bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of physical activity with psychological distress and happiness in mothers of children with autism spectrum disorders during the COVID-19 pandemic
Authors: Tsunoda Kenji , Nagase Kai , Fujita Kumi 
Published: August 2023

Abstract
Background
The coronavirus disease 2019 (COVID-19) pandemic may have severely impacted the psychological status of mothers of children with autism spectrum disorder (ASD). Although a previous study reported that physical activity (PA) moderated psychological distress in parents of children with ASD during the COVID-19 pandemic, the effect of PA on the happiness levels of such parents during the pandemic remains unclear. This study investigated the associations among PA, psychological distress, and happiness in mothers of children with ASD during the COVID-19 pandemic.

Methods
This cross-sectional study was designed to evaluate mothers of children with disabilities. Questionnaires were collected from mothers living in Yamaguchi and Okayama Prefectures, Japan, between February and December 2022. During this period, three large waves of the COVID-19 pandemic occurred in Japan. Of the 601 respondents, 334 mothers had children with ASD and offered valid data. PA was assessed using the short form of the International Physical Activity Questionnaire. Psychological distress and happiness were assessed using the six-item Kessler Psychological Distress Scale (K6) and the Subjective Happiness Scale (SHS).

Results
The mothers had markedly higher K6 scores (6.49) and more than half of them had moderate-to-severe psychological distress, whereas the SHS scores (4.46) were similar to that of the general Japanese population. In a multivariable-adjusted model based on the analysis of covariance, the K6 score was not associated with any PA items. In contrast, SHS scores were positively associated with moderate-intensity PA (MPA) and total moderate- to vigorous-intensity PA (MVPA), independent of K6. In the post-hoc test, mothers who did some (4.52) or enough (≥ 150 min/week) MPA (4.56) had a higher SHS score than those who did not (4.09). Similarly, mothers who engaged in sufficient (≥ 600 MET-min/week) total MVPA had higher SHS scores (4.57) than those who did not engage in MVPA (4.12).

Conclusions
The mothers of children with ASD during the COVID-19 pandemic had markedly higher psychological distress, though none of the PA items were associated with stress levels. However, PA was positively associated with happiness in mothers of children with ASD independent of their stress levels.
The mechanism of Qijing Mingmu decoction on cellular senescence of conjunctivochalasis
Authors: Xiang Minhong , Liu Jiang , Ma Kai , Sha Yongyi , Zhan Yueping , Zhang Wei , Kong Xueqing 
Published: August 2023

Abstract
Background
Qijing Mingmu decoction (QJMM), a compound Chinese medicine preparation, which consists of Lycium barbarum, Polygonatum, Ophiopogon japonicus, Poria cocos, Glycyrrhiza, Eclipta prostrata and Ligusticum striatum, has been confirmed to be effective for the treatment of conjunctivochalasis (CCH) in clinic and reduce cellular senescence. However, the underlying mechanism is still unknown. Our previous study revealed that p38-mediated cellular senescence contributed to the pathogenesis of CCH.

Methods
To explore whether p38 might be the potential therapeutic target of QJMM for CCH, CCH fibroblasts were treated with QJMM granule and then the effect of QJMM granule on the expression and promoter activity of p38α was determined by western blot and dual luciferase reporter gene assay, respectively. Meanwhile, the influence of QJMM granule on cell proliferation, oxidative stress, cellular senescence and the expression of the cellular senescence-associated genes were measured by corresponding methods.

Results
QJMM granule significantly decreased the protein expression of p38α and p-p38α in CCH fibroblasts in a dose-dependent manner and inhibited p38α promoter activity. QJMM granule as well as the p38 inhibitor SB203580 reduced the level of reactive oxygen species and increased the activity of superoxide dismutase in CCH fibroblasts. QJMM granule and SB203580 promoted cell proliferation and reduced the percentage of SA-β-Gal-positive cells. The mRNA and protein expression of p53 and p21 was remarkably down-regulated by QJMM granule as well as SB203580 and that of SMP30 was up-regulated in CCH fibroblasts.

Conclusions
Our findings demonstrated that QJMM granule was effective for alleviating cellular senescence of CCH fibroblasts by p38 MAPK signaling and the followed p53/p21 signaling.
Improving self-directed learning ability of medical students using the blended teaching method: a quasi-experimental study
Authors: Lu Si Ying , Ren Xiang Peng , Xu Huang , Han Dong 
Published: August 2023

AbstractBackgroundSelf-directed learning (SDL) is one of the most important abilities for medical students in terms of their future clinical medical practice. During the blended teaching process, teachers can design a variety of learning activities to cultivate students’ SDL abilities. This study aimed to assess the differences between the SDL abilities of medical students using blended and traditional didactic teaching.MethodsThis study included 239 medical students from eight administrative classes. The students were divided into two groups: (1) the experimental group (EG), which included 119 students from four administrative classes, and (2) the control group (CG), which included 120 students from the remaining four classes. From February to July 2022, blended teaching methods were applied to the EG group, and SDL abilities were assessed in comparison to the CG group receiving traditional didactic teaching methods.ResultsAt the end of the semester, significant differences (p < 0.05) were observed between EG and CG in all six SDL ability factors. Furthermore, when k-means cluster analysis was used to analyze the learning behavior of students in the EG after classifying them as comprehensive, interactive, and passive types, significant differences were observed in all six Self-directed learning factors of students with the comprehensive type, whereas significant differences were observed in four factors (setting learning goals and plans, self-monitoring and regulation, information processing, and communication and cooperation) of students with the interactive type. For students with passive type, only one factor of SDL (information processing) showed significant improvement. There were on differences between comprehensive, interactive, and passive types of CG.ConclusionThe blended teaching approach is better than the conventional didactic teaching for cultivating clinical medical students’ SDL abilities.
Association of integrin-β2 polymorphism and expression with the risk of rheumatoid arthritis and osteoarthritis in Egyptian patients
Authors: Selim Aliaa M. , Elsabagh Yumn A. , El-Sawalhi Maha M. , Ismail Nabila A. , Senousy Mahmoud A. 
Published: August 2023

Abstract
Background
The genetic architecture of rheumatoid arthritis (RA) and osteoarthritis (OA) are still unclear. Although RA and OA have quite different causes, they share synovial inflammation, risk factors, and some disease-associated genes, including the integrin subunit β2 (ITGB2)/CD18 gene involved in extracellular matrix interactions and immune cell signaling. However, the functional role of ITGB2 genetic variants, its circulating expression pattern, and their clinical usefulness in RA and OA remain unexplored. Our study appraised the association of ITGB2 rs2070946 single nucleotide polymorphism with the vulnerability to RA and OA and its influence on ITGB2 mRNA expression, along with the potential of serum ITGB2 expression in RA and OA diagnosis.

Methods
This study included 70 RA patients, 70 primary OA patients, and 60 healthy volunteers. Genotyping and gene expression analysis were performed using qPCR. Bioinformatics analysis was employed to construct the protein-protein interaction (PPI) network of ITGB2.

Results
Serum ITGB2 mRNA expression was upregulated in both RA and OA compared to healthy controls. ITGB2 rs2070946 was associated with escalating risk of both diseases. RA patients harboring the rs2070946 CC or TC + CC genotypes had higher serum ITGB2 expression than the TT genotype carriers. Likewise, OA patients having the minor homozygote CC genotype had higher serum ITGB2 expression than those carrying the TT, TC or TT + TC genotypes. Serum ITGB2 expression showed profound diagnostic potential for RA and OA in receiver-operating characteristic analysis. In RA, serum ITGB2 expression positively correlated with rheumatoid factor and disease activity score 28 (DAS28). The ITGB2-PPI network enriched in cell-cell adhesion, ICAM-3 receptor activity, T-cell activation, leukocyte adhesion, complement binding, and NF-κB, tumor necrosis factor, and interleukin signaling pathways.

Conclusion
These findings embrace the impact of ITGB2 rs2070946 as a novel genetic biomarker of both RA and OA, which could alter the ITGB2 expression. Serum ITGB2 expression could aid in timely diagnosis of RA and OA.
Prognostic factors for the outcomes of COVID-19 patients infected with SARS-CoV-2 Omicron and Delta variants
Authors: Gunadi  , Hakim Mohamad Saifudin , Wibawa Hendra , Vujira Khanza Adzkia , Puspitarani Dyah Ayu , Supriyati Endah , Trisnawati Ika , Iskandar Kristy , Khair Riat El , Afiahayati  , Siswanto  , Puspadewi Yunika , Irianingsih Sri Handayani , Nugrahaningsih Dwi Aris Agung , Eryvinka Laudria Stella , Utami Fadila Dyah Trie , Devana Edita Mayda , Aditama Lanang , Kinasih Nathania Christi Putri , Hediningsih Yekti , Ananda Nur Rahmi , Marcellus  , Arguni Eggi , Nuryastuti Titik , Wibawa Tri 
Published: August 2023

Abstract
Background
The SARS-CoV-2 Omicron variant has replaced the previously dominant Delta variant because of high transmissibility. However, studies on the impact of the Omicron variant on the severity of COVID-19 are still limited in developing countries. Our study aimed to determine the prognostic factors for the outcomes of patients infected with SARS-CoV-2 Omicron and Delta variants, including age, sex, comorbidities, and smoking.

Methods
In this retrospective cross-sectional study, we involved 352 patients with COVID-19 from Yogyakarta and Central Java provinces, Indonesia, from May 2021 to February 2022, consisting of 164 males and 188 females. We included all patients with the PCR’s Ct value of less than 30 for further whole-genome sequencing.

Results
Ct value and mean age of COVID-19 patients were not significantly different between both groups (p = 0.146 and 0.273, respectively). Patients infected with Omicron (n = 139) and Delta (n = 213) variants showed similar hospitalization (p = 0.396) and mortality rates (p = 0.565). Multivariate analysis of both groups showed that older age (≥ 65 years) had a higher risk for hospitalization (OR = 3.86 [95% CI = 1.29–11.5]; p = 0.015) and fatalities (OR = 3.91 [95% CI = 1.35–11.42]; p = 0.012). In both groups, patients with cardiovascular disease had a higher risk for hospitalization (OR = 5.36 [95% CI = 1.08–26.52]; p = 0.039), whereas patients with diabetes revealed a higher risk for fatalities (OR = 9.47 [95% CI = 3.23–27.01]; p = < 0.001).

Conclusions
Our study shows that patients infected with Omicron and Delta variants reveal similar clinical outcomes, including hospitalization and mortality. Our findings further confirm that older age, cardiovascular disease, and diabetes are substantial prognostic factors for the outcomes of COVID-19 patients. Our findings imply that COVID-19 patients with older age, cardiovascular disease, or diabetes should be treated comprehensively and cautiously to prevent further morbidity and mortality. Furthermore, incomplete data on vaccination status hampered us from analyzing further its impact on hospitalization and mortality in our patients.
IL-25 induces airway remodeling in asthma by orchestrating the phenotypic changes of epithelial cell and fibrocyte
Authors: Yao Xiujuan , Chen Qinglin , Wang Xiangdong , Liu Xiaofang , Zhang Luo 
Published: August 2023

Abstract
Background
Previous studies have shown that IL-25 levels are increased in patients with asthma with fixed airflow limitation (FAL). However, the mechanism by which IL-25 contributes to airway remodeling and FAL remains unclear. Here, we hypothesized that IL-25 facilitates pro-fibrotic phenotypic changes in bronchial epithelial cells (BECs) and circulating fibrocytes (CFs), orchestrates pathological crosstalk from BECs to CFs, and thereby contributes to airway remodeling and FAL.

Methods
Fibrocytes from asthmatic patients with FAL and chronic asthma murine models were detected using flow cytometry, multiplex staining and multispectral imaging analysis. The effect of IL-25 on BECs and CFs and on the crosstalk between BECs and CFs was determined using cell culture and co-culture systems.

Results
We found that asthmatic patients with FAL had higher numbers of IL-25 receptor (i.e., IL-17RB)+-CFs, which were negatively correlated with forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC). The number of airway IL-17RB+-fibrocytes was significantly increased in ovalbumin (OVA)- and IL-25-induced asthmatic mice versus the control subjects. BECs stimulated with IL-25 exhibited an epithelial-mesenchymal transition (EMT)-like phenotypic changes. CFs stimulated with IL-25 produced high levels of extracellular matrix (ECM) proteins and connective tissue growth factors (CTGF). These profibrotic effects of IL-25 were partially blocked by the PI3K-AKT inhibitor LY294002. In the cell co-culture system, OVA-challenged BECs facilitated the migration and expression of ECM proteins and CTGF in CFs, which were markedly blocked using an anti-IL-17RB antibody.

Conclusion
These results suggest that IL-25 may serve as a potential therapeutic target for asthmatic patients with FAL.
Antibacterial peptide PMAP-37(F34-R), expressed in Pichia pastoris, is effective against pathogenic bacteria and preserves plums
Authors: Dong Chunming , Xu Lijun , Lu Weitao , Li Mengru , Zhang Rui , Sun Yanyan , Liu Jian , Chu Xinlei 
Published: August 2023

Abstract
Background
Recently, researchers have focused on the search for alternatives to conventional antibiotics. Antimicrobial peptides are small bioactive peptides that regulate immune activation and have antibacterial activity with a reduced risk of bacterial resistance. Porcine myeloid antibacterial peptide 37 (PMAP-37) is a small-molecule peptide with broad-spectrum antibacterial activity isolated from pig bone marrow, and PMAP-37(F34-R) is its analogue. In this study, PMAP-37(F34-R) was recombinantly expressed in Pichia pastoris, and the recombinant peptide was further investigated for its antibacterial properties, mechanism and preservative in plums.

Results
To obtain a Pichia pastoris strain expressing PMAP-37(F34-R), we constructed a plasmid expressing recombinant PMAP-37(F34-R) (pPICZα-PMAP-37(F34-R)-A) and introduced it into Pichia pastoris. Finally, we obtained a highly active recombinant peptide, PMAP-37(F34-R), which inhibited the activity of both Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration is 0.12–0.24 µg/mL, and it can destroy the integrity of the cell membrane, leading to cell lysis. It has good stability and is not easily affected by the external environment. Hemolysis experiments showed that 0.06 µg/mL-0.36 µg/mL PMAP-37(F34-R) had lower hemolysis ability to mammalian cells, and the hemolysis rate was below 1.5%. Additionally, 0.36 µg/mL PMAP-37(F34-R) showed a good preservative effect in plums. The decay and weight loss rates of the treated samples were significantly lower than those of the control group, and the respiratory intensity of the fruit was delayed in the experimental group.

Conclusions
In this study, we constructed a recombinant Pichia pastoris strain, which is a promising candidate for extending the shelf life of fruits and has potential applications in the development of new preservatives.

Graphical Abstract
MiRNA-related metastasis in oral cancer: moving and shaking
Authors: Eslami Meghdad , Khazeni Saba , Khanaghah Xaniar Mohammadi , Asadi Mohammad Hossein , Ansari Mohamad Amin , Garjan Javad Hayati , Lotfalizadeh Mohammad Hassan , Bayat Mobina , Taghizadieh Mohammad , Taghavi Seyed Pouya , Hamblin Michael R , Nahand Javid Sadri 
Published: August 2023

AbstractAcross the world, oral cancer is a prevalent tumor. Over the years, both its mortality and incidence have grown. Oral cancer metastasis is a complex process involving cell invasion, migration, proliferation, and egress from cancer tissue either by lymphatic vessels or blood vessels. MicroRNAs (miRNAs) are essential short non-coding RNAs, which can act either as tumor suppressors or as oncogenes to control cancer development. Cancer metastasis is a multi-step process, in which miRNAs can inhibit or stimulate metastasis at all stages, including epithelial-mesenchymal transition, migration, invasion, and colonization, by targeting critical genes in these pathways. On the other hand, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), two different types of non-coding RNAs, can regulate cancer metastasis by affecting gene expression through cross-talk with miRNAs. We reviewed the scientific literature (Google Scholar, Scopus, and PubMed) for the period 2000–2023 to find reports concerning miRNAs and lncRNA/circRNA-miRNA-mRNA networks, which control the spread of oral cancer cells by affecting invasion, migration, and metastasis. According to these reports, miRNAs are involved in the regulation of metastasis pathways either by directly or indirectly targeting genes associated with metastasis. Moreover, circRNAs and lncRNAs can induce or suppress oral cancer metastasis by acting as competing endogenous RNAs to inhibit the effect of miRNA suppression on specific mRNAs. Overall, non-coding RNAs (especially miRNAs) could help to create innovative therapeutic methods for the control of oral cancer metastases.
A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods
Authors: Alfano Massimo , Alchera Elisa , Sacchi Angelina , Gori Alessandro , Quilici Giacomo , Locatelli Irene , Venegoni Chiara , Lucianò Roberta , Gasparri Anna Maria , Colombo Barbara , Taiè Giulia , Jose Jithin , Armanetti Paolo , Menichetti Luca , Musco Giovanna , Salonia Andrea , Corti Angelo , Curnis Flavio 
Published: August 2023

Abstract
Background
Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments.

Results
In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRs@PEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism.

Conclusion
GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions.

Graphical Abstract
Identifying prognostic markers in spatially heterogeneous breast cancer microenvironment
Authors: Liu Guohong , Wang Liping , Ji Lili , He Dan , Zeng Lihua , Zhuo Guangzheng , Zhang Qian , Wang Dujuan , Pan Yunbao 
Published: August 2023

AbstractTo gain deeper insights into the microenvironment of breast cancer, we utilized GeoMx Digital Spatial Profiling (DSP) technology to analyze transcripts from 107 regions of interest in 65 untreated breast cancer tissue samples. Our study revealed spatial heterogeneity in the expression of marker genes in tumor cell enriched, immune cell enriched, and normal epithelial areas. We evaluated a total of 55 prognostic markers in tumor cell enriched regions and 15 in immune cell enriched regions, identifying that tumor cell enriched regions had higher levels of follicular helper T cells, resting dendritic cells, and plasma cells than immune cell enriched regions, while the levels of resting CD4 memory in T cells and regulatory (Treg) T cells were lower. Additionally, we analyzed the heterogeneity of HLA gene families, immunological checkpoints, and metabolic genes in these areas. Through univariate Cox analysis, we identified 5 prognosis-related metabolic genes. Furthermore, we conducted immunostaining experiments, including EMILIN2, SURF4, and LYPLA1, to verify our findings. Our investigation into the spatial heterogeneity of the breast cancer tumor environment has led to the discovery of specific diagnostic and prognostic markers in breast cancer.
Successful experience of tofacitinib treatment in patients with Fibrodysplasia Ossificans Progressiva
Authors: Nikishina Irina P. , Arsenyeva Svetlana V. , Matkava Valeria G. , Arefieva Alia N. , Kaleda Mariya I. , Smirnov Alexandr V. , Blank Leonid M. , Kostik Mikhail M. 
Published: August 2023

AbstractFibrodysplasia ossificans progressive (FOP) is an ultra-rare genetic disorder that is caused by a mutation in the ACVR1 gene and provokes severe heterotopic ossification. Since flares of the disease are associated with inflammation, it is assumed that JAK inhibitors can control active FOP due to blocking multiple signaling pathways.