bluuebunny/crossref_metadata_2025_split huggingface dataset:
Moxibustion alleviates depression-like behavior in rats with Crohn’s disease by inhibiting the kynurenine pathway metabolism in the gut-brain axis
Authors: Bao Chunhui , Huang Jin , Wu Huangan , Ma Yueying , Zhou Hongyu , Chen Liming , Yang Dandan , Liu Huirong , Shi Yin , Lu Yuan 
Published: December 2022

BackgroundMoxibustion is a potential therapy for inflammatory bowel disease-related depression, but its specific mechanism of action is unclear. This study aimed to investigate the molecular mechanism by which moxibustion alleviates depressive behavior in rats with Crohn’s disease (CD).MethodsThe CD rat model was established with 2,4,6-trinitrobenzenesulfonic acid. Treatment with moxibustion was applied to Tianshu (ST25, bilateral), Qihai (CV6), and Baihui (GV20) acupoints, and the effect of moxibustion was compared with that of the combination of moxibustion plus indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor, 1-methyltryptophan (1-MT). The effects of moxibustion and moxibustion plus 1-MT combination on colonic inflammation and depressive behavior (assessed by forced swimming test, sucrose preference test, and open field test) were investigated. The changes in IDO1, TNF-α, and IL-1β in rat colon and hippocampus were assessed by Western blot (WB). Gas chromatography-mass spectrometry, immunofluorescence staining, and WB were applied to detect kynurenine pathway (KP) metabolites, hippocampal neuronal activity, and microglia activation, respectively.ResultsBoth moxibustion and moxibustion plus 1-MT combination significantly alleviated intestinal inflammation and depressive behavior, downregulated the levels of IDO1 in the colon and hippocampus, and inhibited inflammation-inducing factors IL-1β and TNF-α, as well as the kynurenine/tryptophan (KYN/TRP) ratio of KP metabolites, and upregulated the kynurenic acid (KYNA)/KYN ratio and the KYNA/quinolinic acid (QUIN) ratio in the hippocampus in rats with CD; Hippocampal ionized calcium-binding adaptor molecule-1 (Iba-1), c-fos protein expression, activated microglia, and neuronal activation was also significantly reduced by moxibustion and moxibustion plus 1-MT. The addition of 1-MT did not significantly increase the therapeutic effect of moxibustion.ConclusionMoxibustion can improve depressive behavior in rats with CD, which may be related to its regulation of KP metabolism in the gut-brain axis and inhibition of hippocampal microglia activation and neuronal activation.
Modular organization of locomotor networks in people with severe spinal cord injury
Authors: Sun Soo Yeon , Giszter Simon F. , Harkema Susan J. , Angeli Claudia A. 
Published: December 2022

IntroductionPrevious studies support modular organization of locomotor circuitry contributing to the activation of muscles in a spatially and temporally organized manner during locomotion. Human spinal circuitry may reorganize after spinal cord injury; however, it is unclear if reorganization of spinal circuitry post-injury affects the modular organization. Here we characterize the modular synergy organization of locomotor muscle activity expressed during assisted stepping in subjects with complete and incomplete spinal cord injury (SCI) of varying chronicity, before any explicit training regimen. We also investigated whether the synergy characteristics changed in two subjects who achieved independent walking after training with spinal cord epidural stimulation.MethodsTo capture synergy structures during stepping, individuals with SCI were stepped on a body-weight supported treadmill with manual facilitation, while electromyography (EMGs) were recorded from bilateral leg muscles. EMGs were analyzed using non-negative matrix factorization (NMF) and independent component analysis (ICA) to identify synergy patterns. Synergy patterns from the SCI subjects were compared across different clinical characteristics and to non-disabled subjects (NDs).ResultsResults for both NMF and ICA indicated that the subjects with SCI were similar among themselves, but expressed a greater variability in the number of synergies for criterion variance capture compared to NDs, and weaker correlation to NDs. ICA yielded a greater number of muscle synergies than NMF. Further, the clinical characteristics of SCI subjects and chronicity did not predict any significant differences in the spatial synergy structures despite any neuroplastic changes. Further, post-training synergies did not become closer to ND synergies in two individuals.DiscussionThese findings suggest fundamental differences between motor modules expressed in SCIs and NDs, as well as a striking level of spatial and temporal synergy stability in motor modules in the SCI population, absent the application of specific interventions.
VTA-NAc glutaminergic projection involves in the regulation of pain and pain-related anxiety
Authors: Abdul Mannan , Yan Hao-Qi , Zhao Wei-Nan , Lyu Xiao-Bin , Xu Zheng , Yu Xiao-Lu , Gao Yi-Hong , Cao Jun-Li 
Published: December 2022

BackgroundBesides the established role of dopamine neurons and projections in nociceptive stimuli, the involvement of ventral tegmental area (VTA) glutamatergic projections to nucleus accumbens (NAc) in pain remains unknown. In the present study, we aimed to examine the role of VTA glutamatergic projections to NAc in painful stimuli and its related behavioral changes.MethodsUnilateral chronic constrictive injury (CCI) of sciatic nerve or intraplantar hind paw injections (i.pl.) of complete Freund’s adjuvant (CFA) were used to develop pathological pain models in wild-type and VGluT2-Cre mice. The involvement of VTA glutamatergic neurons with projections to NAc in CCI-induced pain model was noted by c-Fos labeling and firing rate recordings. Pain response and pain-related behavior changes to the artificial manipulation of the VTA glutamatergic projections to NAc were observed by Hargreaves tests, von Frey tests, open field tests, elevated maze tests, and sucrose preference tests.ResultsGlutamatergic neurons in VTA had efferent inputs to shell area of the NAc. The CCI pain model significantly increased neuronal activity and firing rate in VTA glutamate neurons with projections to NAc. The photoinhibition of these glutamatergic projections relieved CCI-induced neuropathic pain and CFA-induced acute and chronic inflammatory pain. Moreover, pathological neuropathic pain-induced anxiety and less sucrose preference were also relieved by inhibiting the VTA glutamatergic projections to NAc.ConclusionTogether, glutamatergic inputs from VTA to NAc contribute to chronic neuropathic and inflammatory pain and pain-related anxiety and depressive behaviors, providing a mechanism for developing novel therapeutic methods.
Complementary feeding methods and introduction of ultra-processed foods: A randomized clinical trial
Authors: Moreira Paula Ruffoni , Nunes Leandro Meirelles , Giugliani Elsa Regina Justo , Gomes Erissandra , Führ Jordana , Neves Renata Oliveira , Belin Christy Hannah Sanini , Bernardi Juliana Rombaldi 
Published: December 2022

IntroductionComplementary feeding (CF) is defined as a period when foods, other than milk, are introduced to the infant’s diet. Unfortunately, frequent consumption of ultra-processed foods (UPF) has become highly prevalent early in an infant’s life. The aim was to verify the association of CF methods with the introduction of UPF in early childhood.MethodsThis randomized clinical trial involved pairs of mother-infants, allocated in groups receiving different CF interventions: strict Parent-Led Weaning (PLW); strict Baby-Led Introduction to SolidS (BLISS), or mixed-method. The intervention consisted of a counseling session on healthy eating at the child’s 5.5 months of age. A structured questionnaire was created based on the NOVA classification for the definition of UPF and applied at 9 and 12 months. The effect of the CF method intervention was measured by a survival curve for UPF offered for the first time in early childhood between groups. Cox regression was used to estimate its magnitude. The primary analysis was done in three groups (PLW, BLISS, and Mixed) and the secondary analysis was done in two groups (PLW, and BLISS + Mixed).ResultsA total of 139 mother-infant pairs were eligible and 129 followed the study. The prevalence of infants who were exposed to UPF in early childhood was 58.9% (n = 76), being 71.4% in the PLW group, 53.3% in the BLISS group, and 52.4% in the Mixed group, without differences between them (p = 0.133). The PLW group intervention had a greater chance of exposure to ice cream or popsicles (p = 0.032) and sweet crackers (p = 0.009), compared with the other two CF groups. The Cox regression did not find significant differences between the three groups. However, the regression with two groups estimated a 38% reduction in the offer of UPF in the BLISS + Mixed group intervention (p = 0.049).DiscussionThe CF intervention promoting greater infant autonomy (BLISS and Mixed) was associated with a reduction in the offer of UPF in early childhood. This knowledge may contribute to supporting strategies aimed at reducing UPF consumption by the young infant.Brazilian registry of clinical trials (ReBEC)[https://ensaiosclinicos.gov.br/rg/RBR-229scm], identifier [RBR-229scm U1111-1226-9516].
An instant beverage rich in nutrients and secondary metabolites manufactured from stems and leaves of Panax notoginseng
Authors: Liang Zhengwei , Liu Kunyi , Li Ruoyu , Ma Baiping , Zheng Wei , Yang Shengchao , Zhang Guanghui , Zhao Yinhe , Chen Junwen , Zhao Ming 
Published: December 2022

IntroductionRadix Notoginseng, one of the most famous Chinese traditional medicines, is the dried root of Panax notoginseng (Araliaceae). Stems and leaves of P. notoginseng (SLPN) are rich in secondary metabolites and nutrients, and authorized as a food resource, however, its utilization needs further research.MethodsA SLPN-instant beverage was manufactured from SLPN through optimization by response surface design with 21-fold of 48.50% ethanol for 39 h, and this extraction was repeated twice; the extraction solution was concentrated to 1/3 volume using a vacuum rotatory evaporator at 45°C, and then spray dried at 110°C. Nutritional components including 14 amino acids, ten mineral elements, 15 vitamins were detected in the SLPN-instant beverage; forty-three triterpenoid saponins, e.g., ginsenoside La, ginsenoside Rb3, notoginsenoside R1, and two flavonoid glycosides, as well as dencichine were identified by UPLC-MS.ResultsThe extraction rate of SLPN-instant beverage was 37.89 ± 0.02%. The majority nutrients were Gly (2.10 ± 0.63 mg/g), His (1.23 ± 0.07 mg/g), α-VE (18.89 ± 1.87 μg/g), β-VE (17.53 ± 1.98 μg/g), potassium (49.26 ± 2.70 mg/g), calcium (6.73 ± 0.27 mg/g). The total saponin of the SLPN-instant beverage was 403.05 ± 34.98 mg/g, majority was notoginsenoside Fd and with contents of 227 ± 2.02 mg/g. In addition, catechin and γ-aminobutyric acid were detected with levels of 24.57 ± 0.21 mg/g and 7.50 ± 1.85 mg/g, respectively. The SLPN-instant beverage showed good antioxidant activities with half maximal inhibitory concentration (IC50) for scavenging hydroxyl (OH–) radicals, superoxide anion (O2–) radicals, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS+) radicals were 0.1954, 0.2314, 0.4083, and 0.3874 mg/mL, respectively.ConclusionWe optimized an analytical method for in depth analysis of the newly authorized food resource SLPN. Together, an instant beverage with antioxidant activity, rich in nutrients and secondary metabolites, was manufactured from SLPN, which may improve the utilization of SLPN.
18F-PSMA-1007 PET/CT-derived semi-quantitative parameters for risk stratification of newly diagnosed prostate cancer
Authors: Dong Siying , Li Yanmei , Chen Jian , Li Yongliang , Yang Pengfei , Li Juan 
Published: December 2022

PurposeThis study aimed to assess the value of 18F-PSMA-1007 positron emission tomography/computed tomography (PET/CT)-derived semi-quantitative parameters of primary tumor for risk stratification of newly diagnosed prostate cancer (PCa).MethodsSixty patients referred for 18F-PSMA-1007 PET/CT imaging for primary PCa were retrospectively analyzed and classified into the low-intermediate-risk (LIR) or high-risk (HR) group. The maximum standardized uptake value (SUVmax) of primary tumor, prostate total lesion PSMA (TL-PSMAp), and prostate PSMA-tumor volume (PSMA-TVp) were measured, and group differences were evaluated using the Mann–Whitney U test. Spearman’s correlation was performed to assess the correlation between the above parameters with prostate-specific antigen (PSA) levels and Gleason score (GS). Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values for SUVmax, TL-PSMAp, and PSMA-TVp to identify high-risk PCa and compare diagnostic efficacy.ResultsAmong 60 patients, 46 were assigned to the HR group and 16 to the LIR group. In all patients, SUVmax, TL-PSMAp, and PSMA-TVp were moderately correlated with pre-treatment PSA values (r = 0.411, p = 0.001; r = 0.663, p &lt; 0.001; and r = 0.549, p &lt; 0.001, respectively). SUVmax and TL-PSMAp were moderately correlated with GS (r = 0.457 and r = 0.448, respectively; p &lt; 0.001), while PSMA-TVp was weakly correlated with GS (r = 0.285, p = 0.027). In the ROC curve analysis, the optimal cut-off values of SUVmax, TL-PSMAp, and PSMA-TVp for identifying high-risk PCa were 9.61, 59.62, and 10.27, respectively, and the areas under the operating curve were 0.828, 0.901, and 0.809, respectively. The sensitivities of SUVmax, TL-PSMAp, and PSMA-TVp were 91.03%, 71.74%, and 63.04%, respectively, and the specificities were 71.43%, 100.00%, and 92.86%, respectively.ConclusionsTL-PSMAp had a superior ability to identify high-risk PCa. The semi-quantitative parameters of primary tumor on 18F-PSMA-1007 PET/CT imaging can be an objective imaging reference index to determine PCa risk stratification.
Breast tumor IGF1R regulates cell adhesion and metastasis: alignment of mouse single cell and human breast cancer transcriptomics
Authors: Obr Alison E. , Bulatowicz Joseph J. , Chang Yun-Juan , Ciliento Virginia , Lemenze Alexander , Maingrette Krystopher , Shang Quan , Gallagher Emily J. , LeRoith Derek , Wood Teresa L. 
Published: December 2022

IntroductionThe acquisition of a metastatic phenotype is the critical event that determines patient survival from breast cancer. Several receptor tyrosine kinases have functions both in promoting and inhibiting metastasis in breast tumors. Although the insulin-like growth factor 1 receptor (IGF1R) has been considered a target for inhibition in breast cancer, low levels of IGF1R expression are associated with worse overall patient survival.MethodsTo determine how reduced IGF1R impacts tumor phenotype in human breast cancers, we used weighted gene co-expression network analysis (WGCNA) of Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) patient data to identify gene modules associated with low IGF1R expression. We then compared these modules to single cell gene expression analyses and phenotypes of mouse mammary tumors with reduced IGF1R signaling or expression in a tumor model of triple negative breast cancer.ResultsWGCNA from METABRIC data revealed gene modules specific to cell cycle, adhesion, and immune cell signaling that were inversely correlated with IGF1R expression in human breast cancers. Integration of human patient data with single cell sequencing data from mouse tumors revealed similar pathways necessary for promoting metastasis in basal-like mammary tumors with reduced signaling or expression of IGF1R. Functional analyses revealed the basis for the enhanced metastatic phenotype including alterations in E- and P-cadherins.DiscussionHuman breast and mouse mammary tumors with reduced IGF1R are associated with upregulation of several pathways necessary for promoting metastasis supporting the conclusion that IGF1R normally helps maintain a metastasis suppressive tumor microenvironment. We further found that reduced IGF1R signaling in tumor epithelial cells dysregulates cadherin expression resulting in reduced cell adhesion.
Neonatal AKI profile using KDIGO guidelines: A cohort study in tertiary care hospital ICU of Lahore, Pakistan
Authors: Gul Rafia , Anwar Zahid , Sheikh Mehmood , Salamat Ayesha , Iqbal Samer , Saleem Furqan , Fatima Samer 
Published: December 2022

Background and objectiveAcute kidney injury (AKI) was observed in sick neonates and was associated with poor outcomes. Our cohort represents the neonatal characteristics of those diagnosed with AKI using Kidney Disease: Improved Global Outcome (KDIGO) guidelines.MethodologyA cohort study was conducted in the NICU of FMH from June 2019 to May 2021. Data were collected on a proforma. All continuous variables were not normally distributed and expressed as the median and interquartile range. Categorical variables were analyzed by proportional differences with the Pearson chi-square test or Fisher's exact tests. A multinomial logistic regression model was used to explore the independent risk factors for AKI. Time to the event (death) and the cohort's survival curves were plotted using the Cox proportional hazard model.ResultsAKI occurred in 473 (37.6%) neonates. The risk factors of AKI were outborn birth [adjusted odds ratio (AOR): 3.987, 95% confidence interval (CI): 2.564–6.200, p: 0.000], birth asphyxia (AOR: 3.567, 95% CI: 2.093–6.080, p: 0.000), inotropic agent (AOR: 2.060, 95% CI: 1.436–2.957, p: 0.000), antenatal steroids (AOR: 1.721, 95% CI: 1.213–2.443, p: 0.002), central lines (AOR: 1.630, 95% CI: 1.155–2.298, p: 0.005) and intraventricular hemorrhage (IVH)/intracranial hemorrhage/disseminated intravascular coagulopathy (AOR: 1.580, 95% CI: 1.119–2.231, p: 0.009). AKI significantly increases the duration of stay and mortality rates by 16.5% vs. 3.9% in neonates with normal renal function (p &lt; 0.001).ConclusionAbout one-third of critically sick neonates had AKI. Significant risk factors for AKI were outborn birth, asphyxia inotropic agents, necrotizing enterocolitis, antenatal steroids central lines, and IVH. AKI is associated with an increased length of stay and increased mortality.
A nomogram for predicting upper urinary tract damage risk in children with neurogenic bladder
Authors: Li Qi , Cai Miao , Pu Qingsong , Wu Shengde , Liu Xing , Lin Tao , He Dawei , Wen Jianguo , Wei Guanghui 
Published: December 2022

PurposeTo establish a predictive model for upper urinary tract damage (UUTD) in children with neurogenic bladder (NB) and verify its efficacy.MethodsA retrospective study was conducted that consisted of a training cohort with 167 NB patients and a validation cohort with 100 NB children. The clinical data of the two groups were compared first, and then univariate and multivariate logistic regression analyses were performed on the training cohort to identify predictors and develop the nomogram. The accuracy and clinical usefulness of the nomogram were verified by receiver operating characteristic (ROC) curve, calibration curve and decision curve analyses.ResultsThere were no significant differences in other parameters between the training and validation cohorts except for age (all P &gt; 0.05). Recurrent urinary tract infection, bladder compliance, detrusor leak point pressure, overactive bladder and clean intermittent catheterization were identified as predictors and assembled into the nomogram. The nomogram showed good discrimination with the area under the ROC curve (AUC) in the training cohort (0.806, 95% CI: 0.737–0.874) and validation cohort (0.831, 95% CI: 0.753–0.0.909). The calibration curve showed that the nomograms were well calibrated, with no significant difference between the predicted and observed probabilities. Decision curve analysis indicated that the nomogram has good clinical applicability.ConclusionThis study presents an effective nomogram incorporating five clinical characteristics that can be conveniently applied to assess NB children' risk of progressing to UUTD.
Underlying beneficial effects of Rhubarb on constipation-induced inflammation, disorder of gut microbiome and metabolism
Authors: Gao Han , He Chengwei , Hua Rongxuan , Liang Chen , Wang Boya , Du Yixuan , Xin Shuzi , Guo Yuexin , Gao Lei , Zhang Lucia , Shang Hongwei , Xu Jingdong 
Published: December 2022

Graphical Abstract1. Constipation leads to the enhanced thickness of muscle layer and sedimentation of collagenous fiber. 2. Constipation promotes not only the pro-inflammtory cytokines secretion but also damage the integrity of intestinal barrier. 3. The present results are significant in at least two major respects in the alternations of the diversity of gut microbiome along with the fluctuation of the fatty acid and bioamine in constipation mice. 4. One unanticipated finding is that the rhubarb extract has the potential to reverse the alterations induced by constipation.
Pan-cancer analysis identifies NT5E as a novel prognostic biomarker on cancer-associated fibroblasts associated with unique tumor microenvironment
Authors: Xue Xin-miao , Liu Yu-yang , Chen Xue-min , Tao Bing-yan , Liu Peng , Zhou Han-wen , Zhang Chi , Wang Li , Jiang Yu-ke , Ding Zhi-wei , Shen Wei-dong , Zhang Jun , Yang Shi-ming , Wang Fang-yuan 
Published: December 2022

Background: Ecto-5′-nucleotidase (NT5E) encodes the cluster of differentiation 73 (CD73), whose overexpression contributes to the formation of immunosuppressive tumor microenvironment and is related to exacerbated prognosis, increased risk of metastasis and resistance to immunotherapy of various tumors. However, the prognostic significance of NT5E in pan-cancer is obscure so far.Methods: We explored the expression level of NT5E in cancers and adjacent tissues and revealed the relationship between the NT5E expression level and clinical outcomes in pan-cancer by utilizing the UCSC Xena database. Then, correlation analyses were performed to evaluate the relationship between NT5E expression and immune infiltration level via EPIC, MCP-counter and CIBERSORT methods, and the enrichment analysis were employed to identify NT5E-interacting molecules and functional pathways. Furthermore, we conducted single-cell analysis to explore the potential role of NT5E on single-cell level based on the CancerSEA database. Meanwhile, gene set enrichment analysis (GSEA) in single-cell level was also conducted in TISCH database and single-cell signature explorer was utilized to evaluate the epithelial-mesenchymal transition (EMT) level in each cell type.Results: The expression level of NT5E was aberrant in almost all cancer types, and was correlated with worse prognosis in several cancers. Notably, NT5E overexpression was related to worse overall survival (OS) in pancreatic adenocarcinoma (PAAD), head and neck squamous cell carcinoma (HNSC), mesothelioma (MESO), stomach adenocarcinoma (STAD), uveal melanoma (UVM) and cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) (p &lt; 0.01). NT5E-related immune microenvironment analysis revealed that NT5E is associated positively with the degree of infiltration of cancer-associated fibroblasts (CAFs) and endothelial cells in most cancers. Enrichment analysis of cellular component (CC) demonstrated the critical part of NT5E played in cell-substrate junction, cell-substrate adherens junction, focal adhesion and external side of plasma membrane. Finally, single-cell analysis of NT5E illuminated that EMT function of CAFs was elevated in basal cell carcinoma (BCC), skin cutaneous melanoma (SKCM), HNSC and PAAD.Conclusion: NT5E could serve as a potential prognostic biomarker for cancers. The potential mechanism may be related to the upregulated EMT function of CAFs, which provides novel inspiration for immunotherapy by targeting CAFs with high NT5E expression.