bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Herbal Product Alleviates Bleomycin-Induced Pulmonary Fibrosis in Mice via Regulating NF-κB/TNF-α Signaling in Macrophages
Authors: Jing Fei , Chen Xi , Xue Jingbo , Huang Kai , Xing Feng , Hu Xudong , Peng Yuan , Liu Chenghai 
Published: April 2023

Background and aim: Pro-inflammatory macrophages aggravated progress of pulmonary fibrosis (PF) both in patients and animal models. Fuzheng Huayu (FZHY) formula, a Chinese herbal product, is effective in treating pulmonary fibrosis in our previous study. But its action mechanism against PF relating to macrophage activation was unclear. This study was designed to evaluate the anti-fibrotic and anti-inflammatory roles of FZHY in pulmonary fibrosis and to elucidate the potential mechanisms.Methods: Network pharmacology was employed to identify the interrelationships among compounds of FZHY, potential targets and putative pathways on anti-pulmonary fibrosis. According to the data of bioinformatics analysis, the key pharmacological target for FZHY against PF was screened. The network pharmacological prediction was validated by a series of experimental assays, including CCK8, western blot and immunofluorescence staining. Then molecular mechanism of FZHY on relating to the predictive target were studied in bleomycin induced pulmonary fibrosis in mice with methylprednisolone as a positive control, and in lipopolysaccharide (LPS) stimulated cultured macrophages in culture, respectively.Results: The network pharmacology analysis reveal that a total of 12 FZHY–PF crossover proteins were filtered into a protein-protein interaction network complex and designated as the potential targets of FZHY against pulmonary fibrosis, while TNF-α signal pathway ranked at the top. FZHY and methylprednisolone could attenuate the lung fibrosis and decrease pulmonary TNF-α expression in bleomycin induced fibrotic mice, without difference between two treatments. While TNF-α was mainly originated from macrophages identified by double fluorescent staining of TNF-α and F4/80. LPS stimulated cultured macrophage polarization and activation demonstrated by the enhance contents of TNF-α and iNOS but decreased level of Arg-1. FZHY could alleviate the LPS stimulated macrophage polarization and activation demonstrated by decreasing TNF-α and iNOS and increasing Arg-1. In particular, FZHY could significantly reduce the production of p65 and the nuclear translocation of phosphorylated p65.Conclusion: Fuzheng Huayu formula has a good effect against pulmonary fibrosis induced by bleomycin in mice, whose action mechanism was associated with down-regulation of NF-κB/TNF-α signaling pathway in pro-inflammatory macrophages. These findings provided an important strategy for developing new agents against lung fibrosis and accelerated FZHY product application on patients with lung fibrosis.
Effect of remimazolam tosilate on the incidence of hypoxemia in elderly patients undergoing gastrointestinal endoscopy: A bi-center, prospective, randomized controlled study
Authors: Liu Fang , Cheng Xiaoyan , Wang Yingjie , Li Kai , Peng Tianliang , Fang Ningning , Pasunooti Kalyan K. , Jun Seungho , Yang Xiaomei , Wu Jianbo 
Published: April 2023

Background: Remimazolam tosilate is a new ultra-short-acting benzodiazepine sedative medicine. In this study, we evaluated the effect of remimazolam tosilate on the incidence of hypoxemia during sedation in elderly patients undergoing gastrointestinal endoscopy.Methods: Patients in the remimazolam group received an initial dose of 0.1 mg/kg and a bolus dose of 2.5 mg of remimazolam tosilate, whereas patients in the propofol group received an initial dose of 1.5 mg/kg and a bolus dose of 0.5 mg/kg of propofol. Patients received ASA standard monitoring (heart-rate, non-invasive blood pressure, and pulse oxygen saturation) during the entire examination process. The primary outcome was the incidence of moderate hypoxemia (defined as 85%≤ SpO2&lt; 90%, &gt;15s) during the gastrointestinal endoscopy. The secondary outcomes included the incidence of mild hypoxemia (defined as SpO2 90%–94%) and severe hypoxemia (defined as SpO2&lt; 85%, &gt;15s), the lowest pulse oxygen saturation, airway maneuvers used to correct hypoxemia, patient’s hemodynamic as well as other adverse events.Results: 107 elderly patients (67.6 ± 5.7 years old) in the remimazolam group and 109 elderly patients (67.5 ± 4.9 years old) in the propofol group were analyzed. The incidence of moderate hypoxemia was 2.8% in the remimazolam group and 17.4% in the propofol group (relative risk [RR] = 0.161; 95% confidence interval [CI], 0.049 to 0.528; p &lt; 0.001). The frequency of mild hypoxemia was less in the remimazolam group, but not statistically significant (9.3% vs. 14.7%; RR = 0.637; 95% CI, 0.303 to 1.339; p = 0.228). There was no significant difference in the incidence of severe hypoxemia between the two groups (4.7% vs. 5.5%; RR = 0.849; 95% CI, 0.267 to 2.698; p = 0.781). The median lowest SpO2 during the examination was 98% (IQR, 96.0%–99.0%) in patients in the remimazolam group, which was significantly higher than in patients in the propofol group (96%, IQR, 92.0%–99.0%, p &lt; 0.001). Patients in the remimazolam group received more drug supplementation during endoscopy than patients in the propofol group (p = 0.014). There was a statistically significant difference in the incidence of hypotension between the two groups (2.8% vs. 12.8%; RR = 0.218; 95% CI, 0.065 to 0.738; p = 0.006). No significant differences were found in the incidence of adverse events such as nausea and vomiting, dizziness, and prolonged sedation.Conclusion: This study explored the safety of remimazolam compared with propofol during gastrointestinal endoscopy in elderly patients. Despite the increased supplemental doses during sedation, remimazolam improved risk of moderate hypoxemia (i.e., 85%≤ SpO2 &lt; 90%) and hypotension in elderly patients.
Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1
Authors: Ren Gang , Ding Yu-Wei , Wang Lu-Lu , Jiang Jian-Dong 
Published: April 2023

Aim: AMPK is the key regulatory kinase mediating the effect of berberine (BBR) and metformin on metabolic improvement. The present study investigated the mechanism of BBR on AMPK activation at low doses, which was different from that of metformin.Methods: Lysosomes were isolated, and AMPK activity assay was performed. PEN2, AXIN1 and UHRF1 were investigated through gain/loss of function approaches, including overexpression, RNA interfering and CRISPR/Cas9-mediated gene knockout. Immunoprecipitation was utilized for detecting the interaction of UHRF1 and AMPKα1 after BBR treatment.Results: BBR activated lysosomal AMPK, but weaker than metformin. AXIN1 mediated BBR’s effect on lysosomal AMPK activation, while PEN2 did not. BBR, but not metformin, decreased UHRF1 expression by promoting its degradation. BBR reduced the interaction between UHRF1 and AMPKα1. And overexpression of UHRF1 abolished the effect of BBR on AMPK activation.Conclusion: BBR activated lysosomal AMPK as dependent on AXIN1, but not PEN2. BBR maintained cellular AMPK activity by reducing UHRF1 expression and its interaction with AMPKα1. The mode of action of BBR was different from that of metformin on AMPK activation.
Pericyte-derived cells participate in optic nerve scar formation
Authors: Preishuber-Pflügl Julia , Mayr Daniela , Altinger Veronika , Brunner Susanne M. , Koller Andreas , Runge Christian , Ladek Anja-Maria , Lenzhofer Markus , Rivera Francisco J. , Tempfer Herbert , Aigner Ludwig , Reitsamer Herbert A. , Trost Andrea 
Published: April 2023

Introduction: Pericytes (PCs) are specialized cells located abluminal of endothelial cells on capillaries, fulfilling numerous important functions. Their potential involvement in wound healing and scar formation is achieving increasing attention since years. Thus, many studies investigated the participation of PCs following brain and spinal cord (SC) injury, however, lacking in-depth analysis of lesioned optic nerve (ON) tissue. Further, due to the lack of a unique PC marker and uniform definition of PCs, contradicting results are published.Methods: In the present study the inducible PDGFRβ-P2A-CreERT2-tdTomato lineage tracing reporter mouse was used to investigate the participation and trans-differentiation of endogenous PC-derived cells in an ON crush (ONC) injury model, analyzing five different post lesion time points up to 8 weeks post lesion.Results: PC-specific labeling of the reporter was evaluated and confirmed in the unlesioned ON of the reporter mouse. After ONC, we detected PC-derived tdTomato+ cells in the lesion, whereof the majority is not associated with vascular structures. The number of PC-derived tdTomato+ cells within the lesion increased over time, accounting for 60–90% of all PDGFRβ+ cells in the lesion. The presence of PDGFRβ+tdTomato- cells in the ON scar suggests the existence of fibrotic cell subpopulations of different origins.Discussion: Our results clearly demonstrate the presence of non-vascular associated tdTomato+ cells in the lesion core, indicating the participation of PC-derived cells in fibrotic scar formation following ONC. Thus, these PC-derived cells represent promising target cells for therapeutic treatment strategies to modulate fibrotic scar formation to improve axonal regeneration.
Multigene phylogeny reveals a cryptic diversity in the genus Dinobryon (Chrysophyceae) with integrative description of five new species
Authors: Jeong Minseok , Wang Yitong , Kim Jong Im , Shin Woongghi 
Published: April 2023

IntroductionThe genus Dinobryon is one of the most recognizable chrysophyte genera, characterized by dendroid colonies with a biflagellate inside each cellulosic lorica. The representative forms of lorica are cylindrical, conical, vase, or funnel shaped, with undulation on the lorica wall. Traditionally, the morphological characteristics of the lorica and the colony organization have been used for the delimitation of Dinobryon species.MethodsTo understand the taxonomy and phylogeny of colonial Dinobryon species, we performed molecular and morphological studies using 39 unialgal cultures and 46 single colony isolations from environmental specimens collected in Korea. We used a nuclear internal transcript spacer (ITS1-5.8S-ITS2) to find the genetic diversity of Dinobryon from environmental samples and a combined dataset from six gene sequences (nuclear SSU and LSU rRNA, plastid LSU rRNA, rbcL and psaA, and mitochondrial CO1 genes) for phylogenetic analysis.Results and discussionWe found 15 different lineages based on the genetic diversity of the nuclear ITS sequences. The phylogenetic tree of the colonial species based on the combined multigene dataset were divided into 18 subclades, including five new species, each with unique molecular signatures for the E23-5 helix of the V4 region in the nuclear SSU rRNA and the E11-1 helix of D7b, and the E20-1 helix of D8 regions in the nuclear LSU rRNA. Morphological studies were focused on lorica dimension and shape, and stomatocyst morphology. The Dinobryon species showed similarities or differences in lorica morphologies between and within species, and also differences in lorica size between culture and environmental samples. Five Dinobryon species formed distinctive stomatocysts, their stomatocyst morphologies, including collar structure, surface ornamentation, and cyst shape, showed unique characteristics in each species and were useful for identification. Here, we propose five new species based on morphological and molecular evidences: D. cylindricollarium, D. exstoundulatum, D. inclinatum, D. similis, and D. spinum.
Psychological distress among Afghan refugees in Norway as a function of their integration
Authors: Brea Larios Dixie , Sam David L. , Sandal Gro Mjeldheim 
Published: April 2023

BackgroundOften, refugees are susceptible to mental health problems due to adversities experienced before, during, and after the flight. Through a cross-sectional study, the present study examines the relationship between different aspects of integration and psychological distress among Afghans living in Norway.MethodsThe participants were recruited through e-mail invitations, refugee-related organizations, and social media platforms. The participants (N = 114) answered questions about integration across multiple dimensions (psychological, social, navigational, economic, and linguistic) in line with the Immigration Policy Lab index (IPL -12/24). Hopkins symptoms checklist (HSCL-25) was used to assess psychological distress.ResultsBased on hierarchical multiple regression analysis, both the psychological dimension (0.269 p &lt; 0.01) and the navigational dimension (0.358 p &lt; 0.05) of integration predicted psychological distress.Discussion/ConclusionThe results suggest that the psychological aspects of integration, such as being part of a community, having feelings of security, and a sense of belonging, are beneficial for the mental health and well-being of the Afghans in Norway and contribute further to other aspects of integration.
Associations between prefrontal PI (16:0/20:4) lipid, TNC mRNA, and APOA1 protein in schizophrenia: A trans-omics analysis in post-mortem brain
Authors: Sano Fumito , Kikushima Kenji , Benner Seico , Xu Lili , Kahyo Tomoaki , Yamasue Hidenori , Setou Mitsutoshi 
Published: April 2023

BackgroundThough various mechanisms have been proposed for the pathophysiology of schizophrenia, the full extent of these mechanisms remains unclear, and little is known about the relationships among them. We carried out trans-omics analyses by comparing the results of the previously reported lipidomics, transcriptomics, and proteomics analyses; all of these studies used common post-mortem brain samples.MethodsWe collected the data from three aforementioned omics studies on 6 common post-mortem samples (3 schizophrenia patients and 3 controls), and analyzed them as a whole group sample. Three correlation analyses were performed for each of the two of three omics studies in these samples. In order to discuss the strength of the correlations in a limited sample size, the p-values of each correlation coefficient were confirmed using the Student’s t-test. In addition, partial correlation analysis was also performed for some correlations, to verify the strength of the impact of each factor on the correlations.ResultsThe following three factors were strongly correlated with each other: the lipid level of phosphatidylinositol (PI) (16:0/20:4), the amount of TNC mRNA, and the quantitative signal intensity of APOA1 protein. PI (16:0/20:4) and TNC showed a positive correlation, while PI (16:0/20:4) and APOA1, and TNC and APOA1 showed negative correlations. All of these correlations reached at p &lt; 0.01. PI (16:0/20:4) and TNC were decreased in the prefrontal cortex of schizophrenia samples, while APOA1 was increased. Partial correlation analyses among them suggested that PI (16:0/20:4) and TNC have no direct correlation, but their relationships are mediated by APOA1.ConclusionThe current results suggest that these three factors may provide new clues to elucidate the relationships among the candidate mechanisms of schizophrenia, and support the potential of trans-omics analyses as a new analytical method.
Accelerating digital health literacy for the treatment of growth disorders: The impact of a massive open online course
Authors: Dimitri Paul , Fernandez-Luque Luis , Koledova Ekaterina , Malwade Shwetambara , Syed-Abdul Shabbir 
Published: April 2023

BackgroundGrowth hormone deficiency (GHD) is a rare disorder characterized by inadequate secretion of growth hormone (GH) from the anterior pituitary gland. One of the challenges in optimizing GH therapy is improving adherence. Using digital interventions may overcome barriers to optimum treatment delivery. Massive open online courses (MOOCs), first introduced in 2008, are courses made available over the internet without charge to a large number of people. Here, we describe a MOOC aiming to improve digital health literacy among healthcare professionals managing patients with GHD. Based on pre- and post-course assessments, we evaluate the improvement in participants’ knowledge upon completion of the MOOC.MethodsThe MOOC entitled ‘Telemedicine: Tools to Support Growth Disorders in a Post-COVID Era’ was launched in 2021. It was designed to cover 4 weeks of online learning with an expected commitment of 2 h per week, and with two courses running per year. Learners’ knowledge was assessed using pre- and post-course surveys via the FutureLearn platform.ResultsOut of 219 learners enrolled in the MOOC, 31 completed both the pre- and post-course assessments. Of the evaluated learners, 74% showed improved scores in the post-course assessment, resulting in a mean score increase of 21.3%. No learner achieved 100% in the pre-course assessment, compared with 12 learners (40%) who achieved 100% in the post-course assessment. The highest score increase comparing the pre- and the post-course assessments was 40%, observed in 16% of learners. There was a statistically significant improvement in post-course assessment scores from 58.1 ± 18.9% to 72.6 ± 22.4% reflecting an improvement of 14.5% (p &lt; 0.0005) compared to the pre-course assessment.ConclusionThis “first-of-its-kind” MOOC can improve digital health literacy in the management of growth disorders. This is a crucial step toward improving the digital capability and confidence of healthcare providers and users, and to prepare them for the technological innovations in the field of growth disorders and growth hormone therapy, with the aim of improving patient care and experience. MOOCs provide an innovative, scalable and ubiquitous solution to train large numbers of healthcare professionals in limited resource settings.
A longitudinal controlled signage intervention to increase stair use at university buildings: Process and impact evaluation using RE-AIM framework
Authors: Muttaqien Zaenal , Wasityastuti Widya , Sofyana Meida , Agustiningsih Denny , Wibowo Rakhmat Ari 
Published: April 2023

IntroductionStair climbing intervention could be suggested to address low occupational physical activity amongst university students and employees. Strong evidence showed the effectiveness of signage intervention in increasing stair use in public areas. However, evidence in worksite settings, including university settings, was inconclusive. This study aimed to evaluate the process and impact of a signage intervention to increase stair use at a university building using the RE-AIM framework.MethodWe conducted a non-randomised controlled pretest-posttest study to examine the effect of signage intervention placed in university buildings in Yogyakarta (Indonesia) between September 2019 and March 2020. The process of designing the signage involved the employees in the intervention building. The main outcome was the change in the proportion of stair use to elevator use measured by manual observations of video recordings from closed-circuit television. A linear mixed model examined the intervention effect by controlling the total visitor count as a confounder. RE-AIM framework was used in the process and impact evaluation.ResultsThe change in the proportion of stair climbing from baseline to the 6th-month phase at the intervention building (+0.067 (95% CI = 0.014–0.120)) was significantly higher than that of the control building. However, the signs did not change the proportion of the stair descending at the intervention building. The signs were potentially viewed 15,077–18,868 times/week by visitors.ConclusionSignage intervention using portable posters could easily be adopted, implemented, and maintained in similar settings. A co-produced low-cost signage intervention was found to have a good reach, effectiveness, adoption, implementation, and maintenance dimension.
Mapping health assessment questionnaire disability index onto EQ-5D-5L in China
Authors: Wan Chuchuan , Wang Qiqi , Xu Zhaoqi , Huang Yuankai , Xi Xiaoyu 
Published: April 2023

ObjectiveThis research aimed to develop the more accurate mapping algorithms from health assessment questionnaire disability index (HAQ-DI) onto EQ-5D-5L based on Chinese Rheumatoid Arthritis patients.MethodsThe cross-sectional data of Chinese RA patients from 8 tertiary hospitals across four provincial capitals was used for constructing the mapping algorithms. Direct mapping using Ordinary least squares regression (OLS), the general linear regression model (GLM), MM-estimator model (MM), Tobit regression model (Tobit), Beta regression model (Beta) and the adjusted limited dependent variable mixture model (ALDVMM) and response mapping using Multivariate Ordered Probit regression model (MV-Probit) were carried out. HAQ-DI score, age, gender, BMI, DAS28-ESR and PtAAP were included as the explanatory variables. The bootstrap was used for validation of mapping algorithms. The average ranking of mean absolute error (MAE), root mean square error (RMSE), adjusted R2 (adjR2) and concordance correlation coefficient (CCC) were used to assess the predictive ability of the mapping algorithms.ResultsAccording to the average ranking of MAE, RMSE, adjR2, and CCC, the mapping algorithm based on Beta performed the best. The mapping algorithm would perform better as the number of variables increasing.ConclusionThe mapping algorithms provided in this research can help researchers to obtain the health utility values more accurately. Researchers can choose the mapping algorithms under different combinations of variables based on the actual data.
The impact of the COVID-19 pandemic on nosocomial infections: a retrospective analysis in a tertiary maternal and child healthcare hospital
Authors: Huang Huifang , Wu Kunhai , Chen Haiming , Wang Jing , Chen Lufei , Lai Zhirun , Lin Shuling 
Published: April 2023

ObjectiveThe constant changes in the control strategies of the Corona Virus Disease 2019 (COVID-19) pandemic have greatly affected the prevention and control of nosocomial infections (NIs). This study assessed the impact of these control strategies on the surveillance of NIs in a regional maternity hospital during the COVID-19 pandemic.MethodsThis retrospective study compared the observation indicators of nosocomial infections and their changing trends in the hospital before and during the COVID-19 pandemic.ResultsIn total, 2,56,092 patients were admitted to the hospital during the study. During the COVID-19 pandemic, the main drug-resistant bacteria in hospitals were Escherichia coli, Streptococcus agalactiae, Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecalis. The detection rate of S. agalactiae increased annually, while that of E. faecalis remained the same. The detection rate of multidrug-resistant bacteria decreased during the pandemic (16.86 vs. 11.42%), especially that of CRKP (carbapenem-resistant Klebsiella pneumoniae 13.14 vs. 4.39, P &lt; 0.001). The incidence of nosocomial infections in the pediatric surgery department decreased significantly (OR: 2.031, 95% CI: 1.405–2.934, P &lt; 0.001). Regarding the source of infection, a significant reduction was observed in respiratory infections, followed by gastrointestinal infections. In the routine monitoring of the ICU, the incidence of central line-associated bloodstream infection (CLABSI) decreased significantly (9.4/1,000 catheter days vs. 2.2/1,000 catheter days, P &lt; 0.001).ConclusionThe incidence of nosocomial infections was lower than that before the COVID-19 pandemic. The prevention and control measures for the COVID-19 pandemic have reduced the number of nosocomial infections, especially respiratory, gastrointestinal, and catheter-related infections.