WebArena: A Realistic Web Environment for Building Autonomous Agents

With advances in generative AI, there is now potential for autonomous agents to manage daily tasks via natural language commands. However, current agents are primarily created and tested in simplified synthetic environments, leading to a disconnect with real-world scenarios. In this paper, we build an environment for language-guided agents that is highly realistic and reproducible. Specifically, we focus on agents that perform tasks on the web, and create an environment with fully functional websites from four common domains: e-commerce, social forum discussions, collaborative software development, and content management. Our environment is enriched with tools (e.g., a map) and external knowledge bases (e.g., user manuals) to encourage human-like task-solving. Building upon our environment, we release a set of benchmark tasks focusing on evaluating the functional correctness of task completions. The tasks in our benchmark are diverse, long-horizon, and designed to emulate tasks that humans routinely perform on the internet. We experiment with several baseline agents, integrating recent techniques such as reasoning before acting. The results demonstrate that solving complex tasks is challenging: our best GPT-4-based agent only achieves an end-to-end task success rate of 14.41%, significantly lower than the human performance of 78.24%. These results highlight the need for further development of robust agents, that current state-of-the-art large language models are far from perfect performance in these real-life tasks, and that WebArena can be used to measure such progress.Comment: Our code, data, environment reproduction resources, and video demonstrations are publicly available at https://webarena.dev

Abnormal Topology of the Structural Connectome in the Limbic Cortico-Basal-Ganglia Circuit and Default-Mode Network Among Primary Insomnia Patients

Purpose: Primary insomnia (PI) is the second most common mental disorder. However, the topologic alterations in structural brain connectome in patients with PI remain largely unknown.Methods: A total of 44 PI patients and 46 age-, gender-, and education level matched healthy control (HC) participants were recruited in this study. Diffusion tensor imaging (DTI) and resting state MRI were used to construct structural connectome for each participant, and the network parameters were employed by non-parametric permutations to evaluate the significant differences between the two groups. Relationships between abnormal network metrics and clinical characteristics, including the disease duration, the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), the Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS), were investigated with Spearman’s correlation analysis in PI patients.Results: PI patients demonstrated small-world architecture with lower global (P = 0.005) and local (P = 0.035) efficiencies compared with the HC group. The unique hub nodal properties in PI patients were mainly in the right limbic cortico-basal-ganglia circuit. Five disrupted subnetworks in PI patients were observed in the limbic cortico-basal-ganglia circuit and left default-mode networks (DMN) (P < 0.05, NBS corrected). Moreover, most unique hub nodal properties in the right limbic cortico-basal-ganglia circuit were significantly correlated with disease duration, and clinical characteristics (SAS, SDS, ISI scores) in PI processing.Conclusion: These findings suggested the abnormal anatomical network architecture may be closely linked to clinical characteristics in PI. The study provided novel insights into the neural substrates underlying symptoms and neurophysiologic mechanisms of PI

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

The lasso structure, biosynthesis, bioactivities and potential applications of Microcin J25: A novel antibacterial agent with unique mechanisms

The overuse and misuse of traditional antimicrobial drugs have led to their weakened effectiveness and the emergence of pathogenic bacterial resistance. Consequently, there has been growing interest in alternative options such as antimicrobial peptides (AMPs) in the pharmaceutical industry. Microcin J25 (MccJ25) has gained significant attention for its potent inhibitory effect on a diverse range of pathogens. Its unique rotaxane structure provides exceptional stability against extreme thermal, pH, and protease degradation, including chymotrypsin, trypsin, and pepsin. Given its remarkable stability and diverse bioactivity, we aim to provide an overview of the physicochemical properties, the mechanism underlying its antimicrobial activity, and the critical functional residues of MccJ25. Additionally, we have summarized the latest strategies for the heterologous expression of MccJ25, and its potential medical use and other applications

A Comprehensive Review of Stratification and Rollover Behavior of Liquefied Natural Gas in Storage Tanks

Liquefied natural gas (LNG), as cleaner transitional energy than coal, is becoming increasingly prominent in the energy structure of various countries based on their low-carbon background, and its demand has grown rapidly worldwide. Storage tanks are the most commonly used LNG storage facilities. Owing to a variety of internal composition and external environmental factors, the instability phenomenon of LNG in the tanks may occur during storage, leading to potential safety risks. An in-depth understanding of the stratification and rollover behavior of LNG is therefore required to ensure and promote efficient utilization and stable storage of LNG. This paper provides a comprehensive review of the current state of LNG stratification and rollover behavior. The factors for causing LNG stratification and rollover behavior in the storage tanks are summarized, methods for characterizing stratification and rollover behavior are discussed, and measures for inhibiting the instability phenomenon of LNG in the tanks are highlighted. Future researchers should conduct further work in enriching the factors affecting the stratification and rollover behavior, improving characterization methods, and developing inhibition measures to ensure the safe and stable storage of LNG

A Two-Echelon Agricultural Product Supply Chain with Freshness and Greenness Concerns: A Cost-Sharing Contract Perspective

Agricultural products are basic needs of human beings, and whether they are cultivated in a green (or organic) manner has direct impact on environment and public health. This research incorporates product freshness and greenness into a two-echelon agricultural product supply chain (APSC). Game theoretic analyses are carried out to examine pricing, freshness, and greenness decisions of the supply chain members with and without cost-sharing for greenness investment. Subsequently, we conduct comparative and sensitivity analyses for these optimal decisions and profits of the APSC members under different cases. Numerical experiment is employed to investigate the impact of key parameters on equilibrium decisions and profitability. Analytical and experimental results show that the cost-sharing contract of greenness investment for agricultural products helps to strengthen the supply chain members’ effort in improving the greenness and freshness levels of the agricultural product, thereby enhancing both individual and channel profitability of the APSC under certain conditions. This research also reveals a widened profit gap between the producer and the retailer under the cost-sharing contract

A systematic review and meta-analysis of balance training in patients with chronic ankle instability

Abstract Background Chronic ankle instability (CAI) is a common yet serious problem for elder patients. This meta-analysis aimed to evaluate the effects of balance training for CAI, to provide evidence for the clinical treatment, and care of CAI patients. Methods Two investigators searched PubMed, EMBASE, Science Direct, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and Weipu Databases up to May 20, 2023, for randomized controlled trials (RCTs) on the effects of balance training for CAI. The mean difference (MD) with 95% confidence intervals (95%CIs) was calculated for each outcome with a fixed or random effect model. Review Manager 5.3 software was used for meta-analysis. Results Nine RCTs involving 341 patients were included. Meta-analysis results showed that compared with blank controls, balanced training treatment of CAI could significantly improve the score of CAI [MD = 3.95, 95% CI (3.26, 4.64), P < 0.00001], SEBT-PM [MD = 4.94, 95% CI (1.88, 8.00), P = 0.002], SEBT-PL [MD = 5.19, 95% CI (1.57, 8.81), P = 0.005], and FAAM Sports [MD = 17.74, 95% CI (14.36, 21.11), P < 0.00001]. Compared with strength training, balance training treatment of CAI improved the score of CAIT [MD = 2.36, 95% CI (0.29, 4.44), P = 0.03], FAAM-ADL [MD = 4.06, 95% CI (1.30, 6.83), P = 0.004]. Conclusion The analysis outcomes indicate that balance training enhances daily activity capability, motor function, and dynamic balance to different extents. Additionally, when comparing the results of balance training and strength training, no significant difference was observed between the two methods in improving the dynamic stability of CAI patients. However, it is noteworthy that balance training exhibits a more pronounced impact on enhancing functional scale scores

MOESM1 of A novel Ffu fusion system for secretory expression of heterologous proteins in Escherichia coli

Additional file 1: Figure S1. Expression levels and solubility of targeted proteins (RVs, CARDS TX, VEGFR-2 and Omp85) fused with His tag. Lane 1, 2 shows the soluble fraction and inclusion bodies of His-fused RVs; lane 3,4 shows the soluble fraction and inclusion bodies of His-fused CARDS TX; lane 5, 6 shows the soluble fraction and inclusion bodies of His-fused VEGFR-2; lane 7, 8 shows the soluble fraction and inclusion bodies of His-fused Omp85. Keys:Soluble fractions (S) and inclusion bodies (ib). The conditions for expression of the proteins were: 0.5 mM IPTG at 25 ℃. Figure S2. The purification of fusion protein Ffu217-CARDS TX after osmotic shock. Keys: M presents protein molecular weight marker; lane 1 presents the soluble fraction of fusion protein Ffu217-CARDS TX, lane 2 presents the final purified Ffu217-CARDS TX. Figure S3. (A) NanoLC-MS/MS analysis of protein Ffu217-CARDS TX by chymotrypsin digestion; (B) NanoLC-MS/MS analysis of protein Ffu217-CARDS TX by trypsin digestion. Table S1. The primers used in this study

Abnormal degree centrality in chronic users of codeine-containing cough syrups: A resting-state functional magnetic resonance imaging study

Codeine-containing cough syrups (CCS) have become one of the most popular drugs of abuse in young population worldwide. However, the neurobiological mechanisms underlying CCS-dependence are yet ill-defined. Therefore, understanding the brain abnormalities in chronic users of CCS is crucial for developing effective interventions. The present study depicted the intrinsic dysconnectivity pattern of whole-brain functional networks at the voxel level in chronic users of CCS. In addition, the degree centrality (DC) changes were correlated to the Barratt Impulsiveness Scale (BIS-11) total score, dose, duration of CCS use, and the age at first use of cough syrups. The current study included 38 chronic CCS users and 34 matched control subjects. All patients were evaluated using the BIS-11. Next, resting-state functional magnetic resonance imaging (rs-fMRI) datasets were acquired from these CCS users and controls. Whole-brain connectivity was analyzed using a graph theory approach: degree centrality (DC). CCS-dependent individuals exhibited low DC values in the left inferior parietal lobule and the left middle temporal gyrus, while high DC values were noted in the right pallidum and the right hippocampus (P < 0.01, AlphaSim corrected). Also, significant correlations were established between average DC value in the left inferior parietal lobule and attentional impulsivity scores and the age at first CCS use. The rs-fMRI study suggested that the abnormal intrinsic dysconnectivity pattern of whole-brain functional networks may provide an insight into the neural substrates of abnormalities in the cognitive control circuit, the reward circuit, and the learning and memory circuit in CCS-dependent individuals. Keywords: Addiction, Codeine-containing cough syrups, Degree centrality, fMRI, Impulsivit

Clonally diverse CD38⁺HLA-DR⁺CD8⁺ T cells persist during fatal H7N9 disease

Virus-specific CD8+ T cells are crucial during H7N9 influenza infection, but CD8+ T cell dysfunction is associated with poor prognosis. Here, the authors use molecular and phenotypic analysis to establish persistence of clonally diverse CD8+ T cell populations during fatal infection