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Abstract Background There is a growing investment in the use of co-creation, reflected by an increase in co-created products, services, and interventions. At the same time, a growing recognition of the significance of co-creators’ experience can be detected but there is a gap in the aggregation of the literature with regard to experience. Therefore, the purpose of this scoping review is to uncover the breadth of existing empirical research on co-creation experience, how it has been defined and assessed, and its key emotional and psychological characteristics in the context of co-created products, services, or interventions among adults. Methods The development of the search strategy was guided by the research question, Arksey, and O’Malley’s scoping review methodology guidelines, and through collaboration with members of the Health CASCADE consortium. The results of the search and the study inclusion process will be reported in full and presented both narratively and by use of the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review (PRISMA-ScR) flow diagram. Comprehensive searches of relevant electronic databases (e.g. Scopus) will be conducted to identify relevant papers. Snowball searches to identify additional papers through included full-text papers will be done using the artificial intelligence tool, namely, Connected Papers. All review steps will involve at least two reviewers. Studies in English, Dutch, Chinese, Spanish, and French, published from the year 1970 onwards, will be considered. Microsoft Excel software will be used to record and chart extracted data. Discussion The resulting scoping review could provide useful insights into adult co-creators’ experience of participating in the co-creation process. An increased understanding of the role of emotional and psychological experiences of participating in co-creation processes may help to inform the co-creation process and lead to potential benefits for the co-creators and co-created outcome. Systematic review registration 10.5281/zenodo.7665851.

Background/Aims Data on the natural course of Chinese patients with ulcerative colitis (UC) was lacking. This study aimed to evaluate the natural history and prognosis of patients with UC in the past 15 years in China. Methods This cohort study included patients with UC in a tertiary hospital in southern China from 2007 to 2021 (cohort I: 2007–2011, cohort II: 2012–2016, cohort III: 2017–2021). Patients’ clinical characteristics and natural history were analyzed retrospectively. Results Of 1,139 included patients, 683 patients presented with proctitis or left-sided colitis at diagnosis and 38.5% of them (263/683) developed proximal disease extension. Fifty-eight percent of patients experienced relapse, chronic continuous and intermittent active course. Five patients (0.4%) developed colorectal tumors/dysplasia. The overall surgery rate was 8.6%, and the rates were 14.2%, 7.8%, and 8.0% in the 3 cohorts, respectively (P=0.059). Average time from diagnosis to surgery decreased from cohorts I to III (144 months vs. 36 months, P

Abstract Introduction Migraine, as a complex neurological disease, brings heavy burden to patients and society. Despite the availability of established therapies, existing medications have limited efficacy. Thus, we aimed to find the drug targets that improve the prognosis of migraine. Method We used Mendelian Randomization (MR) and Summary-data-based MR (SMR) analyses to study possible drug targets of migraine by summary statistics from FinnGen cohorts (nCase = 44,616, nControl = 367,565), with further replication in UK Biobank (nCase = 26,052, nControl = 487,214). Genetic instruments were obtained from eQTLGen and UKB-PPP to verify the drug targets at the gene expression and protein levels. The additional analyses including Bayesian co-localization, the heterogeneity in dependent instruments(HEIDI), Linkage Disequilibrium Score(LDSC), bidirectional MR, multivariate MR(MVMR), heterogeneity test, horizontal pleiotropy test, and Steiger filtering were implemented to consolidate the findings further. Lastly, drug prediction analysis and phenome-wide association study(PheWAS) were employed to imply the possibility of drug targets for future clinical applications. Result The MR analysis of eQTL data showed that four drug targets (PROCR, GSTM4, SLC4A1, and TNFRSF10A) were significantly associated with migraine risk in both the FinnGen and UK Biobank cohorts. However, only GSTM4 exhibited consistent effect directions across the two outcomes(Discovery cohort: OR(95%CI) = 0.94(0.93–0.96); p = 2.70e − 10; Replication cohort: OR(95%CI) = 0.93(0.91–0.94); p = 4.21e − 17). Furthermore, GSTM4 passed the SMR at p 0.05 at both the gene expression and protein levels. The protein-level MR analysis revealed a strong correlation between genetically predicted GSTM4 with a lower incidence of migraine and its subtypes(Overall migraine: OR(95%CI) = 0.91(0.87–0.95); p = 6.98e-05; Migraine with aura(MA): OR(95%CI) = 0.90(0.85–0.96); p = 2.54e-03; Migraine without aura(MO): OR(95%CI) = 0.90(0.83–0.96); p = 2.87e-03), indicating a strong co-localization relationship (PPH4 = 0.86). Further analyses provided additional validation for the possibility of GSTM4 as a migraine treatment target. Conclusion This study identifies GSTM4 as a potential druggable gene and promising therapeutic target for migraine.

Abstract Understanding the mechanisms controlling forest carbon accumulation is crucial for predicting and mitigating future climate change. Yet, it remains unclear whether the dominance of ectomycorrhizal (EcM) trees influences the carbon accumulation of entire forests. In this study, we analyzed forest inventory data from over 4000 forest plots across Northeast China. We find that EcM tree dominance consistently exerts a positive effect on tree, soil, and forest carbon stocks. Moreover, we observe that these positive effects are more pronounced during unfavorable climate conditions, at lower tree species richness, and during early successional stages. This underscores the potential of increasing the dominance of native EcM tree species not only to enhance carbon stocks but also to bolster resilience against climate change in high-latitude forests. Here we show that forest managers can make informed decisions to optimize carbon accumulation by considering various factors such as mycorrhizal types, climate, successional stages, and species richness.

Abstract Background Variations exist in the response of patients with Crohn’s disease (CD) to ustekinumab (UST) treatment, but the underlying cause remains unknown. Our objective was to investigate the involvement of immune cells and identify potential biomarkers that could predict the response to interleukin (IL) 12/23 inhibitors in patients with CD. Methods The GSE207022 dataset, which consisted of 54 non-responders and 9 responders to UST in a CD cohort, was analyzed. Differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Least absolute shrinkage and selection operator (LASSO) regression was used to screen the most powerful hub genes. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performances of these genes. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to estimate the proportions of immune cell types. These significantly altered genes were subjected to cluster analysis into immune cell-related infiltration. To validate the reliability of the candidates, patients prescribed UST as a first-line biologic in a prospective cohort were included as an independent validation dataset. Results A total of 99 DEGs were identified in the integrated dataset. GO and KEGG analyses revealed significant enrichment of immune response pathways in patients with CD. Thirteen genes (SOCS3, CD55, KDM5D, IGFBP5, LCN2, SLC15A1, XPNPEP2, HLA-DQA2, HMGCS2, DDX3Y, ITGB2, CDKN2B and HLA-DQA1), which were primarily associated with the response versus nonresponse patients, were identified and included in the LASSO analysis. These genes accurately predicted treatment response, with an area under the curve (AUC) of 0.938. T helper cell type 1 (Th1) cell polarization was comparatively strong in nonresponse individuals. Positive connections were observed between Th1 cells and the LCN2 and KDM5D genes. Furthermore, we employed an independent validation dataset and early experimental verification to validate the LCN2 and KDM5D genes as effective predictive markers. Conclusions Th1 cell polarization is an important cause of nonresponse to UST therapy in patients with CD. LCN2 and KDM5D can be used as predictive markers to effectively identify nonresponse patients. Trial registration: Trial registration number: NCT05542459; Date of registration: 2022-09-14; URL: https://www.clinicaltrials.gov .

We demonstrate an all-optical method that online produces “microstructured” targets by manipulating a Laguerre-Gaussian (LG) prepulse. Besides the enhancement of the proton number, the cutoff energy is nearly doubled. Such transient “microstructured” targets are characterized using both offline and online approaches. Based on probe experiments and hydrodynamic simulations, we develop a simple model to describe the electron density distribution upon the arrival of the main pulse. Two-dimensional particle-in-cell simulations reveal that the annular plasma acts as an oscillating cavity for hot electrons and results in a cascaded acceleration effect. The combination of low-intensity LG prepulses and ultraintense Gaussian pulses opens another avenue for fine-tuning laser-plasma interactions spatiotemporally in interdisciplinary applications.

Background: No head-to-head trial directly compares the effectiveness of vedolizumab (VDZ) and infliximab (IFX) in patients with ulcerative colitis (UC) who were naïve to biologic therapy. Objectives: We aimed to compare the clinical and endoscopic effectiveness of VDZ and IFX in biologic-naïve patients with UC in real-world settings. Design: It was a multicenter, observational, real-world cohort study conducted at five centers. Methods: Patients diagnosed with UC and treated with either IFX or VDZ as their first-line biologic therapy were retrospectively enrolled. Steroid-free remission, clinical response, clinical remission, and endoscopic healing at week 14 and week 52 were compared between the two groups after propensity score weighting. Results: A total of 199 patients (117 VDZ and 82 IFX) were included in the study. There were no significant differences in steroid-free remission (64.6% vs 56.1%, p = 0.224), clinical response (83.4% vs 73.4%, p = 0.086), or clinical remission (69.4% vs 60.1%, p = 0.174) at week 14. However, VDZ showed better results in steroid-free remission (67.5% vs 44.4%, p = 0.004), clinical response (69.7% vs 47.1%, p = 0.005), and clinical remission (67.5% vs 44.4%, p = 0.004) at week 52. In terms of endoscopic healing, VDZ was similar to IFX at week 14 (25.7% vs 17.4%, p = 0.185), but VDZ had a significantly higher rate at week 52 (29.5% vs 11.8%, p = 0.027). VDZ was found to be superior to IFX in therapeutic continuation (hazard ratio = 0.339, 95% CI: 0.187–0.614, p

Background Co-creation is seen as a way to ensure all relevant needs and perspectives are included and to increase its potential for beneficial effects and uptake process evaluation is crucial. However, existing process evaluation frameworks have been built on practices characterised by top-down developed and implemented interventions and may be limited in capturing essential elements of co-creation. This study aims to provide a review of studies planning and/or conducting a process evaluation of public health interventions adopting a co-creation approach and aims to derive assessed process evaluation components, used frameworks and insights into formative and/or participatory evaluation.Methods We searched for studies on Scopus and the Health CASCADE Co-Creation Database. Co-authors performed a concept-mapping exercise to create a set of overarching dimensions for clustering the identified process evaluation components.Results 54 studies were included. Conceptualisation of process evaluation included in studies concerned intervention implementation, outcome evaluation, mechanisms of impact, context and the co-creation process. 22 studies (40%) referenced ten existing process evaluation or evaluation frameworks and most referenced were the frameworks developed by Moore et al (14%), Saunders et al (5%), Steckler and Linnan (5%) and Nielsen and Randall (5%).38 process evaluation components were identified, with a focus on participation (48%), context (40%), the experience of co-creators (29%), impact (29%), satisfaction (25%) and fidelity (24%).13 studies (24%) conducted formative evaluation, 37 (68%) conducted summative evaluation and 2 studies (3%) conducted participatory evaluation.Conclusion The broad spectrum of process evaluation components addressed in co-creation studies, covering both the evaluation of the co-creation process and the intervention implementation, highlights the need for a process evaluation tailored to co-creation studies. This work provides an overview of process evaluation components, clustered in dimensions and reflections which researchers and practitioners can use to plan a process evaluation of a co-creation process and intervention.

The environment of mountain ecosystems can change greatly in short distances as elevation increases. The effects of elevation change on the distribution and body size of carabid beetles were investigated at elevations of 750–2600 m in the Changbaishan Nature Reserve (Northeast China). The richness and abundance of carabid species decreased significantly as elevation increased. However, the change trends are different in forests and tundra. In the broad-leaved Korean pine forest and coniferous forest at low elevations, carabid beetle species have high richness and abundance. The community composition of carabid beetles was significantly different at different elevations and among different vegetation types. Some species only occurred at specific elevations. There were fewer indicator species in high-elevation areas, but Carabus macleayi Dejean, Nebria pektusanica Horratovich and Pterostichus jaechi Kirschenhofer were mainly found in high-elevation areas. The average body size of species in the carabid beetle community was negatively correlated with elevation. The sizes of the larger Carabus canaliculatus Adams and Carabus venustus Morawitz were negatively correlated with elevation. Their body sizes decreased obviously in the tundra at elevations above 2000 m. Changes in vegetation types at high elevations affect the distribution and body sizes of beetles along the elevation gradient. Some large carabid species may be smaller at high elevations where a unique insect fauna has developed. The body size and distribution range of the carabid may be the factors that affect body size reduction at high elevation. Although some high-elevation species also occur in low-elevation areas, the protection of species diversity in high-elevation areas should be emphasized in the context of global climate change. The results illustrate the mechanisms of carabid beetles’ response to elevation change and the need for carabid beetles’ diversity conservation under global climate change.

Cytoprotection has emerged as an effective therapeutic strategy for mitigating brain injury following acute ischemic stroke (AIS). The sulfonylurea receptor 1-transient receptor potential M4 (SUR1-TRPM4) channel plays a pivotal role in brain edema and neuroinflammation. However, the practical use of the inhibitor glyburide (GLB) is hindered by its low bioavailability. Additionally, the elevated reactive oxygen species (ROS) after AIS exacerbate SUR1-TRPM4 activation, contributing to irreversible brain damage. To overcome these challenges, GLB and superoxide dismutase (SOD) were embedded in a covalent organic framework (COF) with a porous structure and great stability. The resulting S/G@COF demonstrated significant improvements in survival and neurological functions. This was achieved by eliminating ROS, preventing neuronal loss and apoptosis, suppressing neuroinflammation, modulating microglia activation, and ameliorating blood-brain barrier (BBB) disruption. Mechanistic investigations revealed that S/G@COF concurrently activated the Wnt/β-catenin signaling pathway while suppressing the upregulation of SUR1-TRPM4. This study underscores the potential of employing multi-target therapy and drug modification in cytoprotective strategies for ischemic stroke.

Background: As medical institutions shift towards Competency Based Education, more effort is being directed towards understanding how healthcare teams' function competently. While many have studied the competencies required to be a successful clerk, few have examined this question within the context of team function and integration. Our primary objective is to identify how medical clerks successfully integrate and contribute to clinical teaching teams. Methods: We performed a scoping review of the literature using the Ovid MEDLINE database. Data was extracted and thematically analysed in accordance with Arksey and O'Malley's (2005) approach to descriptive analysis. Results: Out of 1368 papers returned by our search, 12 studies were included in this review. Seven main themes were identified amongst the included studies: (1) Communication (2) Taking Responsibility and Appropriate Autonomy (3) Humility and Knowing When to Ask for Help (4) Identity as a Team Member, (5) Self-Efficacy (6) Rapport and Relationship Building (7) Patient Advocacy Conclusion: Analysis of these themes revealed four major findings: (i) The importance of documentation skills and communication towards team contribution (ii) The important connection between professional identity development and self-efficacy (iii) The impact of rapport on the reciprocity of trust between team members (iv) The role of clerks as patient advocates is poorly understood. This review also illustrates that there is a relative dearth of literature in this area. Future studies are needed to develop clear guidance on how clerks should perform these competencies in the context of team function and integration.

Abstract Breast cancer exhibits the highest global incidence among all tumor types. Regardless of the type of breast cancer, metastasis is a crucial cause of poor prognosis. Anoikis, a form of apoptosis initiated by cell detachment from the native environment, is an outside-in process commencing with the disruption of cytosolic connectors such as integrin-ECM and cadherin-cell. This disruption subsequently leads to intracellular cytoskeletal and signaling pathway alterations, ultimately activating caspases and initiating programmed cell death. Development of an anoikis-resistant phenotype is a critical initial step in tumor metastasis. Breast cancer employs a series of stromal alterations to suppress anoikis in cancer cells. Comprehensive investigation of anoikis resistance mechanisms can inform strategies for preventing and regressing metastatic breast cancer. The present review first outlines the physiological mechanisms of anoikis, elucidating the alterations in signaling pathways, cytoskeleton, and protein targets that transpire from the outside in upon adhesion loss in normal breast cells. The specific anoikis resistance mechanisms induced by pathological changes in various spatial structures during breast cancer development are also discussed. Additionally, the genetic loci of targets altered in the development of anoikis resistance in breast cancer, are summarized. Finally, the micro-RNAs and targeted drugs reported in the literature concerning anoikis are compiled, with keratocin being the most functionally comprehensive. Video Abstract

Abstract Background Pneumocephalus is rare in vaginal deliveries. Pneumocephalus may be asymptomatic or present with signs of increased intracranial pressure. However, parturients who received epidural anesthesia with air in their brains may experience low intracranial pressure headaches after giving birth, causing the diagnosis of pneumocephalus to be delayed. We report a case of a parturient who developed post-dural puncture headache combined with pneumocephalus secondary to vaginal delivery following epidural anesthesia. Case presentation A 24-year-old G1P0 Chinese woman at 38 weeks gestation was in labor and received epidural anesthesia using the loss of resistance to air technique and had a negative prior medical history. She presented with postural headache, neck stiffness and auditory changes 2 h after vaginal delivery. The head non-contrast computed tomography revealed distributed gas density shadows in the brain, indicating pneumocephalus. Her headache was relieved by bed rest, rehydration, analgesia, and oxygen therapy and completely disappeared after 2 weeks of postpartum bed rest. Conclusions This is the first report that positional headaches after epidural anesthesia may not indicate low intracranial pressure alone; it may combine with pneumocephalus, particularly when using the loss of resistance to air technique. At this moment, head computed tomography is essential to discover other conditions like pneumocephalus.

ObjectiveThe purpose of this study was to investigate whether the combination of abnormal systemic immune-inflammation index (SII) levels and hyperglycemia increased the risk of cognitive function decline and reduced survival rate in the United States.MethodsThis cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) database from 2011-2014 and enrolled 1,447 participants aged 60 years or older. Restricted cubic splines (RCS), linear regression and kaplan-meier(KM) curve were employed to explore the combined effects of abnormal SII and hyperglycemia on cognitive function and survival rate, and subgroup analysis was also conducted.ResultsThe RCS analysis revealed an inverted U-shaped relationship between lgSII levels and cognitive function. Linear regression analysis indicated that neither abnormal SII nor diabetes alone significantly contributed to the decline in cognitive function compared to participants with normal SII levels and blood glucose. However, when abnormal SII coexisted with diabetes (but not prediabetes), it resulted to a significant decline in cognitive function. After adjusting for various confounding factors, these results remained significant in Delayed Word Recall (β:-0.76, PConclusionThe findings suggest that the impact of diabetes on cognitive function/survival rate is correlated with SII levels, indicating that their combination enhances predictive power.

To meet the demands of laser-ion acceleration at a high repetition rate, we have developed a comprehensive diagnostic system for real-time and in situ monitoring of liquid sheet targets (LSTs). The spatially resolved rapid characterizations of an LST’s thickness, flatness, tilt angle and position are fulfilled by different subsystems with high accuracy. With the help of the diagnostic system, we reveal the dependence of thickness distribution on collision parameters and report the 238-nm liquid sheet generated by the collision of two liquid jets. Control methods for the flatness and tilt angle of LSTs have also been provided, which are essential for applications of laser-driven ion acceleration and others.

We explored the effects of the endothelial nitric oxide synthase (eNOS) gene −786 T > C and 894 G > T locus polymorphisms and the methylenetetrahydrofolate reductase (MTHFR) gene 1298 A > C and 677 C > T locus polymorphisms on preeclampsia (PE) in pregnant women in Quanzhou area and provide reliable and stable predictors PE. This study included 160 normal pregnant women (normal control group) and 160 women with preeclampsia (PE group). Polymorphisms in eNOS gene and MTHFR were analyzed by the polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) technique. eNOS 894 G > T locus and MTHFR 1298 A > C locus had no significant difference between the two groups. In the PE patients, eNOS −786 T allele (OR: 2.07, p = 0.03) and MTHFR 677 C allele (OR: 1.83, p = 0.04) had significantly lower frequency. The nitric oxide (NO) level in patients with eNOS −786 C C was significantly lower than that in those with −786 TT. The homocysteine (Hcy) level in patients with MTHFR 677 TT was significantly higher than that in those with 677 C C. In conclusion, the frequency of the eNOS −786 C C genotype and MTHFR 677 TT genotype are higher in women with PE, which cause lower NO level and higher Hcy level.