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Abstract Sustainable diets can achieve considerable reductions in greenhouse gas emissions and improvements in human health, but changing dietary behavior remains a challenge. We assessed the impacts of two behavioral insights strategies on bridging the intention-action gap related to sustainable and healthy food choices amongst hospital cafeteria patrons. In a pilot survey of hospital staff (N = 1,165), 56% identified limited awareness and availability of sustainable food as barriers to purchasing, although 46% were extremely willing to try sustainable dishes. We examined increasing salience (Study 1), varying availability (Study 2a), and decreasing availability (Study 2b) on sustainable and healthy dish purchases in three hospital cafeterias. Each study ran for seven weeks from March to April, 2023. In total, 10,616 dishes were purchased. In Study 1, increasing salience was associated with significant uptake of sustainable and healthy dishes, but the effect disappeared once the salience intervention was removed. In Study 2a, increasing availability of sustainable dishes corresponded to a significant increase in purchases of sustainable dishes, while decreasing availability in Study 2b followed a downward trend in purchases, suggesting that availability drove dietary choices. We recommend hospitals consider these choice architecture interventions to support the adoption of sustainable and healthy diets.

Abstract Climate change is currently one of humanity’s greatest threats. To help scholars understand the psychology of climate change, we conducted an online quasi-experimental survey on 59,508 participants from 63 countries (collected between July 2022 and July 2023). In a between-subjects design, we tested 11 interventions designed to promote climate change mitigation across four outcomes: climate change belief, support for climate policies, willingness to share information on social media, and performance on an effortful pro-environmental behavioural task. Participants also reported their demographic information (e.g., age, gender) and several other independent variables (e.g., political orientation, perceptions about the scientific consensus). In the no-intervention control group, we also measured important additional variables, such as environmentalist identity and trust in climate science. We report the collaboration procedure, study design, raw and cleaned data, all survey materials, relevant analysis scripts, and data visualisations. This dataset can be used to further the understanding of psychological, demographic, and national-level factors related to individual-level climate action and how these differ across countries.

Abstract Coordinating the immune response and bioenergy metabolism in bone defect environments is essential for promoting bone regeneration. Mitochondria are important organelles that control internal balance and metabolism. Repairing dysfunctional mitochondria has been proposed as a therapeutic approach for disease intervention. Here, an engineered hierarchical hydrogel with immune responsiveness can adapt to the bone regeneration environment and mediate the targeted mitochondria transfer between cells. The continuous supply of mitochondria by macrophages can restore the mitochondrial bioenergy of bone marrow mesenchymal stem cells (BMSC). Fundamentally solving the problem of insufficient energy support of BMSCs caused by local inflammation during bone repair and regeneration. This discovery provides a new therapeutic strategy for promoting bone regeneration and repair, which has research value and practical application prospects in the treatment of various diseases caused by mitochondrial dysfunction.

BackgroundWhether lymph node metastasis in non-small cell lung cancer is critical to clinical decision-making. This study was to develop a non-invasive predictive model for preoperative assessing lymph node metastasis in patients with non-small cell lung cancer (NSCLC) using radiomic features from chest CT images.Materials & methodsIn this retrospective study, 247 patients with resectable non-small cell lung cancer (NSCLC) were enrolled. These individuals underwent preoperative chest CT scans that identified lung nodules, followed by lobectomies and either lymph node sampling or dissection. We extracted both intratumoral and peritumoral radiomic features from the CT images, which were used as covariates to predict the lymph node metastasis status. By using ROC curves, Delong tests, Calibration curve, and DCA curves, intra-tumoral-peri-tumoral model performance were compared with models using only intratumoral features or clinical information. Finally, we constructed a model that combined clinical information and radiomic features to increase clinical applicability.ResultsThis study enrolled 247 patients (117 male and 130 females). In terms of predicting lymph node metastasis, the intra-tumoral-peri-tumoral model (0.953, 95%CI 0.9272-0.9792) has a higher AUC compared to the intratumoral radiomics model (0.898, 95%CI 0.8553-0.9402) and the clinical model (0.818, 95%CI 0.7653-0.8709). The DeLong test shows that the performance of the Intratumoral and Peritumoral radiomics models is superior to that of the Intratumoral or clinical feature model (p

Thailand’s aging population has impacted its labor force. This study examines additional health capacity to work (AHCW) with established methods. Data were obtained from the mortality registry as well as national health, aging, labor force, and welfare surveys. Utilizing the Milligan–Wise method, the estimated AHCW for those aged 50–69 was 1.3 years (an 8.7% increase) for males and 1.9 years (17.8%) for females, based on the 2005 employment–mortality relationship. With the Cutler–Meara–Richards-Shubik method, the estimated AHCW for those aged 60–69 in 2015 ranged from 0.9 years (13.6%) to 2.0 years (31.3%) for males and from 1.2 years (23.2%) to 1.5 years (29.6%) for females. We also found that older informal workers in Thailand need to work to maintain their standards of living due to limited retirement benefits. Effective policy measures should be implemented to protect informal workers’ health, prevent pensioners from being impoverished, facilitate a more flexible working environment, and help workers maintain skills and job competencies.

Introduction: Ischemic stroke (IS) is a detrimental neurological disease with limited treatment options. Recanalization of blocked blood vessels and restoring blood supply to ischemic brain tissue are crucial for post-stroke rehabilitation. The decoction Naodesheng (NDS) composed of five Chinese botanical drugs, including Panax notoginseng (Burk.) F. H. Chen, Ligusticum chuanxiong Hort., Carthamus tinctorius L., Pueraria lobata (Willd.) Ohwi, and Crataegus pinnatifida Bge., is a blood-activating and stasis-removing herbal medicine commonly used for the clinical treatment of cerebrovascular diseases in China. However, the material basis of NDS on the effects of blood circulation improvement and vascular tone regulation remains unclear.Methods: A database comprising 777 chemical metabolites of NDS was constructed. Then, the interactions between various herbal metabolites of NDS and five vascular tone modulation G-protein-coupled receptors (GPCRs), including 5-HT1AR, 5-HT1BR, β2-AR, AT1R, and ETBR, were assessed by molecular docking. Using network analysis and vasomotor experiment of the cerebral basilar artery, the potential material basis underlying the vascular regulatory effects of NDS was further explored.Results: The Naodesheng Effective Component Group (NECG) was found to induce relaxation of rat basilar artery rings precontracted using Endothelin-1 (ET-1) and KCl in vitro in a dose-dependent manner. Several metabolites of NDS, including C. tinctorius, C. pinnatifida, and P. notoginseng, were found to be the main plant resources of metabolites with high docking scores. Furthermore, several metabolites in NDS, including formononetin-7-glucoside, hydroxybenzoyl-coumaric anhydride, methoxymecambridine, puerarol, and pyrethrin II, were found to target multiple vascular GPCRs. Metabolites with moderate-to-high binding energy were verified to have good rat basilar artery-relaxing effects, and the maximum artery relaxation effects of all three metabolites, namely, isorhamnetin, kaempferol, and daidzein, were found to exceed 90%. Moreover, metabolites of NDS were found to exert a synergistic effect by interacting with vascular GPCR targets, and these metabolites may contribute to the cerebrovascular regulatory function of NDS.Discussion: The study reports that various metabolites of NDS contribute to its vascular tone regulating effects and demonstrates the multi-component and multi-target characteristics of NDS. Among them, metabolites with moderate-to-high binding scores in NDS may play an important role in regulating vascular function.

The toxicity of ginkgo kernel is a global concern, restricting its consumption as a medicinal food. This study focuses on eliminating the toxic components, specifically ginkgolic acid, from ginkgo kernel juice. The approach used was probiotic fermentation with autochthonous lactic acid bacteria combined with macroporous resin. Compared to using lactic acid fermentation alone, adding macroporous resin during probiotic fermentation significantly enhanced the removal of toxic ginkgolic acid and 4'-O-methylpyridoxine from ginkgo kernel juice. After 48 h of fermentation with macroporous resin, the contents of ginkgolic acid and 4'-O-methylpyridoxine decreased by more than 69% and 61%, respectively. Interestingly, the adsorption of microbial growth inhibitors, such as ginkgolic acid, 4'-O-methylpyridoxine, and phenolics, by the resin did not hinder the growth of lactic acid bacteria or their metabolic activities involving organic acids and monosaccharides. The study further confirmed that microbial adsorption was the primary reason for removing ginkgolic acid during probiotic fermentation. Also, the adsorption mechanism of ginkgolic acid during probiotic fermentation with macroporous resin was explored. From a mass transfer perspective, incorporating macroporous resin during the probiotic fermentation of ginkgo kernel juice reduced the mass transfer resistance for surface diffusion. Consequently, this lowered the contribution of surface diffusion to the overall diffusion process and facilitated the efficient removal of toxic ginkgolic acid. This work can help to understand the physical mechanism regarding detoxification of ginkgo kernel juice by probiotic fermentation, and offer potential strategies to enhance the safety of ginkgo kernel products.

Abstract In the pathway toward environmental sustainability, it is important that we understand how individuals can make a difference through diverse types of engagement. Theories suggest that transformative change toward a sustainable future requires individuals to engage in not only private actions (e.g. household energy saving, recycling) but also social‐signalling and system‐changing civic actions (e.g. opinion sharing, voting, petition signing and protesting). Yet, past research on pro‐environmental behaviour has primarily focused on private actions, while overlooking individual contributions to facilitating widespread change through civic actions. We use the exotic pet trade as a focal case to understand how individuals may act to promote environmental sustainability through different patterns of engagement and what factors might explain these distinct patters of action. Results from an online survey about behavioural intentions in the United States (n = 527) revealed three types of individual action that could transform the exotic pet trade. Private actions clustered separately from civic actions. Within the category of civic actions, a distinction emerged between lower social‐commitment actions and higher social‐commitment actions, based on the perceived level of social engagement and personal efforts involved. We also found that each type of action was associated with unique factors, highlighting the importance of attitudes, perceived social norms, and relational values for variously promoting individual engagement among the U.S. public. Our findings suggest that these distinct types of action should be treated differently when designing future wildlife conservation campaigns and behaviour change interventions. Read the free Plain Language Summary for this article on the Journal blog.

Healthy community assessment standards significantly influence community design and planning and are an important measure of a community’s ability to support health and well-being. Previous studies have mostly focused on built-environment indicators. However, building a healthy community is a complex issue involving multiple dimensions and factors. The consideration of the full range of health promotion factors is the key to determining their potential impact on individuals’ health. It is necessary to consider multiple perspectives to deepen the understanding of community health influences and enhance the effectiveness of the implementation of the assessment standards. The socio-ecological model (SEM) provides a critical framework for understanding the multiple influences on individual health. In this study, a two-dimensional interdisciplinary analytical framework of “socio-ecological factors–development goals” is developed by integrating development goals that summarize building considerations in assessment standards. Contextual analysis is used to examine the provisions of the following assessment standards: Assessment Standard for Healthy Community (ASHC), Assessment Standard for Healthy Retrofitting of Existing Residential Area (ASHRERA), WELL Community Standard (WELL), and Fitwel Certification System of Community (Fitwel). The results show that community and organization factors are used more than interpersonal and policy factors among the four standards. Humanistic constructions lack attention in the ASHC and ASHRERA standards compared with the other standards. The differences between the four standards indicate that there is a need to focus on regional features and develop locally adapted interventions. This study offers a novel exploration of the potential effectiveness of healthy community assessment standards from a multidisciplinary perspective. The results of this study support standard-setters and planners in the development of interventions to improve building healthy communities using intersectionality frameworks.

Currently, China has entered the development stage of a “low birth rate” demographically. There is a huge contradiction between the unbalanced and inadequate distribution of preschool education facilities (PEFs) and the people’s expectations for “full and good education for children”. This study took the Lingui New District, a typical new urban area in West China as the research area, and through the introduction of POI big data and GIS analysis methods, supplemented by GeoDA Bivariate Moran index analyses, established a kindergarten spatial database. The study found that preschool education facilities have problems such as insufficient quantity, uneven quality, low service coverage, poor accessibility, etc. Therefore, it is suggested to increase the proportion of public affordable preschool education facilities including kindergartens and nurseries, optimize the spatial distribution of preschool education, and improve the accessibility of preschool services to promote affordable, safe, and high-quality development of preschool education and to provide reference suggestions for the revision of relevant standards and the adjustment of the layout of preschool education in undeveloped regions of China.

Abstract Lung adenocarcinoma (LUAD) is a malignant tumor in the respiratory system. The efficacy of current treatment modalities varies greatly, and individualization is evident. Therefore, finding biomarkers for predicting treatment prognosis and providing reference and guidance for formulating treatment options is urgent. Cancer immunotherapy has made distinct progress in the past decades and has a significant effect on LUAD. Immunogenic Cell Death (ICD) can reshape the tumor’s immune microenvironment, contributing to immunotherapy. Thus, exploring ICD biomarkers to construct a prognostic model might help individualized treatments. We used a lung adenocarcinoma (LUAD) dataset to identify ICD-related differentially expressed genes (DEGs). Then, these DEGs were clustered and divided into subgroups. We also performed variance analysis in different dimensions. Further, we established and validated a prognostic model by LASSO Cox regression analysis. The risk score in this model was used to evaluate prognostic differences by survival analysis. The treatment prognosis of various therapies were also predicted. LUAD samples were divided into two subgroups. The ICD-high subgroup was related to an immune-hot phenotype more sensitive to immunotherapy. The prognostic model was constructed based on six ICD-related DEGs. We found that high-risk score patients responded better to immunotherapy. The ICD prognostic model was validated as a standalone factor to evaluate the ICD subtype of individual LUAD patients, which might contribute to more effective therapies.

Abstract Background The slow decline in cardiovascular disease (CVD) mortality and the stagnant or increasing hypertension prevalence in low- and middle-income countries necessitate investigation. Evolving gender disparities suggested that male cardiovascular health disadvantage may be preventable, offering potential for enhancing population cardiovascular health. Despite global body mass index (BMI) increases, its role in shaping the gender disparities remains underexplored. Objective This study investigated the birth cohort dynamics of gender disparities in systolic/diastolic blood pressure (SBP/DBP) in China, one of the world's largest low- and middle-income countries, and explored the potential role of BMI in explaining the changing gender disparities. Methods Data from the China Health and Nutrition Survey (1991–2015) were analyzed using multilevel growth-curve models to estimate gender- and cohort-specific SBP/DBP trajectories among individuals born between 1950 and 1975. Results Men had higher SBP and DBP than women at the sample’s mean age of 41.7 years. The gender disparities in SBP and DBP increased with each successive one-year cohort from 1950 to 1975 by 0.14 mm Hg and 0.09 mm Hg, respectively. Adjusting for BMI reduced the increasing gender disparities in SBP and DBP by 31.9% and 34.4%, respectively. Conclusion Chinese men experienced a greater increase in SBP/DBP across successive cohorts compared to women. The increasing gender disparities in SBP/DBP were partially attributable to a greater BMI increase across cohorts among men. Given these findings, prioritizing interventions that aim to reduce BMI, particularly among men, could potentially alleviate the burden of CVD in China through lowering SBP/DBP.

Abstract Background Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling has been known to play a critical role in maintaining cellular and tissue homeostasis, which also has an essential role in the inflammatory response. However, it remains unidentified whether and how the macrophage PTEN may govern the innate immune signaling stimulator of interferon genes (STING) mediated inflammation and hepatocyte necroptosis in APAP-induced liver injury (AILI). Methods Myeloid-specific PTEN knockout (PTENM−KO) and floxed PTEN (PTENFL/FL) mice were treated with APAP (400 mg/kg) or PBS. In a parallel in vitro study, bone marrow-derived macrophages (BMMs) were isolated from these conditional knockout mice and transfected with CRISPR/Cas9-mediated Notch1 knockout (KO) or CRISPR/Cas9-mediated STING activation vector followed by LPS (100 ng/ml) stimulation. Results Here, we report that myeloid-specific PTEN knockout (PTENM−KO) mice were resistant to oxidative stress-induced hepatocellular injury with reduced macrophage/neutrophil accumulation and proinflammatory mediators in AILI. PTENM−KO increased the interaction of nuclear Notch intracellular domain (NICD) and nuclear factor (erythroid-derived 2)-like 2 (NRF2) in the macrophage nucleus, reducing reactive oxygen species (ROS) generation. Mechanistically, it is worth noting that macrophage NICD and NRF2 co-localize within the nucleus under inflammatory conditions. Additionally, Notch1 promotes the interaction of immunoglobulin kappa J region (RBPjκ) with NRF2. Disruption of the Notch1 signal in PTEN deletion macrophages, reduced RBPjκ and NRF2 binding, and activated STING signaling. Moreover, PTENM−KO macrophages with STING activated led to ROS generation and TNF-α release, resulting in hepatocyte necroptosis upon co-culture with primary hepatocytes. Conclusions Our findings demonstrate that the macrophage PTEN-NICD/NRF2-STING axis is critical to regulating oxidative stress-induced liver inflammation and necroptosis in AILI and implies the therapeutic potential for managing sterile liver inflammation. Video Abstract Graphical Abstract

Abstract The exotic pet trade poses a major threat to biodiversity conservation. To combat biodiversity loss, it is essential to reduce demand for exotic pets and engage people in civic actions for wildlife conservation. Although messaging has been extensively used in conservation practice, little is known about how it can influence attitudes and various types of actions pertaining to the exotic pet trade. This study examined the impact of conservation messaging in the context of exotic pet ownership and wildlife entertainment visitation as common practices of the exotic pet trade. We randomly assigned participants in the United States to one of five messaging conditions: biodiversity loss and animal abuse (M1), zoonotic disease risks (M2), illegality (M3), social disapproval (M4), and neutral biological information as a control condition (M5). We found that all conservation messages (M1–M4) significantly decreased people's favorable attitudes toward the exotic pet trade and their desire to visit wildlife entertainment. However, conservation messaging did not influence the desire for exotic pet ownership or intentions to take civic actions. Our findings highlight the potential of conservation messaging for attitude change and demand reduction for wildlife entertainment, but different approaches are necessary for promoting more effortful actions such as exotic pet ownership and civic actions.

Public and private institutions have gained traction in developing interventions to alter people's behaviours in predictable ways without limiting the freedom of choice or significantly changing the incentive structure. A nudge is designed to facilitate actions by minimizing friction, while a sludge is an intervention that inhibits actions by increasing friction, but the underlying cognitive mechanisms behind these interventions remain largely unknown. Here, we develop a novel cognitive framework by organizing these interventions along six cognitive processes: attention, perception, memory, effort, intrinsic motivation and extrinsic motivation. In addition, we conduct a meta-analysis of field experiments (i.e. randomized controlled trials) that contained real behavioural measures (n = 184 papers, k = 184 observations, N = 2 245 373 participants) from 2008 to 2021 to examine the effect size of these interventions targeting each cognitive process. Our findings demonstrate that interventions changing effort are more effective than interventions changing intrinsic motivation, and nudge and sludge interventions had similar effect sizes. However, these results need to be interpreted with caution due to a potential publication bias. This new meta-analytic framework provides cognitive principles for organizing nudge and sludge with corresponding behavioural impacts. The insights gained from this framework help inform the design and development of future interventions based on cognitive insights.

Beliefs without strong supporting evidence (BWSSE) are commonplace, such as religious beliefs and conspiracy theories. The goals of the current study were to identify dimensions of BWSSE in the general public and study how reasons for holding each dimension depend on the strength of the belief. Participants completed a BWSSE questionnaire online, and principal component analysis suggested that the questionnaire captured 6 dimensions of beliefs that range in strength: New Age Spiritual, Traditional Spiritual, Nonconformist, Science, Mythical, and Conspiracy Theory. Mixed-model analyses of variance showed that while high-strength believers in both New Age and Traditional Spiritual shifted their reasons-for-belief away from ‘just believe’ and towards personal experience, only Traditional Spiritual shifted away from ‘just believe’ to culture. In contrast, for Conspiracy Theory and Mythical, the dominant reason for belief was media, but for Conspiracy Theory only, there was a shift from media to education/personal research for high-strength believers. This demonstrates that although spiritual beliefs are strengthened by personal experience, conspiracy theory beliefs are strengthened by information gathering. Understanding the source of an existing belief is important for debiasing attempts to move people towards beliefs with strong supporting evidence, including greater acceptance of evidence provided by experts, a likely requirement for negotiating global humanitarian emergencies in the not-so-distant future.Statement of Relevance.Beliefs without strong supporting evidence (BWSSE) have been gaining attention in mainstream society; particularly, the sources of information that may contribute to their formation and resistance to correction. Understanding the source of an existing belief is important for debiasing attempts to move people towards beliefs with strong supporting evidence, including greater acceptance of evidence provided by experts, a likely requirement for negotiating global humanitarian emergencies in the not-so-distant future.

Objective Postoperative delirium (POD) is a common complication, and clinical practitioners have taken measures to improve the quality of life after hip replacement surgery. We aim to establish a nomogram to predict POD in elderly patients with femoral neck fractures (FNFs) after hip replacement. Methods A total of 384 elderly patients (267 females) with an average age of 75.8 years who underwent hip replacement from June 2010 to May 2020 were retrospectively reviewed. Patients were divided into delirium and non‐delirium groups according to the confusion assessment method. The risk factors for POD were analyzed by multivariate logistic regression, and the nomogram was established based on the results. Results The incidence of POD was 33.33% (128/384). Univariate analysis showed that advanced age, diabetes, lacunar cerebral infarction, surgery type, intraoperative blood loss, electrolyte imbalance, and anemia were risk factors for POD (p

BackgroundAsthma is one of the most prevalent chronic diseases of childhood and disproportionately affects children with lower socioeconomic status. Controller medications such as inhaled corticosteroids significantly reduce asthma exacerbations and improve symptoms. However, a large proportion of children still have poor asthma control, in part owing to suboptimal adherence. Financial barriers contribute to hindering adherence, as do behavioral factors related to low income. For example, unmet social needs for food, lodging, and childcare may create stress and worry in parents, negatively influencing medication adherence. These needs are also cognitively taxing and force families to focus on immediate needs, leading to scarcity and heightening future discounting; thus, there is the tendency to attribute greater value to the present than to the future in making decisions. ObjectiveIn this project, we will investigate the relationship between unmet social needs, scarcity, and future discounting as well as their predictive power over time on medication adherence in children with asthma. MethodsThis 12-month prospective observational cohort study will recruit 200 families of children aged 2 to 17 years at the Asthma Clinic of the Centre Hospitalier Universitaire Sainte-Justine, a tertiary care pediatric hospital in Montreal, Canada. The primary outcome will be adherence to controller medication, measured using the proportion of prescribed days covered during follow-up. Exploratory outcomes will include health care use. The main independent variables will be unmet social needs, scarcity, and future discounting, measured using validated instruments. These variables will be measured at recruitment as well as at 6- and 12-month follow-ups. Covariates will include sociodemographics, disease and treatment characteristics, and parental stress. Primary analysis will compare adherence to controller medication, measured using the proportion of prescribed days covered, between families with versus those without unmet social needs during the study period using multivariate linear regression. ResultsThe research activities of this study began in December 2021. Participant enrollment and data collection began in August 2022 and are expected to continue until September 2024. ConclusionsThis project will allow the documentation of the impact of unmet social needs, scarcity, and future discounting on adherence in children with asthma using robust metrics of adherence and validated measures of scarcity and future discounting. If the relationship between unmet social needs, behavioral factors, and adherence is supported by our findings, this will suggest the potential for novel targets for integrated social care interventions to improve adherence to controller medication and reduce risk across the life course for vulnerable children with asthma. Trial RegistrationClinicalTrials.gov NCT05278000; https://clinicaltrials.gov/ct2/show/NCT05278000 International Registered Report Identifier (IRRID)PRR1-10.2196/37318

Abstract Two aspects of real-world visual search are typically studied in parallel: category knowledge (e.g., searching for food) and visual patterns (e.g., predicting an upcoming street sign from prior street signs). Previous visual search studies have shown that prior category knowledge hinders search when targets and distractors are from the same category. Other studies have shown that task-irrelevant patterns of non-target objects can enhance search when targets appear in locations that previously contained these irrelevant patterns. Combining EEG (N2pc ERP component, a neural marker of target selection) and behavioral measures, the present study investigated how search efficiency is simultaneously affected by prior knowledge of real-world objects (food and toys) and irrelevant visual patterns (sequences of runic symbols) within the same paradigm. We did not observe behavioral differences between locating items in patterned versus random locations. However, the N2pc components emerged sooner when search items appeared in the patterned location, compared to the random location, with a stronger effect when search items were targets, as opposed to non-targets categorically related to the target. A multivariate pattern analysis revealed that neural responses during search trials in the same time window reflected where the visual patterns appeared. Our finding contributes to our understanding of how knowledge acquired prior to the search task (e.g., category knowledge) interacts with new content within the search task.

Abstract Objective The study objective was to investigate the use of peripheral blood biomarkers as predictors of patient survival. The aim of this study was to identify the baseline peripheral blood biomarkers associated with clinical outcome in patients with early lung cancer (stage I-II) treated with surgery. Methods We included and analysed data from 376 patients with early-stage lung cancer who underwent a standard lobectomy. Univariate and multivariate Cox regression analyses were performed on all patients to assess the relationships between progression-free survival (PFS) and overall survival (OS) and the peripheral blood biomarker metrics measured before surgical treatment. The peripheral blood parameters included monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and dimeric fibrin fragment D (D-dimer). Results After univariate Cox regression analysis, low MLR, low NLR, low PLR and low D-dimer values were significantly associated with both better OS and PFS (all p

Lung squamous carcinoma (LUSC) is a malignant tumor of the respiratory system with highly heterogeneous characteristics. Lactate is the main product of aerobic glycolysis during the metabolic reprogramming of tumors. There is growing evidence that lactate metabolic processes have a broad and sophisticated impact on tumor phenotypic plasticity and tumor microenvironment (TME). However, the pattern of lactate metabolism in patients with LUSC and its impact on TME, phenotype, prognosis, and treatment have not been fully elucidated. In this study, we identified two subtypes with different lactate metabolism patterns in LUSC by non-negative matrix factorization and explored their multi-omics features. We observed that lactate metabolism levels in LUSC extensively influenced tumor immune infiltration patterns, adaptation to the hypoxia environment, and energy metabolic reprogramming. Subsequently, we constructed the lactate metabolism-related prognostic index (LMRPI) using Cox stepwise regression analysis. LMRPI showed excellent stability and accuracy, and based on the median value of LMRPI, LUAD were divided into two subgroups. The two subgroups have different patterns of immune infiltration and somatic mutations. Meanwhile, the two subgroups had different responsiveness to immune checkpoint inhibitor (ICI) therapies and different sensitivity to various chemotherapeutic and molecular targeting agents. In conclusion, we defined two subtypes with different lactate metabolism patterns in LUSC and extensively characterized their multi-omics profile. Furthermore, we developed LMRPI that predicts the prognosis of LUSC patients while also predicting their response to various adjuvant therapies, including immunotherapy, to guide their individualized treatment.

Despite the proliferation of nudge research in the last few decades, very little published work aims to nudge the behavior of policymakers. Here we explore the impact of a well-established nudge on policymakers in the Northwest Territories of Canada. In a pre-registered randomized controlled trial, we emailed an invitation to policymakers (N = 263) to attend an online briefing on gendered impacts of policy. In the treatment condition (N = 133), the invitation contained personal stories of two women whose lives were disproportionally impacted by public policies more than men. In the control condition (N = 130), the invitation did not contain such stories. After the briefing, we sent all participants in both conditions a link to a public pledge that they could sign. The pledge was to lead and advocate for equity-oriented policymaking. Contrary to our prediction, there was a small backfiring effect where policymakers in the treatment condition (3.0%) were less likely to attend the briefing than the control condition (7.7%). However, two policymakers (1.5%) in the treatment condition signed the public pledge compared to one (0.8%) in the control condition. The current findings reveal the limits of using personal stories as a nudge to influence policymakers. We discuss insights gained from this experiment and follow-up debriefings with policymakers on how to improve future behavioral interventions designed to nudge policymakers.

Objective. Untreated protracted bacterial bronchitis (PBB), a chronic wet cough prevalent in children, may lead to chronic suppurative lung disease. However, clinical diagnostic criteria are currently nonspecific; thus, PBB may be misdiagnosed. Thus, we assessed the diagnostic value of fiberoptic bronchoscopy (FOB) and the risk factors associated with PBB. Methods. Children with chronic cough at The First Affiliated Hospital of Anhui Medical University from January 2015 to May 2020 were enrolled and allocated to a suspected PBB (n = 141) or a non-PBB (n = 206) group. All children underwent extensive laboratory, chest imaging, and allergen tests. Children with suspected PBB underwent FOB with bronchoalveolar lavage; lavage and sputum samples were cultured. Results. All 347 children had a chronic wet cough for approximately 2 months. Of 141 children with suspected PBB, 140 received FOB with bronchoalveolar lavage. Visible tracheal changes included pale mucosa, mucosal congestion, edema, swelling, and increased secretions attached to the wall. Sputum was visible primarily in the left main bronchus (78.7%), left lower lobe (59.6%), right upper lobe (62.4%), and right lower lobe (64.5%). Sputum properties and amounts significantly differed between children with vs. without PBB P

Solutions to environmental and social problems are often framed in dichotomous ways, which can be counterproductive. Instead, multiple solutions are often needed to fully address these problems. Here we examine how framing influences people's preference for multiple solutions. In a pre-registered experiment, participants (N = 1,432) were randomly assigned to one of four framing conditions. In the first three conditions, participants were presented with a series of eight problems, each framed with multiple causes, multiple impacts, or multiple solutions to the problem. The control condition did not present any framing information. Participants indicated their preferred solution, perceived severity and urgency of the problem, and their dichotomous thinking tendency. Pre-registered analyses showed that none of the three frames had a significant impact on preference for multiple solutions, perceived severity, perceived urgency, or dichotomous thinking. However, exploratory analyses showed that perceived severity and urgency of the problem were positively correlated with people's preference for multiple solutions, while dichotomous thinking was negatively correlated. These findings showed no demonstrable impact of framing on multi-solution preference. Future interventions should focus on addressing perceived severity and urgency, or decreasing dichotomous thinking to encourage people to adopt multiple solutions to address complex environmental and social problems.

About 70% of non-small cell lung cancer (NSCLC) patients require radiotherapy. However, due to the difference in radiation sensitivity, the treatment outcome may differ for the same pathology and choice of treatment. Poly (ADP-ribose) polymerase 1 (PARP-1) is a key gene responsible for DNA repair and is involved in base excision repair as well as repair of single strand break induced by ionizing radiation and oxidative damage. In order to investigate the relationship between PARP-1 gene polymorphism and radiation sensitivity in NSCLC, we collected 141 primary NSCLC patients undergoing three-dimensional conformal radiotherapy. For each case, the gross tumor volumes (GTV) before radiation and that after 40 Gy radiation were measured to calculate the tumor regression rate. TaqMan real-time polymerase chain reaction was performed to genotype the single-nucleotide polymorphisms (SNPs). Genotype frequencies for PARP-1 genotypes were 14.2% for C/C, 44.7% for C/G and 41.1% for G/G. The average tumor regression rate after 40 Gy radiation therapy was 35.1% ± 0.192. Tumor regression rate of mid-term RT of C/C genotype was 44.6% ± 0.170, which was higher than that of genotype C/G and G/G (32.4% ± 0.196 and 34.8% ± 0.188, respectively) with statistical significance (F = 3.169 p = 0.045). The higher tumor regression rate in patients with C/C genotype suggested that G allele was a protective factor against radiation therapy. Using the median tumor regression rate of 34%, we divided the entire cohort into two groups, and found that the frequency distribution of PARP-1 gene rs3219073 had significant difference between these two groups (p < 0.05). These results showed that PARP-1 gene polymorphism may affect patient radiation sensitivity and predict the efficacy of radiotherapy. It therefore presents an opportunity for developing new therapeutic targets to improve radiotherapy outcome.

Abstract Background The small-area deprivation indices are varied across countries due to different social context and data availability. Due to lack of chronic disease-related social deprivation index (SDI) in Hong Kong, China, this study aimed to develop a new SDI and examine its association with cancer mortality. Methods A total of 14 socio-economic variables of 154 large Tertiary Planning Unit groups (LTPUGs) in Hong Kong were obtained from 2016 population by-census. LTPUG-specific all-cause and chronic condition-related mortality and chronic condition inpatient episodes were calculated as health outcomes. Association of socio-economic variables with health outcomes was estimated for variable selection. Candidates for SDI were constructed with selected socio-economic variables and tested for criterion validity using health outcomes. Ecological association between the selected SDI and cancer mortality were examined using zero-inflated negative binomial regression. Results A chronic disease-related SDI constructed by six area-level socio-economic variables was selected based on its criterion validity with health outcomes in Hong Kong. It was found that social deprivation was associated with higher cancer mortality during 2011–2016 (most deprived areas: incidence relative risk [IRR] = 1.40, 95% confidence interval [CI]: 1.27–1.55; second most deprived areas: IRR = 1.34, 95%CI: 1.21–1.48; least deprived areas as reference), and the cancer mortality gap became larger in more recent years. Excess cancer death related to social deprivation was found to have increased through 2011–2016. Conclusions Our newly developed SDI is a valid and routinely available measurement of social deprivation in small areas and is useful in resource allocation and policy-making for public health purpose in communities. There is a potential large improvement in cancer mortality by offering relevant policies and interventions to reduce health-related deprivation. Further studies can be done to design strategies to reduce the expanding health inequalities between more and less deprived areas.

BackgroundA comparison and ranking of the clinical effects of various acupuncture and acupuncture-related therapies on patients with mild cognitive impairment.MethodsUsing network meta-analysis, we assessed the direct and indirect evidence from relevant research. Seven databases [PubMed, Web of Science, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), VIP Database, and Wanfang database] were examined to find randomized controlled trials of acupuncture-related therapies for individuals with mild cognitive impairment. Two researchers independently reviewed the literature, retrieved the data, and evaluated the risk of bias in the included studies. The data were analyzed using Stata15.0 and R3.6.1 software.ResultsA total of 27 randomized controlled trials involving 2,210 patients were included. Bayesian NMA showed that manual acupuncture combined with conventional therapy, moxibustion combined with conventional therapy, manual acupuncture, and electroacupuncture were most effective in improving the MMSE score. The most effective interventions related to the MoCA score were moxibustion combined with conventional therapy, followed by manual acupuncture combined with conventional therapy, acupressure combined with conventional therapy, and manual acupuncture combined with moxibustion. Manual acupuncture combined with moxibustion was dominant in the cluster ranking. The results of the node splitting method revealed that direct and indirect evidence were consistent (P > 0.05). In addition, publication bias was detected.ConclusionThis research will add to the body of knowledge about the safety and efficacy of acupuncture-related therapies in the treatment of mild cognitive impairment. The results of this study will also assist in the choice of clinical guidelines that optimize acupuncture treatment for patients with mild cognitive impairment.

Objective To examine the relationship between baseline union status (ie, including marriage and cohabitation) and mortality, paying attention to gender differentials, through an 11-year follow-up of a large cohort in Thailand.Design Cohort data from Thai Cohort Study (TCS) were linked official death records over an 11-year follow-up period.Setting Community-based adults in Thailand.Participants 87 151 Thai adults participated in TCS cohort.Method Cox regression models measured longitudinal associations between union status and 11-year mortality.Results From 2005 (baseline) to 2016, persons who cohabited and lived with a partner, married persons but not living with a partner and separated/divorced/widowed people were more likely to die compared with those married and living together with a partner. Those who did not have good family support had a higher death risk than those having good family support.Single or cohabiting women had higher risks of mortality than women who were married and living together with a partner throughout follow-up, while separated/divorced/widowed men had higher risks of mortality than counterpart males.Conclusions Our study reveals the protective effect of marriage and living together on mortality in Thailand, an understudied setting where institutionalisation of cohabitation is low leading to a limited mortality protection. Public policies for moderating mortality should thus be gender nuanced, culturally and institutionally specific. Also, we demonstrate that in settings such as Thailand, where marital status is not always defined in the same way as in western cultures, the need to measure cohabitation in locally relevant terms is important.

Background: Increasing evidence supports that lactate plays an important role in tumor proliferation, invasion and within the tumor microenvironment (TME). This is particularly relevant in lung adenocarcinoma (LUAD). Therefore, there is a current need to investigate lactate metabolism in LUAD patients and how lactate metabolism is affected by different therapies.Methods: Data from LUAD patients were collected from The Cancer Genome Atlas (TCGA) and patients were divided into two subtypes according to 12 lactate metabolism-related genes to explore the effect of lactate metabolism in LUAD. We established a lactate-related prognostic indicator (LRPI) based on different gene expression profiles. Subsequently, we investigated associations between this LRPI and patient survival, molecular characteristics and response to therapy. Some analyses were conducted using the Genomics of Drug Sensitivity in Cancer (GDSC) database.Results: The two LUAD subtypes exhibited different levels of lactate metabolism, in which patients that displayed high lactate metabolism also had a worse prognosis and a poorer immune environment. Indeed, LRPI was shown to accurately predict the prognosis of LUAD patients. Patients with a high LRPI showed a poor prognosis coupled with high sensitivity to chemotherapy using GDSC data. Meanwhile, these patients exhibited a high responsiveness to immunotherapy in TMB (Tumor mutation burden) and TIDE (Tumor Immune Dysfunction and Exclusion) analyses.Conclusion: We validated the effect of lactate metabolism on the prognosis of LUAD patients and established a promising biomarker. LRPI can predict LUAD patient survival, molecular characteristics and response to therapy, which can aid the individualized treatment of LUAD patients.

Tea is a popular beverage with a long history of safe and healthy use. Tea polysaccharide is a bioactive component extracted from tea, which has attracted more and more attention in recent decades. In this article, an acidic polysaccharide Gougunao tea polysaccharide (GPS) was isolated from Gougunao green tea by hot water extraction and ethanol precipitation. After purification by a diethylaminoethyl (DEAE) Sepharose Fast Flow column and a Sephacryl S-400 column, several homogalacturonan (HG) and rhamnogalacturonan-I (RG-I) fractions were obtained. Fraction GPS2b with the highest yield was selected for structural characterization by methylation and nuclear magnetic resonance (NMR) analysis. GPS2b was found to be an HG-type pectic polysaccharide (degree of methyl esterification [DE], 51.6%) with low molecular weight (Mw, 36.8 kDa). It was mainly composed of →4)-α-GalpA- (1→ and →4)-α-GalpA-6-OMe-(1→. In addition, a minor highly branched RG-I domain was identified in this fraction. The investigation of structural features of tea polysaccharides can provide insights to understand their structure-bioactivity relationship.

Polarization is pervasive in the current sociopolitical discourse. Polarization tends to increase cognitive inflexibility where people become less capable of updating their beliefs upon new information or switching between different ways of thinking. Cognitive inflexibility can in turn increase polarization. We propose that this positive feedback loop between polarization and cognitive inflexibility is a form of threat response that has benefited humans throughout their evolutionary history. This feedback loop, which can be driven by conflict mindset, group conformity, and simplification of information, facilitates the formation of strong bonds within a group that are able to eliminate threats and increase individual fitness. Although cognitive inflexibility is conventionally seen as maladaptive, here we argue that cognitive inflexibility may be an adaptation under polarization. That is, in a highly polarized society most people only interact with members of their own social group, without having to confront perspectives from another group or interacting with out-group members. In this context, cognitive inflexibility creates rigid cognitive specialization, a set of cognitive traits that allow people to operate efficiently within their social circles but not outside of it. Although rigid cognitive specialization benefits individuals in the short term, it may lead to more polarization over the long run, and thus produce more conflict between groups. We call on future research to examine the link between cognitive inflexibility and rigid cognitive specialization.

Abstract The functional trait diversity of species assemblages can predict the provision of ecosystem services such as pollination and carbon sequestration, but it is unclear whether the same trait‐based framework can be applied to identify the factors that underpin cultural ecosystem services and disservices. To explore the relationship between traits and the contribution of species to cultural ecosystem services and disservices, we conducted 404 questionnaire surveys with birdwatchers and local residents in Guanacaste, Costa Rica. We used an information–theoretic approach to identify which of 20 functional traits for 199 Costa Rican bird species best predicted their cultural ecosystem service scores related to birdwatching, acoustic aesthetics, education and local identity, as well as disservices (e.g. harm to crops). We found that diet was the most important variable explaining perceptions of cultural ecosystem service and disservice providers. Aesthetic traits such as plumage colour and pattern were important in explaining birdwatching scores. We also found people have a high affinity for forest‐affiliated birds. The insight that functional traits can explain variation among cultural perspectives on values derived from birds offers a first step towards a trait‐based system for understanding the species attributes that underpin cultural ecosystem services and disservices.

Cancer vaccines are emerging as a viable strategy for cancer treatment. In the current study, we screened for genes associated with the prognosis of patients with lung adenocarcinoma and positively correlated with antigen-presenting cell infiltration and identified KLRG1 and CBFA2T3 as potential tumor antigens for mRNA vaccines in lung adenocarcinoma (LUAD). Further analyses of immune subtypes revealed that patients with early-stage LUAD, high immune cell infiltration, high immune checkpoint expression, and low tumor mutation burden might benefit from mRNA vaccination. Moreover, we identified four biomarkers that can be used to assess mRNA vaccination suitability. We also identified potentially sensitive anti-cancer drugs for populations not suitable for vaccination by means of anti-cancer drug susceptibility prediction. Overall, we provided a new perspective for mRNA vaccine treatment strategies for LUAD and emphasized the importance of precise and personalized treatments.

As the world contends with the far-ranging impacts of the COVID-19 pandemic, ongoing environmental crises have, to some extent, been neglected during the pandemic. One reason behind this shift in priorities is the scarcity mindset triggered by the pandemic. Scarcity is the feeling of having less than what is necessary, and it causes people to prioritize immediate short-term needs over long-term ones. Scarcity experienced in the pandemic can reduce the willingness to engage in pro-environmental behavior, leading to environmental degradation that increases the chance of future pandemics. To protect pro-environmental behavior, we argue that it should not be viewed as value-laden and effortful, but rather reconceptualized as actions that address a multitude of human needs including pragmatic actions that conserve resources especially during scarcity. To bolster environmental protection, systematic changes are needed to make pro-environmental behavior better integrated into people's lives, communities, and cities, such that it is more accessible, less costly, and more resilient to future disturbances.

BackgroundIncreasing evidence has demonstrated that long non-coding RNAs (lncRNAs) play a crucial part in maintaining genomic instability. We therefore identified genome instability-related lncRNAs and constructed a prediction signature for early stage lung adenocarcinoma (LUAD) as well in order for classification of high-risk group of patients and improvement of individualized therapies.MethodsEarly stage LUAD RNA-seq and clinical data from The Cancer Genome Atlas (TCGA) were randomly divided into training set (n = 177) and testing set (n = 176). A total of 146 genomic instability-associated lncRNAs were identified based on somatic mutation profiles combining lncRNA expression profiles from TCGA by the “limma R” package. We performed Cox regression analysis to develop this predictive indicator. We validated the prognostic signature by an external independent LUAD cohort with microarray platform acquired from the Gene Expression Omnibus (GEO).ResultsA genome instability-related six-lncRNA-based gene signature (GILncSig) was established to divide subjects into high-risk and low-risk groups with different outcomes at statistically significant levels. According to the multivariate Cox regression and stratification analysis, the GILncSig was an independent predictive factor. Furthermore, the six-lncRNA signature achieved AUC values of 0.745, 0.659, and 0.708 in the training set, testing set, and TCGA set, respectively. When compared with other prognostic lncRNA signatures, the GILncSig also exhibited better prediction performance.ConclusionThe prognostic lncRNA signature is a potent tool for risk stratification of early stage LUAD patients. Our study also provided new insights for identifying genome instability-related cancer biomarkers.

Abstract The current biodiversity crisis involves major shifts in biological communities at local and regional scales. The consequences for Earth's life‐support systems are increasingly well‐studied, but knowledge of how community shifts affect cultural services associated with wildlife lags behind. We integrated bird census data (3 years across 150 point‐count locations) with questionnaire surveys (>400 people) to evaluate changes in culturally important species across climate and land‐use gradients in Costa Rica. For farmers, urbanites, and birdwatchers alike, species valued for identity, bequest, birdwatching, acoustic aesthetics, and education were more likely to occupy wetter regions and forested sites, whereas disliked species tended to occupy drier and deforested sites. These results suggest that regional climate drying and habitat conversion in the Neotropics are likely to threaten the most culturally important bird species. This study provides a novel and generalizable pathway for assessing the effects of environmental changes on cultural services and integrating the sociocultural and ecological dimensions of biodiversity.

BackgroundEsophageal cancer is one of the most common cancer types, with its most common distant metastatic site being the lung. Currently, population-based data regarding the proportion and prognosis of patients with esophageal cancer with lung metastases (ECLM) at the time of diagnosis is insufficient. Therefore, we aimed to determine the proportion of patients with ECLM at diagnosis, as well as to investigate the prognostic parameters of ECLM.MethodsThis population-based observational study obtained data from the Surveillance, Epidemiology, and End Results (SEER) database registered between 2010 and 2016. Multivariable logistic regression was performed to identify predictors of the presence of ECLM at diagnosis. Multivariable Cox regression and competing risk analysis were used to assess prognostic factors in patients with ECLM. Median survival was estimated using Kaplan–Meier curves.ResultsOf 10,965 patients diagnosed with esophageal cancer between 2010 and 2016, 713 (6.50%) presented with initial lung metastasis at diagnosis. Lung metastasis represented 27.15% of all cases with metastatic disease to any distant site. Considering all patients with esophageal cancer, multivariable logistic regression indicated that pathology grade, pathology type, T staging, N staging, race, and number of extrapulmonary metastatic sites were predictive factors for the occurrence of lung metastases at diagnosis. The median survival time of patients with ECLM was 4.0 months. Patients receiving chemotherapy or chemoradiotherapy had the longest median overall survival, 7.0 months. Multivariable Cox regression indicated that age, histology type, T2 staging, number of extrapulmonary metastatic sites, and treatment (chemotherapy, radiotherapy, or chemoradiotherapy) were independent predictors for overall survival (OS). Multivariable competing risk analysis determined that age, number of extrapulmonary metastatic sites, and treatment were independent predictors for esophageal cancer-specific survival (CSS).ConclusionThe findings of this study may provide important information for the early diagnosis of ECLM, as well as aid physicians in choosing appropriate treatment regimens for these patients.

Chronic inflammatory pain is a severe clinical symptom that aggravates the life quality of patients and places a huge economic burden on individuals and society. As one complementary and alternative therapy, electroacupuncture (EA) is widely used in clinical practice to treat chronic inflammatory pain based on its safety and efficacy. Previous studies have revealed the potential role of adenosine, neuropeptides, and inflammatory factors in EA analgesia in various pain models, but the identity of some of the signaling pathways involved remain unknown. In the present study, we explored whether neuregulin1 (NRG1)-ErbB4 signaling is involved in EA analgesia in inflammatory pain. Repeated EA treatment at the acupoints Zusanli (ST36) and Sanyinjiao (SP6) for 3 consecutive days remarkably attenuated mechanical allodynia and thermal hyperalgesia in complete Freund’s adjuvant (CFA)-treated mice, with an increased expression of NRG1 in spinal cord (SC). We found that ErbB4 kinase participated in both the EA and NRG1 mediated analgesic effects on inflammatory pain by pharmacological inhibition or genetic ablation ErbB4 in vivo. Intriguingly, the mice with conditional knockout of ErbB4 from PV+ interneurons in SC showed abnormal basal mechanical threshold. Meanwhile, NRG1 treatment could not relieve tactile allodynia in PV-Erbb4–/– mice or AAV-PV-Erbb4–/– mice after CFA injection. These experimental results suggest that regulating NRG1-ErbB4 signaling in SC could reduce pain hypersensitivity and contribute to EA analgesia in inflammatory pain.

Neuroinflammation is considered as one of the crucial pathogenesis in promoting neurodegenerative progress of Alzheimer’s disease (AD). As complementary and alternative therapy, electroacupuncture (EA) stimulation has been widely used in clinical practice for anti-inflammation. However, whether EA promotes the cognitive deficits resulting from neuroinflammation in AD remains unclear. In this study, the presenilin 1 and 2 conditional double knockout (PS cDKO) mice, exhibited a series of AD-like pathology, robust neuroinflammatory responses, and memory deficits, were used to evaluate the potential neuroprotective effect of EA at Baihui (GV 20) and Shenting (GV 24) by behavioral testing, electrophysiology recording, and molecular biology analyzing. First, we observed that EA improved memory deficits and impaired synaptic plasticity. Moreover, EA possesses an ability to suppress the hyperphosphorylated tau and robust elevated NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in PS cDKO mice. Importantly, MCC950, a potent and selective inhibitor of NLPR3 inflammasome, has similar effects on inhibiting the hyperphosphorylated tau and the robust elevated NLRP3 components and neuroinflammatory responses of PS cDKO mice as well as EA treatment. Furthermore, EA treatment is not able to further improve the AD-like phenotypes of PS cDKO mice in combination with the MCC950 administration. Therefore, EA stimulation at GV 20 and GV 24 acupoints may be a potential alternative therapy for deterring cognitive deficits in AD through suppression of NLRP3 inflammasome activation.

Alzheimer's disease (AD) has become a worldwide disease that is harmful to human health and brings a heavy economic burden to healthcare system. Xiao-Xu-Ming Decoction (XXMD) has been widely used to treat stroke and other neurological diseases for more than 1000 years in China. However, the synergistic mechanism of the constituents in XXMD for the potential treatment of AD is still unclear. Therefore, the present study aimed to predict the potential targets and uncover the material basis of XXMD for the potential treatment of AD. A network pharmacology-based method, which combined data collection, drug-likeness filtering and absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties filtering, target prediction and network analysis, was used to decipher the effect and potential targets of XXMD for the treatment of AD. Then, the acetylcholinesterase (AChE) inhibitory assay was used to screen the potential active constituents in XXMD for the treatment of AD, and the molecular docking was furtherly used to identify the binding ability of active constituents with AD-related target of AChE. Finally, three in vitro cell models were applied to evaluate the neuroprotective effects of potential lead compounds in XXMD. Through the China Natural Products Database, Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database, Traditional Chinese Medicine (TCM)-Database @Taiwan and literature, a total of 1481 compounds in XXMD were finally collected. After ADME/T properties filtering, 908 compounds were used for the further study. Based on the prediction data, the constituents in XXMD formula could interact with 41 AD-related targets. Among them, cyclooxygenase-2 (COX-2), estrogen receptor α (ERα) and AChE were the major targets. The constituents in XXMD were found to have the potential to treat AD through multiple AD-related targets. 62 constituents in it were found to interact with more than or equal to 10 AD-related targets. The prediction results were further validated by in vitro biology experiment, resulting in several potential anti-AD multitarget-directed ligands (MTDLs), including two AChE inhibitors with the IC50 values ranging from 4.83 to 10.22 μM. Moreover, fanchinoline was furtherly found to prevent SH-SY5Y cells from the cytotoxicities induced by sodium nitroprusside, sodium dithionate and potassium chloride. In conclusion, XXMD was found to have the potential to treat AD by targeting multiple AD-related targets and canonical pathways. Fangchinoline and dauricine might be the potential lead compounds in XXMD for the treatment of AD.

Objective: COVID-19 has left no healthcare system untouched. In New South Wales (NSW), the most populous state in Australia, COVID-19 case numbers have to date been relatively low. However, that does not mean the state’s healthcare system has been unaffected. Preparations to create sufficient capacity to accommodate a COVID-19 surge resulted in widespread deferment of scheduled medical procedures and appointments. Patterns of healthcare-seeking behaviour changed, with a reluctance to visit healthcare settings. The aim of this study was to quantify the changes in activity seen in the NSW health system in the first half of 2020. Methods: Healthcare data were drawn from multiple sources, including primary care, ambulance, emergency departments and inpatient settings. Volumes of healthcare activity in 2020, overall, by urgency of cases and by reasons for care were compared with the figures for the same period in 2019. Changes in the modality of care provision were also examined. Results: In March to June 2020, compared with the same period in 2019, primary care face-to-face consultations decreased by 22.1%, breast screening activity by 51.5%, ambulance incidents by 7.2%, emergency department visits by 13.9%, public hospital inpatient episodes by 14.3%, and public hospital planned surgical activity by 32.6%. Conclusion: There were substantial declines in a wide range of healthcare activities across the NSW health system between March and June 2020 due to the impact of the COVID-19 pandemic. Although activity levels were recovering by September 2020, they had not yet returned to ‘normal’. The implications of these changes – and the indirect impact of COVID-19 – require further study.

Background/Aims: This study investigated the role of the microRNA miR-298 and its target Act1 in ischemic stroke. Methods: Cell viability was assessed with the 3-(4,5-dimethythiazol-2- yl)-2,5-diphenyl tetrazolium bromide assay. Apoptotic cells were detected by flow cytometry, and mRNA and protein expression were assessed by quantitative real-time PCR and western blotting, respectively. The regulatory relationship between miR-298 and Act1 was evaluated with the luciferase assay. To clarify the role of Act1 following ischemic stroke, the transcript was knocked down by short interfering RNA. The in vitro findings were validated in a mouse model of middle cerebral artery occlusion by administration of miR-298 mimic. Results: Act1 was upregulated whereas miR-298 was downregulated in ischemic stroke. miR-298 overexpression by transfection of a mimic suppressed Act1 protein levels in vitro and in vivo, and the luciferase assay showed that miR-298 directly binds to the 3’ untranslated region of the Act1 transcript. miR-298 overexpression enhanced cell apoptosis and autophagy and exacerbated ischemic infarction and neurological deficits, effects that were exerted via negative regulation of Act1/c-Jun N-terminal kinase (JNK)/nuclear factor (NF)-κB signaling and downstream autophagy pathways. Conclusions: Upregulation of miR-298 following ischemic stroke promotes brain injury in vitro and vivo by inhibiting the Act1/JNK/NF-κB signaling cascade and the downstream autophagy pathway. Therapeutic strategies that target miR-298 could be beneficial for the treatment of ischemic stroke.

Abstract Background Valid and comparable cause of death (COD) statistics are crucial for health policy analyses. Variations in COD assignment across geographical areas are well-documented while socio-institutional factors may affect the process of COD and underlying cause of death (UCD) determination. This study examines the comparability of UCD statistics in Hong Kong and Shanghai, having two political systems within one country, and assesses how socio-institutional factors influence UCD comparability. Methods A mixed method was used. Quantitative analyses involved anonymized official mortality records. Mortality rates were analyzed by location of death. To analyze the odds ratio of being assigned to a particular UCD, logistic regressions were performed. Qualitative analyses involved literature reviews and semi-structural interviews with key stakeholders in death registration practices. Thematic analysis was used. Results Age-standardized death rates from certain immediate conditions (e.g., septicemia, pneumonia, and renal failure) were higher in Hong Kong. Variations in UCD determination may be attributed to preference of location of death, procedures of registering deaths outside hospital, perceptions on the causal chain of COD, implications of the selected UCD for doctors’ professional performance, and governance and processes of data quality review. Conclusions Variations in socio-institutional factors were related to the process of certifying and registering COD in Hong Kong and Shanghai. To improve regional data comparability, health authorities should develop standard procedures for registering deaths outside hospital, provide guidelines and regular training for doctors, develop a unified automated coding system, consolidate a standard procedure for data review and validity checks, and disseminate information concerning both UCD and multiple causes of death.

Despite the scientific consensus, some people still remain skeptical about climate change. In fact, there is a growing partisan divide over the last decade within the United States in the support for climate policies. Given the same climate evidence, why do some people become concerned while others remain unconvinced? Here we propose a motivated attention framework where socio-political motivations shape visual attention to climate evidence, altering perceptions of the evidence and subsequent actions to mitigate climate change. To seek support for this framework, we conducted three experiments. Participants viewed a graph of annual global temperature change while they were eyetracked and estimated the average change. We found that political orientation may bias attention to climate change evidence, altering the perception of the same evidence (Experiment 1). We further examined how attentional biases influence subsequent actions to mitigate climate change. We found that liberals were more likely to sign a climate petition or more willing to donate to an environmental organization than conservatives, and attention guides climate actions in different ways for liberals and conservatives (Experiment 2). To seek causal evidence, we biased attention to different parts of the temperature curve by coloring stronger climate evidence in red or weak climate evidence in red. We found that liberals were more likely to sign the petition or more willing to donate when stronger evidence was in red, but conservatives were less likely to act when stronger evidence was in red (Experiment 3). This suggests that drawing attention to motivationally consistent information increases actions in liberals, but discouraged conservatives. The findings provide initial preliminary evidence for the motivated attention framework, suggesting an attentional divide between liberals and conservatives in the perception of climate evidence. This divide might further reinforce prior beliefs about climate change, creating further polarization. The current study raises a possible attentional mechanism for ideologically motivated reasoning and its impact on basic perceptual processes. It also provides implications for the communication of climate science to different socio-political groups with the goal of mobilizing actions on climate change.

Studies on attentional selection typically use unpredictable and meaningless stimuli, such as simple shapes and oriented lines. The assumption is that using these stimuli minimizes effects due to learning or prior knowledge, such that the task performance indexes a “pure” measure of the underlying cognitive ability. However, prior knowledge of the test stimuli and related stimuli acquired before or during the task impacts performance in meaningful ways. This mini review focuses on prior knowledge of object associations, because it is an important, yet often ignored, aspect of attentional selection. We first briefly review recent studies demonstrating that how objects are selected during visual search depends on the participant’s prior experience with other objects associated with the target. These effects appear with both task-relevant and task-irrelevant knowledge. We then review how existing object associations may influence subsequent learning of new information, which is both a driver and a consequence of selection processes. These insights highlight the importance of one aspect of prior knowledge for attentional selection and information acquisition. We briefly discuss how this work with young adults may inform other age groups throughout the lifespan, as learners gradually increase their prior knowledge. Importantly, these insights have implications for developing more accurate measurements of cognitive abilities.

Stroke still has a high incidence with a tremendous public health burden and it is a leading cause of mortality and disability. However, biomarkers for early diagnosis are absent and the metabolic alterations associated with ischemic stroke are not clearly understood. The objectives of this case-control study are to identify serum biomarkers and explore the metabolic alterations of ischemic stroke.Metabonomic analysis was performed using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis was employed to study 60 patients with or without ischemic stroke (30 cases and 30 controls).Serum metabolic profiling identified a series of 12 metabolites with significant alterations, and the related metabolic pathways involved glycerophospholipid, sphingolipid, phospholipid, fat acid, acylcarnitine, heme, and purine metabolism. Subsequently, multiple logistic regression analyses of these metabolites showed uric acid, sphinganine and adrenoyl ethanolamide were potential biomarkers of ischemic stroke with an area under the receiver operating characteristic curve of 0.941.These findings provide insights into the early diagnosis and potential pathophysiology of ischemic stroke.

Conservation of biodiversity is determined in part by human preferences. Preferences relevant to conservation have been examined largely via explicit measures (e.g., a self-reported degree of liking), with implicit measures (e.g., preconscious, automatic evaluations) receiving relatively less attention. This is the case despite psychological evidence from other contexts that implicit preferences are more informative of behavior. Thus, the type of measure that predicts conservation intentions for biodiversity is unknown. We conducted three studies to examine conservation intentions in light of people's explicit and implicit preferences toward four endangered species (sea otter, American badger, caribou, yellow-breasted chat) and four biomes (forest, ocean, grassland, tundra). In Study 1 (n = 55), we found that people implicitly preferred caribou most, but explicitly preferred sea otter most, with a significant multiple regression where participants' explicit preferences dictated their stated intended donations for conservation of each species. In Study 2 (n = 57) we found that people implicitly and explicitly preferred forest and ocean over grassland and tundra. Explicit rather than implicit preferences predicted the intended donation for conservation of the ocean biome. Study 3 involved a broader online sample of participants (n = 463) and also found that explicit preferences dictated the intended donations for conservation of biomes and species. Our findings reveal discrepancies between implicit and explicit preferences toward species, but not toward biomes. Importantly, the results demonstrate that explicit rather than implicit preferences predict conservation intentions for biodiversity. The current findings have several implications for conservation and the communication of biodiversity initiatives.

Most real-world judgments and decisions require the consideration of multiple types of evidence. For example, judging the severity of environmental damage, medical illness, or negative economic trends often involves tracking and integrating evidence from multiple sources (i.e. different natural disasters, physical symptoms, or financial indicators). We hypothesized that the requirement to track and integrate across distinct types of evidence would affect severity judgments of multifaceted problems, compared to simpler problems. To test this, we used scenarios depicting crop damage. Each scenario involved either two event types (i.e. mold damage and insect damage), or one event type. Participants judged the quality of the crop following each scenario. In Experiments 1 and 2, subjective judgments were attenuated if the scenario depicted multiple event types, relative to scenarios depicting single event types. This was evident as a shallower slope of subjective severity ratings, as a function of objectively quantifiable severity, for scenarios with multiple event types. In Experiment 3, we asked whether alternation between event types might contribute to this attenuation. Each scenario contained two event types, and the sequence of events either alternated frequently between types or was organized into two sequential groups. Subjective judgments were attenuated for scenarios with frequently alternating sequences. The results demonstrate that alternation between distinct event types attenuates subjective judgments of severity. This suggests that a requirement to integrate evidence across multiple sources places extra demands on the cognitive system, which reduces the perceived evidence strength.

In urban China, mortality from injuries has increased over the past five decades. By contrast, life expectancy has continued to increase and has come to nearly equal life expectancy in developed countries. Currently, most of the life expectancy lost due to injury (65%) in urban China would be recovered if injury rates were the same as in countries with low injury-related mortality. Fundamentally, the rising trend in urban injury mortality in China reflects a continued focus on injury treatment rather than prevention in the face of fast socioeconomic development and increasing exposure to risk factors for injury. Despite improved injury prevention legislation and a "Safe Community" campaign, urban China needs to modify its approach to urban injury management and focus on prevention. The gap between urban China and countries with low injury mortality can be closed by means of legislation, strengthened law enforcement and the establishment of safer communities. Risks affecting children and migrants deserve greater attention, and the government needs to allocate more resources to injury prevention, especially to urban areas in the central-west region of China. Based on the population size of urban China, measures for the prevention of injury mortality would save an annual 436.4 million years of life.

Interventions that promote pro-environmental behaviours are increasingly necessary in reducing use of high-emissions goods and services to meet international climate change targets. Here we assess the greenhouse gas emissions reductions associated with behavioural interventions in three high-emitting domains (personal vehicle use, meat consumption, and household energy use) based on an analysis of the peer-reviewed literature. We examined 40 studies from 1991–2018 involving 886 576 subjects. We found that some of the most robust interventions shown to reduce emissions were financial incentives for personal vehicles, defaults for reduced meat consumption, and feedback for home energy use. We estimate mean annual reductions of 571 kgCO _2 e per vehicle driver for reduced vehicle use, 51 kgCO _2 e per individual for reduced meat consumption, and 149 kgCO _2 e per household for reduced energy use. Despite substantial attention to behavioural interventions in the literature, we find that few studies are suitable for quantifying emissions reductions ( N = 6 for diet, N = 5 for personal vehicles) and few ( N = 3) are conducted outside OECD countries. Due to this imbalance in the literature, we focus our findings on western economies. We find substantial variation in the emission reductions achieved with different interventions within each domain; interventions in diet ranged from reductions of 231 kgCO _2 e to increases of 116 kgCO _2 e per person per year (both statistically significant). Further, emissions reductions are sensitive to external factors, such as the emissions intensity of the electrical grid, which may change over time. Key gaps in the literature include a lack of studies conducted using randomized controlled trials or follow-ups, and in high-impact areas for emissions reductions including air travel. We highlight promising areas of intervention, such as habit changes to promote mode shifts in personal transportation, which would benefit from an analysis of greenhouse gas emissions reductions in future research.