bluuebunny/crossref_metadata_2025_split huggingface dataset:
Siglec15 is a prognostic indicator and a potential tumor-related macrophage regulator that is involved in the suppressive immunomicroenvironment in gliomas
Authors: Wang Jinchao , Xu Linzong , Ding Qian , Li Xiaoru , Wang Kai , Xu Shangchen , Liu Bin 
Published: May 2023

BackgroundSiglec15 is rising as a promising immunotherapeutic target in bladder, breast, gastric, and pancreatic cancers. The aim of the present study is to explore the prognostic value and immunotherapeutic possibilities of Siglec15 in gliomas using bioinformatics and clinicopathological methods.MethodsThe bioinformatics approach was used to examine Siglec15 mRNA expression in gliomas based on TCGA, CGGA, and GEO datasets. Then, the predictive value of Siglec15 expression on progression-free survival time (PFST) and overall survival time (OST) in glioma patients was comprehensively described.The TCGA database was screened for differentially expressed genes (DEGs) between the high and low Siglec15 expression groups, and enrichment analysis of the DEGs was performed. The Siglec15 protein expression and its prognostic impact in 92 glioma samples were explored using immunohistochemistry Next, the relationships between Siglec15 expression and infiltrating immune cells, immune regulators and multiple immune checkpoints were analysed.ResultsBioinformatics analyses showed that high Siglec15 levels predicted poor clinical prognosis and adverse recurrence time in glioma patients. In the immunohistochemical study serving as a validation set, Siglec15 protein overexpression was found in 33.3% (10/30) of WHO grade II, 56% (14/25) of WHO grade III, and 70.3% (26/37) of WHO grade IV gliomas respectively. Siglec15 protein overexpression was also found to be an independent prognostic indicator detrimental to the PFST and OST of glioma patients. Enrichment analysis showed that the DEGs were mainly involved in pathways associated with immune function, including leukocyte transendothelial migration, focal adhesion, ECM receptor interaction, and T-cell receptor signaling pathways. In addition, high Siglec15 expression was related to M2 tumor-associated macrophages (TAMs), N2 tumor-infiltrating neutrophils, suppressive tumor immune microenvironment, and multiple immune checkpoint molecules. Immunofluorescence analysis confirmed the colocalization of Siglec15 and CD163 on TAMs.ConclusionSiglec15 overexpression is common in gliomas and predicts an adverse recurrence time and overall survival time. Siglec15 is a potential target for immunotherapy and a potential TAMs regulator that is involved in the suppressed immunomicroenvironment in gliomas.
Osteopontin depletion in macrophages perturbs proteostasis via regulating UCHL1-UPS axis and mitochondria-mediated apoptosis
Authors: Rentsendorj Altan , Raedschelders Koen , Fuchs Dieu-Trang , Sheyn Julia , Vaibhav Vineet , Porritt Rebecca A. , Shi Haoshen , Dagvadorj Jargalsaikhan , de Freitas Germano Juliana , Koronyo Yosef , Arditi Moshe , Black Keith L. , Gaire Bhakta Prasad , Van Eyk Jennifer E. , Koronyo-Hamaoui Maya 
Published: May 2023

IntroductionOsteopontin (OPN; also known as SPP1), an immunomodulatory cytokine highly expressed in bone marrow-derived macrophages (BMMΦ), is known to regulate diverse cellular and molecular immune responses. We previously revealed that glatiramer acetate (GA) stimulation of BMMΦ upregulates OPN expression, promoting an anti-inflammatory, pro-healing phenotype, whereas OPN inhibition triggers a pro-inflammatory phenotype. However, the precise role of OPN in macrophage activation state is unknown.MethodsHere, we applied global proteome profiling via mass spectrometry (MS) analysis to gain a mechanistic understanding of OPN suppression versus induction in primary macrophage cultures. We analyzed protein networks and immune-related functional pathways in BMMΦ either with OPN knockout (OPNKO) or GA-mediated OPN induction compared with wild type (WT) macrophages. The most significant differentially expressed proteins (DEPs) were validated using immunocytochemistry, western blot, and immunoprecipitation assays.Results and discussionWe identified 631 DEPs in OPNKO or GA-stimulated macrophages as compared to WT macrophages. The two topmost downregulated DEPs in OPNKO macrophages were ubiquitin C-terminal hydrolase L1 (UCHL1), a crucial component of the ubiquitin-proteasome system (UPS), and the anti-inflammatory Heme oxygenase 1 (HMOX-1), whereas GA stimulation upregulated their expression. We found that UCHL1, previously described as a neuron-specific protein, is expressed by BMMΦ and its regulation in macrophages was OPN-dependent. Moreover, UCHL1 interacted with OPN in a protein complex. The effects of GA activation on inducing UCHL1 and anti-inflammatory macrophage profiles were mediated by OPN. Functional pathway analyses revealed two inversely regulated pathways in OPN-deficient macrophages: activated oxidative stress and lysosome-mitochondria-mediated apoptosis (e.g., ROS, Lamp1-2, ATP-synthase subunits, cathepsins, and cytochrome C and B subunits) and inhibited translation and proteolytic pathways (e.g., 60S and 40S ribosomal subunits and UPS proteins). In agreement with the proteome-bioinformatics data, western blot and immunocytochemical analyses revealed that OPN deficiency perturbs protein homeostasis in macrophages—inhibiting translation and protein turnover and inducing apoptosis—whereas OPN induction by GA restores cellular proteostasis. Taken together, OPN is essential for macrophage homeostatic balance via the regulation of protein synthesis, UCHL1-UPS axis, and mitochondria-mediated apoptotic processes, indicating its potential application in immune-based therapies.
Effects of bariatric surgery on breast density in adult obese women: systematic review and meta-analysis
Authors: Sun Dezheng , Huang Zhiping , Dong Wenyan , Zhao Xiang , Liu Chaoqian , Sheng Yuan 
Published: May 2023

IntroductionBariatric surgery is one of the most effective methods for treating obesity. It can effectively reduce body weight and reduce the incidence of obesity-related breast cancer. However, there are different conclusions about how bariatric surgery changes breast density. The purpose of this study was to clarify the changes in breast density from before to after bariatric surgery.MethodsThe relevant literature was searched through PubMed and Embase to screen for studies. Meta-analysis was used to clarify the changes in breast density from before to after bariatric surgery.ResultsA total of seven studies were included in this systematic review and meta-analysis, including a total of 535 people. The average body mass index decreased from 45.3 kg/m2 before surgery to 34.4 kg/m2 after surgery. By the Breast Imaging Reporting and Data System score, the proportion of grade A breast density from before to after bariatric surgery decreased by 3.83% (183 vs. 176), grade B (248 vs. 263) increased by 6.05%, grade C (94 vs. 89) decreased by 5.32%, and grade D (1 vs. 4) increased by 300%. There was no significant change in breast density from before to after bariatric surgery (OR=1.27, 95% confidence interval (CI) [0.74, 2.20], P=0.38). By the Volpara density grade score, postoperative volumetric breast density increased (standardized mean difference = -0.68, 95% CI [-1.08, -0.27], P = 0.001).DiscussionsBreast density increased significantly after bariatric surgery, but this depended on the method of detecting breast density. Further randomized controlled studies are needed to validate our conclusions.
Medication use and contextual factors associated with meeting guideline-based glycemic levels in diabetes among a nationally representative sample
Authors: McDaniel Cassidi C. , Lo-Ciganic Wei-Hsuan , Garza Kimberly B. , Kavookjian Jan , Fox Brent I. , Chou Chiahung 
Published: May 2023

IntroductionBased on the long-lasting diabetes management challenges in the United States, the objective was to examine glycemic levels among a nationally representative sample of people with diabetes stratified by prescribed antihyperglycemic treatment regimens and contextual factors.MethodsThis serial cross-sectional study used United States population-based data from the 2015 to March 2020 National Health and Nutrition Examination Surveys (NHANES). The study included non-pregnant adults (≥20 years old) with non-missing A1C and self-reported diabetes diagnosis from NHANES. Using A1C lab values, we dichotomized the outcome of glycemic levels into &lt;7% versus ≥7% (meeting vs. not meeting guideline-based glycemic levels, respectively). We stratified the outcome by antihyperglycemic medication use and contextual factors (e.g., race/ethnicity, gender, chronic conditions, diet, healthcare utilization, insurance, etc.) and performed multivariable logistic regression analyses.ResultsThe 2042 adults with diabetes had a mean age of 60.63 (SE = 0.50), 55.26% (95% CI = 51.39–59.09) were male, and 51.82% (95% CI = 47.11–56.51) met guideline-based glycemic levels. Contextual factors associated with meeting guideline-based glycemic levels included reporting an “excellent” versus “poor” diet (aOR = 4.21, 95% CI = 1.92–9.25) and having no family history of diabetes (aOR = 1.43, 95% CI = 1.03–1.98). Contextual factors associated with lower odds of meeting guideline-based glycemic levels included taking insulin (aOR = 0.16, 95% CI = 0.10–0.26), taking metformin (aOR = 0.66, 95% CI = 0.46–0.96), less frequent healthcare utilization [e.g., none vs. ≥4 times/year (aOR = 0.51, 95% CI = 0.27–0.96)], being uninsured (aOR = 0.51, 95% CI = 0.33–0.79), etc.DiscussionMeeting guideline-based glycemic levels was associated with medication use (taking vs. not taking respective antihyperglycemic medication classes) and contextual factors. The timely, population-based estimates can inform national efforts to optimize diabetes management.
Therapeutic prospect on umbilical cord mesenchymal stem cells in animal model with primary ovarian insufficiency: a meta-analysis
Authors: Wang Xinrun , Li Tianye , Bai Xuechai , Zhu Yun , Zhang Meiliang , Wang Liang 
Published: May 2023

BackgroundPrimary ovarian insufficiency (POI) leads to not only infertile but several adverse health events to women. Traditional treatment methods have their own set of limitations and drawbacks that vary in degree. Application of human umbilical cord mesenchymal stem cell (hUCMSC) is a promising strategy for POI. However, there is a lack of literatures on application of hUCMSC in human. Animal experimental model, however, can reflect the potential effectiveness of this employment. This study aimed to evaluate the curative effect of hUCMSC on animals with POI on a larger scale.MethodsTo gather data, Pubmed, Embase, and Cochrane Library were searched for studies published up to April 2022. Various indices, including the animals' estrous cycle, serum sex hormone levels, and follicle number in the ovary, were compared between the experimental group and those with Premature Ovarian Insufficiency (POI).ResultsThe administration of human umbilical cord-derived mesenchymal stem cells (hUCMSC) has been shown to significantly improve the estrous cycle (RR: 3.32, 95% CI: [1.80, 6.12], I2 = 0%, P = 0.0001), but robustly decrease its length (SMD: −1.97, 95% CI: [−2.58, −1.36], I2 = 0%, P &lt; 0.00001). It can also strikingly increase levels of serum estradiol (SMD: 5.34, 95% CI: [3.11, 7.57], I2 = 93%, P &lt; 0.00001) and anti-müllerian hormone (SMD: 1.92, 95% CI: [0.60, 3.25], I2 = 68%, P = 0.004). Besides, it lowers levels of serum follicle-stimulating hormone (SMD: −3.02, 95% CI: [−4.88, −1.16], I2 = 93%, P = 0.001) and luteinising hormone (SMD: −2.22, 95% CI: [−3.67, −0.76], I2 = 78%, P = 0.003), and thus collectively promotes folliculogenesis (SMD: 4.90, 95% CI: [3.92, 5.88], I2 = 0%, P &lt; 0.00001).ConclusionsBased on the presented findings, it is concluded that the administration of hUCMSC in animal models with POI can result in significant improvements in several key indicators, including estrous cycle recovery, hormone level modulation, and promotion of folliculogenesis. These positive outcomes suggest that hUCMSC may have potential as a treatment for POI in humans. However, further research is needed to establish the safety and efficacy of hUCMSC in humans before their clinical application.Systematic review registrationhttps://inplasy.com/inplasy-2023-5-0075/, identifier: INPLASY202350075.
Large-scale analysis of putative plasmids in clinical multidrug-resistant Escherichia coli isolates from Vietnamese patients
Authors: Nguyen Quang Huy , Le Thi Thu Hang , Nguyen Son Thai , Nguyen Kieu-Oanh Thi , Quyen Dong Van , Hayer Juliette , Bañuls Anne-Laure , Tran Tam Thi Thanh 
Published: May 2023

IntroductionIn the past decades, extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant (CR) Escherichia coli isolates have been detected in Vietnamese hospitals. The transfer of antimicrobial resistance (AMR) genes carried on plasmids is mainly responsible for the emergence of multidrug-resistant E. coli strains and the spread of AMR genes through horizontal gene transfer. Therefore, it is important to thoroughly study the characteristics of AMR gene-harboring plasmids in clinical multidrug-resistant bacterial isolates.MethodsThe profiles of plasmid assemblies were determined by analyzing previously published whole-genome sequencing data of 751 multidrug-resistant E. coli isolates from Vietnamese hospitals in order to identify the risk of AMR gene horizontal transfer and dissemination.ResultsThe number of putative plasmids in isolates was independent of the sequencing coverage. These putative plasmids originated from various bacterial species, but mostly from the Escherichia genus, particularly E. coli species. Many different AMR genes were detected in plasmid contigs of the studied isolates, and their number was higher in CR isolates than in ESBL-producing isolates. Similarly, the blaKPC-2, blaNDM-5, blaOXA-1, blaOXA-48, and blaOXA-181 β-lactamase genes, associated with resistance to carbapenems, were more frequent in CR strains. Sequence similarity network and genome annotation analyses revealed high conservation of the β-lactamase gene clusters in plasmid contigs that carried the same AMR genes.DiscussionOur study provides evidence of horizontal gene transfer in multidrug-resistant E. coli isolates via conjugative plasmids, thus rapidly accelerating the emergence of resistant bacteria. Besides reducing antibiotic misuse, prevention of plasmid transmission also is essential to limit antibiotic resistance.
Network meta-analysis of comparative efficacy of animal-assisted therapy vs. pet-robot therapy in the management of dementia
Authors: Du Hongdi , Bo Lin , Lai Xiaoxing , Zhu Hongwei , Huo Xiaopeng 
Published: May 2023

ObjectiveThis network meta-analysis aimed to compare and rank the efficacy of animal-assisted therapy (AAT) and pet-robotic therapy (PRT) in the management of dementia.MethodsRelevant studies were identified by searching PubMed, EMBASE, the Cochrane Library, SCOPUS, and Web of Science (WoS) until October 13, 2022. Traditional meta-analysis was first conducted based on the random-effects model, then random network meta-analysis was conducted to determine the relative efficacy and rank probability of AAT and PRT.ResultsNineteen randomized controlled trials (RCTs) were included in this network meta-analysis. Network meta-analysis revealed that PRT marginally benefited agitation alleviation compared with control (standard mean difference [SMD]: −0.37, 95% confidence interval [95%CI]: −0.72 to −0.01) although both AAT and PRT did not improve cognitive function, reduce depression, and improve Quality of Life (QoL). The SUCRA probabilities indicated that PRT ranked better than AAT in agitation, cognitive function, and QoL, although there were no differences between the two therapies.ConclusionThe present network meta-analysis reveals that PRT may help alleviate agitated behaviors in people with dementia. However, future studies are warranted to establish evidence of the effectiveness of PRT and further evaluate the differences between different robot types in managing dementia.
The effect of seed location on functional connectivity: evidence from an image-based meta-analysis
Authors: Li Meng-Ting , Sun Jia-Wei , Zhan Lin-Lin , Antwi Collins Opoku , Lv Ya-Ting , Jia Xi-Ze , Ren Jun 
Published: May 2023

IntroductionDefault mode network (DMN) is the most involved network in the study of brain development and brain diseases. Resting-state functional connectivity (rsFC) is the most used method to study DMN, but different studies are inconsistent in the selection of seed. To evaluate the effect of different seed selection on rsFC, we conducted an image-based meta-analysis (IBMA).MethodsWe identified 59 coordinates of seed regions of interest (ROIs) within the default mode network (DMN) from 11 studies (retrieved from Web of Science and Pubmed) to calculate the functional connectivity; then, the uncorrected t maps were obtained from the statistical analyses. The IBMA was performed with the t maps.ResultsWe demonstrate that the overlap of meta-analytic maps across different seeds’ ROIs within DMN is relatively low, which cautions us to be cautious with seeds’ selection.DiscussionFuture studies using the seed-based functional connectivity method should take the reproducibility of different seeds into account. The choice of seed may significantly affect the connectivity results.
C1ql4 regulates breast cancer cell stemness and epithelial-mesenchymal transition through PI3K/AKT/NF-κB signaling pathway
Authors: Xu Fan , Wang Jiali , Zhen Shuman , Duan Yuqing , Li Qingshan , Liu Lihua 
Published: May 2023

BackgroundThe stemness characteristic of breast cancer (BC) is a crucial factor underlying cancer recurrence and metastasis after operative therapy and chemoradiotherapy. Understanding the potential mechanism of breast cancer stem cells (BCSCs) may ameliorate the prognosis of patients.MethodsWe collected clinical specimens of BC patients for staining and statistical analysis to verify the expression status and clinical significance of complement C1q-like 4 (C1ql4). Western blot and qRT-PCR were employed to detect the expression of molecules. Flow cytometry was used to examine cell cycle, cell apoptosis and the portion of BCSCs. Wound healing and Transwell assays were used to detect cell metastasis. The effect of C1ql4 on breast cancer progression in vivo was examined in a nude mouse tumor bearing model.ResultsOur clinical analysis showed that C1ql4 was highly expressed in BC tissues and cell lines, and the high expression of C1ql4 was significantly corelated with the malignancy of BC patients. Moreover, we also found that C1ql4 was overexpressed in BCSCs. C1ql4 knockdown suppressed the BCSC and EMT properties, promoted cell cycle progression, enhanced BC cell apoptosis, and inhibited cell migration and invasion, whereas the C1ql4 overexpression exhibited the opposite effects. Mechanistically, C1ql4 promoted the activation and nuclear location of NF-κB and the expression of downstream factors TNF-α and IL-1β. Moreover, inhibition of PI3K/AKT signaling suppressed the C1ql4-induced stemness and EMT.ConclusionsOur findings suggest that C1ql4 promotes the BC cell stemness and EMT via modulating the PI3K/AKT/NF-κB signaling, and provides a promising target for BC treatment.
Juvenile idiopathic arthritis with systemic onset with inflammatory bone lesions: two case reports of patients successfully treated with canakinumab and experience gained from literature
Authors: Alexeeva Ekaterina I. , Dvoryakovskaya Tatyana M. , Tsulukiya Irina T. , Kondrateva Natalia M. , Solomatina Natalia M. , Kondratiev Gleb V. , Peshekhonova Luliia V. , Kostik Mikhail M. 
Published: May 2023

Non-bacterial osteomyelitis (NBO) is a rare chronic inflammatory bone disease related to immune system dysregulation. This disease belongs to a family of autoinflammatory diseases. It often coexists with other TNF-α-mediated immune-mediated diseases such as juvenile idiopathic arthritis (JIA) and inflammatory bowel diseases. Previously, interleukin-1-driven inflammation was described predominantly in monogenic cases of NBO, such as DIRA syndrome or Majeed syndrome. However, the association between NBO and JIA with systemic onset (soJIA) has not been described yet.Herein, we describe the cases of two patients with soJIA with inflammatory bone lesions wherein canakinumab (anti-interleukin-1β antibodies) caused remission.
Case descriptionsPatient 1–A 6-month-old boy with typical soJIA suffered a destruction of the 7th to 9th ribs and the left pubic bone. Antibiotics, IVIG, and cyclosporine proved ineffective. Corticosteroids were effective, but due to the factor of corticosteroid dependence, which has some disadvantages, canakinumab with a dosage of 4 mg/kg was initiated every 4 weeks, which completely controlled the disease and allowed to taper corticosteroids.Patient 2—A 2-year-old girl developed chronic non-bacterial osteomyelitis of the 5th rib 2 months after taking corticosteroids prescribed for typical soJIA. She underwent surgical debridement removal, and several courses of antibiotics proved ineffective. She developed macrophage activation syndrome, following which anakinra was prescribed, which resulted in only temporary improvement. Therefore, this drug was switched to canakinumab, which caused corticosteroid-free remission.ConclusionThis is the first description of a rare association of soJIA with inflammatory bone lesions with the proven efficacy of IL-1 blockade. The association of two autoinflammatory conditions should indicate IL-1-driven mechanisms and a possible genetic basis. Follow-up genetic and functional studies are required to better understand the pathogenesis of such overlapping diseases.
Early changes in cerebral metabolism after perinatal hypoxia-ischemia: a study in normothermic and hypothermic piglets
Authors: Andelius Ted C. K. , Bøgh Nikolaj , Pedersen Mette V. , Omann Camilla , Andersen Mads , Andersen Hannah B. , Hjortdal Vibeke E. , Pedersen Michael , Rasmussen Martin B. , Kyng Kasper J. , Henriksen Tine B. 
Published: May 2023

IntroductionHypoxic ischemic encephalopathy (HIE) after a perinatal insult is a dynamic process that evolves over time. Therapeutic hypothermia (TH) is standard treatment for severe to moderate HIE. There is a lack of evidence on the temporal change and interrelation of the underlying mechanisms that constitute HIE under normal and hypothermic conditions. We aimed to describe early changes in intracerebral metabolism after a hypoxic-ischemic insult in piglets treated with and without TH and in controls.MethodsThree devices were installed into the left hemisphere of 24 piglets: a probe measuring intracranial pressure, a probe measuring blood flow and oxygen tension, and a microdialysis catheter measuring lactate, glucose, glycerol, and pyruvate. After a standardized hypoxic ischemic insult, the piglets were randomized to either TH or normothermia.ResultsGlycerol, a marker of cell lysis, increased immediately after the insult in both groups. There was a secondary increase in glycerol in normothermic piglets but not in piglets treated with TH. Intracerebral pressure, blood flow, oxygen tension, and extracellular lactate remained stable during the secondary increase in glycerol.ConclusionThis exploratory study depicted the development of the pathophysiological mechanisms in the hours following a perinatal hypoxic-ischemic insult with and without TH and controls.