Persistent acute kidney injury biomarkers: A systematic review and meta-analysis.

BACKGROUND: Various biomarkers reportedly predict persistent acute kidney injury (AKI) despite their varying predictive performance across clinical trials. This study aims to compare the accuracy of various biomarkers in predicting persistent AKI in different populations and regions. METHODS: In this meta-analysis, we searched for urinary C-C motif chemokine ligand 14 (CCL14), Tissue inhibitor of metalloproteinase-2&insulin-like growth factor-binding protein-7 (TIMP-2&IGFBP7), Neutrophil Gelatinase-Associated Lipocalin (NGAL), plasma Cystatin C (pCysC), Soluble urokinase plasminogen activator receptor (suPAR), Proenkephalin (PenK) and urinary dickkopf-3:urinary creatinine (uDKK3:uCr) from various databases including Medline, PubMed, Embase, and Cochrane. This was geared towards predicting persistent AKI in adults (>18 years). Hierarchically summarized subject work characteristic curves (HSROC) and diagnostic odds ratio (DOR) values were used to summarize the diagnostic accuracy of the biomarkers. Further, meta-regression and subgroup analyses were carried out to identify sources of heterogeneity as well as evaluate the best predictive biomarkers in different populations and regions. RESULTS: We screened 31 studies from 2,356 studies and assessed the diagnostic value of 7 biomarkers for persistent AKI. Overall, CCL14 had the best diagnostic efficacy with an AUC of 0.79 (95 % CI 0.75-0.82), whereas TIMP-2 & IGFBP7, NGAL, and pCysC had diagnostic efficacy of 0.75 (95 % CI 0.71-0.79),0.71 (95 % CI 0.67-0.75), and 0.7007, respectively. Due to a limited number of studies, PenK, uDKK3:uCr, and suPAR were not subjected to meta-analysis; however, relevant literature reported diagnostic efficacy above 0.70. Subgroup analyses based on population, region, biomarker detection time, AKI onset time, and AKI duration revealed that in the intensive care unit (ICU) population, the AUC of CCL14 was 0.8070, the AUC of TIMP-2 & IGFBP7 was 0.726, the AUC of pCysC was 0.72, and the AUC of NGAL was 0.7344; in the sepsis population, the AUC of CCL14 was 0.85, the AUC of TIMP-2&IGFBP7 was 0.7438, and the AUC of NGAL was 0.544; in the post-operative population, the AUC of CCL14 was 0.83-0.93, the AUC of TIMP-2&IGFBP7 was 0.71, and the AUC of pCysC was 0.683. Regional differences were observed in biomarker prediction of persistent kidney injury, with AUCs of 0.8558 for CCL14, 0.7563 for TIMP-2 & IGFBP7, and 0.7116 for NGAL in the Eurasian American population. In the sub-African population, TIMP-2 & IGFBP7 had AUCs of 0.7945, 0.7418 for CCL14, 0.7097 for NGAL, and 0.7007 for pCysC. for TIMP-2 & IGFBP7 was 0.7945, AUC for CCL14 was 0.7418, AUC for NGAL was 0.7097, and AUC for pCysC was 0.7007 in the sub-African population. Duration of biomarker detection, AKI onset, and AKI did not influence the optimal predictive performance of CCL14. Subgroup analysis and meta-regression of CCL14-related studies revealed that CCL14 is the most appropriate biomarker for predicting persistent stage 2-3 AKI, with heterogeneity stemming from sample size and AKI staging. CONCLUSION: This meta-analysis discovered CCL14 as the best biomarker to predict persistent AKI, specifically persistent stage 2-3 AKI.

Different patterns of structural network impairments in two amyotrophic lateral sclerosis subtypes driven by 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance hybrid imaging.

The structural network damages in amyotrophic lateral sclerosis patients are evident but contradictory due to the high heterogeneity of the disease. We hypothesized that patterns of structural network impairments would be different in amyotrophic lateral sclerosis subtypes by a data-driven method using 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance hybrid imaging. The data of positron emission tomography, structural MRI and diffusion tensor imaging in fifty patients with amyotrophic lateral sclerosis and 23 healthy controls were collected by a 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance hybrid. Two amyotrophic lateral sclerosis subtypes were identified as the optimal cluster based on grey matter volume and standardized uptake value ratio. Network metrics at the global, local and connection levels were compared to explore the impaired patterns of structural networks in the identified subtypes. Compared with healthy controls, the two amyotrophic lateral sclerosis subtypes displayed a pattern of a locally impaired structural network centralized in the sensorimotor network and a pattern of an extensively impaired structural network in the whole brain. When comparing the two amyotrophic lateral sclerosis subgroups by a support vector machine classifier based on the decreases in nodal efficiency of structural network, the individualized network scores were obtained in every amyotrophic lateral sclerosis patient and demonstrated a positive correlation with disease severity. We clustered two amyotrophic lateral sclerosis subtypes by a data-driven method, which encompassed different patterns of structural network impairments. Our results imply that amyotrophic lateral sclerosis may possess the intrinsic damaged pattern of white matter network and thus provide a latent direction for stratification in clinical research.

Co-sputtering strategy to construct robust sodiophilic interfaces for anode-less sodium metal batteries.

A copper-bismuth composite coating was fabricated by a facile co-sputtering strategy to enhance the sodiophilicity and structural stability of the substrate. The composite coating with lower bismuth content can maintain the sodiophilicity and form a thin and dense SEI during cycling, thus improving the reversibility of the anode-less sodium metal batteries.

Citrus Fruits Produce Direct Defense Responses against Oviposition by Bactrocera minax (Diptera: Tephritidae).

Plants perceive and orchestrate defense responses when herbivorous insects are ovipositing. Fruits, as a crucial reproductive organ in plants, have rarely been researched on the responses to insect eggs. Here, we found that oviposition by the specialist insect Bactrocera minax in navel oranges activated the lignin synthesis pathway and cell division, causing mechanical pressure that crushed the eggs. Transcriptome and metabolome analyses revealed an enrichment of oviposition-induced genes and metabolites within the lignin synthesis pathway, which was confirmed by histochemical staining. Furthermore, hydrogen peroxide (H2O2) accumulation was observed at the oviposition sites. Plant defense-related hormones jasmonic acid (JA) and salicylic acid (SA) exhibited rapid induction after oviposition, while indole-3-acetic acid (IAA) activation occurred in the later stages of oviposition. Additionally, secondary metabolites induced by prior egg deposition were found to influence larval performance. Our studies provide molecular evidence that host fruits have evolved defense mechanisms against insect eggs and pave the way for future development of insect-resistant citrus varieties.

Erratum to "Bifunctional Tumor-Targeted Bioprobe for Phototheranosis".

[This corrects the article DOI: 10.34133/bmr.0002.].

Fermented blueberry pomace supplementation improves egg quality, liver synthesis, and ovary antioxidant capacity of laying hens.

The present study aimed to investigate the effects of dietary fermented blueberry pomace (FBP) supplementation on production performance, egg quality and nutritional value, plasma biochemical parameters, follicle number, reproductive hormones, lipid metabolism, and antioxidant capacity of laying hens during the late laying period. A total of 320 (345-d-old) Yukou Jingfen No. 8 laying hens were randomly divided into 4 groups, with eight replicates per group and 10 hens per replicate. The birds were fed a basal diet (control group) and a basal diet supplemented with 0.25, 0.5, and 1.0% FBP. The trial lasted 56 d. The results showed that FBP (0.25-1.0%) supplementation increased the egg albumen height and Haugh unit compared with the control group on d 14, while 0.5 to 1.0% FBP increased the eggshell thickness compared with the 0.25% FBP group on d 28 of the trial (P < 0.05). The methionine content in egg white was higher (P < 0.05) in the 1.0% FBP group compared with the 0.25% FBP group. The CAT activity in the ovary was increased (P < 0.05) in the FBP groups compared with the control group, while plasma GSH-PX activity was higher (P < 0.05) in the 1.0% FBP group compared with the 0.25% FBP and 0.5% FBP groups. Dietary FBP supplementation up-regulated (P < 0.05) gene expressions related to lipid metabolism in the liver (ACC, FAS, SCD1, and SREBP1) and yolk precursor synthesis (ESR2 and VTG II). Moreover, CYP11A1 expression in the ovary was up-regulated (P < 0.05) in the FBP groups compared with the control group, as well as in the 0.25% FBP group compared with the 1.0% FBP group. In summary, dietary FBP supplementation improved egg quality and nutritional value, ovarian antioxidant capacity, and yolk precursor synthesis, while 1.0% FBP had better effects than 0.25 and 0.5% doses.

The link between serum cotinine levels and gallstones prevalence in adults: a cross-sectional analysis using NHANES data (2017-2020).

Background: Gallstones represent a prevalent health issue globally, resulting in significant annual healthcare costs. While tobacco exposure is recognized for its association with numerous diseases, its correlation with gallstones remains contentious. Serum cotinine, a metabolite of nicotine, serves as a widely utilized indicator for assessing tobacco exposure. Crucially, no research has yet examined the association between serum cotinine levels and the gallstones. Methods: This study is designed as a cross-sectional analysis, utilizing data from the NHANES public database. The relationship between serum cotinine levels and gallstones was analyzed using multinomial logistic regression models and smooth curve fitting. Subgroup analyses and interaction tests were performed to examine the potential contributions of different populations and covariates to the findings. Results: A total of 5,856 participants were included in this study. After adjusting for relevant covariates, the multiple logistic regression model results indicated that for each unit increase in serum cotinine concentration above 0.29 ng/mL, there was a 29% increase in the prevalence of gallstones. Furthermore, smooth curve fitting analysis revealed a positive correlation between these variables. These findings underscore the impact of tobacco exposure on gallstone prevalence. Conclusion: This study demonstrates a positive correlation between tobacco exposure, as measured by serum cotinine levels, and the prevalence of gallstones, thus adding to the body of existing research on this relationship.

METTL3 inhibitor suppresses the progression of prostate cancer via IGFBP3/AKT pathway and synergizes with PARP inhibitor.

The RNA N6-methyladenosine (m6A) regulator METTL3 is an important regulatory gene in various progressive processes of prostate cancer (PCa). METTL3 inhibitors have been reported to possess potent tumor suppression capacity in some cancer types. Nevertheless, the detailed influence and mechanism of METTL3 inhibitors on PCa progression and their potential synergy with other drugs are poorly understood. In this study, we demonstrated that METTL3 was overexpressed and associated with poor survival in most PCa patients. METTL3 inhibitor STM2457 reduced m6A levels of PCa cells, thus inhibiting their proliferation, colony formation, migration, invasion, and stemness in vitro. Furthermore, STM2457 suppressed PCa progression in both the CDX and PDX models in vivo. MeRIP-seq analysis coupled with biological validation revealed that STM2457 influenced multiple biological processes in PCa cells, mainly through the IGFBP3/AKT pathway. We also proved that STM2457 induced DNA damage and showed synergistic anti-PCa effects with the PARP inhibitor olaparib both in vitro and in vivo. All in all, this work provides a novel therapeutic strategy for targeting RNA m6A modifications for the treatment of PCa and provides a meaningful reference for further clinical trials.

The role of perioperative factors in the prognosis of cancer patients: A coin has two sides.

Cancer, the second leading cause of mortality globally, poses a significant health challenge. The conventional treatment for solid tumors involves surgical intervention, followed by chemo- and radio-therapies as well as target therapies, but the recurrence and metastasis of cancers remain a major issue. Anesthesia is essential for ensuring patient comfort and safety during surgical procedures. Despite its crucial role during the surgery, the precise effect of anesthesia on cancer patient outcomes is not clearly understood. This comprehensive review aims to elucidate the various anesthesia strategies used in the perioperative care of cancer patients and their potential effects on patients' prognosis, but understanding the complex relationship between anesthesia and cancer outcomes is crucial, given the complexity in cancer treaments. Examining potential implications of anesthesia strategies on cancer patient prognosis may help better understand treatment efficacy and risk factors of cancer recurrence and metastasis. Through a detailed analysis of anesthesia practices in cancer surgery, this review aims to provide insights that may lead to improving the existing anesthesia protocols and ultimately reduce risk factors for patient outcomes in the field of oncology.

Clinicopathological and prognostic features of colorectal mucinous adenocarcinomas: a systematic review and meta-analysis.

BACKGROUND: Many studies have explored the clinicopathological features and prognosis between colorectal mucinous adenocarcinoma (MAC) and adenocarcinoma (AC) and have given different results. This meta-analysis summarizes previous evidence and evaluates the clinicopathological and prognostic features of MAC relative to AC in colorectal cancers (CRCs). METHODS: The meta-analysis was conducted by searching the databases of PubMed, China National Knowledge Infrastructure (CNKI), WANFANG data, Embase, and Web of Science. Pooled odds ratios (ORs) and hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated to assess the clinicopathological and prognostic differences between MAC and AC. RESULTS: Fifty-six studies involving 803157 patients met the inclusion criteria and were included in this meta-analysis. The clinicopathological features of MAC were greatly different from AC, except for lymphatic invasion (OR = 1.07, 95% CI: 0.99-1.15, P = 0.09) and perineural invasion (OR = 0.92, 95% CI: 0.79-1.06, P = 0.09). Further investigation found that MAC predicted poor OS (HR = 1.04, 95% CI: 1.03-1.04, P < 0.01), but not DFS in CRCs (HR = 1.01,95% CI: 0.88- 1.17, P = 0.85). Subgroup analysis found that MAC was obviously correlated with OS in patients with different recruitment time, with tumor located in rectum, from different regions, with different sample sizes and with TNM stage in II, and calculated by different data types(P < 0.01). CONCLUSIONS: This study shows that MAC displays obviously different clinicopathological features compared with AC. And MAC has a poor OS relative to AC but the DFS was comparable.

Optimizing Deep Learning Models with Improved BWO for TEC Prediction.

The prediction of total ionospheric electron content (TEC) is of great significance for space weather monitoring and wireless communication. Recently, deep learning models have become increasingly popular in TEC prediction. However, these deep learning models usually contain a large number of hyperparameters. Finding the optimal hyperparameters (also known as hyperparameter optimization) is currently a great challenge, directly affecting the predictive performance of the deep learning models. The Beluga Whale Optimization (BWO) algorithm is a swarm intelligence optimization algorithm that can be used to optimize hyperparameters of deep learning models. However, it is easy to fall into local minima. This paper analyzed the drawbacks of BWO and proposed an improved BWO algorithm, named FAMBWO (Firefly Assisted Multi-strategy Beluga Whale Optimization). Our proposed FAMBWO was compared with 11 state-of-the-art swarm intelligence optimization algorithms on 30 benchmark functions, and the results showed that our improved algorithm had faster convergence speed and better solutions on almost all benchmark functions. Then we proposed an automated machine learning framework FAMBWO-MA-BiLSTM for TEC prediction, where MA-BiLSTM is for TEC prediction and FAMBWO for hyperparameters optimization. We compared it with grid search, random search, Bayesian optimization algorithm and beluga whale optimization algorithm. Results showed that the MA-BiLSTM model optimized by FAMBWO is significantly better than the MA-BiLSTM model optimized by grid search, random search, Bayesian optimization algorithm, and BWO.

Perioperative toripalimab plus neoadjuvant chemotherapy might improve outcomes in resectable esophageal cancer: an interim analysis of a phase III randomized clinical trial.

BACKGROUND: In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high-level clinical evidence. This study aimed to compare the safety and long-term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE. METHODS: A prospective, single-center, open-label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event-free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed. RESULTS: Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1-3M0 to T2-3N0-3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1-year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1-year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien-Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment-related AEs did not differ between the two groups (12.5% versus 12.4%). CONCLUSIONS: The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.

Involvement of mitochondrial fatty acid ß-oxidation in the antiviral innate immune response in head kidney macrophages of large yellow croaker (Larimichthys crocea).

As a vital pathway for cellular energy production, mitochondrial fatty acid ß-oxidation (FAO) is essential in regulating immune responses to bacterial pathogens and maintaining intracellular homeostasis in vertebrates. However, the specific role of FAO in antiviral innate immune response in macrophages remains insufficiently understood. In this study, virus infection simulated by poly(I:C) inhibited FAO, as indicated by the reduced expression of FAO-related genes and proteins in the head kidney of large yellow croaker, with similar results observed in poly(I:C)-stimulated macrophages. Then, inhibition of FAO by supplementary mildronate in vivo and etomoxir treatment in vitro revealed varying increases in the mRNA expression of antiviral innate immune response genes after stimulated by poly(I:C) in the head kidney and macrophages. Notably, etomoxir significantly facilitated the transcriptional up-regulation of the IFNh promoter by IRF3. Moreover, inhibiting FAO by knockdown of cpt1b promoted antiviral innate immune response triggered by poly(I:C) in macrophages. Conversely, activating FAO through overexpression of cpt1b or cpt2 significantly reduced the mRNA levels of antiviral response genes in macrophages stimulated by poly(I:C). Unlike etomoxir, cpt1b overexpression inhibited the transcriptional up-regulation of the IFNh promoter by IRF3. Furthermore, in vivo dietary palm oil feeding and in vitro exposure to palmitic acid inhibited the antiviral innate immune response triggered by poly(I:C) in the head kidney and macrophages, respectively. These effects were partly associated with FAO activation, as evidenced by etomoxir. In summary, this study elucidates FAO's critical role in regulating antiviral innate immune response in head kidney macrophages. These findings not only deepen insights into the interaction between metabolic remodeling and host immune responses, but also offer valuable guidance for developing nutritional strategies to improve antiviral immunity in aquaculture.

Enhancing flame retardancy and multi-functionalization of environmentally friendly cotton fabrics with a polydimethylsiloxane-based polyurethane.

Phosphorus-containing flame retardants are prone to result in the buildup of biotoxins, while halogen flame retardants easily lead to hazardous gases. Therefore, it is crucial to develop a multifunctional flame-retardant cotton fabric without phosphorus and halogen. Herein, single-ended hydroxy-terminated polydimethylsiloxane (PDMS-ID) was synthesized through single-ended hydrosilicone oil and 1,4-butanediol, followed by the preparation of a waterborne polyurethane (RWPU) containing side chain polydimethylsiloxane through the reaction of PDMS-ID with isocyanate prepolymer. Characterization data shows that its particle size distribution is relatively dispersed while maintaining good emulsification performance. Based on this, a halogen-free and phosphorus-free multifunctional flame retardant cotton fabric (COF-BBN@RWPU) was successfully prepared through treatment with boric acid/borax/3-aminopropyltriethoxysilane solution and subsequent RWPU encapsulation. In vertical flammability test (VFT), COF-BBN@RWPU has a char length of 57 mm and a limiting oxygen index (LOI) of 42.3 % with a 11 % weight gain while pure cotton was burned through with a LOI of 18.0 %. In addition, the total heat release and total smoke release of COF-BBN@RWPU decreased by 80.0 % and 47.2 %, compared with pure cotton. Additionally, COF-BBN@RWPU can achieve a maximum contact angle of 140.1° with an oil-water separation rate of 98.4 %. This study presents an eco-friendly approach to achieving the multifunctionality of cellulose fabrics.

Porous Gelatin Methacrylate Gel Engineered by Freeze-Ultraviolet Promotes Osteogenesis and Angiogenesis.

Alveolar bone defect reconstruction is a common challenge in stomatology. To address this, a thermosensitive/photosensitive gelatin methacrylate (GelMA) gel was developed based on various air solubilities and light-curing technologies. The gel was synthesized by using a freeze-ultraviolet (FUV) method to form a porous and quickly (within 15 min) solidifying modified network structure. Unlike other gel scaffolds limited by complex preparation procedures and residual products, this FUV-GelMA gel shows favorable manufacturing ability, promising biocompatibility, and adjustable macroporous structures. The results from a rat model suggested that this gel scaffold creates a conducive microenvironment for mandible reconstruction and vascularization. In vitro experiments further confirmed that the FUV-GelMA gel promotes osteogenic differentiation of human bone marrow mesenchymal stem cells and angiogenesis of human umbilical vein endothelial cells. Investigation of the underlying mechanism focused on the p38 mitogen-activated protein kinase (MAPK) pathway. We found that SB203580, a specific inhibitor of p38 MAPK, abolished the therapeutic effects of the FUV-GelMA gel on osteogenesis and angiogenesis, both in vitro and in vivo. These findings introduced a novel approach for scaffold-based tissue regeneration in future clinical applications.

The Effect of Heat Aging on the Microstructure and Properties of Spray-Deposited AlZnMgCu Alloy Extruded Plates.

The heat-aging process, a practical aging technology that not only improves the comprehensive performance of Al alloys but also reflects the requirements of short processes, has an extremely practical significance. The effects of the heating rate and termination temperature on the "heat-aging" behavior of a spray-deposited AlZnMgCu alloy hot-extruded plate were investigated using hardness, electrical conductivity, room-temperature tensile strength, exfoliation corrosion experiments, and transmission electron microscopy microstructure (TEM) observation. The results show that as the termination temperature increases, the hardness of the spray-deposited AlZnMgCu alloy first increases to a peak and then rapidly decreases, while the electrical conductivity continues to increase. The increase in the heating rate improves the peak hardness corresponding to the termination temperature. The heat treatment process of heating at a speed of 20 °C/h to 200 °C after the spray deposition has similar mechanical and corrosion resistance properties to the RRA process and can effectively reduce the heating time from 40 h to 8 h, thus establishing a heat treatment process for spray-deposited AlZnMgCu alloy extruded plate with high aging efficiency.

Relationship between CCL2 gene 2518A/G (rs1024611) polymorphism and age-related macular degeneration susceptibility: meta-analysis and trial sequential analysis.

PURPOSE: This study aimed to investigate the association between the CC-cytokine ligand-2 (CCL2) 2518A/G (rs1024611) single nucleotide polymorphism (SNP) and susceptibility to age-related macular degeneration (AMD). METHODS: PubMed, Embase, Web of Science, and other databases were searched for articles published before August 24, 2023. After searching, data extraction, and quality assessment, meta-analysis and trial sequential analysis were conducted using RevMan 5.4, Stata 17.0, and TSA 0.9.5.10 Beta software. Combined OR, P values, and 95% confidence intervals (CIs) were calculated. Sensitivity analysis, subgroup analysis and publication bias assessment were also performed. RESULTS: Six articles, comprising 1186 cases and 1124 controls, were included. No significant statistical difference was found in six main outcomes. However, due to observed heterogeneity and high sensitivity, subgroup analysis was performed, revealing statistically significant differences across different regions. No significant publication bias was observed. Trial sequential analysis suggested the need for additional follow-up case-control studies to further validate the findings. CONCLUSION: The CCL2 gene 2518A/G (rs1024611) polymorphism is associated with AMD susceptibility. Among Caucasian populations in West Asia and Europe, the G allele is protective against AMD, whereas in East and South Asia, it poses a risk factor.

Guided Cooperation in Hierarchical Reinforcement Learning via Model-Based Rollout.

Goal-conditioned hierarchical reinforcement learning (HRL) presents a promising approach for enabling effective exploration in complex, long-horizon reinforcement learning (RL) tasks through temporal abstraction. Empirically, heightened interlevel communication and coordination can induce more stable and robust policy improvement in hierarchical systems. Yet, most existing goal-conditioned HRL algorithms have primarily focused on the subgoal discovery, neglecting interlevel cooperation. Here, we propose a novel goal-conditioned HRL framework named Guided Cooperation via Model-Based Rollout (GCMR; code is available at https://github.com/HaoranWang-TJ/GCMR_ACLG_official), aiming to bridge interlayer information synchronization and cooperation by exploiting forward dynamics. First, the GCMR mitigates the state-transition error within off-policy correction via model-based rollout, thereby enhancing sample efficiency. Second, to prevent disruption by the unseen subgoals and states, lower level Q -function gradients are constrained using a gradient penalty with a model-inferred upper bound, leading to a more stable behavioral policy conducive to effective exploration. Third, we propose a one-step rollout-based planning, using higher level critics to guide the lower level policy. Specifically, we estimate the value of future states of the lower level policy using the higher level critic function, thereby transmitting global task information downward to avoid local pitfalls. These three critical components in GCMR are expected to facilitate interlevel cooperation significantly. Experimental results demonstrate that incorporating the proposed GCMR framework with a disentangled variant of hierarchical reinforcement learning guided by landmarks (HIGL), namely, adjacency constraint and landmark-guided planning (ACLG), yields more stable and robust policy improvement compared with various baselines and significantly outperforms previous state-of-the-art (SOTA) algorithms.

Prevalence, risk factors, and outcomes of dysphagia after stroke: a systematic review and meta-analysis.

Background: Dysphagia is a common complication after stroke, which not only brings adverse outcomes but also greatly affects the quality of life of patients. At present, there is no systematic review or meta-analysis to comprehensively evaluate the epidemiological characteristics of post-stroke dysphagia (PSD). A systematic review of the prevalence, risk factors, and prognosis of PSD is essential. Methods: Through 31 December 2022, a comprehensive literature search was performed for observational studies related to PSD. Five databases were retrieved. Random-effects models were used to estimate the pooled prevalence, odds ratio (OR), and 95% CIs. Results: A total of 34 studies were included, and the results showed that the overall prevalence of PSD was 46.6% (95% CI, 0.405-0.528). The prevalence of dysphagia in ischemic stroke and hemorrhagic stroke was 43.6% (95% CI 0.370-0.501) and 58.8% (95% CI 0.519-0.654), respectively. The prevalence of PSD in Africa was 49.4% (95% CI, 0.196-0.792), in Asia was 40.1% (95% CI, 0.348-0.454), in Europe was 45.8% (95% CI, 0.327-0.590), in North America was 44.3% (95% CI, 0.370-0.517), in South America was 57.5% (95% CI, 0.441-0.708), and in Oceania was 64.1% (95%CI, 0.558, 0.724). In risk factor analysis, hypertension, previous stroke, and atrial fibrillation were significantly associated with the occurrence of PSD, pooled OR = 1.179 [(95% CI, 1.002-1.386), p < 0.05], pooled OR = 1.514 [(95% CI, 1.204-1.905), p < 0.001], and pooled OR = 1.980 [(95% CI, 1.580-2.481), p < 0.001]. In outcome studies, the prevalence of aphasia and dysarthria in PSD was 35.6% (95% CI, 0.213-0.499) and 54.5% (95% CI, 0.293-0.798), respectively. The prevalence of respiratory tract infection was 27.1% (95%CI, -0.038-0.579), and the prevalence of pneumonitis was 32.1% (95% CI, 0.224-0.418). Persistence of dysphagia at discharge and at 1 month was 74.5% (95% CI, 0.621-0.869) and 50.9% (95% CI, 0.142-0.876), respectively. Mortality rates for PSD patients during admission and discharge at 1 month, 3 months, and 1 year were 11.8% (95% CI, 0.083-0.152), 26.5% (95% CI, 0.170-0.359), 25.7% (95% CI, 0.19-0.324), and 31.3% (95% CI, 0.256-0.369), respectively. Conclusion: This study found that the overall prevalence of PSD was 46.6%. Prevalence is most influenced by the diagnosis method. Hypertension, history of stroke, atrial fibrillation, patient age, and stroke severity were risk factors significantly associated with PSD. The prevalence of aphasia, dysarthria, respiratory tract infection, and pneumonitis in PSD patients is 2-4 times that of patients without PSD.Systematic review registration: www.crd.york.ac.uk/PROSPERO, PROSPERO, CRD42021252967.

In situ self-assembled near-infrared phototherapeutic agent: unleashing hydrogen free radicals and coupling with NADPH oxidation.

Investigation of electron transfer (ET) between photosensitizers (PSs) and adjacent substrates in hypoxic tumors is integral to highly efficient tumor therapy. Herein, the oxygen-independent ET pathway to generate hydrogen free radicals (H˙) was established by the in situ self-assembled phototherapeutic agent d-ST under near-infrared (NIR)-light irradiation, coupled with the oxidation of reduced coenzyme NADPH, which induced ferroptosis and effectively elevated the therapeutic performance in hypoxic tumors. The higher surface energy and longer exciton lifetimes of the fine crystalline d-ST nanofibers were conducive to improving ET efficiency. In hypoxic conditions, the excited d-ST can effectively transfer electrons to water to yield H˙, during which the overexpressed NADPH with rich electrons can power the electron flow to facilitate the generation of H˙, accompanied by NADP+ formation, disrupting cellular homeostasis and triggering ferroptosis. Tumor-bearing mouse models further showed that d-ST accomplished excellent phototherapy efficacy. This work sheds light onto the versatile electron pathways between PSs and biological substrates.