bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of benralizumab on airway geometry and dynamics in severe eosinophilic asthma: a single-arm study design exploring a functional respiratory imaging approach
Authors: Genofre Eduardo , Carstens Donna , DeBacker Wilfried , Muchmore Patrick , Panettieri Reynold A. , Rhodes Kirsty , Shih Vivian H. , Trudo Frank 
Published: May 2023

Abstract
Background
Severe eosinophilic asthma (SEA) is characterised by elevated blood/sputum eosinophil counts and airway inflammation, which can lead to mucus plug-mediated airway obstruction, increased exacerbation frequency, declines in lung function, and death. Benralizumab targets the alpha-subunit of the interleukin-5 receptor found on eosinophils, leading to rapid and near complete eosinophil depletion. This is expected to result in reduced eosinophilic inflammation, reduced mucus plugging and improved airway patency and airflow distribution.

Methods
BURAN is an interventional, single-arm, open-label, uncontrolled, prospective, multicentre study during which participants will receive three 30 mg subcutaneous doses of benralizumab at 4-week intervals. This study will use functional respiratory imaging (FRI), a novel, quantitative method of assessing patients’ lung structure and function based on detailed, three-dimensional models of the airways, with direct comparison of images taken at Weeks 0 and 13. Patients aged ≥ 18 years with established SEA who may be receiving oral corticosteroids and/or other asthma controller medications, who are inadequately controlled on inhaled corticosteroid-long-acting β2-agonist therapies and who have had ≥ 2 asthma exacerbations in the previous 12 months will be included. The objectives of BURAN are to describe changes in airway geometry and dynamics, measured by specific image-based airway volume and other FRI endpoints, following benralizumab therapy. Outcomes will be evaluated using descriptive statistics. Changes in FRI parameters, mucus plugging scores and central/peripheral ratio will be quantified as mean percent change from baseline (Week 0) to Week 13 (± 5 days) and statistical significance will be evaluated using paired t-tests. Relationships between FRI parameters/mucus plugging scores and conventional lung function measurements at baseline will be assessed with linear regression analyses for associations between outcomes, scatterplots to visualise the relationship, and correlation coefficients (Spearman’s rank and Pearson’s) to quantify the strength of these associations.

Conclusions
The BURAN study will represent one of the first applications of FRI—a novel, non-invasive, highly sensitive method of assessing lung structure, function and health—in the field of biologic respiratory therapies. Findings from this study will increase understanding of cellular-level eosinophil depletion mechanisms and improvements in lung function and asthma control following benralizumab treatment.
Trial registration EudraCT: 2022-000152-11 and NCT05552508
H3K4me3-related lncRNAs signature and comprehensive analysis of H3K4me3 regulating tumor immunity in lung adenocarcinoma
Authors: Fan Tao , Zhu Mingchuang , Muhammad Shan , Xiao Chu , Li Shuofeng , Tian He , Liu Yu , Xue Liyan , Zheng Bo , Li Chunxiang , He Jie 
Published: May 2023

Abstract
Backgroud
The role of epigenetic modifications in tumorigenesis has been widely reported. However, the role and mechanism of H3K4me3 modification in lung adenocarcinoma (LUAD) are rarely reported systematically. We, therefore, sought to analyze the characteristics of LUAD associated with H3K4me3 modification, build an H3K4me3-lncRNAs score model to predict the prognosis of patients with LUAD and clarify the potential value of H3K4me3 in immunotherapy of LUAD.

Methods
We evaluated H3K4me3-lncRNA patterns and H3K4me3-lncRNA scores of 477 LUAD samples based on 53 lncRNAs closely correlated to H3K4me3 regulators and comprehensive analyzed the role of these patterns in tumorigenesis and tumor immunity. Using Gene set variation analysis (GSVA), we systematically evaluated the H3K4me3 level of every sample and deeply analyzed the effect of H3K4me3 on the prognosis of LUAD. In addition, we included two independent immunotherapy cohorts to study the impact of high H3K4me3 score on the prognosis of patients. We also used an independent cohort with 52 matched paraffin specimens of LUAD to verify the impact of high H3K3me3 expression on the prognosis of patients.

Results
We identified three H3K4me3-lncRNA patterns that exhibited specific immune characteristics. Characterized by immunosuppressive and increased TGFβ-mediated epithelial-mesenchymal transition (EMT), patients with high H3K4me3-lncRNA score had a poor overall survival and decreased H3K4me3 score. H3K4me3 score was significantly positively correlated with CD4+T-cell and CD8+T-cell activation, programmed cell death and immune checkpoints (ICs) expression, and was negatively correlated with MYC pathway, TP53 pathway, and cell proliferation. Patients with high H3K4me3 score showed elevated expression of ICs, potentiated CD4 T-cell and CD8 T-cell activation, increased programmed cell death, and suppressed cell proliferation and TGFβ-mediated EMT. Patients with high H3K4me3 score and high expression of CTLA4, ICOS, TIGIT, PDCD1LG2, IDO1, CD274, PDCD1, LAG3, or HAVCR2 had the best survival advantage. Two independent immunotherapy cohorts verified that patients with high H3K4me3 score showed an increased inflamed tumor microenvironment (TME) phenotype and enhanced anti-PD-1/L1 immunotherapy response. Immunohistochemistry (IHC) data from 52 matched paraffin specimens of LUAD confirmed that the protein level of H3K4me3 in tumor was significantly lower than that of paracancerous tissues and H3K4me3 brought significant survival benefits to patients with LUAD.

Conclusions
We build an H3K4me3-lncRNAs score model to predict the prognosis of patients with LUAD. More importantly, this study revealed characteristics of H3K4me3 modification in LUAD and clarified the important potential role of H3K4me3 on tumor immunotherapy and patients’ survival.
Optimized enantioselective (S)-2-hydroxypropiophenone synthesis by free- and encapsulated-resting cells of Pseudomonas putida
Authors: Kordesedehi Reihaneh , Asadollahi Mohammad Ali , Shahpiri Azar , Biria Davoud , Nikel Pablo Iván 
Published: May 2023

AbstractBackgroundAromatic α-hydroxy ketones, such asS-2-hydroxypropiophenone (2-HPP), are highly valuable chiral building blocks useful for the synthesis of various pharmaceuticals and natural products. In the present study, enantioselective synthesis of 2-HPP was investigated by free and immobilized whole cells ofPseudomonas putidaATCC 12633 starting from readily-available aldehyde substrates. Whole resting cells ofP. putida, previously grown in a culture medium containing ammonium mandelate, are a source of native benzoylformate decarboxylase (BFD) activity. BFD produced by inducedP. putidaresting cells is a highly active biocatalyst without any further treatment in comparison with partially purified enzyme preparations. These cells can convert benzaldehyde and acetaldehyde into the acyloin compound 2-HPP by BFD-catalyzed enantioselective cross-coupling reaction.ResultsThe reaction was carried out in the presence of exogenous benzaldehyde (20 mM) and acetaldehyde (600 mM) as substrates in 6 mL of 200 mM phosphate buffer (pH 7) for 3 h. The optimal biomass concentration was assessed to be 0.006 g dry cell weight (DCW) mL− 1. 2-HPP titer, yield and productivity using the free cells were 1.2 g L− 1, 0.56 g 2-HPP/g benzaldehyde (0.4 mol 2-HPP/mol benzaldehyde), 0.067 g 2-HPP g− 1DCW h− 1, respectively, under optimized biotransformation conditions (30 °C, 200 rpm). Calcium alginate (CA)–polyvinyl alcohol (PVA)-boric acid (BA)-beads were used for cell entrapment. Encapsulated whole-cells were successfully employed in four consecutive cycles for 2-HPP production under aerobic conditions without any noticeable beads degradation. Moreover, there was no production of benzyl alcohol as an unwanted by-product.ConclusionsBioconversion by wholeP. putidaresting cells is an efficient strategy for the production of 2-HPP and other α-hydroxyketones.Graphical abstract
Elevated postprandial triglyceride-rich lipoproteins in patients with diabetes and stable coronary artery disease correlated with early renal damage and systemic inflammation
Authors: Guo Xu , Zhai Yujia , Song Chenliang , Mi Zhen , Peng Jiya , Guo Jing , Teng Xianzhuo , Zhang Daqing 
Published: May 2023

Abstract
Background
Dyslipidaemia is key in the development of coronary heart disease (CHD) in patients with diabetes mellitus (DM). Accumulated evidence supports that diabetic nephropathy increases the mortality risk of patients with CHD, while the influence of diabetic dyslipidaemia on renal damage in patients with DM and CHD remains unknown. Moreover, recent data indicate that postprandial dyslipidaemia has predictive value in terms of CHD prognosis, especially in patients with DM. The study aimed to determine the relationship of triglyceride-rich lipoproteins (TRLs) after daily Chinese breakfast on systemic inflammation and early renal damage in Chinese patients with DM and SCAD.

Methods
Patients with DM diagnosed with SCAD while in the Department of Cardiology of Shengjing Hospital from September 2016 to February 2017 were enrolled in this study. Fasting and 4-h postprandial blood lipids, fasting blood glucose, glycated haemoglobin, urinary albumin-to-creatinine ratio (UACR), serum interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) concentrations, and other parameters were measured. Fasting and postprandial blood lipid profiles and inflammatory cytokines were analysed using a paired t-test. The association between variables was analysed using Pearson or Spearman bivariate analysis. P < 0.05 was considered to be statistically significant.

Results
The study enrolled 44 patients in total. Compared with fasting state, postprandial total cholesterol high-density lipoprotein-cholesterol (HDL-C),low-density lipoprotein-cholesterol (LDL-C) and non-high-density lipoprotein-cholesterol (non-HDL-C) all showed no significant change. Postprandial serum triglyceride (TG) concentration increased significantly compared with that at fasting (1.40 ± 0.40 vs. 2.10 ± 0.94 mmol/L, P < 0.001), as did serum remnant lipoprotein-cholesterol (RLP-C) (0.54 ± 0.18 mmol/L vs. 0.64 ± 0.25 mmol/L). Pearson analysis revealed that serum TG and RLP-C positively correlated before and after breakfast. Moreover, during fasting, positive correlations were observed between TG and serum IL-6, TNF-α, and UACR. Positive correlations were observed between RLP-C and IL-6, UACR under fasting condition, while both TG and RLP-C were positively correlated with postprandial serum IL-6, TNF-α, and UACR concentrations. Finally, positive correlations were observed between UACR and IL-6 and TNF-α concentration under both fasting and postprandial conditions.

Conclusions
An increase in postprandial TRLs was observed in Chinese patients with DM and SCAD after daily breakfast, and this increase may be related to early renal injury via the induction of systemic inflammation.
“We are the ones who will have to make the change”: Cuban health cooperation and the integration of Cuban medical graduates into practice in the Pacific
Authors: McLennan Sharon , Werle Cristine 
Published: May 2023

AbstractBackgroundThis paper responds to Asante et al. (in Hum Resour Health, 2014), providing an updated picture of the impacts of Cuban medical training in the Pacific region based on research carried out in 2019–2021, which focused on the experiences of Pacific Island doctors trained in Cuba and their integration into practice in their home countries.MethodsThe research focussed on two case studies—Solomon Islands and Kiribati. Study methods for this research included multi-sited ethnographic methods and semi-structured interviews as well as qualitative analysis of policy documents, reports, and media sources.ResultsThe Cuban health assistance programme has had a significant impact on the medical workforce in the Pacific region increasing the number of doctors employed by Pacific Ministries of Health between 2012 and 2019. Qualitatively, there have been some notable improvements in the medical workforce and health delivery over this period. However, the integration of the Cuban-trained doctors into practise has been challenging, with criticisms of their clinical, procedural and communication skills, and the need for the rapid development of bridging and internship training programmes (ITPs) which were inadequately planned for at the outset of the programme.ConclusionsThe Cuban programme in the Pacific is an important model of development assistance for health in the region. While Cuba’s offer of scholarships was the trigger for a range of positive outcomes, the success of the programme has relied on input from a range of actors including support from other governments and institutions, and much hard work by the graduates themselves, often in the face of considerable criticism. Key impacts of the programme to date include the raw increase in the number of doctors and the development of the ITPs and career pathways for the graduates, although this has also led to the reorientation of Cuban graduates from preventative to curative health. There is considerable potential for these graduates to contribute to improved health outcomes across the region, particularly if their primary and preventative health care skills are utilised.
Natural autoimmunity in oligoarticular juvenile idiopathic arthritis
Authors: Tsitsami Elena , Sarrigeorgiou Ioannis , Tsinti Maria , Rouka Erasmia C. , Zarogiannis Sotirios G. , Lymberi Peggy 
Published: May 2023

Abstract
Background
Oligoarticular juvenile idiopathic arthritis (oligo-JIA) is considered as an antigen-driven lymphocyte-mediated autoimmune disease. Natural antibodies (NAbs) are pre-immune antibodies produced in the absence of exogenous antigen stimulation, participating in both, innate and adaptive immunity. Considering their major immunoregulatory role in homeostasis and autoimmune pathogenesis, we designed this study to further elucidate their role in oligo-JIA pathogenesis.

Methods
Seventy children with persistent oligo-JIA and 20 healthy matched controls were enrolled in the study. Serum IgM and IgA antibodies against human G-actin, human IgG F(ab΄)2 fragments and the hapten TriNitroPhenol (TNP) as well as the total concentration of serum IgM and IgA were measured by in-house enzyme-immunoassays. Kolmogorov–Smirnov normality test, Kruskal–Wallis H and Mann–Whitney tests were used to assess data distribution, and significant differences of non-parametric data between groups of the study. Backward regression analysis was used to analyze the effect of multiple factors (age, gender, disease activity, anti-nuclear antibody positivity, presence of uveitis) on continuous dependent variables (activities and activity/ concentration ratios of IgM and IgA NAbs).

Results
The ratios of IgA anti-TNP, anti-actin and anti-F(ab΄)2 levels to total serum IgA concentration were found to be significantly increased in patients with oligo-JIA compared to healthy subjects. Significantly elevated levels of IgM anti-TNP antibodies were also found in children with inactive oligo-JIA compared to those of children with active disease and of healthy controls. In the presence of anterior uveitis, IgM anti-TNP levels were significantly higher than in patients without uveitis or in healthy controls. Backward regression analysis revealed that the disease activity and the presence of anterior uveitis independently affect IgM anti-TNP levels.

Conclusuions
Our findings are in accordance with the hypothesis that NAbs contribute to the pathogenesis of autoimmune diseases and provide additional evidence that disturbances in natural autoimmunity may contribute to the as yet unclarified pathogenesis of oligo-JIA.
Zeaxanthin epoxidase is involved in the carotenoid biosynthesis and light-dependent growth of the marine alga Nannochloropsis oceanica
Authors: Liu Meijing , Ding Wei , Pan Yufang , Hu Hanhua , Liu Jin 
Published: May 2023

Abstract
Background
The marine alga Nannochloropsis oceanica, an emerging model belonging to Heterokont, is considered as a promising light-driven eukaryotic chassis for transforming carbon dioxide to various compounds including carotenoids. Nevertheless, the carotenogenic genes and their roles in the alga remain less understood and to be further explored.

Results
Here, two phylogenetically distant zeaxanthin epoxidase (ZEP) genes from N. oceanica (NoZEP1 and NoZEP2) were functionally characterized. Subcellular localization experiment demonstrated that both NoZEP1 and NoZEP2 reside in the chloroplast yet with differential distribution patterns. Overexpression of NoZEP1 or NoZEP2 led to increases of violaxanthin and its downstream carotenoids at the expense of zeaxanthin in N. oceanica, with the extent of changes mediated by NoZEP1 overexpression being greater as compared to NoZEP2 overexpression. Suppression of NoZEP1 or NoZEP2, on the other hand, caused decreases of violaxanthin and its downstream carotenoids as well as increases of zeaxanthin; similarly, the extent of changes mediated by NoZEP1 suppression was larger than that by NoZEP2 suppression. Interestingly, chlorophyll a dropped following violaxanthin decrease in a well-correlated manner in response to NoZEP suppression. The thylakoid membrane lipids including monogalactosyldiacylglycerol also correlated with the violaxanthin decreases. Accordingly, NoZEP1 suppression resulted in more attenuated algal growth than NoZEP2 suppression did under either normal light or high light stage.

Conclusions
The results together support that both NoZEP1 and NoZEP2, localized in the chloroplast, have overlapping roles in epoxidating zeaxanthin to violaxanthin for the light-dependent growth, yet with NoZEP1 being more functional than NoZEP2 in N. oceanica. Our study provides implications into the understanding of carotenoid biosynthesis and future manipulation of N. oceanica for carotenoid production.
Multi-omics profiling reveals potential alterations in rheumatoid arthritis with different disease activity levels
Authors: Chen Jianghua , Li Shilin , Zhu Jing , Su Wei , Jian Congcong , Zhang Jie , Wu Jianhong , Wang Tingting , Zhang Weihua , Zeng Fanwei , Chang Shengjia , Jia Lihua , Su Jiang , Zhao Yi , Wang Jing , Zeng Fanxin 
Published: May 2023

Abstract
Background
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease, the pathogenesis of which is not clear. Clinical remission, or decreased disease activity, is the aim of treatment for RA. However, our understanding of disease activity is inadequate, and clinical remission rates for RA are generally poor. In this study, we used multi-omics profiling to study potential alterations in rheumatoid arthritis with different disease activity levels.

Methods
Fecal and plasma samples from 131 rheumatoid arthritis (RA) patients and 50 healthy subjects were collected for 16S rRNA sequencing, internally transcribed spacer (ITS) sequencing, and liquid chromatography-tandem mass spectrometry (LC–MS/MS). The PBMCS were also collected for RNA sequencing and whole exome sequencing (WES). The disease groups, based on 28 joints and ESR (DAS28), were divided into DAS28L, DAS28M, and DAS28H groups. Three random forest models were constructed and verified with an external validation cohort of 93 subjects.

Results
Our findings revealed significant alterations in plasma metabolites and gut microbiota in RA patients with different disease activities. Moreover, plasma metabolites, especially lipid metabolites, demonstrated a significant correlation with the DAS28 score and also associations with gut bacteria and fungi. KEGG pathway enrichment analysis of plasma metabolites and RNA sequencing data demonstrated alterations in the lipid metabolic pathway in RA progression. Whole exome sequencing (WES) results have shown that non-synonymous single nucleotide variants (nsSNV) of the HLA-DRB1 and HLA-DRB5 gene locus were associated with the disease activity of RA. Furthermore, we developed a disease classifier based on plasma metabolites and gut microbiota that effectively discriminated RA patients with different disease activity in both the discovery cohort and the external validation cohort.

Conclusion
Overall, our multi-omics analysis confirmed that RA patients with different disease activity were altered in plasma metabolites, gut microbiota composition, transcript levels, and DNA. Our study identified the relationship between gut microbiota and plasma metabolites and RA disease activity, which may provide a novel therapeutic direction for improving the clinical remission rate of RA.
Characteristic and fate determination of adipose precursors during adipose tissue remodeling
Authors: Ye Jiayin , Gao Cheng , Liang Yong , Hou Zongliu , Shi Yufang , Wang Ying 
Published: May 2023

AbstractAdipose tissues are essential for actively regulating systemic energy balance, glucose homeostasis, immune responses, reproduction, and longevity. Adipocytes maintain dynamic metabolic needs and possess heterogeneity in energy storage and supply. Overexpansion of adipose tissue, especially the visceral type, is a high risk for diabetes and other metabolic diseases. Changes in adipocytes, hypertrophy or hyperplasia, contribute to the remodeling of obese adipose tissues, accompanied by abundant immune cell accumulation, decreased angiogenesis, and aberrant extracellular matrix deposition. The process and mechanism of adipogenesis are well known, however, adipose precursors and their fate decision are only being defined with recent information available to decipher how adipose tissues generate, maintain, and remodel. Here, we discuss the key findings that identify adipose precursors phenotypically, with special emphasis on the intrinsic and extrinsic signals in instructing and regulating the fate of adipose precursors under pathophysiological conditions. We hope that the information in this review lead to novel therapeutic strategies to combat obesity and related metabolic diseases.