Hyperuricemia Subtypes Classified According to Renal Uric Acid Handling Manifesting Distinct Phenotypic and Genetic Profiles in People With Gout.

OBJECTIVE: Hyperuricemia can be stratified into four subtypes according to renal uric acid handling. The aim of this study was to comprehensively describe the biologic characteristics (including genetic background) of clinically defined hyperuricemia subtypes in two large geographically independent gout cohorts. METHODS: Hyperuricemia subtype was defined as renal uric acid overload (ROL), renal uric acid underexcretion (RUE), combined, or renal normal. Twenty single nucleotide polymorphisms (SNPs) previously identified as gout risk loci or associated with serum urate (SU) concentration in the East Asian population were genotyped. Weighted polygenic risk scores were calculated to assess the cumulative effect of genetic risks on the subtypes. RESULTS: Of the 4,873 participants, 8.8% had an ROL subtype, 60.9% RUE subtype, 23.1% combined subtype, and 7.2% normal subtype. The ROL subtype was independently associated with older age at onset, lower SU, tophi, and diabetes mellitus; RUE was associated with lower body mass index (BMI) and non-diabetes mellitus; the combined subtype was associated with younger age at onset, higher BMI, SU, estimated glomerular filtration rate (eGFR), and smoking; and the normal subtype was independently associated with older age at onset, lower SU, and eGFR. Thirteen SNPs were associated with gout with 6 shared loci and subtype-dependent risk loci patterns. High polygenic risk scores were associated with ROL subtype (odds ratio [OR] = 9.63, 95% confidence interval [95% CI] 4.53-15.12), RUE subtype (OR = 2.18, 95% CI 1.57-3.03), and combined subtype (OR = 6.32, 95% CI 4.22-9.48) compared with low polygenic risk scores. CONCLUSION: Hyperuricemia subtypes classified according to renal uric acid handling have subtype-specific clinical and genetic features, suggesting subtype-unique pathophysiologic mechanisms.

Natural Changbai mineral water reduces obesity risk through regulating metabolism and gut microbiome in a hyperuricemia male mouse model.

Access to clean and safe drinking water is essential. This study aimed to evaluate the effect of a kind of small molecular natural mineral water, C-cell mineral water on hyperuricemia male mice metabolism condition. A 13-week drinking water intervention study was conducted in Uox-knockout mice (KO). The hepatic metabolite profiling and related genes expression were detected by UPLC-TOF-MS and transcriptomic, and the gut microbiota of KO mice was determined by metagenomics sequencing. Results showed that the body weight of mice fed with C-cell water was remarkably lower than that of control mice on D 77 and D 91. Hepatic metabolite profiling revealed a shift in the pathway of glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, and biosynthesis of cofactors in KO mice fed with C-cell mineral water. Increased energy metabolism levels were related to increased hepatic expression of genes responsible for coenzyme metabolism and lipid metabolism. Gut microbiota was characterized by increasing activity of beneficial bacteria Blautia, and reducing activity of pathobiont bacteria Parasutterella. These genera have been reported to be associated with obesity. Small molecular mineral-rich natural water ingestion regulates metabolism and gut microbiota, protecting against obesity induced by hyperuricemia through mediating a microbiota-liver axis.

COVID-19 Vaccination and Gout Flare Risk in Patients With Infrequent or Frequent Flares: A Prospective Cohort Study.

OBJECTIVE: To assess post-COVID-19 vaccination gout flare risk with differing baseline flare burden. METHODS: We prospectively studied gout patients with infrequent or frequent flares, defined as ≤1 flare/year or ≥2 flares/year, respectively. COVID-19 vaccine-naive patients managed with urate-lowering therapy between February and June 2021 were included and voluntarily decided on vaccination. Participants were followed for 12 weeks after enrollment or first vaccine dose. Gout flares and risk factors were compared between groups. RESULTS: Of 530 participants, 308 (58.1%) had infrequent flares and 222 (41.9%) had frequent flares at baseline, with 248 (142 infrequent and 106 frequent) receiving two-dose COVID-19 vaccination. Vaccination increased cumulative flare incidence at 12 weeks in the infrequent but not the frequent flare group (26.1% vs 10.8%, P = 0.001, compared with 60.4% vs 65.5%, P = 0.428). Flare incidence in the final 4 weeks of observation decreased significantly only in the vaccinated infrequent flare group (4.3% vs 12.0%, P = 0.017). Multivariable analyses showed that vaccination (odds ratio [OR] 2.82, 95% confidence interval [95% CI] 1.50-5.30, P = 0.001), flare in the preceding year (OR 1.95, 95% CI 1.03-3.71, P = 0.04), and body mass index (OR 1.09, 95% CI 1.01-1.19, P = 0.03) were independently associated with increased flare risk in the infrequent flare group. Baseline serum urate (mg/dl) was an independent risk factor in the frequent flare group (OR 1.23, 95% CI 1.05-1.45, P = 0.012). CONCLUSION: COVID-19 vaccination was associated with increased early gout flares only in patients with previously infrequent flares.

Superiority of Low-Dose Benzbromarone Add-On to Low-Dose Febuxostat Compared With Febuxostat Monotherapy in Gout With Combined-Type Hyperuricemia.

OBJECTIVE: There is an unmet need for simpler urate-lowering therapy (ULT) regimens that achieve the serum urate target and improve the overall quality of gout care. We report a comparative effectiveness trial of febuxostat monotherapy versus benzbromarone add-on to low-dose febuxostat in gout specifically with combined renal urate underexcretion and overload. METHODS: A prospective randomized trial was conducted on patients with combined-type hyperuricemia and estimated glomerular filtration rate >60 mL/min/1.73 m2 1:1 randomly assigned to febuxostat and benzbromarone combination therapy (initially febuxostat at 20 mg/day, with benzbromarone at 25 mg/day added onto 20 mg/day of febuxostat if not at target) or febuxostat monotherapy (initially 20 mg/day, escalating to 40 mg/day if not at target). The primary end point at 12 weeks was the proportion achieving a serum urate (SU) level <360 µmol/L. Other outcomes included altered liver and kidney function, new-onset urolithiasis, and gout flares. RESULTS: There were 250 participants randomized; 219 completed 12-week treatment. More patients in the febuxostat and benzbromarone combination group achieved the SU target compared to patients in the febuxostat monotherapy group (75.5% vs 47.7%; odds ratio 3.37 [95% confidence interval 1.90-5.98]). Safety profiles were comparable between the two groups. CONCLUSION: Simply adding on low-dose benzbromarone (25 mg/day) to low-dose (20 mg/day) febuxostat showed superior urate lowering compared to febuxostat monotherapy in gout with a combined-type hyperuricemia. For selected patients, expedited achievement of the SU target in more than 75% of patients using one titration step and low xanthine oxidase inhibitor and uricosuric doses is a potential alternative to standard ULT regimens.

Response to febuxostat according to clinical subtypes of hyperuricemia: a prospective cohort study in primary gout.

BACKGROUND: While xanthine oxidase inhibitors target uric acid production, renal urate underexcretion is the predominant subtypes in gout. This study was to compare treatment response to the XOI febuxostat in a gout cohort according to clinical subtypes of hyperuricemia. METHODS: A prospective cohort study was conducted to compare the efficacy and safety of febuxostat (initially 20 mg daily, escalating to 40 mg daily if not at target) in 644 gout patients with the three major clinical subtypes for 12 weeks. Hyperuricemia was defined as the renal overload subtype, the renal underexcretion subtype, or the combined subtype based on UUE > or ≤ 600 mg/d/1.73 m2 and FEUA < or ≥ 5.5%. The primary endpoint was the rate of achieving serum urate (SU) < 6 mg/dL at week 12. RESULTS: Fewer participants with combined subtype achieved the SU target, 45.5% compared with 64.8% with overload subtype (P = 0.007), and 56.6% with underexcretion subtype (P = 0.022). More participants with combined subtype (82%) had febuxostat escalated to 40 mg than those with overload (62%, P = 0.001) or underexcretion subtype (68%, P = 0.001). In all participants, combined subtype hyperuricemia (OR = 0.64, 95%CI 0.41-0.99, P = 0.048) and baseline SU (OR = 0.74, 95%CI 0.62-0.89, P = 0.001) were independently associated with lower rates of achieving SU target. CONCLUSIONS: People with combined subtype have a lower response to febuxostat, compared to those with either overload or underexcretion subtype. Assessment of hyperuricemia subtype may provide useful clinical data in predicting febuxostat response.

Group 13 five- and six-membered rings with rare 2π aromaticity.

According to Hückel's rule, cyclic species are aromatic if they have 4n + 2 (n = 0, 1, 2, etc.) π electrons. However, large aromatic rings (atom number > 4) with minimum 2π electrons (i.e., n = 0) are rather rare because of the structural instability stemming from the deficient π electrons compared to the ring size. To date, the largest 2π-aromatic ring is a five-membered Ga5 core reported in a recent experiment. Herein, density functional theory calculations predicted seven inverse-sandwich Na2(MH)5 and half-sandwich Ca(MH)5 or Ca(MH)6 (M = Al, Ga or In) structures. They all have planar central five- or six-membered Al/Ga/In rings, rather negative binding energies and large HOMO-LUMO gaps. Their dianionic metal rings exhibit obvious aromatic characters and appreciable diatropic ring currents due to the good delocalization of 2π electrons donated by the Na/Ca metals. Interestingly, they also have novel collective bonding with the Na/Ca atoms interacting with both the metal ring and surrounding H atoms. These metalloaromatic rings not only greatly enrich the precious family of 2π aromatics, but also increase the maximum ring atom number from five to six, thus paving the way for Hückel-type 2π-aromatic large rings.

Cadmium exposure dysregulates purine metabolism and homeostasis across the gut-liver axis in a mouse model.

Cadmium (Cd) exposure has been associated with the development of enterohepatic circulation disorders and hyperuricemia, but the possible contribution of chronic low-dose Cd exposure to disease progression is still need to be explored. A mouse model of wild-type mice (WT) and Uox-knockout mice (Uox-KO) to find out the toxic effects of chronic low-dose Cd exposure on liver purine metabolism by liquid chromatography-mass spectrometry (LC-MS) platform and associated intestinal flora. High throughput omics analysis including metabolomics and transcriptomics showed that Cd exposure can cause disruption of purine metabolism and energy metabolism. Cd changes several metabolites associated with purine metabolism (xanthine, hypoxanthine, adenosine, uridine, inosine) and related genes, which are associated with elevated urate levels. Microbiome analysis showed that Cd exposure altered the disturbance of homeostasis in the gut. Uox-KO mice were more susceptible to Cd than WT mice. Our findings extend the understanding of potential toxicological interactions between liver and gut microbiota and shed light on the progression of metabolic diseases caused by Cd exposure.

Efficacy and safety of tart cherry supplementary citrate mixture on gout patients: a prospective, randomized, controlled study.

BACKGROUND: Low urine pH, which may be mediated by metabolic syndrome (MetS), is common in gout. Tart cherries are shown to improve MetS symptoms and possess anti-inflammatory properties. However, the efficacy of tart cherry supplements on urine pH has yet to be studied. OBJECTIVES: This study aimed to investigate the efficacy and safety of tart cherry supplementary citrate (TaCCi) mixture on urine pH, serum urate (sUA), C-reactive protein (CRP), and gout flares in gout patients initiating urate-lowering therapy (ULT), in comparison to citrate mixture and sodium bicarbonate. METHODS: A prospective, randomized (1:1:1), open-label, parallel-controlled trial was conducted among 282 men with gout and fasting urine pH ≤ 6, who were initiating ULT with febuxostat (initially 20 mg daily, escalating to 40 mg daily if serum urate ≥ 360 µmol/L). Participants were randomized to groups taking either sodium bicarbonate, citrate mixture, or TaCCi mixture. All participants were followed every 4 weeks until week 12. Urine pH and sUA were co-primary outcomes, with various biochemical and clinical secondary endpoints. RESULTS: Urine pH increased to a similar extent in all three groups. SUA levels declined in all three groups as well, with no significant differences observed between the groups. At week 12, the TaCCi mixture group exhibited a greater reduction in the urine albumin/creatinine ratio (UACR) compared to the other two groups (p < 0.05). Participants taking TaCCi mixture or citrate mixture experienced fewer gout flares than those in the sodium bicarbonate group over the study period (p < 0.05). Additionally, the TaCCi mixture group had a lower CRP level at week 12 relative to the other two groups (p < 0.01). Adverse events were similar across all three groups. CONCLUSION: The TaCCi mixture had similar efficacy and safety on urine alkalization and sUA-lowering as the citrate mixture and sodium bicarbonate in patients with gout. However, the TaCCi mixture resulted in greater improvements in UACR and CRP, which suggests that tart cherry supplements may provide additional benefits for renal protection and reduce inflammation in gout, particularly when starting ULT. TRIAL REGISTRATION: This project was registered in ChiCTR ( www.chictr.org.cn ), with the registration number: ChiCTR2100050749.

Human Motion Prediction via Dual-Attention and Multi-Granularity Temporal Convolutional Networks.

Intelligent devices, which significantly improve the quality of life and work efficiency, are now widely integrated into people's daily lives and work. A precise understanding and analysis of human motion is essential for achieving harmonious coexistence and efficient interaction between intelligent devices and humans. However, existing human motion prediction methods often fail to fully exploit the dynamic spatial correlations and temporal dependencies inherent in motion sequence data, which leads to unsatisfactory prediction results. To address this issue, we proposed a novel human motion prediction method that utilizes dual-attention and multi-granularity temporal convolutional networks (DA-MgTCNs). Firstly, we designed a unique dual-attention (DA) model that combines joint attention and channel attention to extract spatial features from both joint and 3D coordinate dimensions. Next, we designed a multi-granularity temporal convolutional networks (MgTCNs) model with varying receptive fields to flexibly capture complex temporal dependencies. Finally, the experimental results from two benchmark datasets, Human3.6M and CMU-Mocap, demonstrated that our proposed method significantly outperformed other methods in both short-term and long-term prediction, thereby verifying the effectiveness of our algorithm.

Graph-Structure-Based Multigranular Belief Fusion for Human Activity Recognition.

The belief functions (BFs) introduced by Shafer in the mid of 1970s are widely applied in information fusion to model epistemic uncertainty and to reason about uncertainty. Their success in applications is however limited because of their high-computational complexity in the fusion process, especially when the number of focal elements is large. To reduce the complexity of reasoning with BFs, we can envisage as a first method to reduce the number of focal elements involved in the fusion process to convert the original basic belief assignments (BBAs) into simpler ones, or as a second method to use a simple rule of combination with potentially a loss of the specificity and pertinence of the fusion result, or to apply both methods jointly. In this article, we focus on the first method and propose a new BBA granulation method inspired by the community clustering of nodes in graph networks. This article studies a novel efficient multigranular belief fusion (MGBF) method. Specifically, focal elements are regarded as nodes in the graph structure, and the distance between nodes will be used to discover the local community relationship of focal elements. Afterward, the nodes belonging to the decision-making community are specially selected, and then the derived multigranular sources of evidence can be efficiently combined. To evaluate the effectiveness of the proposed graph-based MGBF, we further apply this new approach to combine the outputs of convolutional neural networks + attention (CNN + Attention) in the human activity recognition (HAR) problem. The experimental results obtained with real datasets prove the potential interest and feasibility of our proposed strategy with respect to classical BF fusion methods.

Elevated serum CA72-4 predicts gout flares during urate lowering therapy initiation: a prospective cohort study.

OBJECTIVE: Gout flares during urate-lowering therapy (ULT) initiation are common, but predictors of these flares are poorly understood. The aim of this study was to determine whether serum CA72-4 is an independent predictor for gout flares during ULT initiation. METHODS: A prospective cohort study was conducted between March 2021 and January 2022. Men with gout, at least one gout flare in the past year, and at least three serum CA72-4 measurements in the previous six months were enrolled. Participants were grouped according to their highest recorded serum CA72-4 levels (above or within the normal range). All participants took oral febuxostat 20 mg daily without flare prophylaxis therapy, and attended face-to-face visits every four weeks until 24 weeks. The incidence of gout flare was compared between the two groups. Backward stepwise logistic regression analyses were used to identify risk factors associated with flares. Receiver operating characteristic curve analysis was used to evaluate prediction efficacy. RESULTS: A total of 193 completed the study (79 with high CA72-4; 114 with normal CA72-4). The cumulative incidence of at least one gout flare was 48.1% (62.1% in the high CA72-4 group, 38.4% in the normal CA72-4 group, P = 0.001), and recurrent (≥2) flares was 33.0% (47.1% in the high CA72-4 group, 23.2% in the normal CA72-4, P < 0.001). High CA72-4, disease duration, intra-articular tophus size, glucose, high-density lipoprotein-cholesterol and ESR were independent risk factors for gout flares. Serum CA72-4 alone predicted recurrent flares with an area under the curve of 0.63 (95% CI = 0.54, 0.71), and 0.78 (95% CI = 0.71, 0.85) when combined with other independent variables. CONCLUSION: High serum CA72-4 predicts the risk of gout flares during ULT initiation. TRIAL REGISTRATION: ChiCTR; https://www.chictr.org.cn/; ChiCTR2100043573.

Profiling of serum oxylipins identifies distinct spectrums and potential biomarkers in young people with very early onset gout.

OBJECTIVE: Oxylipins modulate inflammation via complex pathways. The oxylipin profile in gout remains unexplored. In this study, we systemically profiled oxylipins in young men and identified new oxylipin biomarkers for clinical use in differentiating gout from hyperuricaemia. MATERIAL AND METHODS: Oxylipin profiling was performed in 90 men (30 very early onset gout, 30 asymptomatic hyperuricaemia [HU] and 30 normouricaemia [NU], all aged <20 years) divided into discovery and validation sample sets. The dataset was analysed based on orthogonal projection to latent structure-discriminant analysis. Correlation network and pathway enrichment were conducted to reveal potential oxylipin-involved pathways of gout. Candidate oxylipins were further evaluated and optimized in the validation cohort, and differential oxylipin biomarkers combined with or without serum urate were applied to construct diagnostic models. RESULTS: In discovery stage, 21 differential oxylipins in the gout vs HU comparisons and 14 differential oxylipins in the gout vs NU comparisons were discovered. Correlation network analysis was performed and 14(S)-HDHA (14S-hydroxy-4Z,7Z,10Z,12E,16Z,19Z-docosahexaenoic acid) was identified as a hub metabolite in both comparisons. Seven down-regulated oxylipins in the gout vs HU group and five down-regulated oxylipins in the gout vs NU group were validated. Diagnostic models were constructed with the above oxylipins, with 14(S)-HDHA alone having an area under the curve of 1 (95% CI, 1, 1) in both comparisons. CONCLUSIONS: Young men with very early onset gout have distinct oxylipin spectrums, especially those derived from arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid. Differential oxylipins could serve as candidate serum biomarkers in differentiating gout from hyperuricaemia.

A pushing-grasping collaborative method based on deep Q-network algorithm in dual viewpoints.

In the field of intelligent manufacturing, robot grasping and sorting is important content. However, there are some disadvantages in the traditional single-view-based manipulator grasping methods by using a 2D camera, where the efficiency and the accuracy of grasping are both low when facing the scene of stacking and occlusion for the reason that there is information missing by single-view 2D camera-based methods while acquiring scene information, and the methods of grasping only can't change the difficult-to-grasp scene which is stack and occluded. Regarding the issue above, a pushing-grasping collaborative method based on the deep Q-network in dual viewpoints is proposed in this paper. This method in this paper adopts an improved deep Q-network algorithm, with an RGB-D camera to obtain the information of objects' RGB images and point clouds from two viewpoints, which solved the problem of lack of information missing. What's more, it combines the pushing and grasping actions with the deep Q-network, which make it have the ability of active exploration, so that the trained manipulator can make the scenes less stacking and occlusion, and with the help of that, it can perform well in more complicated grasping scenes. In addition, we improved the reward function of the deep Q-network and propose the piecewise reward function to speed up the convergence of the deep Q-network. We trained different models and tried different methods in the V-REP simulation environment, and it drew a conclusion that the method proposed in this paper converges quickly and the success rate of grasping objects in unstructured scenes raises up to 83.5%. Besides, it shows the generalization ability and well performance when novel objects appear in the scenes that the manipulator has never grasped before.

Colchicine prophylaxis is associated with fewer gout flares after COVID-19 vaccination.

OBJECTIVES: COVID-19 vaccination often triggers a constellation of transitory inflammatory symptoms. Gout is associated with several comorbidities linked to poor outcomes in COVID-19, and gout flares can be triggered by some vaccinations. We analysed the risk of gout flares in the first 3 months after COVID-19 vaccination with inactivated virus, and whether colchicine can prevent gout flares following post-COVID-19 vaccination. METHODS: A clinical delivery population-based cross-sectional study was conducted in the Gout Clinic at the Affiliated Hospital of Qingdao University between February and October 2021. Study participants were selected using a systematic random sampling technique among follow-up patients with gout. We collected data, including vaccinations and potential risk factors, using a combination of interviews, health QR codes and medical records. Logistic regression was used to adjust for covariates. RESULTS: We enrolled 549 gout participants (median age 39 years, 84.2% vaccinated). For the 462 patients who received COVID-19 vaccine, 203 (43.9%) developed at least one gout flare in the 3 months after vaccination. Most of these flares were experienced within 1 month after the first (99/119 (83.2%)) or second (70/115 (60.9%)) dose of vaccine. Compared with unvaccinated participants, COVID-19 vaccination was associated with higher odds of gout flare within 3 months (adjusted OR 6.02; 95% CI 3.00 to 12.08). Colchicine use was associated with 47% less likelihood of postvaccine gout flare. CONCLUSION: COVID-19 vaccination was associated with increased odds of gout flare, which developed mainly in month 1 after each vaccine dose, and was negatively associated with colchicine prophylaxis.

Association of acidic urine pH with impaired renal function in primary gout patients: a Chinese population-based cross-sectional study.

BACKGROUND: Patients with gout frequently have low urinary pH, which is associated with the nephrolithiasis. However, the specific distribution of urinary pH and potential relationship of acidic urine pH to broader manifestations of kidney disease in gout are still poorly understood. METHODS: A 2016-2020 population-based cross-sectional study was conducted among 3565 gout patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University to investigate the association between low urinary pH and kidney disease. We studied patients that we defined to have "primary gout", based on the absence of > stage 2 CKD. All subjects underwent 14 days of medication washout and 3-day standardized metabolic diet. We obtained general medical information, blood and urine biochemistries, and renal ultrasound examination on the day of the visit. The primary readouts were urine pH, eGFR, nephrolithiasis, renal cysts, microhematuria, and proteinuria. Patients were assigned into 5 subgroups (urine pH ≤5.0, 5.0 6.9), aligning with the clinical significance of urine pH. RESULTS: Overall, the median urine pH and eGFR of all patients was 5.63 (IQR 5.37~6.09), and 98.32 (IQR 86.03~110.6), with acidic urine in 46.5% of patients. The prevalence of nephrolithiasis, microhematuria, and proteinuria were 16.9%, 49.5%, and 6.9%, respectively. By univariate analysis, eGFR was significantly associated with age, sex, duration of gout, tophus, body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, serum utare, hypertension, diabetes, and urine pH. On multivariable analysis, eGFR was associated with age, sex, diastolic blood pressure, serum uric acid, hypertension, diabetes, and urine pH. Acidic urine pH, especially urine pH < 5.0, was significantly associated with the prevalence of kidney disease, including > stage 1 CKD, nephrolithiasis, kidney cyst, and microhematuria. Patients with 6.2 ≤ urine pH ≤ 6.9 and SU ≤ 480 µmol/L had the highest eGFR with the lowest prevalence of nephrolithiasis, microhematuria, and proteinuria. CONCLUSIONS: Approximately half of gout subjects had acidic urine pH. Urine pH < 5.0 was associated with significantly increased nephrolithiasis, renal cyst, microhematuria, and proteinuria. The results support prospective clinical investigation of urinary alkalinization in selected gout patients with acidic urine pH.

Decrease in Serum Urate Level Is Associated With Loss of Visceral Fat in Male Gout Patients.

Objective: To clarify the relationship between serum urate (SU) decrease and visceral fat area (VFA) reduction in patients with gout. Methods: We retrospectively analyzed 237 male gout patients who had two sets of body composition and metabolic measurements within 6 months. Subjects included had all been treated with urate-lowering therapy (ULT) (febuxostat 20-80 mg/day or benzbromarone 25-50 mg/day, validated by the medical record). All patients were from the specialty gout clinic of The Affiliated Hospital of Qingdao University. The multiple linear regression model evaluated the relationship between change in SU [ΔSU, (baseline SU) - (final visit SU)] and change in VFA [ΔVFA, (baseline VFA) - (final visit VFA)]. Results: ULT resulted in a mean (standard deviation) decrease in SU level (464.22 ± 110.21 µmol/L at baseline, 360.93 ± 91.66 µmol/L at the final visit, p <0.001) accompanied by a decrease in median (interquartile range) VFA [97.30 (81.15-118.55) at baseline, 90.90 (75.85-110.05) at the final visit, p < 0.001]. By multiple regression model, ΔSU was identified to be a significant determinant variable of decrease in VFA (beta, 0.302; p = 0.001). Conclusions: The decrease in SU level is positively associated with reduced VFA. This finding provides a rationale for clinical trials to affirm whether ULT promotes loss of visceral fat in patients with gout.

Robust Tightly Coupled Pose Measurement Based on Multi-Sensor Fusion in Mobile Robot System.

Currently, simultaneous localization and mapping (SLAM) is one of the main research topics in the robotics field. Visual-inertia SLAM, which consists of a camera and an inertial measurement unit (IMU), can significantly improve robustness and enable scale weak-visibility, whereas monocular visual SLAM is scale-invisible. For ground mobile robots, the introduction of a wheel speed sensor can solve the scale weak-visibility problem and improve robustness under abnormal conditions. In this paper, a multi-sensor fusion SLAM algorithm using monocular vision, inertia, and wheel speed measurements is proposed. The sensor measurements are combined in a tightly coupled manner, and a nonlinear optimization method is used to maximize the posterior probability to solve the optimal state estimation. Loop detection and back-end optimization are added to help reduce or even eliminate the cumulative error of the estimated poses, thus ensuring global consistency of the trajectory and map. The outstanding contribution of this paper is that the wheel odometer pre-integration algorithm, which combines the chassis speed and IMU angular speed, can avoid the repeated integration caused by linearization point changes during iterative optimization; state initialization based on the wheel odometer and IMU enables a quick and reliable calculation of the initial state values required by the state estimator in both stationary and moving states. Comparative experiments were conducted in room-scale scenes, building scale scenes, and visual loss scenarios. The results showed that the proposed algorithm is highly accurate-2.2 m of cumulative error after moving 812 m (0.28%, loopback optimization disabled)-robust, and has an effective localization capability even in the event of sensor loss, including visual loss. The accuracy and robustness of the proposed method are superior to those of monocular visual inertia SLAM and traditional wheel odometers.

Reporting quality of clinical practice guidelines regarding gout and hyperuricemia according to the RIGHT checklist: systematic review.

BACKGROUND: The Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist was used to assess the reporting quality of 2009-2019 clinical practice guidelines (CPGs) regarding gout and hyperuricemia, aimed to improve the reporting quality of future guidelines. METHODS: We searched PubMed, the Chinese Biomedical Literature database, the Wanfang Database, and the China National Knowledge Infrastructure from January 2009 to June 2019 for guidelines regarding gout and hyperuricemia. We also searched the websites of guideline development organizations (the Guidelines International Network, the National Institute for Health and Clinical Excellence, the American College of Rheumatology, and the European League Against Rheumatism (EULAR)). Furthermore, supplementary guidelines reported in included articles were systematically searched, as well as Google Scholar. RESULTS: Seventeen guidelines were included, of which one was in Chinese and 16 were in English. The mean reporting rate of the 35 items specified was 14.9 (42.5%); only five CPGs (29.4%) had a reporting rate >50%. Of the 35 items, three were very frequently reported. The reporting proportion of the seven domains (basic information, background, evidence, recommendations, review and quality assurance, funding and declaration and management of interests, and other information) were 64.7%, 36.8%, 50.6%, 42.9%, 8.82%, 33.8%, and 31.4%, respectively. CONCLUSION: The reporting quality of the present guidelines for gout and hyperuricemia is relatively poor. We suggest that the RIGHT reporting checklist should be used by CPG developers to ensure higher reporting quality of future guidelines.

Serum Metabolomics Identifies Dysregulated Pathways and Potential Metabolic Biomarkers for Hyperuricemia and Gout.

OBJECTIVE: To systematically profile metabolic alterations and dysregulated metabolic pathways in hyperuricemia and gout, and to identify potential metabolite biomarkers to discriminate gout from asymptomatic hyperuricemia. METHODS: Serum samples from 330 participants, including 109 with gout, 102 with asymptomatic hyperuricemia, and 119 normouricemic controls, were analyzed by high-resolution mass spectrometry-based metabolomics. Multivariate principal components analysis and orthogonal partial least squares discriminant analysis were performed to explore differential metabolites and pathways. A multivariate methods with Unbiased Variable selection in R (MUVR) algorithm was performed to identify potential biomarkers and build multivariate diagnostic models using 3 machine learning algorithms: random forest, support vector machine, and logistic regression. RESULTS: Univariate analysis demonstrated that there was a greater difference between the metabolic profiles of patients with gout and normouricemic controls than between the metabolic profiles of individuals with hyperuricemia and normouricemic controls, while gout and hyperuricemia showed clear metabolomic differences. Pathway enrichment analysis found diverse significantly dysregulated pathways in individuals with hyperuricemia and patients with gout compared to normouricemic controls, among which arginine metabolism appeared to play a critical role. The multivariate diagnostic model using MUVR found 13 metabolites as potential biomarkers to differentiate hyperuricemia and gout from normouricemia. Two-thirds of the samples were randomly selected as a training set, and the remainder were used as a validation set. Receiver operating characteristic analysis of 7 metabolites yielded an area under the curve of 0.83-0.87 in the training set and 0.78-0.84 in the validation set for distinguishing gout from asymptomatic hyperuricemia by 3 machine learning algorithms. CONCLUSION: Gout and hyperuricemia have distinct serum metabolomic signatures. This diagnostic model has the potential to improve current gout care through early detection or prediction of progression to gout from hyperuricemia.

Effects of fenofibrate therapy on renal function in primary gout patients.

OBJECTIVE: To investigate the incidence and potential risk factors for development of fenofibrate-associated nephrotoxicity in gout patients. METHODS: A total of 983 gout patients on fenofibrate treatment who visited the dedicated Gout Clinic at the Affiliated Hospital of Qingdao University between September 2016 and June 2020 were retrospectively enrolled from the electronic records system. Fenofibrate-associated nephrotoxicity was defined as an increase in serum creatinine (SCr) ≥0.3 mg/dl within 6 months of fenofibrate initiation. The change trend of SCr and uric acid levels during the treatment period were assessed by a generalised additive mixed model (GAMM). Multivariate analysis was performed for risk factors affecting elevated SCr. RESULTS: A total of 100 (10.2%) patients experienced an increase in SCr ≥0.3 mg/dl within 6 months after fenofibrate initiation. The median change of SCr in the whole cohort was 0.11 mg/dl [interquartile range (IQR) 0.03-0.20], whereas it was 0.36 (0.33-0.45) in the fenofibrate-associated nephrotoxicity group. In a multivariable regression model, chronic kidney disease (CKD) [odds ratio (OR) 2.39 (95% CI 1.48, 3.86)] and tophus [OR 2.29 (95% CI 1.39, 3.78)] were identified to be risk predictors, independent of measured covariates, of fenofibrate-associated nephrotoxicity. During the treatment period, although SCr temporarily increased, serum urate and triglyceride concentrations decreased using the interaction analysis of GAMM. Of those with fenofibrate withdrawal records, the SCr increase in 65% of patients was reversed after an average of 49 days off the drug. CONCLUSIONS: This observational study implied that fenofibrate-associated nephrotoxicity occurs frequently in gout patients, especially in patients with tophi or CKD. The potential renal risks of fenofibrate usage in gout needs additional research.