Science Funding Research Articles

Risk of chronic kidney disease in individuals on lithium therapy in Iceland: a nationwide retrospective cohort study

The association between lithium use and chronic kidney disease, and the effect of comorbidities on this association are poorly understood. Our aim was to examine the risk of developing stage 3 or higher chronic kidney disease among people receiving lithium therapy. This was a retrospective, population-based cohort study of all adults (aged ≥18 years) in Iceland treated with lithium for a mood disorder who had two or more serum creatinine measurements available in the years 2008-17, irrespective of duration of lithium therapy, identified from the Prescription Medicines Register of the Directorate of Health, or through blood lithium measurements. The control group comprised all eligible outpatients with mood disorders (ICD-10 codes F30-F39) who had not been prescribed lithium and who had attended the national tertiary referral centre in 2014-16. Individuals with chronic kidney disease (identified by ICD codes or an estimated glomerular filtration rate [eGFR] <60 mL/min per 1·73 m2) before Jan 1, 2008, or those with glomerular disease, genetic or congenital kidney disease, or small kidneys diagnosed before or after 2008 were excluded. Chronic kidney disease stages 3 and higher were defined according to the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease, and the eGFR was calculated from serum creatinine; all ICD-10 and ICD-9 diagnosis codes, serum creatinine and blood lithium concentrations, and urine albumin-to-creatinine ratios were obtained from health-care institutions and laboratories. Risk of developing stage 3 or higher chronic kidney disease between Jan 1, 2008, and Dec 31, 2017, was assessed using time-to-event regression analysis, accounting for competing risk of death. People with lived experience were not involved in the design or conduct of this study. We identified 4310 individuals (2695 who had received lithium and 1615 control participants), of whom 3198 were included in the study. 2025 (75·1%) individuals in the lithium group (1165 [57·5%] female and 860 [42·5%] male) and 1173 (72·6%) in the control group (737 [62·8%] female and 436 [37·2%] male) were included in the study at end of follow-up. The mean age of the study sample at the end of follow-up was 46·6 years (SD 16·4; range 18·5-98·9). Ethnicity data were not available. In the lithium group, 211 (10·4%) of 2025 individuals developed stage 3 or higher chronic kidney disease, compared with 35 (3·0%) of 1173 individuals in the control group (hazard ratio [HR] 1·90, 95% CI 1·32-2·75 after adjusting for sex, age, and comorbid conditions). Compared with control participants, the risk of stage 3 or higher chronic kidney disease was significantly increased for subgroups with a mean blood lithium concentration of 0·60-0·79 mmol/L (HR 2·93, 95% CI 1·97-4·36) or 0·80-0·99 mmol/L (4·31, 2·66-6·99), but not for the subgroup with a mean blood lithium concentration of 0·30-0·59 mmol/L (1·22, 0·78-1·90). Analyses also showed that age, initial eGFR, diabetes, and history of acute kidney injury were significant risk factors for developing stage 3 or higher chronic kidney disease. Individuals with mood disorders receiving lithium treatment had an increased risk of developing stage 3 or higher chronic kidney disease in a blood concentration-dependent manner. We also found that other factors, including age, initial eGFR, and comorbidities were associated with increased risk of for developing stage 3 or higher chronic kidney disease. Overall, our findings suggest that in addition to considering other risk factors (eg, age or clinical comorbidities), careful monitoring of blood lithium concentrations and use of the lowest effective lithium dose for adequate mood stabilisation is recommended for helping to mitigate the risk of chronic kidney disease. Akureyri Hospital Research Fund and Landspitali University Hospital Science Fund.

Exposure to air pollution increases susceptibility to ulcerative colitis through epigenetic alterations in CXCR2 and MHC class III region

This study aims to confirm the associations of air pollution with ulcerative colitis (UC) and Crohn's disease (CD); to explore interactions with genetics and lifestyle; and to characterize potential epigenetic mechanisms. We identified over 450,000 individuals from the UK Biobank and investigated the relationship between air pollution and incident inflammatory bowel disease (IBD). Cox regression was utilized to calculate hazard ratios (HRs), while also exploring potential interactions with genetics and lifestyle factors. Additionally, we conducted epigenetic Mendelian randomization (MR) analyses to examine the association between air pollution-related DNA methylation and UC. Finally, our findings were validated through genome-wide DNA methylation analysis of UC, as well as co-localization and gene expression analyses. Higher exposures to NOx (HR=1.20, 95% CI 1.05-1.38), NO2 (HR=1.19, 95% CI=1.03-1.36), PM2.5 (HR=1.19, 95% CI=1.05-1.36) and combined air pollution score (HR=1.26, 95% CI=1.11-1.45) were associated with incident UC but not CD. Interactions with genetic risk score and lifestyle were observed. In MR analysis, we found five and 22 methylated CpG sites related to PM2.5 and NO2 exposure to be significantly associated with UC. DNA methylation alterations at CXCR2 and sites within the MHC class III region, were validated in genome-wide DNA methylation analysis, co-localization analysis and analysis of colonic tissue. We report a potential causal association between air pollution and UC, modified by lifestyle and genetic influences. Biological pathways implicated include epigenetic alterations in key genetic loci, including CXCR2 and susceptible loci within MHC class III region. Xue Li was supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) and the National Nature Science Foundation of China (No. 82204019). ET was supported by the CRUK Career Development Fellowship (C31250/A22804) and the Research Foundation Flanders (FWO). JW was supported by Belgium by a PhD Fellowship strategic basic research (SB) grant (1S06023N). JKN was supported by the National Science Center, Poland (No. 2020/39/D/NZ5/02720). The IBD Character was supported by the European Union's Seventh Framework Programme [FP7] grant IBD Character (No. 2858546).

Decisions Making in Information Security Investments: Impact of System Vulnerability and Investment Timing on Resource-Sharing Platforms

This study distinguishes enterprises into high- and low-type categories based on enterprise value and cost efficiency, examining their strategic behaviors in three investment timing games: move simultaneously, the high-type enterprise moves first, and the low-type enterprise moves first. By comparing the three games, we find that both types of enterprises would always exert more effort in the sequential game than in the simultaneous game, and the later-move advantage makes both types of enterprises prefer to become the follower in the game. We also find that the enhanced cost efficiency advantage or enterprise value gap possessed by the high-type enterprise would widen the effort gap between the two types of enterprises, and enhance the low-type enterprise’s incentive to be the follower. Moreover, the existence of system vulnerability not only causes both types of enterprises to reduce their security effort that generates free-riding behaviors but also can first discourage and then encourage enterprises from moving in advance. We further propose a liability-based mechanism to tackle the free-riding problem. We reveal an exact optimal liability coefficient, whether in the simultaneous or sequential game and find that the high-type enterprise should undertake more compensation when its dominant position becomes more obvious and the low-type enterprise could therefore undertake decreased liability. Last, we extend the model to multiple enterprises and show that the results are robust. Funding: This work was supported by the Shanghai Science and Technology Development Foundation [Grant 24692107700]; the Humanities and Social Science Fund of Ministry of Education of China [Grant 23YJA630100]; Fundamental Research Funds for the Central Universities; DHU Distinguished Young Professor Program; and the Shanghai Social Science Foundation [Grant 2022ZGL009]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/deca.2024.0190 .

Manufacturing

Manufacturing is dedicated to industrial production, in which raw materials are transformed into finished products on a large scale and included in the economy´s secondary sector. The Scopus database was used for the bibliometric analysis, based on the term {manufacturing}. The better result shows in the function of the number of documents produced: year 2023; source Proceedings of SPIE; author Franke J. and Wang, L.; affiliation Ministry of Education of China; country USA; document type article; scientific area engineering and funding support National Natural Science Foundation of China.

Research on Ecological Restoration Strategies for Abandoned Mines Based on Ecology-Oriented Development

The ecological restoration of abandoned mines poses a significant challenge within China’s broader efforts toward the protection and restoration of the nation’s ecosystems. Based on the ecology-oriented development (EOD) model, a differential game framework for the ecological restoration of abandoned mines was constructed in this study, involving both government and corporate entities as players. Our analysis focused on various factors, including investment levels in ecological restoration quality, the quality of ecological restoration itself, investment levels in environmentally sensitive industry development, the quality of environmentally sensitive industries, environmentally sensitive product pricing strategies, and profit dynamics for both players across four distinct modes. Our findings reveal several key insights. First, extending the government’s concession period incentivizes enterprises to increase investment in both the quality of ecological restoration of abandoned mines and the development of environmentally sensitive industries. Second, the government should prefer the cooperative mode to introduce social capital for the ecology-oriented development of abandoned mines. Third, in noncooperative mode, for technology-intensive industries, the government’s industrial support policy is more mutually beneficial; conversely, for labor-intensive industries, the ecological restoration compensation policy yields higher mutual gains. Lastly, differentiated incentive policies implemented by the government across various modes prompt the input of enterprises in ecological restoration quality and environmentally sensitive industry development. Based on these findings, we offer specific policy recommendations to guide governmental efforts in promoting EOD for the ecological restoration of abandoned mines. Funding: This work was supported by the Sichuan Office of Philosophy and Social Science [Grant SC22C004] and the National Social Science Fund of China [Grant 22XKS015].

The EU’s Fifth Freedom: Why and How to Develop the ‘Freedom of Knowledge’

The goal of a fifth EU freedom – the ‘freedom of knowledge’ – emerged from working towards a unified European research area, expanding upon the four basic freedoms of the Single Market. This additional freedom is not yet guaranteed and so this task should be taken up anew. Here, I support this goal by explicating the meaning of the ‘fifth freedom’, then justifying its importance via four arguments concerning scientific progress, freedom of research, the economic and technological progress of societies, and the democratic ideals of the European project. To end the main article, I then argue that this freedom should be viewed as a right. In the supplementary material, I present problems that arise in the administration, funding, and organization of science within the EU to demonstrate that the fifth freedom is still a long way from being a reality. The evidence includes cases of national rules and practices that reduce or block the mobility of EU researchers and weaken collaboration and progress. For each type of problem, I present specific policy proposals for advancing the fifth freedom goal. The proposals are directed at academic administrations, funding agencies, and political actors at the regional, national, and European levels.

Effects of comprehensive smoke-free legislation on smoking behaviours and macroeconomic outcomes in Shanghai, China: a difference-in-differences analysis and modelling study

China has one of the highest levels of tobacco consumption globally, and there is no national smoke-free legislation. Although more than 20 Chinese cities have passed local smoke-free laws since 2008, evidence on their effectiveness in reducing smoking behaviours and their economic benefits is scarce. By exploiting a natural quasi-experiment, whereby a comprehensive public smoking ban was implemented in Shanghai in March, 2017, this study aims to assess the impact of the policy on individual smoking behaviours and quantify its effect on macroeconomic outcomes. In this difference-in-differences analysis and modelling study, we used data on smoking behaviours from the 2012, 2014, 2016, and 2018 waves of the China Family Panel Studies. We used a difference-in-differences approach to investigate trends in smoking prevalence in respondents in Shanghai, relative to respondents from other direct-administered municipalities, provincial capital cities, and subprovincial municipalities (control group), after the implementation of a smoking ban in 2017. All respondents aged 18 years or older were included, with the exception of people who lived in Beijing and rural areas. The primary variable of interest in the difference-in-differences analysis was self-reported smoking status. Based on the difference-in-differences estimation of reduction in smoking prevalence, we then used a health-augmented macroeconomic model to estimate the potential macroeconomic gains if such a ban was implemented across China for the period 2017-35. 14 688 respondents were included in the analysis: 5766 from Shanghai and 8922 from the control group. After the implementation of the smoking ban in Shanghai in 2017, smoking prevalence decreased by 2·2 percentage points (95% CI 2·1-2·3), equivalent to an 8·4% reduction in the number of current smokers. The smoking ban had a larger effect on men, people with a higher level of education, unmarried people, and younger people when compared with their respective counterparts. The modelling analysis showed that implementing a nationwide comprehensive public smoking ban similar to that in Shanghai would result in a 0·04-0·07% increase in the national gross domestic product in China between 2017 and 2035, outweighing the economic costs of smoking ban enforcement. The smoking ban in Shanghai shows that a comprehensive public smoking ban with strict enforcement is effective in curbing smoking behaviours. Moreover, the implementation of a comprehensive public smoking ban across China would be cost-effective. National Social Science Fund of China.

Gelation embolism agents suppress clinical TACE-incited pro-metastatic microenvironment against hepatocellular carcinoma progression

Current embolic agents in transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) encounter instability and easy leakage, discounting TACE efficacy with residual HCC. Moreover, clinical TACE aggravates hypoxia and pro-metastatic microenvironments, rendering patients with HCC poor prognosis. Herein, we developed Zein-based embolic agents that harness water-insoluble but ethanol-soluble Zein to encompass doxorubicin (DOX)-loaded mesoporous hollow MnO2 (HMnO2). The conditions and capacity of HMnO2 to generate reactive oxygen species (ROS) were assayed. Mechanical examinations of Zein-HMnO2@DOX were performed to evaluate its potential as the embolic agent. Invitro experiments were carried out to evaluate the effect of Zein-HMnO2@DOX on HCC. The subcutaneous HCC mouse model and rabbit VX2 HCC model were established to investigate its anti-tumor and anti-metastasis efficacy and explore its potential anti-tumor mechanism. The high adhesion and crosslinking of Zein with HMnO2@DOX impart Zein-HMnO2@DOX with strong mechanical strength to resist deformation and wash-off. Zein gelation and HMnO2 decomposition in response to water and acidic tumor microenvironment, respectively, enable continuous DOX release and Fenton-like reaction for reactive oxygen species (ROS) production and O2 release to execute ROS-enhanced TACE. Consequently, Zein-based embolic agents outperform clinically-used lipiodol to significantly inhibit orthotopic HCC growth. More significantly, O2 release down-regulates hypoxia inducible factor (HIF-1α), vascular endothelial growth factor (VEGF) and glucose transporter protein 1 (GLUT1), which thereby re-programmes TACE-aggravated hypoxic and pro-metastatic microenvironments to repress HCC metastasis towards lung. Mechanistic explorations uncover that such Zein-based TACE agents disrupt oxidative stress, angiogenesis and glycometabolism pathways to inhibit HCC progression. This innovative work not only provides a new TACE agent for HCC, but also establishes a new strategy to ameliorate TACE-aggravated hypoxia and metastasis motivation against clinically-common HCC metastasis after TACE operation. Excellent Young Science Fund for National Natural Science Foundation of China (82022033); National Natural Science Foundation of China (Grant No. 82373086, 82102761); Major scientific and technological innovation project of Wenzhou Science and Technology Bureau (Grant No. ZY2021009); Shanghai Young Top-Notch Talent.

From amoeboid myosin to unique targeted medicines for a genetic cardiac disease.

The importance of fundamental basic research in the quest for much needed clinical treatments is a story that constantly must be retold. Funding of basic science in the USA by the National Institutes of Health and other agencies is provided under the assumption that fundamental research eventually will lead to improvements in healthcare worldwide. Understanding how basic research is connected to clinical developments is important, but just part of the story. Many basic science discoveries never see the light of day in a clinical setting because academic scientists are not interested in or do not have the inclination and/or support for entering the world of biotechnology. Even if the interest and inclination are there, often the unknowns about how to enter that world inhibit taking the initial step. Young investigators often ask me how I incorporated biotech opportunities into my otherwise purely academic research endeavors. Here I tell the story of the foundational basic science and early events of my career that led to forming the biotech companies responsible for the development of unique cardiac drugs, including mavacamten, a first in class human β-cardiac myosin inhibitor that is changing the lives of hypertrophic cardiomyopathy patients.

Fast Convex Optimization via Time Scale and Averaging of the Steepest Descent

In a Hilbert setting, we develop a gradient-based dynamic approach for fast solving convex optimization problems. By applying time scaling, averaging, and perturbation techniques to the continuous steepest descent (SD), we obtain high-resolution ordinary differential equations of the Nesterov and Ravine methods. These dynamics involve asymptotically vanishing viscous damping and Hessian-driven damping (either in explicit or implicit form). Mathematical analysis does not require developing a Lyapunov analysis for inertial systems. We simply exploit classical convergence results for SD and its external perturbation version, then use tools of differential and integral calculus, including Jensen’s inequality. The method is flexible, and by way of illustration, we show how it applies starting from other important dynamics in optimization. We consider the case in which the initial dynamic is the regularized Newton method, then the case in which the starting dynamic is the differential inclusion associated with a convex lower semicontinuous potential, and finally we show that the technique can be naturally extended to the case of a monotone cocoercive operator. Our approach leads to parallel algorithmic results, which we study in the case of fast gradient and proximal algorithms. Our averaging technique shows new links between the Nesterov and Ravine methods. Funding: The research of R.I. Boţ and D.-K. Nguyen was supported by the Austrian Science Fund (FWF), projects W 1260 and P 34922-N.

Global radiotherapy demands and corresponding radiotherapy-professional workforce requirements in 2022 and predicted to 2050: a population-based study

Addressing the challenge of cancer control requires a comprehensive, integrated, and global health-system response. We aimed to estimate global radiotherapy demands and requirements for radiotherapy professionals from 2022 to 2050. We conducted a population-based study using data from the Global Cancer Observatory (GLOBOCAN) 2022 and predicted global radiotherapy demands and workforce requirements in 2050. We obtained incidence figures for 29 types of cancer across 183 countries and derived the cancer-specific radiotherapy use rate using the 2013 Collaboration for Cancer Outcomes Research and Evaluation model. We delineated the proportion of people with cancer who require radiotherapy and can be accommodated within the existing installed capacity, assuming an optimal use rate of 50% or 64%, in both 2022 and 2050. A use rate of 50% corresponds to the global average and a use rate of 64% considers potential re-treatment scenarios, as indicated by the 2013 Collaboration for Cancer Outcomes Research and Evaluation (CCORE) radiotherapy use rate model. We established specified requirements for teletherapy units at a ratio of 1:450 patients, for radiation oncologists at a ratio of 1:250 patients, for medical physicists at a ratio of 1:450 patients, and for radiation therapists at a ratio of 1:150 patients in all countries and consistently using these ratios. We collected current country-level data on the radiotherapy-professional workforce from national health reports, oncology societies, or other authorities from 32 countries. In 2022, there were an estimated 20·0 million new cancer diagnoses, with approximately 10·0 million new patients needing radiotherapy at an estimated use rate of 50% and 12·8 million at an estimated use rate of 64%. In 2050, GLOBOCAN 2022 data indicated 33·1 million new cancer diagnoses, with 16·5 million new patients needing radiotherapy at an estimated use rate of 50% and 21·2 million at an estimated use rate of 64%. These findings indicate an absolute increase of 8·4 million individuals requiring radiotherapy from 2022 to 2050 at an estimated use rate of 64%; at an estimated use rate of 50%, the absolute increase would be 6·5 million individuals. Asia was estimated to have the highest radiotherapy demand in 2050 (11 119 478 [52·6%] of 21 161 603 people with cancer), followed by Europe (3 564 316 [16·8%]), North America (2 546 826 [12·0%]), Latin America and the Caribbean (1 837 608 [8·7%]), Africa (1 799 348 [8·5%]), and Oceania (294 026 [1·4%]). We estimated that the global radiotherapy workforce in 2022 needed 51 111 radiation oncologists, 28 395 medical physicists, and 85 184 radiation therapists and 84 646 radiation oncologists, 47 026 medical physicists, and 141 077 radiation therapists in 2050. We estimated that the largest proportion of the radiotherapy workforce in 2050 would be in upper-middle-income countries (101 912 [38·8%] of 262 624 global radiotherapy professionals). Urgent strategies are required to empower the global health-care workforce and facilitate the fundamental human right of access to suitable health care. A collective effort with innovative and cost-contained health-care strategies from all stakeholders is warranted to enhance global accessibility to radiotherapy and address challenges in cancer care. China Medical Board Global Health Leadership Development Program, Shanghai Science and Technology Committee Fund, China Ministry of Science and Technology Department of International Cooperation High Level Cooperation and Exchange Projects, and Fudan University Office of Global Partnerships Key Projects Development Fund. For the Arabic, Chinese, French, Russian and Spanish translations of the summary see Supplementary Materials section.

A traditional ecological knowledge summit

A traditional ecological knowledge summit The Global Center for Climate Change and Transboundary Waters (GCTW) cohosts a Traditional Ecological Knowledge Summit (1), as Gail Krantzberg (2), Peter Czajkowski, Dawn Martin-Hill, Rohini Patel, Hiliary Monteith, and Drew Gronewold explain. The Global Center for Climate Change and Transboundary Waters (GCTW) integrates hydroclimate modeling, water quality forecasting, and community-engaged mixed methods that harmonize and propagate Traditional Ecological Knowledge (TEK), Indigenous Knowledge (IK), and Western Science (WS) into robust 21st-century transboundary water resources governance protocols. The U.S. National Science Foundation and the Canadian Social Science and Humanities Research Council fund the Center. It supports a multinational network of researchers that is designed to promote information sharing across borders.

A Dynamic Principal-Agent Problem with One-Sided Commitment

In this paper, we consider a principal-agent problem where the agent is allowed to quit by incurring a cost. When the current agent quits the job, the principal will hire a new one, possibly with a different type. We characterize the principal’s dynamic value function, which could be discontinuous at the boundary, as the (unique) minimal solution of an infinite dimensional system of Hamilton-Jacobi-Bellman equations, parameterized by the agent’s type. This dynamic problem is time consistent in a certain sense. Some interesting findings are worth mentioning. First, self-enforcing contracts are typically suboptimal. The principal would rather let the agent quit and hire a new one. Next, the standard contract for a committed agent may also be suboptimal because of the presence of different types of agents in our model. The principal may prefer no commitment from the agent; then, the principal can hire a cheaper one from the market at a later time by designing the contract to induce the current agent to quit. Moreover, because of the cost incurred to the agent, the principal will see only finitely many quittings. Funding: J. Zhang is supported in part by the NSF [Grants DMS-1908665 and DMS-2205972]. Z. Zhu is supported by The Hong Kong University of Science and Technology (Guangzhou) Start-Up Fund [Grant G0101000240] and the Guangzhou-HKUST(GZ) Joint Funding Program [Grant 2024A03J0630].

Association of uric acid and fructose levels in polycystic ovary syndrome.

Is there a relationship between serum uric acid and fructose levels in polycystic ovary syndrome (PCOS)? Elevated serum uric acid levels in women with PCOS positively correlate with serum fructose levels, and elevated serum fructose levels are an independent risk factor for hyperuricemia in women with PCOS. Our previous study suggested a link between elevated serum fructose levels and PCOS. Fructose is unique as it generates uric acid during metabolism, and high uric acid levels are associated with metabolic disorders and an increased risk of anovulation. However, the relationship between serum uric acid and fructose levels in women with PCOS remains unclear. In a case-control study of 774 women (482 controls and 292 patients with PCOS) between May and October 2020 at the Shengjing Hospital of China Medical University, the relationship between uric acid and fructose levels in women with PCOS was examined. Participants were divided into subgroups based on various factors, including BMI, insulin resistance, dyslipidemia, metabolic syndrome, and hyperuricemia. Serum uric acid concentrations were measured using enzymatic assays, and serum fructose levels were determined using a fluorescent enzyme immunoassay. Dietary fructose data were collected through a validated food-frequency questionnaire of 81 food items. We applied restricted cubic splines to a flexibly model and visualized the linear/nonlinear relationships between serum uric acid and fructose levels in PCOS. Multivariate logistic analysis was executed to assess the association between serum fructose levels and hyperuricemia in PCOS. Human granulosa cell and oocyte mRNA profile sequencing data were downloaded for mapping uric acid and fructose metabolism genes in PCOS. Further downstream analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and protein-protein interactions were then carried out on the differentially expressed genes (DEGs). The correlation between uric acid and fructose metabolism genes was calculated using the Pearson correlation coefficient. The GeneCards database was used to identify DEGs related to uric acid and fructose metabolism in PCOS, and then several DEGs were confirmed by quantitative real-time PCR. Both serum fructose and uric acid levels were significantly increased in women with PCOS compared with the control women (P < 0.001), and there was no statistically significant difference in dietary fructose intake between PCOS and controls, regardless of metabolic status. There was a positive linear correlation between serum uric acid and fructose levels in women with PCOS (Poverall < 0.001, Pnon-linear = 0.30). In contrast, no correlation was found in control women (Poverall = 0.712, Pnon-linear = 0.43). Additionally, a non-linear association was observed in the obese subgroup of patients with PCOS (Poverall < 0.001, Pnon-linear = 0.02). Serum uric acid levels were linearly and positively associated with serum fructose levels in patients with PCOS with insulin resistance, dyslipidemia, and metabolic syndrome. Furthermore, even after adjusting for confounding factors, elevated serum fructose levels were an independent risk factor for hyperuricemia in patients with PCOS (P = 0.001; OR, 1.380; 95% CI, 1.207-1.577). There were 28 uric acid and 25 fructose metabolism genes which showed a significant correlation in PCOS. Seven upregulated genes (CAT, CRP, CCL2, TNF, MMP9, GCG, and APOB) related to uric acid and fructose metabolism in PCOS ovarian granulosa cells were ultimately successfully validated using quantitative real-time PCR. Due to limited conditions, more possible covariates (such as smoking and ethnicity) were not included, and the underlying molecular mechanism between fructose and uric acid levels in women with PCOS remains to be further investigated. The results of this study and our previous research indicate that the high uric acid status of PCOS may be mediated by fructose metabolism disorders, highlighting the importance of analyzing fructose metabolism, and especially its metabolic byproduct uric acid, during the clinical diagnosis of PCOS. These results suggest the adverse effects of high uric acid in PCOS, and the importance of taking early interventions regarding uric acid levels to reduce the occurrence and development of further clinical signs, such as metabolic disorders in women with PCOS. This work was supported by: the National Natural Science Foundation of China (No. 82371647, No. 82071607, and No. 32100691); LiaoNing Revitalization Talents Program (No. XLYC1907071); Fok Ying Tung Education Foundation (No. 151039); and Outstanding Scientific Fund of Shengjing Hospital (No. 202003). No competing interests were declared. N/A.

Industry-University Collaboration and Commercializing Chinese Corporate Innovation

We construct a comprehensive data set of medium- and large-sized industrial firms and research universities in China and examine how Chinese firms’ commercialization of their technologies is related to their experience in industry-university collaboration (IUC). We propose that firms’ IUC experience constitutes an inimitable complementary asset that facilitates their technology commercialization. Our empirical analyses show that firms generate more new product sales and produce more product-oriented patents when they have more patents that are coassigned to universities or when they have more academic publications coauthored with university staff in the past. Such a relation is strengthened when firms have higher absorptive capacity, when firms are in industries that depend more on basic science, and when firms are located closer to their collaborating universities. Additional tests point out four channels through which firms’ IUC experience benefits their technology commercialization: knowledge acquisition, talent recruiting, direct technology transfers, and technological complementarity. This paper was accepted by Sridhar Tayur, entrepreneurship and innovation. Funding: D. H. Hsu acknowledges research support from the Mack Institute for Innovation Management at the University of Pennsylvania. P.-H. Hsu acknowledges the Yushan Fellow Program by the Ministry of Education and National Science and Technology Council, Taiwan [MOE-108-YSFMS-0004-012-P1, NSTC 113-2410-H-007-008-MY3, MOST 109-2628-H-007-001-MY4] and the E.SUN Academic Award. K. Zhou acknowledges research support from the Major Project of the National Social Science Fund of China [Grant 20&amp;ZD103], the National Natural Science Foundation of China [Grant 71991474] and the 111 Project of China [Grant D23001]. T. Zhou acknowledges research support from the National Natural Science Foundation of China [Grant 72003206]. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.00788 .

Value-Positivity for Matrix Games

Matrix games are the most basic model in game theory, and yet robustness with respect to small perturbations of the matrix entries is not fully understood. In this paper, we introduce value positivity and uniform value positivity, two properties that refine the notion of optimality in the context of polynomially perturbed matrix games. The first concept captures how the value depends on the perturbation parameter, and the second consists of the existence of a fixed strategy that guarantees the value of the unperturbed matrix game for every sufficiently small positive parameter. We provide polynomial-time algorithms to check whether a polynomially perturbed matrix game satisfies these properties. We further provide the functional form for a parameterized optimal strategy and the value function. Finally, we translate our results to linear programming and stochastic games, where value positivity is related to the existence of robust solutions. Funding: This research was supported by Fondation CFM pour la Recherche, the H2020 European Research Council [Grant ERC-CoG-863818 (ForM-SMArt)], the Austrian Science Fund [Grant 10.55776/COE12], ANID Chile [Grant ACT210005], and Agence Nationale de la Recherche [Grant ANR-21-CE40-0020].

Risks of competing discourses of scientific responsibility in global ocean futures

Accelerated innovation in climate-impacted oceans is outpacing standards of scientific responsibility. Standards of responsibility are critical because they shape research agendas, funding flows, scientific practice, and how innovations are regulated. Here, we examine responsibility debates among 243 marine scientists and end-users proposing, trialling and/or implementing 76 innovations for climate-impacted oceans. We identify three distinct discourses: ‘science outside society’, ‘science for society’ and ‘science with society’. Competition within and across these discourses reveals heightened tensions between the need to protect scientific autonomy and freedom, and moral duty to ensure socially just and desirable ocean futures. Without thorough debate and oversight, the wide-reaching power of such unresolved tensions could propel marine science and ocean futures into volatile ethical and moral territory. Better connection and articulation of standards of responsibility with scientific motivations, practices, and funding are key to ensuring the transparency and accountability required to progress equitable and sustainable oceans.

Evaluations in science communication. Current state and future directions

Evaluations are becoming more important in science communication. But both science communication practitioners and researchers are not sufficiently utilizing the potential of evaluations yet. In this essay, we first define four requirements for rigorous evaluations of science communication activities and projects. To substantiate our argument, we take stock of the scientific literature, uncover deficiencies in current evaluation practices and identify potential causes. We conclude with laying out how different actors in the field — including science communication practitioners, professional associations, scientific institutions and funding bodies as well as researchers — can contribute to advancing evaluation practices in science communication as well as research on it.

An effective framework for measuring the novelty of scientific articles through integrated topic modeling and cloud model

Novelty is a critical characteristic of innovative scientific articles, and accurately identifying novelty can facilitate the early detection of scientific breakthroughs. However, existing methods for measuring novelty have two main limitations: (1) Metadata-based approaches, such as citation analysis, are retrospective and do not alleviate the pressures of the peer review process or enable timely tracking of scientific progress; (2) Content-based methods have not adequately addressed the inherent uncertainty between the qualitative concept of novelty and the textual representation of papers. To address these issues, we propose a practical and effective framework for measuring the novelty of scientific articles through integrated topic modeling and cloud model, referred to as MNSA-ITMCM. In this framework, papers are represented as topic combinations, and novelty is reflected in the organic reorganization of these topics. We use the BERTopic model to generate semantically informed topics, and then apply a topic selection algorithm based on maximum marginal relevance to obtain a topic combination that balances similarity and diversity. Furthermore, we leverage the cloud model from fuzzy mathematics to quantify novelty, overcoming the uncertainty inherent in natural language expression and topic modeling to improve the accuracy of novelty measurement. To validate the effectiveness of our framework, we conducted empirical evaluations on papers from the Cell 2021 journal (biomedical domain) and the ICLR 2023 conference (computer science domain). Through correlation analysis and prediction error analysis, our framework demonstrated the ability to identify different types of novel papers and accurately predict their novelty levels. The proposed framework is applicable across diverse scientific disciplines and publication venues, benefiting researchers, librarians, science evaluation agencies, policymakers, and funding organizations by improving the efficiency and comprehensiveness of identifying novelty research.

A transformer-based deep learning model for early prediction of lymph node metastasis in locally advanced gastric cancer after neoadjuvant chemotherapy using pretreatment CT images

Early prediction of lymph node status after neoadjuvant chemotherapy (NAC) facilitates promptly optimization of treatment strategies. This study aimed to develop and validate a deep learning network (DLN) using baseline computed tomography images to predict lymph node metastasis (LNM) after NAC in patients with locally advanced gastric cancer (LAGC). A total of 1205 LAGC patients were retrospectively recruited from three hospitals between January 2013 and March 2023, constituting a training cohort, an internal validation cohort, and two external validation cohorts. A transformer-based DLN was developed using 3D tumor images to predict LNM after NAC. A clinical model was constructed through multivariate logistic regression analysis as a baseline for subsequent comparisons. The performance of the models was evaluated through discrimination, calibration, and clinical applicability. Furthermore, Kaplan-Meier survival analysis was conducted to assess overall survival (OS) of LAGC patients at two follow-up centers. The DLN outperformed the clinical model and demonstrated a robust performance for predicting LNM in the training and validation cohorts, with areas under the curve (AUCs) of 0.804 (95% confidence interval [CI], 0.752-0.849), 0.748 (95% CI, 0.660-0.830), 0.788 (95% CI, 0.735-0.835), and 0.766 (95% CI, 0.717-0.814), respectively. Decision curve analysis exhibited a high net clinical benefit of the DLN. Moreover, the DLN was significantly associated with the OS of LAGC patients [Center 1: hazard ratio (HR), 1.789, P<0.001; Center 2:HR, 1.776, P=0.013]. The transformer-based DLN provides early and effective prediction of LNM and survival outcomes in LAGC patients receiving NAC, with promise to guide individualized therapy. Future prospective multicenter studies are warranted to further validate our model. National Natural Science Foundation of China (NO. 82373432, 82171923, 82202142), Project Funded by China Postdoctoral Science Foundation (NO. 2022M720857), Regional Innovation and Development Joint Fund of National Natural Science Foundation of China (NO. U22A20345), National Science Fund for Distinguished Young Scholars of China (NO. 81925023), Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application (NO. 2022B1212010011), High-level Hospital Construction Project (NO. DFJHBF202105), Natural Science Foundation of Guangdong Province for Distinguished Young Scholars (NO. 2024B1515020091).