bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acod1/itaconate activates Nrf2 in pulmonary microvascular endothelial cells to protect against the obesity-induced pulmonary microvascular endotheliopathy
Authors: Zhu Li , Wu Zhuhua , Liu Yingli , Ming Yue , Xie Pei , Jiang Miao , Qi Yong 
Published: May 2024

Abstract
Background
Obesity is the main risk factor leading to the development of various respiratory diseases, such as asthma and pulmonary hypertension. Pulmonary microvascular endothelial cells (PMVECs) play a significant role in the development of lung diseases. Aconitate decarboxylase 1 (Acod1) mediates the production of itaconate, and Acod1/itaconate axis has been reported to play a protective role in multiple diseases. However, the roles of Acod1/itaconate axis in the PMVECs of obese mice are still unclear.

Methods
mRNA-seq was performed to identify the differentially expressed genes (DEGs) between high-fat diet (HFD)-induced PMVECs and chow-fed PMVECs in mice (|log2 fold change| ≥ 1, p ≤ 0.05). Free fatty acid (FFA) was used to induce cell injury, inflammation and mitochondrial oxidative stress in mouse PMVECs after transfection with the Acod1 overexpressed plasmid or 4-Octyl Itaconate (4-OI) administration. In addition, we investigated whether the nuclear factor erythroid 2-like 2 (Nrf2) pathway was involved in the effects of Acod1/itaconate in FFA-induced PMVECs.

Results
Down-regulated Acod1 was identified in HFD mouse PMVECs by mRNA-seq. Acod1 expression was also reduced in FFA-treated PMVECs. Acod1 overexpression inhibited cell injury, inflammation and mitochondrial oxidative stress induced by FFA in mouse PMVECs. 4-OI administration showed the consistent results in FFA-treated mouse PMVECs. Moreover, silencing Nrf2 reversed the effects of Acod1 overexpression and 4-OI administration in FFA-treated PMVECs, indicating that Nrf2 activation was required for the protective effects of Acod1/itaconate.

Conclusion
Our results demonstrated that Acod1/Itaconate axis might protect mouse PMVECs from FFA-induced injury, inflammation and mitochondrial oxidative stress via activating Nrf2 pathway. It was meaningful for the treatment of obesity-caused pulmonary microvascular endotheliopathy.
Screening and genetic engineering of marine-derived Aspergillus terreus for high-efficient production of lovastatin
Authors: Na Han , Zheng Yao-yao , Jia Yaoning , Feng Jingzhao , Huang Jizi , Huang Jihao , Wang Chang-Yun , Yao Guangshan 
Published: May 2024

Abstract
Background
Lovastatin has widespread applications thanks to its multiple pharmacological effects. Fermentation by filamentous fungi represents the major way of lovastatin production. However, the current lovastatin productivity by fungal fermentation is limited and needs to be improved.

Results
In this study, the lovastatin-producing strains of Aspergillus terreus from marine environment were screened, and their lovastatin productions were further improved by genetic engineering. Five strains of A. terreus were isolated from various marine environments. Their secondary metabolites were profiled by metabolomics analysis using Ultra Performance Liquid Chromatography–Mass spectrometry (UPLC–MS) with Global Natural Products Social Molecular Networking (GNPS), revealing that the production of secondary metabolites was variable among different strains. Remarkably, the strain of A. terreus MJ106 could principally biosynthesize the target drug lovastatin, which was confirmed by High Performance Liquid Chromatography (HPLC) and gene expression analysis. By one-factor experiment, lactose was found to be the best carbon source for A. terreus MJ106 to produce lovastatin. To improve the lovastatin titer in A. terreus MJ106, genetic engineering was applied to this strain. Firstly, a series of strong promoters was identified by transcriptomic and green fluorescent protein reporter analysis. Then, three selected strong promoters were used to overexpress the transcription factor gene lovE encoding the major transactivator for lov gene cluster expression. The results revealed that compared to A. terreus MJ106, all lovE over-expression mutants exhibited significantly more production of lovastatin and higher gene expression. One of them, LovE-b19, showed the highest lovastatin productivity at a titer of 1512 mg/L, which represents the highest production level reported in A. terreus.

Conclusion
Our data suggested that combination of strain screen and genetic engineering represents a powerful tool for improving the productivity of fungal secondary metabolites, which could be adopted for large-scale production of lovastatin in marine-derived A. terreus.
Assessing the role of programmed cell death signatures and related gene TOP2A in progression and prognostic prediction of clear cell renal cell carcinoma
Authors: Wang Qingshui , Liu Jiamin , Li Ruiqiong , Wang Simeng , Xu Yining , Wang Yawen , Zhang Hao , Zhou Yingying , Zhang Xiuli , Chen Xuequn , Zhuang Wei , Lin Yao 
Published: May 2024

AbstractKidney Clear Cell Carcinoma (KIRC), the predominant form of kidney cancer, exhibits a diverse therapeutic response to Immune Checkpoint Inhibitors (ICIs), highlighting the need for predictive models of ICI efficacy. Our study has constructed a prognostic model based on 13 types of Programmed Cell Death (PCD), which are intertwined with tumor progression and the immune microenvironment. Validated by analyses of comprehensive datasets, this model identifies seven key PCD genes that delineate two subtypes with distinct immune profiles and sensitivities to anti-PD-1 therapy. The high-PCD group demonstrates a more immune-suppressive environment, while the low-PCD group shows better responses to PD-1 treatment. In particular, TOP2A emerged as crucial, with its inhibition markedly reducing KIRC cell growth and mobility. These findings underscore the relevance of PCDs in predicting KIRC outcomes and immunotherapy response, with implications for enhancing clinical decision-making.
Causal relationship between serum metabolites and juvenile idiopathic arthritis: a mendelian randomization study
Authors: Zhang Han , Ma Xiao , Liu Wanlu , Wang Ze , Zhang Zian , Chen GuanHong , Zhang Yingze , Wang Tianrui , Yu Tengbo , Zhang Yongtao 
Published: May 2024

Abstract
Background
Juvenile Idiopathic Arthritis (JIA) is a condition that occurs when individuals under the age of 16 develop arthritis that lasts for more than six weeks, and the cause is unknown. The development of JIA may be linked to serum metabolites. Nevertheless, the association between JIA pathogenesis and serum metabolites is unclear, and there are discrepancies in the findings across studies.

Methods
In this research, the association between JIA in humans and 486 serum metabolites was assessed using genetic variation data and genome-wide association study. The identification of causal relationships was accomplished through the application of univariate Mendelian randomization (MR) analysis. Various statistical methods, including inverse variance weighted and MR-Egger, were applied to achieve this objective. To ensure that the findings from the MR analysis were trustworthy, a number of assessments were carried out. To ensure the accuracy of the obtained results, a range of techniques were utilised including the Cochran Q test, examination of the MR-Egger intercept, implementation of the leave-one-out strategy, and regression analysis of linkage disequilibrium scores. In order to identify the specific metabolic pathways associated with JIA, our primary objective was to perform pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes.

Results
Two-sample summary data MR analyses and sensitivity analyses showed that five metabolites were significantly causally associated with JIA, including two risk factors—kynurenine (odds ratio [OR]: 16.39, 95% confidence interval [CI]: 2.07-129.63, p = 5.11 × 10− 6) and linolenate (OR: 16.48, 95% CI: 1.32-206.22, p = 0.030)—and three protective factors—3-dehydrocarnitine (OR: 0.32, 95% CI: 0.14–0.72, p = 0.007), levulinate (4-oxovalerate) (OR: 0.40, 95% CI: 0.20–0.80, p = 0.010), and X-14,208 (phenylalanylserine) (OR: 0.68, 95% CI: 0.51–0.92, p = 0.010). Furthermore, seven metabolic pathways, including α-linolenic acid metabolism and pantothenate and CoA biosynthesis, are potentially associated with the onset and progression of JIA.

Conclusion
Five serum metabolites, including kynurenine and 3-dehydrocarnitine, may be causally associated with JIA. These results provide a theoretical framework for developing effective JIA prevention and screening strategies.
Distinct clinical features of transplanted children with Parvovirus B19 infection
Authors: Jia Ran , Cao Lingfeng , Lu Lijuan , Zhong Huaqing , Xu Menghua , Liu Pengcheng , Zhu Xunhua , Su Liyun , Xu Jin 
Published: May 2024

Abstract
Background
The immature and suppressed immune response makes transplanted children a special susceptible group to Parvovirus B19 (PVB19). However, the clinical features of transplanted children with PVB19 infection haven’t been comprehensively described.

Methods
We searched the medical records of all the transplant recipients who attended the Children’s Hospital of Fudan University from 1 Oct 2020 to 31 May 2023, and reviewed the medical literature for PVB19 infection cases among transplanted children.

Results
A total of 10 cases of PVB19 infection were identified in 201 transplanted children at our hospital, and the medical records of each of these cases were shown. Also, we retrieved 40 cases of PVB19 infection among transplanted children from the literature, thus summarizing a total of 50 unique cases of PVB19 infection. The median time to the first positive PVB19 DNA detection was 14 weeks post-transplantation. PVB19 IgM and IgG were detected in merely 26% and 24% of the children, respectively. The incidence of graft loss/dysfunction was as high as 36%. Hematopoietic stem cell transplant (HSCT) recipients showed higher PVB19 load, lower HGB level, greater platelet damage, lower PVB19 IgM/IgG positive rates, and more graft dysfunction than solid-organ transplant (SOT) recipients, indicating a more incompetent immune system.

Conclusions
Compared with the published data of transplanted adults, transplanted children displayed distinct clinical features upon PVB19 infection, including lower PVB19 IgM/IgG positive rates, more graft dysfunction, and broader damage on hematopoietic cell lines, which was even more prominent in HSCT recipients, thus should be of greater concern.
Measurement of perceived pressures in psychiatry: paper-and-pencil and computerized adaptive version of the P-PSY35 scale
Authors: Golay Philippe , Martinez Debora , Bachelard Mizué , Silva Benedetta , Brodard Alexandra , Perrin Jonathan , Pedro Fernando Nolan , Renaud Lou-Ann , Bonsack Charles , Morandi Stéphane 
Published: May 2024

Abstract
Purpose
Formal coercion in psychiatry is widely studied yet much less is known about pressures patients may experience, partly because of the very few measures available. The goal of this study was to validate the P-PSY35 (Pressures in Psychiatry Scale) and provide a paper-and-pencil and a computerised adaptive test (CAT) to measure pressures experienced by patients in psychiatry.

Methods
The P-PSY35 items were developed with users. Patients were evaluated during psychiatric hospitalisation or through an online survey. Mokken scale analysis and Item response theory (IRT) were used to select and estimate the items parameters. A Monte-Carlo simulation was performed to evaluate the number of items needed to transform the paper-and-pencil test into a reliable psychometric CAT.

Results
A total of 274 patients were assessed. The P-PSY35 demonstrated good internal validity, internal consistency, convergent and divergent validity. The P-PSY35 could be substantially shortened while maintaining excellent reliability using the CAT procedure.

Conclusion
The P-PSY35 was developed in collaboration with users. It is a psychometrically rigorous tool designed to measure experienced pressures in French-language. The development and successful validation of the P-PSY35 represent a welcome step towards implementing and evaluating programs aimed at reducing negative consequences of coercion.
Translating global evidence into local implementation through technical assistance: a realist evaluation of the Bloomberg philanthropies initiative for global Road safety
Authors: Neill Rachel , Hernández Angélica López , Koon Adam D. , Bachani Abdulgafoor M. 
Published: May 2024

Abstract
Background
Traffic-related crashes are a leading cause of premature death and disability. The safe systems approach is an evidence-informed set of innovations to reduce traffic-related injuries and deaths. First developed in Sweden, global health actors are adapting the model to improve road safety in low- and middle-income countries via technical assistance (TA) programs; however, there is little evidence on road safety TA across contexts. This study investigated how, why, and under what conditions technical assistance influenced evidence-informed road safety in Accra (Ghana), Bogotá (Colombia), and Mumbai (India), using a case study of the Bloomberg Philanthropies Initiative for Global Road Safety (BIGRS).

Methods
We conducted a realist evaluation with a multiple case study design to construct a program theory. Key informant interviews were conducted with 68 government officials, program staff, and other stakeholders. Documents were utilized to trace the evolution of the program. We used a retroductive analysis approach, drawing on the diffusion of innovation theory and guided by the context-mechanism-outcome approach to realist evaluation.

Results
TA can improve road safety capabilities and increase the uptake of evidence-informed interventions. Hands-on capacity building tailored to specific implementation needs improved implementers’ understanding of new approaches. BIGRS generated novel, city-specific analytics that shifted the focus toward vulnerable road users. BIGRS and city officials launched pilots that brought evidence-informed approaches. This built confidence by demonstrating successful implementation and allowing government officials to gauge public perception. But pilots had to scale within existing city and national contexts. City champions, governance structures, existing political prioritization, and socio-cultural norms influenced scale-up.

Conclusion
The program theory emphasizes the interaction of trust, credibility, champions and their authority, governance structures, political prioritization, and the implement-ability of international evidence in creating the conditions for road safety change. BIGRS continues to be a vehicle for improving road safety at scale and developing coalitions that assist governments in fulfilling their role as stewards of population well-being. Our findings improve understanding of the complex role of TA in translating evidence-informed interventions to country-level implementation and emphasize the importance of context-sensitive TA to increase impact.
A protoplast-based transient gene expression assay for the identification of heat and oxidative stress-regulatory genes in perennial ryegrass
Authors: Lei Shanshan , Zhu Yaolong , Jia Weiyu , Zhang Jing , Chi Yingjun , Xu Bin 
Published: May 2024

Abstract
Background
With the accumulating omics data, an efficient and time-saving transient assay to express target genes is desired. Mesophyll protoplasts, maintaining most stress-physiological responses and cellular activities as intact plants, offer an alternative transient assay to study target genes’ effects on heat and oxidative stress responses.

Results
In this study, a perennial ryegrass (Loliumperenne L.) mesophyll protoplast-based assay was established to effectively over- or down-regulate target genes. The relative expression levels of the target genes could be quantified using RT-qPCR, and the effects of heat and H2O2-induced oxidative stress on protoplasts’ viability could be quantitatively measured. The practicality of the assay was demonstrated by identifying the potential thermos-sensor genes LpTT3.1/LpTT3.2 in ryegrass that over-expressing these genes significantly altered protoplasts’ viability rates after heat stress.

Conclusion
This protoplast-based rapid stress regulatory gene identification assay was briefed as ‘PRIDA’ that will complement the stable genetic transformation studies to rapidly identify candidate stress-regulatory genes in perennial ryegrass and other grass species.
Short developmental milestone risk assessment tool to identify Duchenne muscular dystrophy in primary care
Authors: van Dommelen Paula , van Dijk Oisín , de Wilde Jeroen A. , Verkerk Paul H. 
Published: May 2024

Abstract
Background
In patients without a family history, Duchenne muscular dystrophy (DMD) is typically diagnosed at around 4–5 years of age. It is important to diagnose DMD during infancy or toddler stage in order to have timely access to treatment, opportunities for reproductive options, prevention of potential fatal reactions to inhaled anesthetics, awareness of a child’s abilities needed for good parenting, and opportunities for enrolment in clinical trials.

Method
We aimed to develop a short risk assessment tool based on developmental milestones that may contribute to the early detection of boys with DMD in primary care. As part of the case-control 4D-DMD study (Detection by Developmental Delay in Dutch boys with DMD), data on developmental milestones, symptoms and therapies for 76 boys with DMD and 12,414 boys from a control group were extracted from the health records of youth health care services and questionnaires. Multiple imputation, diagnostic validity and pooled backward logistic regression analyses with DMD (yes/no) as the dependent variable and attainment of 26 milestones until 36 months of age (yes/no) as the independent variable were performed. Descriptive statistics on symptoms and therapies were provided.

Results
A tool with seven milestones assessed at specific ages between 12 and 36 months resulted in a sensitivity of 79% (95CI:67–88%), a specificity of 95.8% (95%CI:95.3–96.2), and a positive predictive value of 1:268 boys. Boys with DMD often had symptoms (e.g. 43% had calf muscle pseudohypertrophy) and were referred to therapy (e.g. 59% for physical therapy) before diagnosis.

Discussion
This tool followed by the examination of other DMD-related symptoms could be used by youth health care professionals during day-to-day health assessments in the general population to flag children who require further action.

Conclusions
The majority of boys (79%) with DMD can be identified between 12 and 36 months of age with this tool. It increases the initial a priori risk of DMD from 1 in 5,000 to approximately 1 in 268 boys. We expect that other neuromuscular disorders and disabilities can also be found with this tool.
Investigating the spatiotemporal patterns and clustering of attendances for mental health services to inform policy and resource allocation in Thailand
Authors: Rotejanaprasert Chawarat , Thanutchapat Papin , Phoncharoenwirot Chiraphat , Mekchaiporn Ornrakorn , Chienwichai Peerut , Maude Richard J 
Published: May 2024

Abstract
Background
Mental illness poses a substantial global public health challenge, including in Thailand, where exploration of access to mental health services is limited. The spatial and temporal dimensions of mental illness in the country are not extensively studied, despite the recognized association between poor mental health and socioeconomic inequalities. Gaining insights into these dimensions is crucial for effective public health interventions and resource allocation.

Methods
This retrospective study analyzed mental health service utilization data in Thailand from 2015 to 2023. Temporal trends in annual numbers of individuals visiting mental health services by diagnosis were examined, while spatial pattern analysis employed Moran’s I statistics to assess autocorrelation, identify small-area clustering, and hotspots. The implications of our findings for mental health resource allocation and policy were discussed.

Results
Between 2015 and 2023, mental health facilities documented a total of 13,793,884 visits. The study found anxiety, schizophrenia, and depression emerged as the top three illnesses for mental health visits, with an increase in patient attendance following the onset of the COVID-19 outbreak. Spatial analysis identified areas of significance for various disorders across different regions of Thailand. Positive correlations between certain disorder pairs were found in specific regions, suggesting shared risk factors or comorbidities.

Conclusions
This study highlights spatial and temporal variations in individuals visiting services for different mental disorders in Thailand, shedding light on service gaps and socioeconomic issues. Addressing these disparities requires increased attention to mental health, the development of appropriate interventions, and overcoming barriers to accessibility. The findings provide a baseline for policymakers and stakeholders to allocate resources and implement culturally responsive interventions to improve mental health outcomes.
An exploratory study on spatiotemporal clustering of suicide in Korean adolescents
Authors: Choi Won-Seok , Roh Beop-Rae , Jon Duk-In , Ryu Vin , Oh Yunhye , Hong Hyun Ju 
Published: May 2024

Abstract
Background
Adolescent suicides are more likely to form clusters than those of other age groups. However, the definition of a cluster in the space–time dimension has not been established, neither are the factors contributing to it well known. Therefore, this study aimed to identify space–time clusters in adolescent suicides in Korea and to examine the differences between clustered and non-clustered cases using novel statistical methods.

Methods
From 2016 to 2020, the dates and locations, including specific addresses from which the latitude and longitude of all student suicides (aged 9–18 years) in Korea were obtained through student suicide reports. Sociodemographic characteristics of the adolescents who died by suicide were collected, and the individual characteristics of each student who died by suicide were reported by teachers using the Strengths and Difficulties Questionnaire (SDQ). Density-Based Spatial Clustering of Applications with Noise (DBSCAN) analysis was used to assess the clustering of suicides.

Results
We identified 23 clusters through the data analysis of 652 adolescent suicides using DBSCAN. By comparing the size of each cluster, we identified 63 (9.7%) spatiotemporally clustered suicides among adolescents, and the temporal range of these clusters was 7–59 days. The suicide cluster group had a lower economic status than the non-clustered group. There were no significant differences in other characteristics between the two groups.

Conclusion
This study has defined the space–time cluster of suicides using a novel statistical method. Our findings suggest that when an adolescent suicide occurs, close monitoring and intervention for approximately 2 months are needed to prevent subsequent suicides. Future research using DBSCAN needs to involve a larger sample of adolescents from various countries to further corroborate these findings.