bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomics and metabolomics analysis of L-phenylalanine overproduction in Escherichia coli
Authors: Sun Wei , Ding Dongqin , Bai Danyang , Lin Yang , Zhu Yaru , Zhang Cuiying , Zhang Dawei 
Published: April 2023

Abstract
Background
Highly efficient production of L-phenylalanine (L-Phe) in E. coli has been achieved by multiple rounds of random mutagenesis and modification of key genes of the shikimate (SHIK) and L-Phe branch pathways. In this study, we performed transcriptomic (16, 24 and 48 h) and metabolomic analyses (8, 16, 24, 32,40, and 48 h) based on time sequences in an engineered E. coli strain producing L-Phe, aiming to reveal the overall changes of metabolic activities during the fermentation process.

Results
The largest biomass increase rate and the highest production rate were seen at 16 h and 24 h of fermentation, respectively reaching 5.9 h−1 and 2.76 g/L/h, while the maximal L-Phe titer of 60 g/L was accumulated after 48 h of fermentation. The DEGs and metabolites involved in the EMP, PP, TCA, SHIIK and L-Phe-branch pathways showed significant differences at different stages of fermentation. Specifically, the significant upregulation of genes encoding rate-limiting enzymes (aroD and yidB) and key genes (aroF, pheA and aspC) pushed more carbon flux toward the L-Phe synthesis. The RIA changes of a number of important metabolites (DAHP, DHS, DHQ, Glu and PPN) enabled the adequate supply of precursors for high-yield L-Phe production. In addition, other genes related to Glc transport and phosphate metabolism increased the absorption of Glc and contributed to rerouting the carbon flux into the L-Phe-branch.

Conclusions
Transcriptomic and metabolomic analyses of an L-Phe overproducing strain of E. coli confirmed that precursor supply was not a major limiting factor in this strain, whereas the rational distribution of metabolic fluxes was achieved by redistributing the carbon flux (for example, the expression intensity of the genes tyrB, aspC, aroL and aroF/G/H or the activity of these enzymes is increased to some extent), which is the optimal strategy for enhancing L-Phe production.
Asymptomatic Plasmodium falciparum carriage and clinical disease: a 5-year community-based longitudinal study in The Gambia
Authors: Ahmad Abdullahi , Mohammed Nuredin Ibrahim , Joof Fatou , Affara Muna , Jawara Musa , Abubakar Ismaela , Okebe Joseph , Ceesay Serign , Hamid-Adiamoh Majidah , Bradley John , Amambua-Ngwa Alfred , Nwakanma Davis , D’Alessandro Umberto 
Published: April 2023

Abstract
Background
Carriers of persistent asymptomatic Plasmodium falciparum infections constitute an infectious reservoir that maintains malaria transmission. Understanding the extent of carriage and characteristics of carriers specific to endemic areas could guide use of interventions to reduce infectious reservoir.

Methods
In eastern Gambia, an all-age cohort from four villages was followed up from 2012 to 2016. Each year, cross-sectional surveys were conducted at the end of the malaria transmission season (January) and just before the start of the next one (June) to determine asymptomatic P. falciparum carriage. Passive case detection was conducted during each transmission season (August to January) to determine incidence of clinical malaria. Association between carriage at the end of the season and at start of the next one and the risk factors for this were assessed. Effect of carriage before start of the season on risk of clinical malaria during the season was also examined.

Results
A total of 1403 individuals—1154 from a semi-urban village and 249 from three rural villages were enrolled; median age was 12 years (interquartile range [IQR] 6, 30) and 12 years (IQR 7, 27) respectively. In adjusted analysis, asymptomatic P. falciparum carriage at the end of a transmission season and carriage just before start of the next one were strongly associated (adjusted odds ratio [aOR] = 19.99; 95% CI 12.57–31.77, p < 0.001). The odds of persistent carriage (i.e. infected both in January and in June) were higher in rural villages (aOR = 13.0; 95% CI 6.33–26.88, p < 0.001) and in children aged 5–15 years (aOR = 5.03; 95% CI 2.47–10.23, p =  < 0.001). In the rural villages, carriage before start of the season was associated with a lower risk of clinical malaria during the season (incidence risk ratio [IRR] 0.48, 95% CI 0.27–0.81, p = 0.007).

Conclusions
Asymptomatic P. falciparum carriage at the end of a transmission season strongly predicted carriage just before start of the next one. Interventions that clear persistent asymptomatic infections when targeted at the subpopulation with high risk of carriage may reduce the infectious reservoir responsible for launching seasonal transmission.
To what extent has the Iranian Health Transformation Plan addressed inequality in healthcare financing in Iran?
Authors: Moeeni Maryam , Nosratnejad Shirin , Rostampour Manizhe , Ponnet Koen 
Published: April 2023

Abstract
Background
One of the major goals of health systems is providing a financing strategy without inequality; this has a significant impact on people’s access to healthcare. The present study aimed to investigate the inequality in households’ financial contribution (HFC) to health expenditure both before and after the implementation of the Iranian Health Transformation Plan (HTP) in 2014.

Methods
This study is a secondary analysis of two waves of a national survey conducted in Iran. The data were collected from the Households Income and Expenditure Survey in 2013 and 2015. The research sample included 76,195 Iranian households. The inequality in households’ financial contributions to the health system was assessed using the Gini coefficient, and the concentration index (CI). In addition, by using econometric modeling, the relationship between the implementation of the HTP and inequality in HFC was studied. The households’ financial contribution included healthcare and health insurance prepayments.

Results
The Gini coefficient values were 0.67 and 0.65 in 2013 and 2015, respectively, indicating a medium degree of inequality in HFC in both years. The CI values were 0.54 and 0.56 in 2013 and 2015, respectively, suggesting that inequalities in HFC were in favor of higher income quintiles in the years before and after the implementation of the HTP. Regression analysis showed that households with a female head, with an unemployed head, or with a head having income without a job were contributing more to financing health expenditure. The presence of a household member over the age of 65 was associated with a higher level of HFC. The implementation of the HTP had a negative relationship with the HFC.

Conclusion
The HTP, aiming to address inequality in the financing system, did not achieve the intended goal as expected. The implementation of the HTP neglected certain factors at the household level, such as the presence of family members older than the age of 65, a female household head, and unemployment. This resulted in a failure to reduce the inequality of the HFC. We suggest that, in the future, policymakers take into account factors at the household level to reduce inequality in the HFC.
Uncovering COVID-19 infection determinants in Portugal: towards an evidence-based spatial susceptibility index to support epidemiological containment policies
Authors: Alves André , da Costa Nuno Marques , Morgado Paulo , da Costa Eduarda Marques 
Published: April 2023

AbstractBackgroundCOVID-19 caused the largest pandemic of the twenty-first century forcing the adoption of containment policies all over the world. Many studies on COVID-19 health determinants have been conducted, mainly using multivariate methods and geographic information systems (GIS), but few attempted to demonstrate how knowing social, economic, mobility, behavioural, and other spatial determinants and their effects can help to contain the disease. For example, in mainland Portugal, non-pharmacological interventions (NPI) were primarily dependent on epidemiological indicators and ignored the spatial variation of susceptibility to infection.MethodsWe present a data-driven GIS-multicriteria analysis to derive a spatial-based susceptibility index to COVID-19 infection in Portugal. The cumulative incidence over 14 days was used in a stepwise multiple linear regression as the target variable along potential determinants at the municipal scale. To infer the existence of thresholds in the relationships between determinants and incidence the most relevant factors were examined using a bivariate Bayesian change point analysis. The susceptibility index was mapped based on these thresholds using a weighted linear combination.ResultsRegression results support that COVID-19 spread in mainland Portugal had strong associations with factors related to socio-territorial specificities, namely sociodemographic, economic and mobility. Change point analysis revealed evidence of nonlinearity, and the susceptibility classes reflect spatial dependency. The spatial index of susceptibility to infection explains with accuracy previous and posterior infections. Assessing the NPI levels in relation to the susceptibility map points towards a disagreement between the severity of restrictions and the actual propensity for transmission, highlighting the need for more tailored interventions.ConclusionsThis article argues that NPI to contain COVID-19 spread should consider the spatial variation of the susceptibility to infection. The findings highlight the importance of customising interventions to specific geographical contexts due to the uneven distribution of COVID-19 infection determinants. The methodology has the potential for replication at other geographical scales and regions to better understand the role of health determinants in explaining spatiotemporal patterns of diseases and promoting evidence-based public health policies.
Efficacy of CU06-1004 via regulation of inflammation and endothelial permeability in LPS-induced acute lung injury
Authors: Kim Yeomyeong , Bae Cho-Rong , Kim Dongyeop , Kim Hyejeong , Lee Sunghye , Zhang Haiying , Noh Minyoung , Kim Young-Myeong , Mochizuki Naoki , Kwon Young-Guen 
Published: April 2023

Abstract
Background
Acute lung injury (ALI) is a life-threatening condition that fundamentally results from inflammation and edema in the lung. There are no effective treatments available for clinical use. Previously, we found that as a leakage blocker CU06-1004 prevents endothelial barrier disruption and enhances endothelial cell survival under inflammatory conditions. In this study, we aimed to elucidate the effect of CU06-1004 in terms of prevention of inflammation and endothelial dysfunction in an ALI mouse model.

Methods
An ALI model was established that included intraperitoneal administration of LPS. Following LPS administration, survival rates and lung wet/dry ratios were assessed. Histological analysis was performed using hematoxylin and eosin staining. Scanning electron microscopy was used to examine alveolar and capillary morphology. Cytokines such as IL-1β, IL-6, and TNF-α were analyzed using an ELISA assay of bronchoalveolar lavage fluid (BALF) and serum. Neutrophil infiltration was observed in BALF using Wright-Giemsa staining, and myeloperoxidase (MPO) activity was assessed. Pulmonary vascular leakage was confirmed using Evans-blue dye, and the expression of junctional proteins was evaluated using immunofluorescent staining. Expression of adhesion molecules was observed using immunofluorescence staining. NF-κB activation was determined using immunohistochemistry and western blot analysis.

Results
Survival rates and pulmonary edema were ameliorated with CU06-1004 treatment. Administration of CU06-1004 normalized histopathological changes induced by LPS, and alveolar-capillary wall thickening was reduced. Compared with the LPS-challenged group, after CU06-1004 treatment, the infiltration of immune cells was decreased in the BALF, and MPO activity in lung tissue was reduced. Similarly, in the CU06-1004 treatment group, pro-inflammatory cytokines were significantly inhibited in both BALF and serum. Evans-blue leakage was reduced, and the expression of junctional proteins was recovered in the CU06-1004 group. Adhesion molecules were downregulated and NF-κB activation was inhibited after CU06-1004 treatment.

Conclusions
These results suggested that CU06-1004 had a therapeutic effect against LPS-induced ALI via alleviation of the inflammatory response and protection of vascular integrity.
Cost-utility of vitamin D supplementation to prevent acute respiratory infections in children
Authors: Buendía Jefferson Antonio , Patiño Diana Guerrero 
Published: April 2023

Abstract
Introduction
Increasing evidence has demonstrated the effectiveness and safety of vitamin D supplementation to prevent acute respiratory infections in children. More economic evaluations incorporating the new evidence and in the pediatric population are needed to know the efficiency of this treatment. This study aimed to determine the cost-utility of vitamin D supplementation to prevent acute respiratory infections in pediatric patients.

Methods
A decision tree model was used to estimate the cost and quality-adjusted life-years (QALYs) of vitamin D supplementation in healthy school children between 1 and 16 years. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay (WTP) value of $19,000.

Results
The base-case analysis showed that vitamin D supplementation was associated with lower costs and higher QALYs than strategy without this supplementation. The QALYs per person estimated in the model for those treatments were 0,99 with vitamin D supplementation and 0,98 without vitamin D supplementation. The total costs per person were US$ 1354 for vitamin D supplementation and US$ 1948 without vitamin D supplementation. This position of absolute dominance of vitamin D supplementation makes it unnecessary to estimate the incremental cost-effectiveness ratio.

Conclusion
In conclusion, our study shows that Vitamin D supplementation is a cost-effective strategy to prevent ARI in pediatric patients, from a societal perspective.
N,N-Dimethyl-3β-hydroxycholenamide attenuates neuronal death and retinal inflammation in retinal ischemia/reperfusion injury by inhibiting Ninjurin 1
Authors: Shi Yunhong , Liu Yidan , Wu Caiqing , Liu Xiuxing , Hu Wenfei , Yang Zhenlan , Li Zhidong , Li Yangyang , Deng Caibin , Wei Kun , Gu Chenyang , Chen Xuhao , Su Wenru , Zhuo Yehong 
Published: April 2023

Abstract
Background
Retinal ischemia–reperfusion (RIR) injury refers to an obstruction in the retinal blood supply followed by reperfusion. Although the molecular mechanism underlying the ischemic pathological cascade is not fully understood, neuroinflammation plays a crucial part in the mortality of retinal ganglion cells.

Methods
Single-cell RNA sequencing (scRNA-seq), molecular docking, and transfection assay were used to explore the effectiveness and pathogenesis of N,N-dimethyl-3β-hydroxycholenamide (DMHCA)-treated mice with RIR injury and DMHCA-treated microglia after oxygen and glucose deprivation/reoxygenation (OGD/R).

Results
DMHCA could suppress inflammatory gene expression and attenuate neuronal lesions, restoring the retinal structure in vivo. Using scRNA-seq on the retina of DMHCA-treated mice, we provided novel insights into RIR immunity and demonstrated nerve injury-induced protein 1 (Ninjurin1/Ninj 1) as a promising treatment target for RIR. Moreover, the expression of Ninj1, which was increased in RIR injury and OGD/R-treated microglia, was downregulated in the DMHCA-treated group. DMHCA suppressed the activation of the nuclear factor kappa B (NF-κB) pathways induced by OGD/R, which was undermined by the NF-κB pathway agonist betulinic acid. Overexpressed Ninj1 reversed the anti-inflammatory and anti-apoptotic function of DMHCA. Molecular docking indicated that for Ninj1, DMHCA had a low binding energy of − 6.6 kcal/mol, suggesting highly stable binding.

Conclusion
Ninj1 may play a pivotal role in microglia-mediated inflammation, while DMHCA could be a potential treatment strategy against RIR injury.
Cross-cultural adaptation, validity and reliability of the Persian translation of the Western Ontario Shoulder Instability Index (WOSI)
Authors: Kheradmand Ehsan , Rahimi Seyed Mohsen , Nakhaei Amroodi Morteza , Nejati Parisa , Griffin Sharon 
Published: April 2023

Abstract
Purpose
The Western Ontario Shoulder Instability Index (WOSI) is the most commonly used patient-reported outcome measure to record the quality of life in patients with shoulder instability. The current study aimed to translate the WOSI into the Persian language and evaluate its psychometric properties.

Methods
The translation procedure of the WOSI was performed according to a standard guideline. A total of 52 patients were included in the study and responded to the Persian WOSI, Oxford shoulder score (OSS), Oxford shoulder instability score (OSIS), and disabilities of arm, shoulder and hand (DASH). A sub-group of 41 patients responded for the second time to the Persian WOSI after an interval of 1–2 weeks. The internal consistency, test–retest reliability using intraclass correlation coefficient (ICC), measurement error, minimal detectable change (MDC), and floor and ceiling effect were analyzed. The hypothesis testing method was used to assess construct validity by calculating Pearson correlation coefficient between WOSI and DASH, OSS, and OSIS.

Results
Cronbach's alpha value was 0.93, showing strong internal consistency. Test–retest reliability was good to excellent (ICC = 0.90). There was no floor and ceiling effect. The standard error of measurement and MDC were 8.30% and 23.03%, respectively. Regarding construct validity, 83.3% of the results agreed with hypotheses. High correlations were observed between WOSI and DASH, OSS and OSIS (0.746, 0.759 and 0.643, respectively) indicating excellent validity for the Persian WOSI.

Conclusion
The current study results demonstrated that the Persian WOSI is a valid and reliable instrument and can be used in the clinic and research for Persian-speaking patients with shoulder instability.
Daurisoline attenuates H2O2-induced chondrocyte autophagy by activating the PI3K/Akt/mTOR signaling pathway
Authors: Zhang Yang , Liu Wenguang , Liu Zhonghao , Liu Yi 
Published: April 2023

Abstract
Background
Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage degeneration and intra-articular inflammation. Daurisoline (DAS) is an isoquinoline alkaloid isolated from Rhizoma Menispermi, whose antitumor and anti-inflammatory pharmacological effects have been demonstrated, but the effects of DAS on OA have rarely been researched. In this study, we aimed to explore the potential role of DAS in OA and its partial mechanism.

Materials and methods
The cytotoxicity of H2O2 and DAS toward chondrocytes was detected by the Cell Counting Kit-8 assay. Safranin O staining was used to detect chondrocyte phenotype changes. Cell apoptosis was measured by both flow cytometry and quantitative analysis of the protein levels of the apoptosis-related factors Bax, Bcl-2 and cleaved caspase-3 by western blot. Western blotting and immunofluorescence were used to assess the expression of the autophagy-related proteins LC3, Beclin-1 and p62. In addition, key signal pathway targets and matrix-degrading indicators were measured by western blot.

Results
Our results indicated that H2O2 induced human chondrocyte apoptosis and activated autophagy in a dose-dependent manner. DAS treatment dose-dependently reversed the expression of apoptosis-related proteins (Bax, Bcl-2 and cleaved caspase3) and the apoptosis rate induced by H2O2. Western blot and immunofluorescence analyses showed that DAS decreased the H2O2-induced upregulation of the autophagy marker Beclin-1 and the LC3 II/LC3 I ratio and upregulated the p62 protein level. Mechanistically, DAS inhibited autophagy through the activation of the classical PI3K/AKT/mTOR signaling pathway and protected chondrocytes from apoptosis. In addition, DAS alleviated the H2O2-induced degradation of type II collagen and the high expression of matrix metalloproteinase 3 (MMP3) and MMP13.

Conclusion
Our research demonstrated that DAS alleviated chondrocyte autophagy caused by H2O2 through activation of the PI3K/AKT/mTOR signaling pathway and protected chondrocytes from apoptosis and matrix degradation. In conclusion, these findings suggest that DAS may serve as a promising therapeutic strategy for OA.
Social media use of adolescents who died by suicide: lessons from a psychological autopsy study
Authors: Balt Elias , Mérelle Saskia , Robinson Jo , Popma Arne , Creemers Daan , van den Brand Isa , van Bergen Diana , Rasing Sanne , Mulder Wico , Gilissen Renske 
Published: April 2023

Abstract
Background
while there are many benefits for young people to use social media, adverse effects such as cyberbullying, online challenges, social comparison and imitation may provoke and aggravate suicidal thoughts and behaviors. The influence of social media on mental health and suicidal thoughts and behaviours has been amply studied, but there is little empirical evidence for its potential role in adolescent suicides. The current study aimed to inform digital suicide prevention strategies by examining the meaning of social media in the lives of young suicide victims and elucidating the harmful and supportive effects of social media use on their wellbeing and distress.

Methods
data were analyzed from a psychological autopsy study of 35 adolescents who died by suicide in the Netherlands (43% of all adolescents who died by suicide in that year). These were 18 girls and 17 boys. All were under the age of twenty years, with an average of seventeen years. Interpretative Phenomenological Analysis was performed of 55 semi structured interviews with peers and parents of the decedents.

Results
young people benefitted from peer support and recovery stories. However, various themes were discussed relating to the harmful effects of social media, including dependency, triggers and imitation, challenges, cybervictimization and psychological entrapment. The themes of dependency and triggers and imitation were more salient in young females. A group of girls cultivated an online identity around their suicidal thoughts and behaviours. Next-of-kin, particularly parents, faced various challenges to talk to the adolescents about social media use, including technological illiteracy, online anonymity, and the youths’ closedness.

Conclusions
based on the findings, we recommend education to stimulate the digital literacy of parents, health workers and educators, supporting conscientious social media use in young people, and extending the prevention of cyberbullying. We encourage future research to examine how virtual social networks may sustain suicidal thoughts and behaviour, and to further investigate the effectiveness of digital interventions, like moderated peer support and the use of positive role models.