bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network pharmacology and experimental validation methods to reveal the active compounds and hub targets of Curculigo orchioides Gaertn in rheumatoid arthritis
Authors: Liu Xia , Huang Mingchun , Wang Lijuan , Li Jie , Wu Weihui , Wang Qin 
Published: November 2023

Abstract
Background
Rheumatoid arthritis (RA) is an autoimmune disease that can lead to joint destruction and deformity. Curculigo orchioides Gaertn (CO) was previously revealed to play a significant role in RA treatment. However, the main active ingredients and molecular mechanisms of CO in regulating RA are still unclear.

Methods
The active ingredients of CO were obtained from the Traditional Chinese Medicine Systems Pharmacology database and published literature. The targets corresponding to these compounds and the targets linked to RA were collected from public databases. The “ingredient-target” and “protein–protein interaction” networks were constructed to screen the main active ingredients and hub targets of CO in the treatment of RA. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment assays were used to elucidate the potential pharmacological mechanism of CO in RA. Molecular docking was performed to detect the binding between the main active ingredients and hub targets. Collagen-induced arthritis rats were used to validate the hub targets of CO against RA.

Results
Network pharmacological topology analysis showed that caffeine, 2,4-dichloro-5-methoxy-3-methylphenol, curculigoside, orcinol glucoside, and orcin were the main active ingredients of CO, and matrix metalloproteinase 9 (MMP9), transcription factor AP-1 (JUN), prostaglandin-endoperoxide synthase 2 (PTGS2), brain-derived neurotrophic factor, and receptor-type tyrosine-protein phosphatase C were the hub targets of CO for RA treatment. Molecular docking revealed that curculigoside and orcinol glucoside had effective binding potential with MMP9, JUN, and PTGS2, respectively. In vivo experiments demonstrated that CO alleviated RA symptoms and inhibited the expression of MMP9, JUN, and PTGS2 proteins.

Conclusions
Our study demonstrates the main active ingredients and potential targets of CO against RA, laying an experimental foundation for the development and application of CO as an anti-RA drug.
Rheumatoid arthritis increases the risk of malignant neoplasm of bone and articular cartilage: a two-sample bidirectional mendelian randomization study
Authors: Yang Mingyi , Su Yani , Xu Ke , Xie Jiale , Wen Pengfei , Liu Lin , Yang Zhi , Xu Peng 
Published: November 2023

Abstract
Objective
Prior research has revealed a heightened prevalence of neoplasms in individuals diagnosed with rheumatoid arthritis (RA). The primary objective of this study is to delve into the causal association between RA and two distinct types of neoplasms: benign neoplasm of bone and articular cartilage (BNBAC) and malignant neoplasm of bone and articular cartilage (MNBAC).

Methods
We employed summary data from genome-wide association analyses (GWAS) to investigate the causal relationship between RA and two neoplasms, BNBAC and MNBAC, using a two-sample bidirectional Mendelian randomization (MR) study design. The IEU OpenGWAS database provided the GWAS summary data for RA, while the Finnish consortium supplied the GWAS summary data for BNBAC and MNBAC. Our analysis involved the utilization of eight distinct MR methods, namely random-effects inverse variance weighted (IVW), MR Egger, weighted median, simple mode, weighted mode, maximum likelihood, penalized weighted median, and fixed effects IVW. Subsequently, we conducted assessments to evaluate heterogeneity, horizontal pleiotropy, outliers, the impact of a single-nucleotide polymorphism (SNP), and adherence to the assumption of normal distribution in the MR analysis.

Results
The results from the MR analysis revealed that there was no significant genetic association between RA and BNBAC (P = 0.427, odds ratio [OR] 95% confidence interval [CI] = 0.971 [0.904–1.044]). However, a positive genetic association was observed between RA and MNBAC (P = 0.001, OR 95% CI = 1.413 [1.144–1.745]). Conducting a reverse MR analysis, we found no evidence to support a genetic causality between BNBAC (P = 0.088, OR 95% CI = 1.041 [0.994–1.091]) or MNBAC (P = 0.168, OR 95% CI = 1.013 [0.995–1.031]) and RA. Our MR analysis demonstrated the absence of heterogeneity, horizontal pleiotropy, and outliers and confirmed that the effect was not driven by a single SNP. Additionally, the data exhibited a normal distribution.

Conclusion
The findings of this study demonstrate that RA constitutes a significant risk factor for MNBAC. In the context of clinical application, it is advisable to conduct MNBAC screening in RA patients and remain vigilant regarding its potential manifestation. Importantly, the outcomes of this investigation introduce a fresh vantage point into the understanding of the tumorigenesis associated with RA.
Inflammatory dilated cardiomyopathy associated with psoriasis: a case report
Authors: Riasi Hamidreza , Asgari Jafarabadi Emad , Enayati Hadis , Fanoodi Ali , Salehi Shiva , Jamshidi Ali-Reza , Salehi Forod , Rezaee Azam 
Published: November 2023

Abstract
Background
Psoriasis is a chronic inflammatory skin disease with a genetic basis. Psoriasis is accepted as a systemic, immune-mediated disease. Hypertension, obesity, metabolic disorders including diabetes mellitus and hyperlipidemia, and psychiatric disorders are more prevalent among children with psoriasis compared to children without psoriasis. In this study, we report a case of dramatic response of inflammatory cardiomyopathy to anti-inflammatory treatment of psoriasis; which might reveal similar pathogenesis basis of these two diseases.

Case presentation
A 9-year-old Caucasian boy presenting with signs and symptoms of heart failure refractory to conventional therapies was admitted to our pediatric cardiology service. As the patient also had psoriasis, and considering the fact that there might be an association between the two conditions, immunosuppressive drugs were administered, which led to a dramatic improvement in heart function.

Conclusions
The results of this study add to evidence linking psoriasis with inflammatory dilated cardiomyopathy. Clinicians, particularly cardiologists, must pay special attention to the cardiac complications of systemic diseases.
Synergistic effect of chitosan-alginate composite hydrogel enriched with ascorbic acid and alpha-tocopherol under hypoxic conditions on the behavior of mesenchymal stem cells for wound healing
Authors: Ghahremani-nasab Maryam , Akbari‑Gharalari Naeimeh , Rahmani Del Bakhshayesh Azizeh , Ghotaslou Armita , Ebrahimi-kalan Abbas , Mahdipour Mahdi , Mehdipour Ahmad 
Published: November 2023

Abstract
Background
In regenerative medicine, especially skin tissue engineering, the focus is on enhancing the quality of wound healing. Also, several constructs with different regeneration potentials have been used for skin tissue engineering. In this study, the regenerative properties of chitosan-alginate composite hydrogels in skin wound healing under normoxic and hypoxic conditions were investigated in vitro.

Methods
The ionic gelation method was used to prepare chitosan/alginate (CA) hydrogel containing CA microparticles and bioactive agents [ascorbic acid (AA) and α-tocopherol (TP)]. After preparing composite hydrogels loaded with AA and TP, the physicochemical properties such as porosity, pore size, swelling, weight loss, wettability, drug release, and functional groups were analyzed. Also, the hemo-biocompatibility of composite hydrogels was evaluated by a hemolysis test. Then, the rat bone marrow mesenchymal stem cells (rMSCs) were seeded onto the hydrogels after characterization by flow cytometry. The survival rate was analyzed using MTT assay test. The hydrogels were also investigated by DAPI and H&E staining to monitor cell proliferation and viability. To induce hypoxia, the cells were exposed to CoCl2. To evaluate the regenerative potential of rMSCs cultured on CA/AA/TP hydrogels under hypoxic conditions, the expression of the main genes involved in the healing of skin wounds, including HIF-1α, VEGF-A, and TGF-β1, was investigated by real-time PCR.

Results
The results demonstrated that the prepared composite hydrogels were highly porous, with interconnected pores that ranged in sizes from 20 to 188 μm. The evaluation of weight loss showed that the prepared hydrogels have the ability to biodegrade according to the goals of wound healing. The reduction percentage of CA/AA/TP mass in 21 days was reported as 21.09 ± 0.52%. Also, based on wettability and hemolysis tests of the CA/AA/TP, hydrophilicity (θ = 55.6° and 53.7°) and hemocompatibility with a hemolysis ratio of 1.36 ± 0.19 were evident for them. Besides, MTT assay, DAPI, and H&E staining also showed that the prepared hydrogels provide a suitable substrate for cell growth and proliferation. Finally, based on real-time PCR, increased expression levels of VEGF and TGF-β1 were observed in rMSCs in hypoxic conditions cultured on the prepared hydrogels.

Conclusions
In conclusion, this study provides evidence that 3D CA/AA/TP composite hydrogels seeded by rMSCs in hypoxic conditions have great potential to improve wound healing.

Graphical abstract
Global prevalence of COVID-19-induced acute respiratory distress syndrome: systematic review and meta-analysis
Authors: Azagew Abere Woretaw , Beko Zerko Wako , Ferede Yohannes Mulu , Mekonnen Habtamu Sewunet , Abate Hailemichael Kindie , Mekonnen Chilot Kassa 
Published: November 2023

Abstract
Background
Acute respiratory distress syndrome (ARDS) is potentially a fatal form of respiratory failure among COVID-19 patients. Globally, there are inconsistent findings regarding ARDS among COVID-19 patients. Therefore, this study aimed to estimate the pooled prevalence of COVID-19-induced ARDS among COVID-19 patients worldwide.

Methods
To retrieve relevant studies, the authors searched Embase, MEDLINE, PubMed, Web of Science, Cochrane Library, Google, and Google Scholar using a combination of search terms. The search was conducted for articles published from December 2019 to September 2022. Articles were searched and screened by title (ti), abstract (ab), and full-text (ft) by two reviewers independently. The quality of each included article was assessed using the Newcastle–Ottawa Assessment Scale. Data were entered into Microsoft Word and exported to Stata version 14 for analysis. Heterogeneity was detected using the Cochrane Q statistics and I-square (I2). Then the sources of variations were identified by subgroup and meta-regression analysis. A random effect meta-analysis model was used. The publication bias was detected using the graphic asymmetry test of the funnel plot and/or Egger’s test (p value < 0.05). To treat the potential publication bias, trim and fill analysis were computed. The protocol has been registered in an international database, the Prospective Register of Systematic Reviews (PROSPERO) with reference number: CRD42023438277.

Results
A total of 794 studies worldwide were screened for their eligibility. Of these 11 studies with 2845 participants were included in this systematic review and meta-analysis. The overall pooled prevalence of COVID-19-induced ARDS in the world was found to be 32.2% (95%CI = 27.70–41.73%), I2 = 97.3%, and p value < 0.001).

Conclusion
The pooled prevalence of COVID-19-induced ARDS was found to be high. The virus remains a global burden because its genetic causes are constantly changing or it mutated throughout the pandemic to emerge a new strain of infection. Therefore, interventions such as massive vaccination, early case detection, screening, isolation, and treatment of the cases need to be implemented to tackle its severity.
Perioperative myocardial injury is associated with increased postoperative non-cardiac complications in patients undergoing vascular surgery: a post hoc analysis of a randomised clinical pilot trial
Authors: Valadkhani A. , Gupta A. , Bell M. 
Published: November 2023

Abstract
Background
Elevated cardiac biomarkers, such as high-sensitivity cardiac Troponin T and N-terminal pro-B-type natriuretic peptide improve the prediction of major adverse cardiac events. However, very few trials have investigated the association between perioperative cardiac injury and non-cardiac complications. The primary aim of this study was to determine the association between peri-operative myocardial injury and non-cardiac complications in patients undergoing vascular surgery. Additionally, the association between elevated pre-operative high-sensitivity cardiac Troponin T or N-terminal pro-B-type natriuretic peptide and non-cardiac complications was explored.

Methods
This study is a post hoc analysis of a multicentre randomised controlled trial. Patients were recruited from three centres in Sweden between 2016 and 2019. Cardiac troponin level was measured pre-operatively and at 4, 24, and 48 h after the start of surgery in patients undergoing vascular surgery. N-terminal pro-B-type natriuretic peptide was measured pre-operatively. The primary outcome was a composite of major postoperative non-cardiac complications assessed at 30 days.

Results
A total of 184 patients undergoing peripheral or aortic vascular surgery were included in this study. The primary endpoint occurred in 67 (36%) patients. Perioperative myocardial injury was significantly associated with non-cardiac complications, with an adjusted odds ratio (OR) of 2.71 (95% confidence interval 1.33–5.55, P = 0.01). Sensitivity and specificity were 0.40 and 0.81, respectively. No association was found between pre-operative hs-cTnT or NT-proBNP and non-cardiac complications.

Conclusion
In this pilot study, we found that new peri-operative myocardial injury is associated with an increased risk of non-cardiac complications within 30 days after index surgery in patients undergoing vascular surgery. Pre-operative high-sensitivity cardiac Troponin T or N-terminal pro-B-type natriuretic peptide did not appear to predict non-cardiac complications. Larger studies are needed to confirm our findings.

Trial registration
EudraCT database: 2016-001584-36
JUNB affects hair follicle development and regeneration by promoting the proliferation of dermal papilla cells in goat
Authors: Zhang Tongtong , Li Fang , Li Xiang , Zhou Xiongbo , Zheng Yujie , Wang Xin 
Published: November 2023

Abstract
Background
The process of hair follicle morphogenesis, development, and regeneration essentially depends on the interaction between skin epidermis and dermis, while dermal papilla (DP) cells play a vital role in this process. Transcription factors recognize specific DNA sequences to regulate gene transcription during hair follicle development. Our previous sequencing data have demonstrated that JUNB is differentially expressed between the induction and differentiation stages during hair follicle development of cashmere goat. However, the underlying mechanism of JUNB currently remains unknown.

Results
The function of JUNB on DP cells was explored by EdU, MTT, CCK-8, and flow cytometry analysis, which showed that JUNB significantly promoted the cell viability and proliferation. Subsequently, the underlying regulation mechanism of JUNB was investigated. The dual-luciferase reporter assay and RT-qPCR results revealed that TCF3 was a target gene of JUNB. And the expressions of Wnt signaling pathway-related genes, CTNNB1 (β-catenin), Cyclin D1, and C-myc, were significantly promoted at mRNA and protein levels. The homology analysis based on JUNB protein sequences revealed that goat and mouse had high homology among 11 species. Therefore, C57 BL/6 mice were selected as the animal model for further in vivo experiment. The result showed that JUNB promoted hair regeneration of mouse, and the HE and immunofluorescence staining results of skin tissues further proved it.

Conclusions
Taken together, our results revealed that JUNB promoted the proliferation of DP cells by regulating Wnt signaling pathway, thereby affecting hair regeneration, which would provide molecular target for improving cashmere quality and breeding of cashmere goats.

Graphical Abstract
Adapting co-design methodology to a virtual environment: co-designing a communication intervention for adult patients in critical care
Authors: Istanboulian Laura , Rose Louise , Yunusova Yana , Dale Craig 
Published: November 2023

Abstract
Background
Research co-design is recommended to reduce misalignment between researcher and end-user needs and priorities for healthcare innovation. Engagement of intensive care unit patients, clinicians, and other stakeholders in co-design has historically relied upon face-to-face meetings. Here, we report on our co-design processes for the development of a bundled intensive care unit patient communication intervention that used exclusively virtual meeting methods in response to COVID-19 pandemic social distancing restrictions.

Methods
We conducted a series of virtual co-design sessions with a committee of stakeholder participants recruited from a medical-surgical intensive care unit of a community teaching hospital in Toronto, Canada. Published recommendations for co-design methods were used with exclusively virtual adaptations to improve ease of stakeholder participation as well as the quality and consistency of co-design project set-up, facilitation, and evaluation. Virtual adaptations included the use of email for distributing information, videos, and electronic evaluations as well as the use of a videoconferencing platform for synchronous meetings. We used a flexible meeting plan including asynchronous virtual methods to reduce attendance barriers for time-constrained participants.

Results
Co-design participants included a patient and a family member (n = 2) and professionally diverse healthcare providers (n = 9), plus a facilitator. Overall, participants were engaged and reported a positive experience with the virtually adapted co-design process. Reported benefits included incorporation of diverse viewpoints in the communication intervention design and implementation plan. Challenges related to lack of hands-on time during development of the co-designed intervention and participant availability to meet regularly albeit virtually.

Conclusions
This report describes the methods, benefits, and challenges of adapting in-person co-design methods to a virtual environment to produce a bundled communication intervention for use in the adult intensive care unit during the COVID-19 pandemic. Adapting recommended co-design methods to a virtual environment can provide further opportunities for stakeholder participation in intervention design.
The implications of Chinese investments on Mediterranean trade and maritime hubs
Authors: Oulmakki Ouail , Rodrigue Jean-Paul , Hernandez Meza Andrey , Verny Jérôme 
Published: November 2023

AbstractBy improving the connectivity between China and Europe, Chinese investments aim to redefine China’s position within global transport networks and logistics flows. This article explores the evolution of port activity in the Mediterranean following the implementation of investment strategies through an analysis of container flows and the impact generated by China on the Mediterranean ports. It compares port centrality to assess what influences the Belt and Road Initiative has had on containers flows from its inception until 2019 (pre Covid-19 pandemic). The main results underline that during its inception phase, the BRI had no discernable impacts on port polarization. Further, trade imbalances decreased and even slightly grew in favor of Mediterranean countries. The presence of Chinese investors, COSCO and China Merchants Group, in port operations impacted regional dynamics, mainly in the port of Piraeus in Greece, which became a hub. Connectivity between the main Mediterranean ports and China grew considerably after the BRI, especially with Egypt, Spain, and Morocco, where Chinese port investments have been considerable. The ports receiving the most Chinese investments see the most significant changes in their ranking in the regional port system.
Developmental and epileptic encephalopathy 44 due to compound heterozygous variants in the UBA5 gene: a case report
Authors: Zhang Suli , Lin Shuangzhu , Wang Wanqi , Gan Yuru , Wang Cui , Li Bangtao , Pang Qiming 
Published: November 2023

Abstract
Background
Developmental and epileptic encephalopathy (DEE) is a group of rare inherited disorders characterized by intellectual disability, delayed development, epileptic seizures, and other related symptoms. DEE44 is caused by mutations in the UBA5 gene, which encodes a ubiquitin-like protein involved in protein degradation and cell signaling. However, there is limited information on the genotype–phenotype correlation of DEE44, and its clinical features remain to be fully characterized.

Case presentation
We report a 12-month-old infant who presented with epileptic spastic seizures beginning at 4 months of age, accompanied by overall developmental delay, short stature, microcephaly, inability to hold his head upright, chasing vision, and high muscle tone in the extremities. Genetic findings showed compound heterozygous mutations of the UBA5 gene: NM_024818 c.562C > T(p.R188X) from the mother and NM_024818 c.214C > T(p.R72C) from the father.

Conclusions
This case report expands the clinical spectrum of DEE44 and highlights the importance of considering DEE44 in the differential diagnosis of developmental delay and epilepsy, even in the absence of classical symptoms suggestive of the condition. We hope that this case report will advance the understanding of DEE44 and improve the expertise of clinicians and early diagnose of this disease.
Proposal for diagnosis using FLAIR image aimed for pediatric MELAS with recurrent stroke-like episodes on MRI system cannot take ASL imaging
Authors: Shimada Makoto , Ikeda Tae , Fukui Ryohei , Kida Katsuhiro , Matsuura Ryutaro , Akagawa Takuya , Goto Sachiko 
Published: November 2023

Abstract
Background
Arterial spin-labeling (ASL) imaging is currently the most useful method for diagnosing mitochondrial encephalomyopathy, lactic acidosis, and stroke-like attack syndrome (MELAS). However, ASL is often an optional feature of standard MRI systems. Therefore, not all MRI systems can perform ASL imaging. In contrast, fluid-attenuated inversion recovery (FLAIR) imaging is one of the common sequences in brain MRI because FLAIR imaging can be performed regardless of the specifications of the equipment. This study aimed to compare the diagnostic performance of quantitative analysis of signal intensity obtained from fluid-attenuated inversion recovery (FLAIR) images with ASL images for MELAS with recurrent stroke-like episodes (SLEs). A total of 68 cases with normal magnetic resonance imaging findings and 25 cases diagnosed MELAS with recurrent SLEs were included. We evaluated the frontal lobe and cuneus as target areas and compared the regional cerebral blood flow (rCBF) values obtained from ASL images with the normalized signal intensity (nSI) obtained from FLAIR images.

Results
The sensitivity and specificity for diagnosing MELAS from linear discriminant analysis (LDA) obtained from the rCBF values were 0.84 and 0.941, respectively, and those of nSI were 0.8 and 0.897, respectively. The area under the ROC curves (AUC) calculated from the receiver operating characteristic (ROC) curve analysis using rCBF values and nSI were 0.889 and 0.804, respectively.

Conclusion
Quantitative analysis using the signal intensity of the FLAIR image could have a diagnostic performance equivalent to that of rCBF values obtained from ASL images.