-encoded p185 suppressed the growth and aggressiveness of CRC cells in vitro and in vivo. Mechanistically, p185 counteracted UCHL3-mediated deubiquitination of phosphoglycerate dehydrogenase (PHGDH) by competitively binding to the C1 domain of UCHL3, resulting in PHGDH degradation and a subsequent reduction in serine and glycine biosynthesis. These data revealed that the circMYBL2-encoded p185 isoform serves as a tumor suppressor to inhibit the progression of CRC by reducing serine biosynthesis.

The presence of micropapillary and/or solid subtypes is an independent prognostic factor for patients undergoing curative resection for stage I lung adenocarcinoma with ground-glass opacity.

Background: Non-predominant or even minimal micropapillary and/or solid (MP/S) subtypes have been reported to exert an unfavorable prognostic influence on surgically resected lung adenocarcinoma (ADC). Currently, there is a lack of evidence to demonstrate that high-grade pathological subtypes, including MP/S components, impact the prognosis of patients with surgically resected lung ADCs with ground-glass opacity (GGO). In this investigation, we explored the prognostic implications of minimal MP/S components in lung ADCs with GGO. Methods: A retrospective cohort study was conducted on 1,004 consecutive patients undergoing curative resection for pathologic stage (p-stage) I lung ADCs featuring GGO on computed tomography (CT) scans between January 2014 and December 2016. Tumors were categorized into MP/S positive (MP/S+) group and MP/S negative (MP/S-) group. MP/S+ tumors were defined when MP/S subtypes constituted ≥1% of the entire tumor. The prognostic impact of MP/S subtypes was evaluated using Kaplan-Meier analysis, Cox proportional hazard model and restricted cubic spine (RCS) model. Results: A total of 86 (8.6%) cases with MP/S+ tumors and 918 (91.4%) cases with MP/S- tumors were identified. The solid component tumor diameter and pathological invasive tumor size of MP/S+ tumors were both significantly larger than that of MP/S- tumors (13.0 vs. 4.0 mm, P<0.001, and 18.0 vs. 10.0 mm, P<0.001, respectively). After a median follow-up of 7.3 years, the presence of MP/S components was significantly associated with decreased RFS (5-year RFS, MP/S+ 88.3% vs. MP/S- 97.4%; P<0.001; HR =1.02). The presence of a histologic lepidic (Lep) component demonstrated a prognostic advantage in both MP/S- (5-year RFS, MP/S-Lep+ 98.0% vs. MP/S-Lep- 95.3%; P=0.01; HR =0.89) and MP/S+ subgroups (5-year RFS, MP/S+Lep+ 93.4% vs. MP/S+Lep- 83.2%; P=0.10; HR =0.84). MP/S+ components ≥5% were the only tumor-related factor that independently affected RFS [hazard ratio (HR) =1.77; 95% confidence interval (CI): 1.07-2.94] according to multivariate analysis. There was a progressively negative impact of the proportion of MP/S subtypes on RFS as illustrated by RCS model. Conclusions: The presence of MP/S patterns in stage I GGO-featured lung ADCs exhibit significant prognostic value and may have implications for tailored postoperative treatment and surveillance strategies, especially when the proportion exceeds 5% of the entire tumor.

ESKtides: a comprehensive database and mining method for ESKAPE phage-derived antimicrobial peptides.

'Superbugs' have received increasing attention from researchers, such as ESKAPE bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.), which directly led to about 1 270 000 death cases in 2019. Recently, phage peptidoglycan hydrolases (PGHs)-derived antimicrobial peptides were proposed as new antibacterial agents against multidrug-resistant bacteria. However, there is still a lack of methods for mining antimicrobial peptides based on phages or phage PGHs. Here, by using a collection of 6809 genomes of ESKAPE isolates and corresponding phages in public databases, based on a unified annotation process of all the genomes, PGHs were systematically identified, from which peptides were mined. As a result, a total of 12 067 248 peptides with high antibacterial activities were respectively determined. A user-friendly tool was developed to predict the phage PGHs-derived antimicrobial peptides from customized genomes, which also allows the calculation of peptide phylogeny, physicochemical properties, and secondary structure. Finally, a user-friendly and intuitive database, ESKtides (http://www.phageonehealth.cn:9000/ESKtides), was designed for data browsing, searching and downloading, which provides a rich peptide library based on ESKAPE prophages and phages. Database URL:  10.1093/database/baae022.

Role of LGL1 in cerebellar primordium of embryonic mice.

Lethal giant larvae 1 (LGL1) is originally recognized as a tumor suppressor, implicated in maintaining cell polarity in Drosophila and mammalian cells. Cell polarity plays a crucial role in tumorigenesis. We previously established Pax2-LGL1 -/- conditional knockout mice but did not focus on the tumorigenesis in cerebellar primordium. HE staining was used to detect the morphological structure of the cerebellar primordium during early embryonic development in Pax2-LGL1 -/- mice. Immunofluorescence assays were used to detect the expression of polar molecules. TUNEL staining assessed tissue apoptosis. Our findings reveal that deletion of LGL1 leads to the emergence of neuroblastoma-like tissues within the cerebellum primordium during early embryogenesis. This outcome can be attributed to alterations in expression patterns of polar molecules Cdc42 and ß-catenin following early deletion of LGL1, resulting in loss of cell polarity among neuroepithelial cells and subsequent formation of tumor-like tissues. However, further histological examination demonstrated that these tumor-like tissues disappear from embryonic day 15.5 onwards within the cerebellar primordium of Pax2-LGL1 -/- mice due to apoptosis-mediated cellular compensation. Our data emphasize the importance of LGL1 in maintaining neuroepithelial cell polarity and reveal a novel role for LGL1 in regulating tumorigenesis and ablation in the cerebellar primordium.

Navigating the landscapes of spatial transcriptomics: How computational methods guide the way.

Spatially resolved transcriptomics has been dramatically transforming biological and medical research in various fields. It enables transcriptome profiling at single-cell, multi-cellular, or sub-cellular resolution, while retaining the information of geometric localizations of cells in complex tissues. The coupling of cell spatial information and its molecular characteristics generates a novel multi-modal high-throughput data source, which poses new challenges for the development of analytical methods for data-mining. Spatial transcriptomic data are often highly complex, noisy, and biased, presenting a series of difficulties, many unresolved, for data analysis and generation of biological insights. In addition, to keep pace with the ever-evolving spatial transcriptomic experimental technologies, the existing analytical theories and tools need to be updated and reformed accordingly. In this review, we provide an overview and discussion of the current computational approaches for mining of spatial transcriptomics data. Future directions and perspectives of methodology design are proposed to stimulate further discussions and advances in new analytical models and algorithms. This article is categorized under: RNA Methods > RNA Analyses in Cells RNA Evolution and Genomics > Computational Analyses of RNA RNA Export and Localization > RNA Localization.

Tumor characteristics, brain functional activity, and connectivity of tinnitus in patients with vestibular schwannoma: a pilot study.

Background: The mechanism underlying tinnitus remains unclear, and when it coexists with vestibular schwannoma (VS), it can significantly diminish the quality of life for affected patients. This study aimed to determine the correlation between preoperative clinical characteristics of VS, postoperative changes in brain function, and tinnitus in patients with VS through a cohort study. Methods: We collected data from 80 patients with VS preoperatively and 28 patients with VS preoperatively and postoperatively, and recruited 28 healthy controls. We used Chi-squared tests and unpaired t-tests to identify clinical characteristics with a significant preoperative effect. We used paired t-tests to identify brain regions where patients demonstrated significant changes in amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) postoperatively. Tinnitus severity was evaluated using the Tinnitus Handicap Inventory (THI) and Visual Analogue Scale (VAS). Pearson correlation coefficients were applied to assess the relationship between the changes in ALFF and ReHo and the changes in THI and VAS scores postoperatively. We also conducted seed- and region of interest (ROI)-based functional connectivity (FC) analyses. Results: Before surgery, patients with VS with tinnitus (n=49) had smaller tumors (t=3.293; P<0.001), more solid tumor (χ2=4.559; P=0.033), and less extrusion into the cerebellum brain stem (χ2=10.345; P=0.001) than those without tinnitus (n=31). After surgery, the 28 patients with VS showed a significant reduction in ALFF in the left Cerebellum_Crus2 (a lobule in the cerebellum anatomy) (ROI 1) and a significant reduction in ReHo in the left Cerebellum_Crus1 (a lobule in the cerebellum anatomy) (ROI 2) and the right precuneus (ROI 3). Conversely, ReHo was significantly increased in the right precentral gyrus (ROI 4) [cluster-level P value family-wise error (PFWE) <0.05]. The changes in ALFF values were negatively correlated with changes in the VAS score (r=-0.32; P<0.05). The FC strengths of patients between ROI 2 and the left and right posterior cingulate gyrus were significantly decreased postoperatively [false discovery rate (FDR) correction; P<0.05]. Conclusions: Preoperative tinnitus in patients with VS may be influenced by tumor characteristics. The functional activities of brain regions are possibly altered postoperatively, which may be involved in the maintenance of postoperative tinnitus. Notably, the changes in ALFF are correlated with tinnitus.

Development and validation of a clinic-radiological model to predict tumor spread through air spaces in stage I lung adenocarcinoma.

OBJECTIVES: Tumor spread through air spaces (STAS) is associated with poor prognosis and impacts surgical options. We aimed to develop a user-friendly model based on 2-[18F] FDG PET/CT to predict STAS in stage I lung adenocarcinoma (LAC). MATERIALS AND METHODS: A total of 466 stage I LAC patients who underwent 2-[18F] FDG PET/CT examination and resection surgery were retrospectively enrolled. They were split into a training cohort (n = 232, 20.3% STAS-positive), a validation cohort (n = 122, 27.0% STAS-positive), and a test cohort (n = 112, 29.5% STAS-positive) according to chronological order. Some commonly used clinical data, visualized CT features, and SUVmax were analyzed to identify independent predictors of STAS. A prediction model was built using the independent predictors and validated using the three chronologically separated cohorts. Model performance was assessed using ROC curves and calculations of AUC. RESULTS: The differences in age (P = 0.009), lesion density subtype (P < 0.001), spiculation sign (P < 0.001), bronchus truncation sign (P = 0.001), and SUVmax (P < 0.001) between the positive and negative groups were statistically significant. Age ≥ 56 years [OR(95%CI):3.310(1.150-9.530), P = 0.027], lesion density subtype (P = 0.004) and SUVmax ≥ 2.5 g/ml [OR(95%CI):3.268(1.021-1.356), P = 0.005] were the independent factors predicting STAS. Logistic regression was used to build the A-D-S (Age-Density-SUVmax) prediction model, and the AUCs were 0.808, 0.786 and 0.806 in the training, validation, and test cohorts, respectively. CONCLUSIONS: STAS was more likely to occur in older patients, in solid lesions and higher SUVmax in stage I LAC. The PET/CT-based A-D-S prediction model is easy to use and has a high level of reliability in diagnosing.

The value of musculoskeletal ultrasound in predicting gout flares in index joints: A prospective cohort study of people with gout starting urate-lowering therapy.

OBJECTIVES: To evaluate whether ultrasound findings of monosodium urate (MSU) crystal deposition predict frequent gout flares in index joints over 12 months. METHODS: This single-center study enrolled people with at least one gout flare involving the MTP1, ankle or knee joint. The most painful or most frequently joint was identified as index joint for analysis. All participants were started on urate-lowering therapy and had an ultrasound scan of the index joints at the baseline visit. OMERACT scores (for tophus, double contour sign and aggregates) were used to analyze whether ultrasound scores predicted frequent (≥2) gout flares in the index joint over 12 months. RESULTS: Frequent flares were significantly higher in those with ultrasound findings in all index joints (MTP1: tophus: 85.0% vs 46.0%, P < 0.001, aggregates: 78.8% vs 59.0%, P < 0.01; ankle: tophus: 54.6% vs 20.8%, P < 0.001; aggregates: 60.0% vs 35.9%, P < 0.05; knee: tophus: 68.4% vs 28.6%, P < 0.05). For the MTP1, for each 1-point increase in tophus score, the odds of frequent gout flares increased by 5.19 [(95%CI: 1.26-21.41), 7.91 [(95%CI: 2.23-28.14), and 13.79 [(95%CI: 3.79-50.20)] fold respectively. For the ankle, a tophus score of 3 markedly improved the prediction of the frequent flares [OR= 9.24 (95%CI=2.85-29.91)]. Semi-quantitative sum scores were associated with frequent flares with an OR (95%CI) of 13.66 (3.44-54.18), P < 0.001 at the MTP1, 7.05 (1.98-25.12), P < 0.001 at the ankle. CONCLUSION: Ultrasound features of MSU crystal deposition at the MTP1 and knee predict subsequent risk of frequent gout flares in the same joints following initiation of urate-lowering therapy, with the highest risk in those with high tophus scores.