bluuebunny/crossref_metadata_2025 huggingface dataset:
A preliminary investigation of presenteeism and cognitive preferences among head nurses: a cross-sectional study
Authors: Li Wenzhen , Shan Geyan , Wang Shengnan , Wang Hongxia , Wang Wei , Li Yongxin
Published: September 2023

Background

Individual health is essential for productivity at work. However, presenteeism, which is defined as attending work while ill, is common. Nursing is a profession with a high incidence of presenteeism, leading to diverse negative outcomes. Considering the unique and significant role of head nurses and the influence of cognitive factors on presenteeism, the current study aimed to investigate the incidence of presenteeism among head nurses, their cognitive preference towards presenteeism, and the association between the two.

Methods

This preliminary investigation was a cross-sectional study conducted from July to August 2022. Participants were 233 head nurses recruited via convenience sampling from six hospitals located in Zhengzhou, Henan Province, China. The Nurse Presenteeism Questionniare (NPQ) and an original cognitive preference questionnaire were used to measure head nurses’ experience of presenteeism and cognitive preference towards presenteeism. Descriptive statistics and sample t-tests were performed for data analysis.

Results

In the past six months, 96.6% of the head nurses exhibited signs of presenteeism. The specific symptoms were discomfort in the lower back, dizziness or headache, cold (e.g., stuffy nose or cough), abdominal pain (including menstrual pain), and whole-body fatigue or discomfort. 95.7% of head nurses’ anticipation preference toward presenteeism inclined to rest at home; additionally, more than 80% of the head nurses considered presenteeism detrimental to both individuals and organizations. Further, 63.9% of the head nurses were inclined toward conduct discouragement in the face of subordinates’ presenteeism. There was no significant difference in presenteeism between head nurses with various anticipation preferences (p > 0.05) and benefit preferences (p > 0.05). However, the differences in presenteeism among head nurses with various management preferences were significant (t = 2.60, p = 0.01). Specifically, head nurses who favored encouraging subordinate presenteeism had higher presenteeism scores compared to those who discouraged it.

Conclusions

Presenteeism among head nurses remains a universal workplace phenomenon. There was inconsistency among head nurses’ anticipation preferences, benefit preferences, and presenteeism. However, there was consistency between head nurses’ management preferences and presenteeism.
Development and evaluation of case video-based debriefing on a simulation of high-risk neonatal care for nursing students in South Korea: a mixed-methods study
Authors: Koo Hyun Young , Lee Bo Ryeong , An Hyeran
Published: September 2023

Background

The debriefing process after health care simulations should provide a psychologically safe learning environment for nursing students. Case video-based debriefing on a simulation of high-risk neonatal care can help nursing students feel psychologically safe and make learning more effective. In this study, we developed case video-based debriefing materials for a simulation of high-risk neonatal care for nursing students in South Korea and evaluated their effects.

Methods

This mixed-methods study, consisting of a survey and an in-depth interview, was conducted between August and December 2022. The participants were 27 nursing students for the development of the case video-based debriefing and 51 nursing students for the evaluation of its effects (25 in the experimental group and 26 in the control group) at a university in South Korea. A case video-based debriefing on a simulation of high-risk neonatal care was developed, and the experimental group took part in case video-based debriefing. The participants’ self-efficacy, critical thinking, state anxiety, and satisfaction with practice were examined. The experimental group’s learning experiences were explored. Quantitative data were analyzed using the chi-square test, the unpaired t-test, and repeated-measures analysis of variance. Qualitative content analysis was conducted.

Results

In the experimental group, critical thinking and satisfaction with practice increased to a greater extent than in the control group. However, the changes in self-efficacy and state anxiety were not significantly different between the experimental and control groups. Four categories were extracted from nursing students who participated in the case video-based debriefing: “learning facilitated by the simulation,” “expanded learning,” “safe learning environment,” and “efficient utilization of case videos.”

Conclusions

Case video-based debriefing on a simulation of high-risk neonatal care effectively enhanced nursing students’ critical thinking and satisfaction with practice, and it will be utilized to improve nursing students’ competency in high-risk neonatal care.
The difference of intestinal microbiota composition between Lantang and Landrace newborn piglets
Authors: Li Ling , Li Shuai , Luo Junyi , Chen Ting , Xi Qianyun , Zhang Yongliang , Sun Jiajie
Published: September 2023

Background

The early development of intestinal microbiota plays a fundamental role in host health and development. To investigate the difference in the intestinal microbial composition between Lantang and Landrace newborn piglets, we amplified and sequenced the V3-V4 region of 16 S rRNA gene in jejunal microbiota of Lantang and landrace newborn.

Results

The findings revealed that the dominant phyla in the jejunum of Lantang piglets were Firmicutes, Actinobacteria and Bacteroidetes, while the dominant phyla of Landrace is Proteobacteria and Fusobacteria. Specifically, Corynebacterium_1, Lactobacillus, Rothia, Granulicatella, Corynebacteriales_unclassified, Corynebacterium, Globicatella and Actinomycetales_unclassified were found to be the dominant genera of Lantang group, while Clostridium_sensu_stricto_1, Escherichia-Shigella, Actinobacillus and Bifidobacterium were the dominant genera of Landrace. Based on the functional prediction of bacteria, we found that bacterial communities from Lantang samples had a significantly greater abundance pathways of fatty acid synthesis, protein synthesis, DNA replication, recombination, repair and material transport across membranes, while the carrier protein of pathogenic bacteria was more abundant in Landrace samples.

Conclusions

Overall, there was a tremendous difference in the early intestinal flora composition between Landang and Landrace piglets, which was related to the breed characteristics and may be one of the reasons affecting the growth characteristics. However, more further extensive studies should be included to reveal the underlying relationship between early intestinal flora composition in different breeds and pig growth characteristics.
Mesenchymal stem cell-derived extracellular vesicles prevent the formation of pulmonary arterial hypertension through a microRNA-200b-dependent mechanism
Authors: Wan Mengzhi , Lu Caiju , Liu Yu , Luo Feng , Zhou Jing , Xu Fei
Published: September 2023

Background

Bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) have been highly studied with their critical roles as carriers of therapeutic targets such as microRNAs (miRNAs) in the treatment of human diseases, including pulmonary arterial hypertension (PAH). Herein, we tried to study the potential of BMSC-EVs to deliver miR-200b for the regulation of macrophage polarization in PAH.

Methods

Rat models of PAH were induced with monocrotaline treatment, followed by miR-200b expression detection in lung tissues, pulmonary artery smooth muscle cells (PASMCs) and macrophages. miR-200b-containing BMSCs or miR-200b-deficient BMSCs were selected to extract EVs. Then, we assessed the changes in rats with PAH-associated disorders as well as in vitro macrophage polarization and the functions of PASMCs after treatment with BMSC-EVs. Moreover, the interaction between miR-200b, phosphodiesterase 1 A (PDE1A) was identified with a luciferase assay, followed by an exploration of the downstream pathway, cAMP-dependent protein kinase (PKA).

Results

miR-200b was reduced in lung tissues, PASMCs and macrophages of rats with PAH-like pathology. BMSC-EVs transferred miR-200b into macrophages, and subsequently accelerated their switch to the M2 phenotype and reversed the PAH-associated disorders. Furthermore, miR-200b carried by BMSC-EVs induced PKA phosphorylation by targeting PDE1A, thereby expediting macrophage polarization.

Conclusion

Our current study highlighted the inhibitory role of BMSC-EV-miR-200b in PAH formation.
Exposure of the static magnetic fields on the microbial growth rate and the sludge properties in the complete-mix activated sludge process (a Lab-scale study)
Authors: Asgari Ghorban , Seid-Mohammadi Abdolmotaleb , Shokoohi Reza , Samarghandi Mohammad Reza , Daigger Glen T. , Malekolkalami Behrooz , Khoshniyat Ramin
Published: September 2023

Background

In this study, the effect of static magnetic fields (SMFs) on improving the performance of activated sludge process to enhance the higher rate of microbial growth biomass and improve sludge settling characteristics in real operation conditions of wastewater treatment plants has been investigated. The effect of SMFs (15 mT), hydraulic retention time, SRT, aeration time on mixed liquor suspended solids (MLSS) concentrations, mixed liquor volatile suspended solids (MLVSS) concentrations, α-factor, and pH in the complete-mix activated sludge (CMAS) process during 30 days of the operation, were evaluated.

Results

There were not any differences between the concentration of MLSS in the case (2148.8 ± 235.6 mg/L) and control (2260.1 ± 296.0 mg/L) samples, however, the mean concentration of MLVSS in the case (1463.4 ± 419.2 mg/L) was more than the control samples (1244.1 ± 295.5 mg/L). Changes of the concentration of MLVSS over time, follow the first and second-order reaction with and without exposure of SMFs respectively. Moreover, the slope of the line and, the mean of α-factor in the case samples were 6.255 and, − 0.001 higher than the control samples, respectively. Changes in pH in both groups of the reactors were not observed. The size of the sluge flocs (1.28 µm) and, the spectra of amid I' (1440 cm−1) and II' (1650 cm−1) areas related to hydrogenase bond in the case samples were higher than the control samples.

Conclusions

SMFs have a potential to being considered as an alternative method to stimulate the microbial growth rate in the aeration reactors and produce bioflocs with the higher density in the second clarifiers.
Suppression of the antitumoral activity of natural killer cells under indirect coculture with cancer-associated fibroblasts in a pancreatic TIME-on-chip model
Authors: Kim Hyun-Ah , Kim Hyunsoo , Nam Min-Kyung , Park Jong Kook , Lee Moo-Yeal , Chung Seok , Lee Kyung-Mi , Kuh Hyo-Jeong
Published: September 2023

Background

Recently, natural killer (NK) cells emerged as a treatment option for various solid tumors. However, the immunosuppressive tumor immune microenvironment (TIME) can reduce the cytotoxic ability of NK cells in pancreatic ductal adenocarcinoma. Cancer-associated fibroblasts within the tumor stroma can suppress immune surveillance by dysregulating factors involved in the cellular activity of NK cells. Herein, the effect of activated pancreatic stellate cells (aPSCs) on NK cell-mediated anticancer efficacy under three-dimensional (3D) coculture conditions was investigated.

Methods

3D cocultures of PANC-1 tumor spheroids (TSs) with aPSCs and NK-92 cells in a collagen matrix were optimized to identify the occurring cellular interactions and differential cytokine profiles in conditioned media using microchannel chips. PANC-1 TSs and aPSCs were indirectly cocultured, whereas NK-92 cells were allowed to infiltrate the TS channel using convective medium flow.

Results

Coculture with aPSCs promoted PANC-1 TSs growth and suppressed the antitumor cytotoxic effects of NK-92 cells. Mutual inhibition of cellular activity without compromising migration ability was observed between aPSCs and NK-92 cells. Moreover, the reduced killing activity of NK-92 cells was found to be related with reduced granzyme B expression in NK cells.

Conclusions

Herein, a novel TIME-on-chip model based on the coculture of PANC-1 TSs, aPSCs, and NK-92 cells was described. This model may be useful for studying the detailed mechanisms underlying NK cells dysregulation and for exploring future therapeutic interventions to restore NK cell activity in the tumor microenvironment.
FAP promotes clear cell renal cell carcinoma progression via activating the PI3K/AKT/mTOR signaling pathway
Authors: Jiang Kun , Xu Li-zhe , Ning Jin-zhuo , Cheng Fan
Published: September 2023

Objective

Herein, we aimed at exploring the FAP expression in clear cell renal cell carcinoma (ccRCC) along with its clinical implication.

Methods

Using computational tools analysis of different freely accessible gene databases, the expression pattern, clinical importance, co-expressed genes, and signaling pathways of FAP in ccRCC were thoroughly investigated. FAP expression was examined in clinical ccRCC specimens through qRT-PCR, western blotting and immunohistochemistry. Furthermore, in vitro and in vivo experiments were carried out using flow cytometry, CCK-8, wound-healing and Transwell assays, as well as xenograft tumor model, respectively.

Results

FAP levels were found to be significantly elevated in ccRCC based on bioinformatic data from public databases. Patients who exhibited higher expression levels of FAP had poorer prognoses, according to Kaplan–Meier analysis of survival data. In addition, diagnostic and prognostic value of FAP in ccRCC was figured out by ROC curve and prognostic nomogram model. In vitro study revealed that the over-expression FAP accelerated cell proliferation, migration as well as invasion, and suppressed cell apoptosis, but silencing of FAP had the opposite effect. FAP suppression reduced the PI3K/AKT/mTOR pathway's stimulation, whereas FAP up-regulation increased the stimulation of the pathway. Blocking the PI3K/AKT/mTOR signaling pathway with the dual PI3K/mTOR inhibitor BEZ235 repressesed cancer-promoting effect of FAP. Additionally, we found that the downregulation of FAP was effective at slowing tumor progression in vivo.

Conclusion

It is possible that FAP could be a reliable biomarker for the diagnosis and prognosis of ccRCC because of its role in the ccRCC progression via triggering the PI3K/AKT/mTOR signaling pathway.
Physical environment features that predict outdoor active play can be measured using Google Street View images
Authors: Boyes Randy , Pickett William , Janssen Ian , Swanlund David , Schuurman Nadine , Masse Louise , Han Christina , Brussoni Mariana
Published: September 2023

Background

Childrens’ outdoor active play is an important part of their development. Play behaviour can be predicted by a variety of physical and social environmental features. Some of these features are difficult to measure with traditional data sources.

Methods

This study investigated the viability of a machine learning method using Google Street View images for measurement of these environmental features. Models to measure natural features, pedestrian traffic, vehicle traffic, bicycle traffic, traffic signals, and sidewalks were developed in one city and tested in another.

Results

The models performed well for features that are time invariant, but poorly for features that change over time, especially when tested outside of the context where they were initially trained.

Conclusion

This method provides a potential automated data source for the development of prediction models for a variety of physical and social environment features using publicly accessible street view images.
Triglyceride-glucose index is associated with hypertension incidence up to 13 years of follow-up in mexican adults
Authors: Argoty-Pantoja Anna D. , Velázquez-Cruz Rafael , Meneses-León Joacim , Salmerón Jorge , Rivera-Paredez Berenice
Published: September 2023

The triglyceride-glucose index (TyG index) is an indicator of insulin resistance that has been studied recently. The relationship between insulin resistance and the risk of hypertension has been documented previously. However, there is limited knowledge regarding the association of the TyG index with hypertension incidence. This study aimed to evaluate the association of the TyG index with changes in blood pressure (BP) and hypertension incidence in Mexican adults. This analysis was performed using the Health Workers Cohort Study data. The TyG index was estimated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2] and divided into categories defined by tertiles. The analysis was conducted using fixed-effects linear regression models (n = 1,545) and Cox proportional hazards regression models (n = 1,113), adjusting for potential confounding variables. The incidence rates (95% CI) for the low, medium, and high categories of the TyG index were 22.1 (17.8, 27.5), 35.8 (30.1, 42.7), and 49.4 (42.1, 57.9), respectively. An increase in the levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP) was observed when changing from a low to a medium (DBP: β 2.55 mmHg, 95% CI 0.81, 4.29) and from a low to a high category of the TyG index (SBP: β 3.10 mmHg, 95% CI 1.16, 5.04; DBP: β 4.91 mmHg, 95% CI 2.88, 6.94). Furthermore, participants within the top category of the TyG index had a 56% higher risk of hypertension than those in the bottom category (HR = 1.56; 95% CI 1.18, 2.08). These results support the hypothesis that the TyG index is associated with high blood pressure in Mexican adults.
Near-infrared photodynamic and photothermal co-therapy based on organic small molecular dyes
Authors: Guo Shuang , Gu Dongyu , Yang Yi , Tian Jing , Chen Xiaoyuan
Published: September 2023

Near-infrared (NIR) organic small molecule dyes (OSMDs) are effective photothermal agents for photothermal therapy (PTT) due to their advantages of low cost and toxicity, good biodegradation, and strong NIR absorption over a wide wavelength range. Nevertheless, OSMDs have limited applicability in PTT due to their low photothermal conversion efficiency and inadequate destruction of tumor regions that are nonirradiated by NIR light. However, they can also act as photosensitizers (PSs) to produce reactive oxygen species (ROS), which can be further eradicated by using ROS-related therapies to address the above limitations of PTT. In this review, the synergistic mechanism, composition, and properties of photodynamic therapy (PDT)–PTT nanoplatforms were comprehensively discussed. In addition, some specific strategies for further improving the combined PTT and PDT based on OSMDs for cancer to completely eradicate cancer cells were outlined. These strategies include performing image-guided co-therapy, enhancing tumor infiltration, increasing H2O2 or O2 in the tumor microenvironment, and loading anticancer drugs onto nanoplatforms to enable combined therapy with phototherapy and chemotherapy. Meanwhile, the intriguing prospects and challenges of this treatment modality were also summarized with a focus on the future trends of its clinical application.

Graphical Abstract
Scale agreement, ceiling and floor effects, construct validity, and relative efficiency of the PROPr and EQ-5D-3L in low back pain patients
Authors: Klapproth Christoph Paul , Fischer Felix , Rose Matthias
Published: September 2023

Background

The PROMIS Preference score (PROPr) is a new health state utility (HSU) score that aims to comprehensively incorporate the biopsychosocial model of health and apply favorable psychometric properties from the descriptive PROMIS system to HSU measurements. However, minimal evidence concerning comparisons to the EQ-5D-3L and the PROPr’s capability to differentiate clinical severity are available. Therefore, the aim of this study was to compare the PROPr to the EQ-5D-3L in terms of scale agreement, ceiling/floor effects, distribution, construct validity, discriminatory power, and relative efficiency (RE) in terms of the Oswestry Disability Index (ODI) for patients with low back pain (LBP).

Methods

We used intra-class correlation coefficients (ICC) and Bland–Altman plots to compare the PROPr and EQ-5D-3L with regared to scale agreement in a cross-sectional routine sample of LBP patients. For distribution, we used the Pearson’s coefficient for skewness and for ceiling/floor effects, a 15%-top/bottom threshold. For convergent validity, we used Pearson’s correlation coefficients. For known-groups validity, we applied a linear regression with interaction terms (predictors sex, age, and ODI level) and an analysis of variance (ANOVA). For discriminatory power, we calculated the effect size (ES) using Cohen’s d and the ratio of the area under the receiver-operating characteristics curves (AUROC-ratio = AUROCPROPr/AUROCEQ-5D-3L). RE was measured using the ratio of F-values (RE = FPROPr/FEQ-5D-3L).

Results

Of 218 LBP patients, 50.0% were female and the mean age was 61.8 years. The mean PROPr (0.20, 95%CI: 0.18; 0.22) and EQ-5D-3L scores (0.55, 95%CI: 0.51; 0.58) showed low agreement (d = 0.35, p < 0.001; ICC 0.27, 95%CI: -0.09; 0.59). The PROPr’s distribution was positively skewed, whereas the EQ-5D-3L’s was negative. Neither tool showed ceiling/floor effects, but all EQ-5D-3L dimensions did. Pearson correlation was r = 0.66 (95%CI: 0.58; 0.73). Differences were invariant to sex and age but not to ODI severity: ESEQ-5D-3L > ESPROPr and RE < 1 in higher ODI severity; ESEQ-5D-3L < ESPROPr and RE > 1 in lower ODI severity. AUROC-ratios did not show significant differences in terms of ODI severity.

Conclusions

All PROPr and EQ-5D-3L biopsychosocial dimensions of health showed impairment in LPB patients. The capability of EQ-5D-3L and PROPr to differentiate ODI levels depends on ODI severity. Joint application of both tools may provide additional information.
Integrative bioinformatics analysis of WDHD1: a potential biomarker for pan-cancer prognosis, diagnosis, and immunotherapy
Authors: Cui Zhiwei , Zou Fan , Wang Rongli , Wang Lijun , Cheng Feiyan , Wang Lihui , Pan Rumeng , Guan Xin , Zheng Nini , Wang Wei
Published: September 2023

Background

Although WD repeat and high-mobility group box DNA binding protein 1 (WDHD1) played an essential role in DNA replication, chromosome stability, and DNA damage repair, the panoramic picture of WDHD1 in human tumors remains unclear. Hence, this study aims to comprehensively characterize WDHD1 across 33 human cancers.

Methods

Based on publicly available databases such as TCGA, GTEx, and HPA, we used a bioinformatics approach to systematically explore the genomic features and biological functions of WDHD1 in pan-cancer.

Results

WDHD1 mRNA levels were significantly increased in more than 20 types of tumor tissues. Elevated WDHD1 expression was associated with significantly shorter overall survival (OS) in 10 tumors. Furthermore, in uterine corpus endometrial carcinoma (UCEC) and liver hepatocellular carcinoma (LIHC), WDHD1 expression was significantly associated with higher histological grades and pathological stages. In addition, WDHD1 had a high diagnostic value among 16 tumors (area under the ROC curve [AUC] > 0.9). Functional enrichment analyses suggested that WDHD1 probably participated in many oncogenic pathways such as E2F and MYC targets (false discovery rate [FDR] < 0.05), and it was involved in the processes of DNA replication and DNA damage repair (p.adjust < 0.05). WDHD1 expression also correlated with the half-maximal inhibitory concentrations (IC50) of rapamycin (4 out of 10 cancers) and paclitaxel (10 out of 10 cancers). Overall, WDHD1 was negatively associated with immune cell infiltration and might promote tumor immune escape. Our analysis of genomic alterations suggested that WDHD1 was altered in 1.5% of pan-cancer cohorts and the “mutation” was the predominant type of alteration. Finally, through correlation analysis, we found that WDHD1 might be closely associated with tumor heterogeneity, tumor stemness, mismatch repair (MMR), and RNA methylation modification, which were all processes associated with the tumor progression.

Conclusions

Our pan-cancer analysis of WDHD1 provides valuable insights into the genomic characterization and biological functions of WDHD1 in human cancers and offers some theoretical support for the future use of WDHD1-targeted therapies, immunotherapies, and chemotherapeutic combinations for the management of tumors.
Predictive factors and repetition numbers for intraoperative additional resection of initially involved soft tissue resection margins in oral squamous cell carcinoma: a retrospective study
Authors: Ooms Mark , Ponke Lisa , Winnand Philipp , Heitzer Marius , Peters Florian , Steiner Tim , Hölzle Frank , Modabber Ali
Published: September 2023

Background

Intraoperative additional resection (IAR) of initially microscopically involved soft tissue resection margins negatively impacts tumor recurrence in oral squamous cell carcinoma (OSCC). Increasing the selected initial macroscopic resection margin distance beyond the tumor tissue may help prevent IAR; however, the existence of predictive factors for IAR and IAR repetition numbers remains unclear. This study aimed to identify predictive factors for IAR and to evaluate the IAR repetition numbers in soft tissue for surgically treated OSCC.

Methods

A cohort of 197 patients surgically treated for OSCC between 2008 and 2019 was retrospectively reviewed (44 patients with IAR and 153 patients without IAR). Clinical parameters (tumor location, midline involvement, clinical T-status, time between staging imaging and surgery, bone resection, monopolar use, and reconstruction flap size) and histopathological parameters (pathologic T-status [pT-status], grading, vascular invasion, and lymphatic invasion) of the two groups were compared.

Results

Patients with and without IAR differed in their histopathological parameters, such as pT-status above 2 (47.7% vs. 28.1%, p = 0.014) and lymphatic invasion (13.6% vs. 4.6%, p = 0.033); however, their clinical parameters were similar (all p > 0.05). Only pT-status above 2 was predictive for IAR in a multivariable regression analysis (odds ratio 2.062 [confidence interval 1.008–4.221], p = 0.048). The IAR repetition numbers varied from zero to two (zero = 84.4%, one = 11.4%, and two = 2.3%).

Conclusions

Only postoperative available pT-status was identified as a predictive factor for IAR, underscoring the importance of improving preoperative or intraoperative tumor visualization in OSCC before selecting the initial macroscopic resection margin distance to avoid IAR.
Transcriptional characteristics and functional validation of three monocyte subsets during aging
Authors: Wang Chen , Cheng Yating , Li Boyu , Qiu Xueping , Hu Hui , Zhang Xiaokang , Lu Zhibing , Zheng Fang
Published: September 2023

Background

Age-associated changes in immunity are inextricably linked to chronic inflammation and age-related diseases, the impact of aging on monocyte subsets is poorly understood.

Methods

Flow cytometry was applied to distinguish three monocyte subsets between 120 young and 103 aged individuals. We then analyzed the expression profiles of three monocyte subsets from 9 young and 9 older donors and CD14+ monocytes from 1202 individuals between 44 and 83 years old. Flow cytometry was used to measure β-galactosidase activities, ROS levels, mitochondrial contents, mitochondrial membrane potentials (MMPs) and intracellular IL-6 levels in three monocyte subsets of young and elderly individuals, and plasma IL-6 levels were detected by electrochemiluminescence immunoassay. Mitochondrial stress and glycolytic rate of CD14+ monocytes from young and aged individuals were measured by Seahorse XFe24 Analyzer.

Results

Compared with young individuals, the percentage of classical subset in aged persons significantly decreased, while the proportion of nonclassical subset increased. Age-related differential genes were obviously enriched in cellular senescence, ROS, oxidative phosphorylation, mitochondrial respiratory chain, IL-6 and ribosome-related pathways. Compared with young individuals, the β-galactosidase activities, ROS contents, intracellular IL-6 levels of three monocyte subsets, and plasma IL-6 levels in aged individuals were significantly elevated, while the MMPs apparently declined with age and the mitochondrial contents were only increased in intermediate and nonclassical subsets. CD14+ monocytes from elderly adults had conspicuously lower basal and spare respiratory capacity and higher basal glycolysis than those from young individuals.

Conclusions

During aging, monocytes exhibited senescence-associated secretory phenotype, mitochondrial dysfunction, decreased oxidative phosphorylation and increased glycolysis and the nonclassical subset displayed the clearest features of aging. Our study comprehensively investigated age-related transcriptional alterations of three monocyte subsets and identified the pivotal pathways of monocyte senescence, which may have significant implications for tactics to alleviate age-related conditions.
Long-term PM2.5 exposure disrupts corneal epithelial homeostasis by impairing limbal stem/progenitor cells in humans and rat models
Authors: Hao Shengjie , Chen Zhijian , Gu Yuzhou , Chen Lu , Sheng Feiyin , Xu Yili , Wu Di , Han Yu , Lu Bing , Chen Shuying , Zhao Wei , Yin Houfa , Wang Xiaofeng , Riazuddin S. Amer , Lou Xiaoming , Fu Qiuli , Yao Ke
Published: September 2023

Background

Limbal stem/progenitor cells (LSPCs) play a crucial role in maintaining corneal health by regulating epithelial homeostasis. Although PM2.5 is associated with the occurrence of several corneal diseases, its effects on LSPCs are not clearly understood.

Methods

In this study, we explored the correlation between PM2.5 exposure and human limbal epithelial thickness measured by Fourier-domain Optical Coherence Tomography in the ophthalmologic clinic. Long- and short-term PM2.5 exposed-rat models were established to investigate the changes in LSPCs and the associated mechanisms.

Results

We found that people living in regions with higher PM2.5 concentrations had thinner limbal epithelium, indicating the loss of LSPCs. In rat models, long-term PM2.5 exposure impairs LSPCs renewal and differentiation, manifesting as corneal epithelial defects and thinner epithelium in the cornea and limbus. However, LSPCs were activated in short-term PM2.5-exposed rat models. RNA sequencing implied that the circadian rhythm in LSPCs was perturbed during PM2.5 exposure. The mRNA level of circadian genes including Per1, Per2, Per3, and Rev-erbα was upregulated in both short- and long-term models, suggesting circadian rhythm was involved in the activation and dysregulation of LSPCs at different stages. PM2.5 also disturbed the limbal microenvironment as evidenced by changes in corneal subbasal nerve fiber density, vascular density and permeability, and immune cell infiltration, which further resulted in the circadian mismatches and dysfunction of LSPCs.

Conclusion

This study systematically demonstrates that PM2.5 impairs LSPCs and their microenvironment. Moreover, we show that circadian misalignment of LSPCs may be a new mechanism by which PM2.5 induces corneal diseases. Therapeutic options that target circadian rhythm may be viable options for improving LSPC functions and alleviating various PM2.5-associated corneal diseases.
The role of gut microbiota in the pathogenesis and treatment of postpartum depression
Authors: Zhang Sheng , Lu Baili , Wang Gang
Published: September 2023

Postpartum depression (PPD) is a common complication of pregnancy in women, and its pathogenesis mainly involves disturbances of the neuroendocrine regulation, immune system, neurotransmitters, hormone secretion, and the gut microbiome. Gut microbes play essential physiological and pathological roles in the gut-brain axis’ pathways which are involved in various central nervous system (CNS) and psychiatric disorders, including PPD. Numerous studies have identified the fundamental role of the gut-brain axis in the pathogenesis and treatment of PPD patients and also correlates with other pathogenic mechanisms of PPD. Disturbances in gut microbes are associated with the disruption of multiple signaling pathways and systems that ultimately lead to PPD development. This review aimed to elucidate the potential connections between gut microbes and the established PPD network, and this might serve as a guide for the development of new efficient diagnostic, therapeutic, and prognostic strategies in the management of PPD.
A correlation study of preoperative lumbar paraspinal muscle quality and L5-S1 lumbar foraminal stenosis degeneration after L4–5 TLIF
Authors: Chen Minghang , Zhang Peng , Lai Jiaxin , Li Sheng , Yu Weijie , Fan Shikang , Teng Honglin
Published: September 2023

Study design

This was a retrospective study.

Objectives

Adjacent segment degeneration (ASD) is a major complication associated with spinal fusion. The lumbar paraspinal muscle is an essential factor influencing the occurrence of ASD. This study aimed to investigate the effect of preoperative lumbar paraspinal muscle quality on L5-S1 adjacent lumbar foraminal stenosis degeneration (ASLFSD) after L4–5 transforaminal lumbar interbody fusion (TLIF).

Methods

A total of 113 patients diagnosed with lumbar spinal stenosis at L4–5 were treated with TLIF. Lumbar paraspinal muscle measurements were obtained preoperatively and bilaterally from axial T2-weighted MR images. The measurements included the total cross-sectional area of psoas (PS-tCSA), of erector spinae (ES-tCSA), and of multifidus (MF-tCSA); and fatty infiltration of psoas (PS-FI), of erector spinae (ES-FI), and of multifidus (MF-FI). Foraminal measurements, including posterior disc height (PDH), disc-to-facet distance (D–F), foraminal height (FH), and foraminal area (FA), were obtained bilaterally using a computed tomography system. The association between lumbar paraspinal muscle quality and changes in foraminal measurements was also studied.

Results

We observed that the FH and FA significantly reduced at 1 year postoperatively at the mean follow-up period of 41.56 ± 8.38 months (range, 43–50 months), and PDH, D–F, FH, and FA all significantly reduced at final follow-up. These changes in foraminal measurements were significantly and negatively correlated with PS-FI, ES-FI, and MF-FI.

Conclusion

During the clinical follow-up, we found that patients with a higher degree of paraspinal muscle FI were more likely to develop L5-S1 ASLFSD after L4–5 TLIF.
Intrauterine phenotype features of fetuses with 7q11.23 microduplication syndrome
Authors: Wang Yunan , Liu Chang , Hu Rong , Geng Juan , Lu Jian , Zhao Xin , Xiong Ying , Wu Jing , Yin Aihua
Published: September 2023

Objective

To share our experience on prenatal diagnosis of 7q11.23 microduplication syndrome and to further delineate the fetal phenotypes of the syndrome.

Methods

A retrospective study was conducted to evaluate seven cases of dup7q11.23 syndrome diagnosed prenatally by chromosomal microarray (CMA). Clinical data were reviewed, including maternal characteristics, indications for prenatal diagnosis, sonographic findings, CMA results, pregnancy outcomes and follow-ups.

Results

Seven cases, including 2 pairs of MCDA twins, were prenatally identified with dup7q11.23 syndrome. The most common prenatal sonographic features were ventriculomegaly, low-lying conus medullaris, and dilated ascending aorta. All 7 fetuses presented with typical 7q11.23 duplications (1.40–1.55 Mb). Parental chromosome analysis was performed in four pairs of parents, and indicated that the duplications of Case 6 and 7 were inherited from their asymptomatic mother.

Conclusion

Our case series suggest that prenatal features of dup7q11.23 cases are diversified, with ventriculomegaly and low-lying conus medullaris being the most common intrauterine phenotypes. Additionally, cleft palate, dilated ascending aorta, and renal abnormalities were also observed, and should be taken into consideration in subsequent studies.
Astrocytes of the optic nerve exhibit a region-specific and temporally distinct response to elevated intraocular pressure
Authors: Mazumder Arpan G. , Julé Amélie M. , Sun Daniel
Published: September 2023

Background

The optic nerve is an important tissue in glaucoma and the unmyelinated nerve head region remains an important site of many early neurodegenerative changes. In both humans and mice, astrocytes constitute the major glial cell type in the region, and in glaucoma they become reactive, influencing the optic nerve head (ONH) microenvironment and disease outcome. Despite recognizing their importance in the progression of the disease, the reactive response of optic nerve head astrocytes remains poorly understood.

Methods

To determine the global reactive response of ONH astrocytes in glaucoma we studied their transcriptional response to an elevation in IOP induced by the microbead occlusion model. To specifically isolate astrocyte mRNA in vivo from complex tissues, we used the ribotag method to genetically tag ribosomes in astrocytes, restricting analysis to astrocytes and enabling purification of astrocyte-associated mRNA throughout the entire cell, including the fine processes, for bulk RNA-sequencing. We also assessed the response of astrocytes in the more distal myelinated optic nerve proper (ONP) as glaucomatous changes manifest differently between the two regions.

Results

Astrocytes of the optic nerve exhibited a region-specific and temporally distinct response. Surprisingly, ONH astrocytes showed very few early transcriptional changes and ONP astrocytes demonstrated substantially larger changes over the course of the experimental period. Energy metabolism, particularly oxidative phosphorylation and mitochondrial protein translation emerged as highly upregulated processes in both ONH and ONP astrocytes, with the former showing additional upregulation in antioxidative capacity and proteolysis. Interestingly, optic nerve astrocytes demonstrated a limited neuroinflammatory response, even when challenged with a more severe elevation in IOP. Lastly, there were a greater number of downregulated processes in both astrocyte populations compared to upregulated processes.

Conclusion

Our findings demonstrate an essential role for energy metabolism in the response of optic nerve astrocytes to elevated IOP, and contrary to expectations, neuroinflammation had a limited overall role. The transcriptional response profile is supportive of the notion that optic nerve astrocytes have a beneficial role in glaucoma. These previously uncharacterized transcriptional response of optic nerve astrocytes to injury reveal their functional diversity and a greater heterogeneity than previously appreciated.
Evaluation of negative binomial and zero-inflated negative binomial models for the analysis of zero-inflated count data: application to the telemedicine for children with medical complexity trial
Authors: Lee Kyung Hyun , Pedroza Claudia , Avritscher Elenir B. C. , Mosquera Ricardo A. , Tyson Jon E.
Published: September 2023

Background

Two characteristics of commonly used outcomes in medical research are zero inflation and non-negative integers; examples include the number of hospital admissions or emergency department visits, where the majority of patients will have zero counts. Zero-inflated regression models were devised to analyze this type of data. However, the performance of zero-inflated regression models or the properties of data best suited for these analyses have not been thoroughly investigated.

Methods

We conducted a simulation study to evaluate the performance of two generalized linear models, negative binomial and zero-inflated negative binomial, for analyzing zero-inflated count data. Simulation scenarios assumed a randomized controlled trial design and varied the true underlying distribution, sample size, and rate of zero inflation. We compared the models in terms of bias, mean squared error, and coverage. Additionally, we used logistic regression to determine which data properties are most important for predicting the best-fitting model.

Results

We first found that, regardless of the rate of zero inflation, there was little difference between the conventional negative binomial and its zero-inflated counterpart in terms of bias of the marginal treatment group coefficient. Second, even when the outcome was simulated from a zero-inflated distribution, a negative binomial model was favored above its ZI counterpart in terms of the Akaike Information Criterion. Third, the mean and skewness of the non-zero part of the data were stronger predictors of model preference than the percentage of zero counts. These results were not affected by the sample size, which ranged from 60 to 800.

Conclusions

We recommend that the rate of zero inflation and overdispersion in the outcome should not be the sole and main justification for choosing zero-inflated regression models. Investigators should also consider other data characteristics when choosing a model for count data. In addition, if the performance of the NB and ZINB regression models is reasonably comparable even with ZI outcomes, we advocate the use of the NB regression model due to its clear and straightforward interpretation of the results.
Pelvic floor parameters predict postpartum stress urinary incontinence: a prospective MRI study
Authors: You Cong , Zhao Yujiao , Zhang Cheng , Chen Mengyao , Shen Wen
Published: September 2023

Objective

To investigate the pelvic floor changes in primiparas with postpartum stress urinary incontinence (SUI) after vaginal delivery using pelvic floor MRI.

Materials and methods

Fifty-two women were enrolled in the primiparous stress urinary incontinent (PSUI) group and 51 in the primiparous continent (PC) group. Thirty nulliparas were also recruited as the nulliparous control (NC) group. Levator ani muscle (LAM) injury, levator hiatus area (LHA), H-line, M-line, the distance from the bladder neck and cervix to the pubococcygeal line (B-PCL and U-PCL), levator plate angle, the anterior angle of the urethra, bladder neck descent, retrovesicourethral angle, functional urethral length, and a bladder neck funnel were evaluated on MRI images. Univariate and multivariate logistic regression analyses were used to explore anatomical predictors for SUI.

Results

The primiparas in the PSUI group showed more obvious LAM injuries than in the PC groups (p = 0.001). LAM function assessment: the PSUI group had larger LHA and shorter B-PCL and U-PCL than the other groups during straining. Assessment of urethral mobility and function: the PSUI group had larger anterior angle of the urethra, bladder neck descent, retrovesicourethral angle, and shorter functional urethral length than the other two groups (all p < 0.05). Up to 88.5% of primiparas in the PSUI group showed bladder funnel (p < 0.001). The logistic regression analysis showed that retrovesicourethral angle, functional urethral length, and the presence of bladder funnel were significantly associated with postpartum SUI (p < 0.05).

Conclusions

Increased retrovesicourethral angle, shortened functional urethral length, and the presence of bladder funnel may be anatomical predictors for SUI in the early postpartum period. Urethral sphincter dysfunction plays an essential role in developing postpartum SUI.

Critical relevance statement

This study used several measurements to reflect the anatomical structure and functional changes of the pelvic floor to identify the best anatomical predictors associated with postpartum stress urinary incontinence (SUI), aiming to provide new insights into treatment strategies for postpartum SUI.

Key points

• Increased retrovesicourethral angle, shortened functional urethral length, and the presence of bladder funnel are more commonly seen in primiparas with SUI.

• The combination of retrovesicourethral angle, functional urethral length, and bladder funnel had the highest diagnostic performance in predicting postpartum SUI (AUC=0.947).

• Urethral sphincter dysfunction may be the main pathophysiological foundation in SUI development.

Graphical Abstract
HSP90, as a functional target antigen of a mAb 11C9, promotes stemness and tumor progression in hepatocellular carcinoma
Authors: Liu Hui-Qi , Sun Li-Xin , Yu Long , Liu Jun , Sun Li-Chao , Yang Zhi-Hua , Shu Xiong , Ran Yu-Liang
Published: September 2023

Background

Identification of promising targeted antigens that exhibited cancer-specific expression is a crucial step in the development of novel antibody-targeted therapies. We here aimed to investigate the anti-tumor activity of a novel monoclonal antibody (mAb) 11C9 and identify the antibody tractable target in the hepatocellular cancer stem cells (HCSCs).

Methods

The identification of the targeted antigen was conducted using SDS-PAGE, western blot, mass spectrometry, and co-immunoprecipitation. Silence of HSP90 was induced by siRNA interference. Positive cells were sorted by fluorescence-activated cell sorting. Double-immunofluorescent (IF) staining and two-color flow cytometry detected the co-expression. Self-renewal, invasion, and drug resistance were assessed by sphere formation, matrigel-coated Transwell assay, and CCK-8 assay, respectively. Tumorigenicity was evaluated in mouse xenograft models. RNA-seq and bioinformatics analysis were performed to explore the mechanism of mAb 11C9 and potential targets.

Results

MAb 11C9 inhibited invasion and self-renewal abilities of HCC cell lines and reversed the cisplatin resistance. HSP90 (~ 95 kDa) was identified as a targeted antigen of mAb 11C9. Tissue microarrays and online databases revealed that HSP90 was overexpressed in HCC and associated with a poor prognosis. FACS and double-IF staining showed the co-expression of HSP90 and CSCs markers (CD90 and ESA). In vitro and in vivo demonstrated the tumorigenic potentials of HSP90. The inhibition of HSP90 by siRNA interference or 17-AAG inhibitor both decreased the number of invasion, sphere cells, and CD90+ or ESA+ cells, as well as reversed the resistance. Bioinformatics analysis and western blot verified that HSP90 activated Wnt/β-catenin signaling.

Conclusions

The study preliminarily revealed the anti-tumor activity of mAb 11C9. More importantly, we identified HSP90 as a targeted antigen of mAb 11C9, which functions as an oncogene in phenotype shaping, stemness maintenance, and therapeutic resistance by activating Wnt/β-catenin signaling.