bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-omics profiling and digital image analysis reveal the potential prognostic and immunotherapeutic properties of CD93 in stomach adenocarcinoma
Authors: Wu Baokang , Fu Lei , Guo Xingqi , Hu Huixin , Li Yang , Shi Yu , Zhang Yizhou , Han Shukun , Lv Chao , Tian Yu 
Published: January 2023

BackgroundRecent evidence highlights the fact that immunotherapy has significantly improved patient outcomes. CD93, as a type I transmembrane glycoprotein, was correlated with tumor-associated angiogenesis; however, how CD93 correlates with immunotherapy in stomach adenocarcinoma (STAD) remains unclear.MethodsTCGA, GTEx, GEO, TIMER2.0, HPA, TISIDB, TCIA, cBioPortal, LinkedOmics, and ImmuCellAI public databases were used to elucidate CD93 in STAD. Visualization and statistical analysis of data were performed by R (Version 4.1.3), GraphPad (Version 8.0.1), and QuPath (Version 0.3.2).ResultsCD93 was highly expressed in STAD compared with adjacent normal tissues. The overexpression of CD93 was significantly correlated with a poor prognosis in STAD. There was a negative correlation between CD93 expression levels with CD93 mutation and methylation in STAD. Our results revealed that CD93 expression was positively associated with most immunosuppressive genes (including PD-1, PD-L1, CTLA-4, and LAG3), immunostimulatory genes, HLA, chemokine, and chemokine receptor proteins in STAD. Furthermore, in STAD, CD93 was noticeably associated with the abundance of multiple immune cell infiltration levels. Functional HALLMARK and KEGG term enhancement analysis of CD93 through Gene Set Enrichment Analysis was correlated with the process of the angiogenesis pathway. Subsequently, digital image analysis results by QuPath revealed that the properties of CD93+ cells were statistically significant in different regions of stomach cancer and normal stomach tissue. Finally, we utilized external databases, including GEO, TISIDB, ImmuCellAI, and TCIA, to validate that CD93 plays a key role in the immunotherapy of STAD.ConclusionOur study reveals that CD93 is a potential oncogene and is an indicative biomarker of a worse prognosis and exerts its immunomodulatory properties and potential possibilities for immunotherapy in STAD.
Effectiveness of therapeutic patient education interventions for chronic diseases: A systematic review and meta-analyses of randomized controlled trials
Authors: Correia Jorge César , Waqas Ahmed , Assal Jean-Philippe , Davies Melanie J. , Somers Florence , Golay Alain , Pataky Zoltan 
Published: January 2023

BackgroundChronic disorders are highly prevalent and are a major contributor to death and disability worldwide. Evidence has shown that therapeutic patient education (TPE) interventions are effective in improving a range of biomedical and psychological outcomes for a variety of chronic disorders. This has been demonstrated in scores of randomized controlled and evidence-synthesis studies. However, no quantitative evidence has been published so far on the content and effective teaching strategies in TPE programs. The present systematic review and meta-analysis aim to bridge this gap by answering the who, what, and how of TPE programs.MethodsUsing a pretested search strategy, we searched the Web of Science, MEDLINE, CINAHL, PsycINFO, and the COCHRANE databases, from inception to August 2019. The search strategy was based on four comprehensive search concepts (patient education, chronic diseases, study design, and outcomes). After a careful screening for eligible studies, two reviewers extracted qualitative and quantitative data from the randomized controlled trials on the TPE interventions. We also developed a taxonomy of curriculum skills and intervention delivery techniques to aid the extraction of data in these domains.ResultsWe found that these interventions were effective in improving biological outcomes (SMD = 0.48; 95% CI: 0.38–0.57), adherence to the treatment regimen (SMD = 0.73; 95% CI: 0.46–1.002), knowledge (SMD = 1.22; 95% CI: 0.79–1.65), self-efficacy (SMD = 0.43; 95% CI: 0.30–0.56), and psychological health (SMD = −0.41; 95% CI: −0.53 to −0.29). This effectiveness was consistent across different delivery formats (individual, group, and electronic) and delivery agents (non-specialists vs. specialists).ConclusionThe flexibility in the choice of mode of delivery and curriculum development gives stakeholders an opportunity to scale up TPE interventions in healthcare settings.Systematic review registrationIdentifier: CRD42019141294.
Metagenome-assembled genomes indicate that antimicrobial resistance genes are highly prevalent among urban bacteria and multidrug and glycopeptide resistances are ubiquitous in most taxa
Authors: Magnúsdóttir Stefanía , Saraiva Joao Pedro , Bartholomäus Alexander , Soheili Majid , Toscan Rodolfo Brizola , Zhang Junya , Nunes da Rocha Ulisses ,   CLUE-TERRA consortium
Published: January 2023

IntroductionEvery year, millions of deaths are associated with the increased spread of antimicrobial resistance genes (ARGs) in bacteria. With the increasing urbanization of the global population, the spread of ARGs in urban bacteria has become a more severe threat to human health.MethodsIn this study, we used metagenome-assembled genomes (MAGs) recovered from 1,153 urban metagenomes in multiple urban locations to investigate the fate and occurrence of ARGs in urban bacteria. Additionally, we analyzed the occurrence of these ARGs on plasmids and estimated the virulence of the bacterial species.ResultsOur results showed that multidrug and glycopeptide ARGs are ubiquitous among urban bacteria. Additionally, we analyzed the deterministic effects of phylogeny on the spread of these ARGs and found ARG classes that have a non-random distribution within the phylogeny of our recovered MAGs. However, few ARGs were found on plasmids and most of the recovered MAGs contained few virulence factors.DiscussionOur results suggest that the observed non-random spreads of ARGs are not due to the transfer of plasmids and that most of the bacteria observed in the study are unlikely to be virulent. Additional research is needed to evaluate whether the ubiquitous and widespread ARG classes will become entirely prevalent among urban bacteria and how they spread among phylogenetically distinct species.
The fate of sulfonamide resistance genes and anthropogenic pollution marker intI1 after discharge of wastewater into a pristine river stream
Authors: Haenelt Sarah , Wang Gangan , Kasmanas Jonas Coelho , Musat Florin , Richnow Hans Hermann , da Rocha Ulisses Nunes , Müller Jochen A. , Musat Niculina 
Published: January 2023

IntroductionCurrently there are sparse regulations regarding the discharge of antibiotics from wastewater treatment plants (WWTP) into river systems, making surface waters a latent reservoir for antibiotics and antibiotic resistance genes (ARGs). To better understand factors that influence the fate of ARGs in the environment and to foster surveillance of antibiotic resistance spreading in such habitats, several indicator genes have been proposed, including the integrase gene intI1 and the sulfonamide resistance genes sul1 and sul2.MethodsHere we used quantitative PCR and long-read nanopore sequencing to monitor the abundance of these indicator genes and ARGs present as class 1 integron gene cassettes in a river system from pristine source to WWTP-impacted water. ARG abundance was compared with the dynamics of the microbial communities determined via 16S rRNA gene amplicon sequencing, conventional water parameters and the concentration of sulfamethoxazole (SMX), sulfamethazine (SMZ) and sulfadiazine (SDZ).ResultsOur results show that WWTP effluent was the principal source of all three sulfonamides with highest concentrations for SMX (median 8.6 ng/l), and of the indicator genes sul1, sul2 and intI1 with median relative abundance to 16S rRNA gene of 0.55, 0.77 and 0.65%, respectively. Downstream from the WWTP, water quality improved constantly, including lower sulfonamide concentrations, decreasing abundances of sul1 and sul2 and lower numbers and diversity of ARGs in the class 1 integron. The riverine microbial community partially recovered after receiving WWTP effluent, which was consolidated by a microbiome recovery model. Surprisingly, the relative abundance of intI1 increased 3-fold over 13 km of the river stretch, suggesting an internal gene multiplication.DiscussionWe found no evidence that low amounts of sulfonamides in the aquatic environment stimulate the maintenance or even spread of corresponding ARGs. Nevertheless, class 1 integrons carrying various ARGs were still present 13 km downstream from the WWTP. Therefore, limiting the release of ARG-harboring microorganisms may be more crucial for restricting the environmental spread of antimicrobial resistance than attenuating ng/L concentrations of antibiotics.
Urinary protein biomarkers based on LC–MS/MS analysis to discriminate vascular dementia from Alzheimer’s disease in Han Chinese population
Authors: Chen Ruijuan , Yi Yuanjing , Xiao Wenbiao , Zhong Bowen , Zhang Le , Zeng Yi 
Published: January 2023

ObjectiveThis study aimed to identify the potential urine biomarkers of vascular dementia (VD) and unravel the disease-associated mechanisms by applying Liquid chromatography tandem-mass spectrometry (LC–MS/MS).MethodsLC–MS/MS proteomic analysis was applied to urine samples from 3 groups, including 14 patients with VD, 9 patients with AD, and 21 normal controls (NC). By searching the MS data by Proteome Discoverer software, analyzing the protein abundances qualitatively and quantitatively, comparing between groups, combining bioinformatics analysis using Gene Ontology (GO) and pathway crosstalk analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG), and literature searching, the differentially expressed proteins (DEPs) of VD can be comprehensively determined at last and were further quantified by receiver operating characteristic (ROC) curve methods.ResultsThe proteomic findings showed quantitative changes in patients with VD compared to patients with NC and AD groups; among 4,699 identified urine proteins, 939 and 1,147 proteins displayed quantitative changes unique to VD vs. NC and AD, respectively, including 484 overlapped common DEPs. Then, 10 unique proteins named in KEGG database (including PLOD3, SDCBP, SRC, GPRC5B, TSG101/STP22/VPS23, THY1/CD90, PLCD, CDH16, NARS/asnS, AGRN) were confirmed by a ROC curve method.ConclusionOur results suggested that urine proteins enable detection of VD from AD and VC, which may provide an opportunity for intervention.
Sodium butyrate ameliorates gut dysfunction and motor deficits in a mouse model of Parkinson’s disease by regulating gut microbiota
Authors: Zhang Yi , Xu Shaoqing , Qian Yiwei , Mo Chengjun , Ai Penghui , Yang Xiaodong , Xiao Qin 
Published: January 2023

BackgroundA growing body of evidence showed that gut microbiota dysbiosis might be associated with the pathogenesis of Parkinson’s disease (PD). Microbiota-targeted interventions could play a protective role in PD by regulating the gut microbiota-gut-brain axis. Sodium butyrate (NaB) could improve gut microbiota dysbiosis in PD and other neuropsychiatric disorders. However, the potential mechanism associated with the complex interaction between NaB and gut microbiota-gut-brain communication in PD needs further investigation.MethodsC57BL/6 mice were subjected to a rotenone-induced PD model and were treated intragastrically with NaB for 4 weeks. The gut function and motor function were evaluated. The α-synuclein expression in colon and substantia nigra were detected by western blotting. Tyrosine hydroxylase (TH)-positive neurons in substantia nigra were measured by immunofluorescence. Moreover, gut microbiota composition was analyzed by 16S rRNA sequencing. Fecal short chain fatty acids (SCFAs) levels were determined by liquid chromatography tandem mass spectrometry (LC–MS). The levels of glucagon like peptide-1 (GLP-1) in tissues and serum were evaluated using enzyme-linked immunosorbent assay (ELISA).ResultsNaB ameliorated gut dysfunction and motor deficits in rotenone-induced mice. Meanwhile, NaB protected against rotenone-induced α-synuclein expression in colon and substantia nigra, and prevented the loss of TH-positive neurons. In addition, NaB could remodel gut microbiota composition, and regulate gut SCFAs metabolism, and restore GLP-1 levels in colon, serum, and substantia nigra in PD mice.ConclusionNaB could ameliorate gut dysfunction and motor deficits in rotenone-induced PD mice, and the mechanism might be associated with the regulation of gut microbiota dysbiosis.
Human gastrin- releasing peptide receptor expression in women with uterine cervix cancer
Authors: Kunos Charles A. , Fabian Denise , Napier Dana , Stonecypher Mark S. , Duncan Ravyn M. , Hurt Jason 
Published: January 2023

Introduction212Pb-DOTAM-GRPR1 is a pharmaceutical radioimmunoconjugate consisiting of an α-particle-emitting radionuclide lead-212 (212Pb), a metal chelator DOTAM (1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane), and a gastrin-releasing peptide receptor (GRPR)-targeted antagonist currently being evaluated as therapy in uterine cervix and other cancer types. Previous studies have revealed that a variable proportion of uterine cervix cancer tumors overexpress the radiopharmaceutical target GRPR when assessed by cell proportion and staining intensity immunoreactive scores (IRS). Tumor response to 212Pb-DOTAM-GRPR1 strongly associates with GRPR overexpression, and therefore, it seems reasonable to assess uterine cervix cancer GRPR immunoreactivity for greater insight into the feasibility of using 212Pb-DOTAM-GRPR1 as a radiopharmaceutical treatment.MethodsWe examined a series of 33 uterine cervix cancer paraffin-embedded tumors in order to establish whether this tumor type overexpresses GRPR at an IRS score of 6 or higher, as 212Pb-DOTAM-GRPR1 is currently being evaluated in clinical trials against tumors showing such a level of expression.ResultsThe results show that five of five (100%) primary adenocarcinomas and 10 of 16 (63%) primary squamous cell tumors overexpress GRPR at an IRS score of 6 or higher.DiscussionThe frequency of overexpression in this study suggests that 212Pb-DOTAM-GRPR1 radiopharmaceutical treatment may be useful in the management of persistent, recurrent, or metastatic uterine cervix cancer patients. A phase I clinical trial involving patients with metastatic uterine cervix cancer is currently underway (NCT05283330).
The effect of antibiotics on the periodontal treatment of diabetic patients with periodontitis: A systematic review and meta-analysis
Authors: Tang Ziwei , Fan Qi , Jiang Qingsong , Li Xiaolong , Wang Yan , Long Hu , Lai Wenli , Jian Fan 
Published: January 2023

Background: The aim of this meta-analysis was to compare the effects of periodontal treatment with or without adjunctive antibiotic on periodontal status and blood glucose level in diabetic patients with periodontitis.Methods: A search using electronic database (MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials) and a manual search were performed up to July 2022. Eligible 13 RCTs were included according to inclusion and exclusion criteria. Reviewers independently performed data screening, data selection, data extraction, and risk of bias. Quality assessment was performed according to the Cochrane Handbook for Systematic Reviews of Interventions. Weighted mean differences and 95% confidence intervals (CIs) for continuous outcomes were calculated using random or fixed-effects models. This review is registered in the PROSPERO database (CRD42022347803).Results: Of the 13 included articles, eight were on the use of systemic antibiotics and five on topical antibiotics. The results showed statistically significant improvement in periodontal status (probing depth, clinical attachment loss and bleeding on probing) at 6 months with systematic antibiotics use (PD-6M p = 0.04, BOP-6M p &lt; 0.0001, CAL-6M p = 0.002). The improvement in PD with topical antibiotics was statistically significant at 1 month (p = 0.0006). However, there was no statistically significant improvement in periodontal status at 3 months with adjuvant systemic antibiotics.Conclusion: Antibiotics can improve the periodontal condition of diabetic patients with periodontitis to a certain extent. In clinical practice, it is necessary to comprehensively consider the balance of benefits and risks before deciding whether to use antibiotics.Systematic Review Registration: Identifier CRD42022347803, https://www.crd.york.ac.uk/PROSPERO/.
Preclinical and clinical evidence for the treatment of non-alcoholic fatty liver disease with soybean: A systematic review and meta-analysis
Authors: Li Yubing , Deng Xinyu , Guo Xiaochuan , Zhang Fangling , Wu Hefei , Qin Xuhua , Ma Xiao 
Published: January 2023

Non-alcoholic fatty liver disease (NAFLD), a prevalent public health issue, involves the accumulation of triglycerides in hepatocytes, which is generally considered to be an early lesion of liver fibrosis and cirrhosis. Thus, the development of treatments for NAFLD is urgently needed. This study explored the preclinical and clinical evidence of soybeans to alleviate NAFLD. Studies indexed in three relevant databases—Web of Science, PubMed, and Embase—between January 2002 and August 2022 were retrieved. A total of 13 preclinical studies and five RCTs that included 212 animals and 260 patients were included in the present analysis. The preclinical analysis showed that liver function indices (AST, SMD = −1.41, p &lt; 0.0001 and ALT, SMD = −1.47, p &lt; 0.0001) were significantly improved in the soybean group compared to the model group, and fatty liver indicators (TG, SMD = −0.78, p &lt; 0.0001; TC, SMD = −1.38, p &lt; 0.0001) and that oxidative stress indices (MDA, SMD = −1.09, p &lt; 0.0001; SOD, SMD = 1.74, p = 0.022) were improved in the soybean group. However, the five RCTs were not entirely consistent with the preclinical results; however, the results confirmed the protective effect on the liver. The results of the clinical RCTs showed that soybean significantly affected liver function, fatty liver, and oxidative stress indicators (ALT, SMD = −0.42, p = 0.006; TG, SMD = −0.31, p = 0.039; MDA, SMD = −0.76, p = 0.007). The current meta-analysis combined preclinical and clinical studies and verified that soybean could protect the liver in NAFLD by regulating lipid metabolism and oxidative stress factors via the Akt/AMPK/PPARα signaling pathway. Soybean might be a promising therapeutic agent for treating non-alcoholic fatty liver disease.Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/#myprospero), identifier (CRD42022335822).
Gallic acid ameliorates dextran sulfate sodium-induced ulcerative colitis in mice via inhibiting NLRP3 inflammasome
Authors: Yu Tian-Yuan , Feng Yi-Ming , Kong Wei-Song , Li Shan-Ni , Sun Xue-Jiao , Zhou Gui , Xie Rui-Fang , Zhou Xin 
Published: January 2023

Background: Ulcerative colitis (UC) is a chronic recurrent inflammatory bowel disease (IBD). The conventional drugs for UC may induce severe side effects. Herbal medicine is considered as a complementary and alternative choice for UC.Purpose: This study aims to estimate the effect of natural polyphenol gallic acid (GA) on the NLRP3 inflammasome with dextran sulfate sodium (DSS)-induced colitis in mice.Study design: The body weights and symptoms of BALB/c mice were recorded. Histological evaluation, ELISA, q-PCR, immunohistochemistry, and western blotting were carried out to observe the morphology, cytokine contents, mRNA expressions, and protein expressions, respectively. Lipopolysaccharide (LPS)-induced RAW264.7 macrophage was used to probe GA’s effect on relative protein expression.Results: GA attenuated weight loss (p &lt; 0.05), relieved symptoms, and ameliorated colonic morphological injury (p &lt; 0.05) in mice with colitis induced by DSS. GA also lowered the contents of TNF-α, IL-1β, IL-18, IL-33, and IFN-γ in the serum and colon of mice, which were elevated by DSS, downregulated protein, and mRNA expressions of the NLRP3 pathway in the colon tissue. Furthermore, GA downregulated the expressions of NLRP3 (p &lt; 0.05), iNOS (p &lt; 0.01), COX2 (p &lt; 0.01), and P-p65 (p &lt; 0.05), and suppressed NO release (p &lt; 0.001) in LPS-induced RAW264.7 cells.Conclusion: GA ameliorated DSS-induced UC in mice via inhibiting the NLRP3 inflammasome. These findings furnish evidence for the anti-inflammatory effect of herbal medicines containing GA on UC.
Does pomegranate extract supplementation improve the clinical symptoms of patients with allergic asthma? A double-blind, randomized, placebo-controlled trial
Authors: Hosseini Seyed Ahmad , Shateri Zainab , Abolnezhadian Farhad , Maraghi Elham , Haddadzadeh Shoushtari Maryam , Zilaee Marzie 
Published: January 2023

Background: Asthma essentially represents a chronic inflammatory disease that manifests as a lifelong condition with different severity throughout the life of patients with asthma. Pomegranate holds three times the antioxidant activity compared to other polyphenol-rich food sources like green tea, which may positively impact asthma.Aim of the study: This research aimed to investigate the pomegranate supplementation influences clinical symptoms, eosinophil, basophil, and neutrophil counts in patients with allergic asthma.Materials and Methods: Participants (n = 64) suffering from mild to moderate allergic asthma were randomly divided into two groups: The control group received placebo capsules and the intervention group received 250 mg pomegranate extract capsules twice a day (for 8 weeks). To analyze the data, we used SPSS software (version 22). The significance level of p-value was considered less than 0.05.Results: The findings showed that the pomegranate extract improved patients’ clinical symptoms like daily breath shortness, nocturnal breath shortness, and limitation of asthma-related activity in the intervention group compared to the control group. Furthermore, eosinophil, basophil, and neutrophil counts were significantly decreased in the intervention group. Also, by comparing the two groups, the levels of change in neutrophils and eosinophils were statistically significant.Conclusion: It appears that the pomegranate extract can ameliorate some clinical symptoms and reduce neutrophils, basophils, and eosinophils in allergic asthma patients.Clinical Trial Registration:https://www.irct.ir/trial/45612; identifier: IRCT20200205046384N1.