bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut Microbiota Dysbiosis in BK Polyomavirus-Infected Renal Transplant Recipients: A Case-Control Study
Authors: Zhang Jian , Qin Hao , Chang Mingyu , Yang Yang , Lin Jun 
Published: May 2022

BackgroundBK polyomavirus infection results in renal allograft dysfunction, and it is important to find methods of prediction and treatment. As a regulator of host immunity, changes in the gut microbiota are associated with a variety of infections. However, the correlation between microbiota dysbiosis and posttransplant BK polyomavirus infection was rarely studied. Thus, this study aimed to characterize the gut microbiota in BK polyomavirus-infected renal transplant recipients in order to explore the biomarkers that might be potential therapeutic targets and establish a prediction model for posttransplant BK polyomavirus infection based on the gut microbiota.MethodsWe compared the gut microbial communities of 25 BK polyomavirus-infected renal transplant recipients with 23 characteristic-matched controls, applying the 16S ribosomal RNA gene amplicon sequencing technique.ResultsAt the phylum level, Firmicutes/Bacteroidetes ratio significantly increased in the BK polyomavirus group. Bacteroidetes was positively correlated with CD4/CD8 ratio. In the top 20 dominant genera, Romboutsia and Roseburia exhibited a significant difference between the two groups. No significant difference was observed in microbial alpha diversity. Beta diversity revealed a significant difference between the two groups. Nine distinguishing bacterial taxa were discovered between the two groups. We established a random forest model using genus taxa to predict BK polyomavirus infectious status, which achieved the best accuracy (80.71%) with an area under the curve of 0.82. Two genera were included in the best model, which were Romboutsia and Actinomyces.ConclusionsBK polyomavirus-infected patients had gut microbiota dysbiosis in which the Firmicutes/Bacteroidetes ratio increased in the course of the viral infection. Nine distinguishing bacterial taxa might be potential biomarkers of BK polyomavirus infection. The random forest model achieved an accuracy of 80.71% in predicting the BKV infectious status, with Romboutsia and Actinomyces included.
Three-Dimensional Modeling of Thyroid Hormone Metabolites Binding to the Cancer-Relevant αvβ3 Integrin: In-Silico Based Study
Authors: Tobi Dror , Krashin Eilon , Davis Paul J. , Cody Vivian , Ellis Martin , Ashur-Fabian Osnat 
Published: May 2022

BackgroundThyroid hormones (TH), T4 and T3, mediate pro-mitogenic effects in cancer cells through binding the membrane receptor αvβ3 integrin. The deaminated analogue tetrac effectively blocks TH binding to this receptor and prevents their action. While computational data on TH binding to the αvβ3 integrin was published, a comprehensive analysis of additional TH metabolites is lacking.MethodsIn-silico docking of 26 TH metabolites, including the biologically active thyroid hormones (T3 and T4) and an array of sulfated, deiodinated, deaminated or decarboxylated metabolites, to the αvβ3 receptor binding pocket was performed using DOCK6, based on the three-dimensional representation of the crystallographic structure of the integrin. As the TH binding site upon the integrin is at close proximity to the well-defined RGD binding site, linear and cyclic RGD were included as a reference. Binding energy was calculated for each receptor-ligand complex using Grid score and Amber score with distance movable region protocol.ResultsAll TH molecules demonstrated negative free energy, suggesting affinity to the αvβ3 integrin. Notably, based on both Grid and Amber scores sulfated forms of 3,3’ T2 (3,3’ T2S) and T4 (T4S) demonstrated the highest binding affinity to the integrin, compared to both cyclic RGD and an array of examined TH metabolites. The major thyroid hormones, T3 and T4, showed high affinity to the integrin, which was superior to that of linear RGD. For all hormone metabolites, decarboxylation led to decreased affinity. This corresponds with the observation that the carboxylic group mediates binding to the integrin pocket via divalent cations at the metal-ion-dependent adhesion (MIDAS) motif site. A similar reduced affinity was documented for deaminated forms of T3 (triac) and T4 (tetrac). Lastly, the reverse forms of T3, T3S, and T3AM showed higher Amber scores relative to their native form, indicating that iodination at position 5 is associated with increased binding affinity compared to position 5’.SummaryThree-dimensional docking of various TH metabolites uncovered a structural basis for a differential computational free energy to the αvβ3 integrin. These findings may suggest that naturally occurring endogenous TH metabolites may impact integrin-mediate intracellular pathways in physiology and cancer.
Experimental Investigation on the Perturbation Length for Air–Water Flow Upstream and Downstream of U-Bends
Authors: Ma Xiaoxu , Liu Taicheng , Dai Nan , Tian Maocheng , Li Shijie 
Published: May 2022

In this work, the perturbation length of vertical U-bend effects on the air–water two-phase flow in their adjacent straight tubes was investigated experimentally at ambient pressure and temperature. The experimental database covered test sections with three inner diameters of U-tubes (9, 12, and 16 mm), two curvature ratios (8.33 and 12.5), and two orientations (downward and upward). The air and water superficial velocities varied from 0.18 to 25.11 m/s and from 0.11 to 1.98 m/s, respectively. The dissipation of U-bend effects in the regions upstream and downstream of U-bends is characterized by the variation regularities of segmental pressure gradients along the contiguous straight tubes. It was found that the significant value of the dimensionless perturbation length (Lp/D) is less than 60 for the experimental conditions in this study. The influences of the inlet volume void fraction, two-phase mixed Froude number, mixed Weber number, and mixed Dean number on dimensionless perturbation length (Lp/D) are similar. With the increase in these parameters, Lp/D presents a unimodal distribution which first increases and then decreases. The maximum value of Lp/D takes place at a volume void fraction of around 90%. New dimensionless correlations to predict the influence length of U-bends on the straight tubes upstream and downstream have been provided. The prediction errors of 80% of data are within ± 30% compared with the present experimental data.
Development of a Novel Immune-Related Gene Signature to Predict Prognosis and Immunotherapeutic Efficiency in Gastric Cancer
Authors: Liu Dongliang , Xu Yuanmin , Fang Yu , Hu Kongwang 
Published: May 2022

Background: Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of tumor-related deaths globally. Herein, we attempted to build a novel immune-related gene (IRG) signature that could predict the prognosis and immunotherapeutic efficiency for GC patients.Methods: The mRNA transcription data and corresponding clinical data of GC were downloaded from The Cancer Genome Atlas (TCGA) database as the training group and the GSE84437 data set as the testing cohort, followed by acquisition of IRGs from the InnateDB resource and ImmPort database. Using the univariate Cox regression analysis, an IRG signature was developed. Several immunogenomic analyses were performed to illustrate the associations between the immune risk score and tumor mutational burden, immune cell infiltrations, function of immune infiltration, clinical characteristics, immune subtype, and immunotherapeutic response.Results: The analysis of 343 GC samples and 30 normal samples from the TCGA database gave rise to 8,713 differentially expressed genes (DEGs) and 513 differentially expressed immune-related genes (DEIRGs) were extracted. The novel IRG signature contained eight DEIRGs (FABP4, PI15, RNASE2, CGB5, INHBE, RLN2, DUSP1, and CD36) and was found to serve as an independent predictive and prognostic factor for GC. Then, the GC patients were separated into the high- and low-risk groups based on the median risk score, wherein the low-risk group presented a better prognosis and was more sensitive to immunotherapy than did the high-risk group. According to the time-dependent ROC curves and AUCs, the immunotherapeutic value of the signature was better than the Tumor Immune Dysfunction and Exclusion (TIDE) and T-cell inflammatory signature (TIS) scores. In addition, the AUCs of the risk score for predicting 1-, 2-, and 3-year OS were 0.675, 0.682, and 0.710, respectively, which indicated that the signature had great predictive power.Conclusion: This study presents a novel IRG signature based on the tumor immune microenvironment, which could improve the prediction of the prognosis and immunotherapeutic efficiency for GC patients. The powerful signature may serve as novel biomarkers and provide therapeutic targets for precision oncology in clinical practice.
Induction of Pyroptosis in Renal Tubular Epithelial Cells Using High Glucose
Authors: Liu Yinghong , He Mingyue , Xiong Hao , Yuan Fang 
Published: May 2022

BackgroundThe micro-inflammatory state is important for the occurrence of diabetic kidney disease (DKD). Here, we aimed to explore the expression of pyroptosis related indicators and ultrastructural characteristics in DKD, and investigate pyroptosis in renal tubular epithelial cells induced by high glucose.MethodsImmunohistochemistry was used to detect expression of the inflammation-related protein NOD-like receptor protein 3 (NLRP3) and pyroptosis key protein gasdermin D (GSDMD) in kidney tissues of DKD patients. HK-2 cells were cultured in vitro and stimulated with different concentrations of glucose. The changes in HK-2 cell ultrastructure were observed using electronmicroscopy, and western blot was used to detect NLRP3, caspase-1 p20, GSDMD-N, interleukin (IL)-1β, and IL-18 expression.ResultsNLRP3 and GSDMD expression in kidney tissues of DKD patients was higher than that in control subjects. Further, GSDMD expression was positively correlated with that of NLRP3 (r = 0.847, P = 0.02). After stimulating HK-2 cells for 24 h with different glucose concentrations, compared with the control group, the 15 and 30 mmol/L glucose groups showed typical ultrastructural changes of pyroptosis. The protein expression of NLRP3, caspase-1 p20, GSDMD-N, IL-1β, and IL-18 expression in high glucose group increased significantly compared with the control group, and was glucose-concentration-dependent.ConclusionHigh glucose can activate inflammasome, cause inflammatory cytokines release, and induce pyroptosis in HK-2 cells. NLRP3-caspase-1 may be involved in GSDMD-mediated pyroptosis. This study shows a novel relationship between glucose concentration and pyroptosis, which can be studied further to design better therapies for patients with DKD.
Comparing Poor and Favorable Outcome Prediction With Machine Learning After Mechanical Thrombectomy in Acute Ischemic Stroke
Authors: Mutke Matthias A. , Madai Vince I. , Hilbert Adam , Zihni Esra , Potreck Arne , Weyland Charlotte S. , Möhlenbruch Markus A. , Heiland Sabine , Ringleb Peter A. , Nagel Simon , Bendszus Martin , Frey Dietmar 
Published: May 2022

Background and PurposeOutcome prediction after mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO) is commonly performed by focusing on favorable outcome (modified Rankin Scale, mRS 0–2) after 3 months but poor outcome representing severe disability and mortality (mRS 5 and 6) might be of equal importance for clinical decision-making.MethodsWe retrospectively analyzed patients with AIS and LVO undergoing MT from 2009 to 2018. Prognostic variables were grouped in baseline clinical (A), MRI-derived variables including mismatch [apparent diffusion coefficient (ADC) and time-to-maximum (Tmax) lesion volume] (B), and variables reflecting speed and extent of reperfusion (C) [modified treatment in cerebral ischemia (mTICI) score and time from onset to mTICI]. Three different scenarios were analyzed: (1) baseline clinical parameters only, (2) baseline clinical and MRI-derived parameters, and (3) all baseline clinical, imaging-derived, and reperfusion-associated parameters. For each scenario, we assessed prediction for favorable and poor outcome with seven different machine learning algorithms.ResultsIn 210 patients, prediction of favorable outcome was improved after including speed and extent of recanalization [highest area under the curve (AUC) 0.73] compared to using baseline clinical variables only (highest AUC 0.67). Prediction of poor outcome remained stable by using baseline clinical variables only (highest AUC 0.71) and did not improve further by additional variables. Prediction of favorable and poor outcomes was not improved by adding MR-mismatch variables. Most important baseline clinical variables for both outcomes were age, National Institutes of Health Stroke Scale, and premorbid mRS.ConclusionsOur results suggest that a prediction of poor outcome after AIS and MT could be made based on clinical baseline variables only. Speed and extent of MT did improve prediction for a favorable outcome but is not relevant for poor outcome. An MR mismatch with small ischemic core and larger penumbral tissue showed no predictive importance.
Poor Pre-operative Nutritional Status Is a Risk Factor of Post-operative Infections in Patients With Gastrointestinal Cancer—A Multicenter Prospective Cohort Study
Authors: Zhang Li , Wang Siwen , Gao Xuejin , Gao Tingting , Huang Lingli , Lian Bo , Gu Yingchao , Chen Jianjiao , Guo Dong , Jia Zhenyi , Wang Yong , Gong Fangyou , Zhou Junde , Xue Zhigang , Chen Zhida , Xu Jielian , Wang Leilei , Qian Jun , Deng Guifang , Hu Hao , Nie Yao , Li Gang , Li Mengbin , Yang Hua , Zhao Wei , Zhou Yanbing , Qin Huanlong , Wu Xiaoting , Wang Kunhua , Chi Qiang , Yu Jianchun , Tang Yun , Zhang Pianhong , Jin Gang , Ouyang Bin , Li Guoli , Hang Dong , Wang Xinying 
Published: May 2022

ObjectiveThis study aimed to assess the prognostic value of the Nutritional Risk Score 2002 (NRS2002) and patient-generated subjective global assessment (PG-SGA) for post-operative infections in patients with gastric cancer (GC) and colorectal cancer (CRC) who underwent curative surgery.MethodsThis prospective study included 1,493 GC patients and 879 CRC patients who underwent curative surgery at 18 hospitals in China between April 2017 and March 2020. The NRS2002 and PG-SGA were performed on the day of admission. The relationship between the nutritional status of patients before surgery and post-surgical incidence of infection was analyzed using univariate and multiple logistic regression analyses.ResultsAccording to NRS2002, the prevalence of nutritional risk was 51.1% in GC patients and 63.9% in CRC patients. According to the PG-SGA, 38.9% of GC patients and 54.2% of CRC patients had malnutrition. Approximately 4.4% of the GC patients and 9.9% of the CRC patients developed infectious complications after surgery. The univariate and multiple logistic regression analyses showed that the risk of infections was significantly higher in GC patients with a high nutritional risk score (NRS2002 ≥5) than in those with a low score (NRS2002 &lt;3), and the PG-SGA score was identified as a predictor of post-operative infection complications of CRC.ConclusionThe pre-operative nutritional status of patients with GC or CRC has an impact on post-operative infection occurrence. NRS2002 ≥5 was a risk factor for post-operative infection in patients with GC, and the PG-SGA B/C was a predictor of infections in patients with CRC.
Prevalence and Clinicopathologic Features of Canine Metastatic Melanoma Involving the Central Nervous System: A Retrospective Analysis and Comparative Review
Authors: Razmara Aryana M. , Wittenburg Luke A. , Al-Nadaf Sami , Toedebusch Ryan G. , Meyers Frederick J. , Toedebusch Christine M. 
Published: May 2022

BackgroundCentral nervous system (CNS) involvement is the leading cause of death in malignant melanoma. Rodent models, while vital to mechanistic investigation, have had limited success identifying effective therapies for melanoma brain metastases. The companion dog withde novomelanoma is a promising complementary model for developmental therapeutic investigation, as these tumors occur in an immunologically outbred host that has shared environmental exposures with humans. However, relatively little is known regarding the prevalence and clinicopathological features of canine melanoma metastasis to the CNS. To further validate the dog as an appropriate model for human metastatic melanoma, the aims of this study were to determine the rate of CNS metastasis and associated clinicopathologic features in canine malignant melanoma.MethodsMedical records of dogs diagnosed with malignant melanoma from 1985-2019 at the University of California Davis Veterinary Medical Teaching Hospital were assessed retrospectively. Clinicopathologic features were compared between dogs with CNS metastasis (CNS+) and dogs without CNS metastasis (CNS-). Site of CNS involvement and associated neurological signs were analyzedviaWilcoxon-Mann-Whitney rank sum and Fisher’s exact tests. Survival data were analyzedviaKaplan-Meier estimates.ResultsCNS metastasis was identified in 38% of dogs in this study (20/53). The oral cavity was the most common site of primary melanoma in both groups [CNS+: n=12 (60%) vs. CNS-: n=22 (67%); p&gt;0.99]. The total burden of metastatic disease was higher in the CNS+ group (CNS+: 4, 95% CI 3-5 vs. CNS-: 3, 95% CI 1-3; p&lt;0.001). The cerebrum was the most common site of CNS metastasis (n=15, 75%) and seizures were the most observed neurological sign (n=9, 64%). There was no difference in overall survival between CNS+ and CNS- groups. However, the median survival time following onset of neurological signs was 9.5 days (95% CI 1-43), with 5 dogs euthanized within 24 hours of the onset of neurological signs.ConclusionsCanine and human MM patients share similar rates of CNS metastasis and clinical presentation. This study will guide clinical management of canines with malignant melanoma and inform future studies using dogs with spontaneously occurring melanoma as a preclinical model for human melanoma brain metastases.
Multimodal MRI-Based Radiomics-Clinical Model for Preoperatively Differentiating Concurrent Endometrial Carcinoma From Atypical Endometrial Hyperplasia
Authors: Zhang Jieying , Zhang Qi , Wang Tingting , Song Yan , Yu Xiaoduo , Xie Lizhi , Chen Yan , Ouyang Han 
Published: May 2022

ObjectivesTo develop and validate a radiomics model based on multimodal MRI combining clinical information for preoperative distinguishing concurrent endometrial carcinoma (CEC) from atypical endometrial hyperplasia (AEH).Materials and MethodsA total of 122 patients (78 AEH and 44 CEC) who underwent preoperative MRI were enrolled in this retrospective study. Radiomics features were extracted based on T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) maps. After feature reduction by minimum redundancy maximum relevance and least absolute shrinkage and selection operator algorithm, single-modal and multimodal radiomics signatures, clinical model, and radiomics-clinical model were constructed using logistic regression. Receiver operating characteristic (ROC) analysis, calibration curves, and decision curve analysis were used to assess the models.ResultsThe combined radiomics signature of T2WI, DWI, and ADC maps showed better discrimination ability than either alone. The radiomics-clinical model consisting of multimodal radiomics features, endometrial thickness &gt;11mm, and nulliparity status achieved the highest area under the ROC curve (AUC) of 0.932 (95% confidential interval [CI]: 0.880-0.984), bootstrap corrected AUC of 0.922 in the training set, and AUC of 0.942 (95% CI: 0.852-1.000) in the validation set. Subgroup analysis further revealed that this model performed well for patients with preoperative endometrial biopsy consistent and inconsistent with postoperative pathologic data (consistent group, F1-score = 0.865; inconsistent group, F1-score = 0.900).ConclusionsThe radiomics model, which incorporates multimodal MRI and clinical information, might be used to preoperatively differentiate CEC from AEH, especially for patients with under- or over-estimated preoperative endometrial biopsy.
Skeletal Muscle Change During Neoadjuvant Therapy and Its Impact on Prognosis in Patients With Gastrointestinal Cancers: A Systematic Review and Meta-Analysis
Authors: Xu Xin-Yi , Jiang Xiao-Man , Xu Qin , Xu Hao , Luo Jin-Hua , Yao Cui , Ding Ling-Yu , Zhu Shu-Qin 
Published: May 2022

BackgroundGastrointestinal cancers are the most common malignant tumors worldwide. As the improvement of survival by surgical resection alone for cancers is close to the bottleneck, recent neoadjuvant therapy has been emphasized and applied in the treatment. Despite the advantage on improving the prognosis, some studies have reported neoadjuvant therapy could reduce skeletal muscle and therefore affect postoperative outcomes. However, the conclusions are still controversial.MethodsPubMed, CINAHL, Embase, and Cochrane Library were searched from inception to September 2, 2021. The inclusion criteria were observational studies, published in English, of individuals aged ≥18 years who underwent neoadjuvant therapy with gastrointestinal cancers and were assessed skeletal muscle mass before and after neoadjuvant therapy, with sufficient data on skeletal muscle change or the association with clinical outcomes. Meta-analysis was conducted by using the STATA 12.0 package when more than two studies reported the same outcome.ResultsA total of 268 articles were identified, and 19 studies (1,954 patients) were included in the review. The fixed effects model showed that the risk of sarcopenia increased 22% after receiving neoadjuvant therapy (HR=1.22, 95% CI 1.14, 1.31, Z=4.286, P&lt;0.001). In the random effects model, neoadjuvant therapy was associated with skeletal muscle loss, with a standardized mean difference of -0.20 (95% CI -0.31, -0.09, Z=3.49, P&lt;0.001) and a significant heterogeneity (I2 =62.2%, P&lt;0.001). Multiple meta regression indicated that population, neoadjuvant therapy type, and measuring tool were the potential sources of heterogeneity. The funnel plot revealed that there was no high publication bias in these studies (Begg’s test, P=0.544) and the sensitivity analysis showed stable results when separately excluding studies. For the postoperative outcomes, the results revealed that muscle loss during neoadjuvant therapy was significantly related to overall survival (HR=2,08, 95% CI =1.47, 2.95, Z=4.12, P&lt;0.001, I2 = 0.0%), but not related to disease-free survival and other short-term outcomes.ConclusionsThis systematic review and meta-analysis revealed that skeletal muscle decreased significantly during neoadjuvant therapy in patients with gastrointestinal cancers and skeletal muscle loss was strongly associated with worse overall survival. More high-quality studies are needed to update and valid these conclusions in a more specific or stratified way.Systematic Review Registration[https://www.crd.york.ac.uk/PROSPERO/], identifier PROSPERO (CRD42021292118)