bluuebunny/crossref_metadata_2025_split huggingface dataset:
Missed meal boluses and poorer glycemic control impact on neurocognitive function may be associated with white matter integrity in adolescents with type 1 diabetes
Authors: Litmanovitch Edna , Geva Ronny , Leshem Avital , Lezinger Mirit , Heyman Eli , Gidron Maor , Yarmolovsky Jessica , Sasson Efrat , Tal Sigal , Rachmiel Marianna 
Published: April 2023

BackgroundThe notion that pediatric type 1 diabetes impacts brain function and structure early in life is of great concern. Neurological manifestations, including neurocognitive and behavioral symptoms, may be present from childhood, initially mild and undetectable in daily life. Despite intensive management and technological therapeutic interventions, most pediatric patients do not achieve glycemic control targets for HbA1c. One of the most common causes of such poor control and frequent transient hyperglycemic episodes may be lifestyle factors, including missed meal boluses.ObjectiveThe aim of this study was to assess the association between specific neurocognitive accomplishments—learning and memory, inhibition ability learning, and verbal and semantic memory—during meals with and without bolusing, correlated to diffusion tensor imaging measurements of major related tracts, and glycemic control in adolescents with type 1 diabetes compared with their healthy siblings of similar age.Study design and methodsThis is a case–control study of 12- to 18-year-old patients with type 1 diabetes (N = 17, 8 male patients, diabetes duration of 6.53 ± 4.1 years) and their healthy siblings (N = 13). All were hospitalized for 30 h for continuous glucose monitoring and repeated neurocognitive tests as a function of a missed or appropriate pre-meal bolus. This situation was mimicked by controlled, patient blinded manipulation of lunch pre-meal bolus administration to enable capillary glucose level of &lt;180 mg/dl and to &gt;240 mg/d 2 hours after similar meals, at a similar time. The diabetes team randomly and blindly manipulated post-lunch glucose levels by subcutaneous injection of either rapid-acting insulin or 0.9% NaCl solution before lunch. A specific neurocognitive test battery was performed twice, after each manipulation, and its results were compared, along with additional neurocognitive tasks administered during hospitalization without insulin manipulation. Participants underwent brain imaging, including diffusion tensor imaging and tractography.ResultsA significant association was demonstrated between glycemic control and performance in the domains of executive functions, inhibition ability, learning and verbal memory, and semantic memory. Inhibition ability was specifically related to food management. Poorer glycemic control (&gt;8.3%) was associated with a slower reaction time.ConclusionThese findings highlight the potential impairment of brain networks responsible for learning, memory, and controlled reactivity to food in adolescents with type 1 diabetes whose glycemic control is poor.
Differential analysis of fish meal substitution with two soybean meals on juvenile pearl gentian grouper
Authors: Pang Aobo , Xin Yu , Xie Ruitao , Wang Zhuoduo , Zhang Wei , Tan Beiping 
Published: April 2023

Fermented soybean meal and soybean protein concentrate are products of soybean that have been processed physically or biologically, and their use as an alternative to fish meal results in a significant reduction in the effects of anti-nutritional factors (ANFs) in soybean on aquatic species. Replacing fish meal with soybean protein concentrate and fermented soybean meal can meet the high protein requirements of carnivorous fish while effectively reducing aquaculture costs; however, excessive substitution can also cause economic losses. In this study, we used transcriptome sequencing to investigate the impacts of fermented soybean meal and soybean protein concentrate on the growth and physiology of pearl gentian grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) juveniles and to examine the mechanisms by which fermented soybean meal and soybean protein concentrate impair the intestinal condition of fish. Originally weighed 12.55 ± 0.06 g, the selected pearl gentian groupers were categorised into three treatment groups: one group was fed fish meal-based diets (FM, control group), one group was fed fish meal- and soybean protein concentrate-based diets (SPC40) and one group was fed fish meal- and fermented soybean meal-based diets (FSBM40), with the same crude protein and crude fat content in all three diets. The experiment was conducted for 10 weeks. The growth results showed that both the fermented soybean meal and soybean protein concentrate diets significantly inhibited the growth of the fish. Based on the results of enzyme activity, substance content and gene expression levels associated with intestinal damage and intestinal inflammation, it is highly likely that the fermented soybean meal and soybean protein concentrate diets affected the intestinal health of the fish and triggered intestinal inflammation. This study provides a theoretical basis to further explore the mechanism of soybean-initiated intestinal problems in fish.
Efficacy and safety of Tuina (Chinese Therapeutic Massage) for knee osteoarthritis: A randomized, controlled, and crossover design clinical trial
Authors: Liu Kaoqiang , Zhan Yunfan , Zhang Yujie , Zhao Ye , Chai Yongli , Lv Hua , Yuan Weian 
Published: April 2023

BackgroundKnee osteoarthritis (KOA) is a highly prevalent joint disease among the middle-aged and elderly population that can lead to pain, functional impairment, decreased quality of life, and a large number of medical expenses. Physical therapy is one of the main treatment methods for KOA. In China, Tuina has been widely used in the treatment of KOA, but up to now, there is no high-quality medical evidence to support its effectiveness and safety. The purpose of this study was to objectively evaluate the efficacy and safety of Tuina in the treatment of KOA.MethodsA crossover design clinical trial was performed on 96 patients. The test group and the control group in the trial were allocated randomly in a ratio of 1:1. The test group received Tuina treatment for 4 weeks first and then received health education intervention for another 4 weeks. The control group received health education intervention for 4 weeks first and then received Tuina treatment for another 4 weeks. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) total score was chosen as the primary outcome. The WOMAC pain score, WOMAC stiffness, WOMAC daily activity score, and visual analog scale (VAS) score were the secondary outcomes. Adverse events during the intervention were collected in both groups.ResultsCompared with the baseline, the WOMAC total score, WOMAC pain score, WOMAC stiffness, WOMAC daily activity, and VAS score of patients in both groups were improved significantly at weeks 4 and 8 (p &lt; 0.001). All patients who received Tuina treatment were significantly superior to those who received health education intervention in the WOMAC total score (194.96, 95% CI = 164.94–224.97, P &lt; 0.001), WOMAC pain score (45.96, 95% CI = 35.82–56.09, P &lt; 0.001), WOMAC stiffness (31.42, 95% CI = 26.37–36.46, P &lt; 0.001), WOMAC daily activity (117.58, 95% CI = 97.56–137.61, P &lt; 0.001), and VAS score (1.07, 95% CI = 0.83–1.32, P &lt; 0.001). Both groups had no serious adverse events during the treatment.ConclusionThis trial demonstrated that Tuina can reduce joint pain in patients with KOA and improve the physical functions of the knee joint effectively and safely.Clinical trial registrationThis trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR-TTRCC-13003157). http://www.chictr.org.cn/showproj.aspx?proj=6402.
Alteration of pro-carcinogenic gut microbiota is associated with clear cell renal cell carcinoma tumorigenesis
Authors: Yang Bo-Yu , Zhao Fang-Zhou , Li Xuan-Hao , Zhao Mei-Shan , Lv Jing-Cheng , Shi Ming-Jun , Li Jun , Zhou Zhi-Yuan , Wang Jing-Jing , Song Jian 
Published: April 2023

ObjectiveIncreasing evidence suggests that gut microbiota is involved in the occurrence and progression of urinary system diseases such as clear cell renal cell carcinoma (ccRCC). However, the mechanism of how alteration of gut metagenome promotes ccRCC remains unclear. Here we aim to elucidate the association of specific gut bacteria and their metabolites with ccRCC.MethodsIn a pilot case-control study among 30 ccRCC patients (RCC group) and 30 healthy controls (Control group), 16S ribosomal RNA (rRNA) gene sequencing were analyzed from fecal samples collected prior to surgery or hospitalization. Alpha diversity and beta diversity analysis of the gut microbiota were performed, and differential taxa were identified by multivariate statistics. Meanwhile, serum metabolism was measured by UHPLC-MS, and differential genes were identified based on the TCGA database.ResultsAlpha diversity found there were no significant microbial diversity differences of gut microbiota between the RCC group and the Control group. However, beta diversity analysis showed that the overall structures of the two groups were significantly separated (p = 0.008). Random Forests revealed the relative abundances of 20 species differed significantly between the RCC group and the Control group, among which nine species were enriched in the RCC group such as Desulfovibrionaceae, and 11 species were less abundant such as four kinds of Lactobacillus. Concomitantly, serum level of taurine, which was considered to be consumed by Desulfovibrionaceae and released by Lactobacillus, has decreased in the RCC group. In addition, macrophage-related genes such as Gabbr1 was upregulated in ccRCC patients.ConclusionReduction of protective bacteria, proliferation of sulfide-degrading bacteria Desulfovibrionaceae, reduction of taurine, and enrichment of macrophage related genes might be the risk predictors of ccRCC.
Integration of microRNA and mRNA analyses depicts the potential roles of Momordica charantia saponin administration in insulin resistance of juvenile common carp (Cyprinus carpio) fed with a high-starch diet
Authors: Fan Ze , Wang Liansheng , Li Chenhui , Wu Di , Li Jinnan , Zhang Haitao , Xiong Siwei , Miao Linghong , Ge Xianping , Li Zhengwei 
Published: April 2023

Background: The regulation of target gene mRNA mediated by microRNA may play an important role in glucose metabolism in fish. Previous research findings of our research group revealed that Momordica charantia saponin (MS) administration in a high-starch diet could improve insulin resistance of common carp through renovating insulin signaling pathways, whose fundamental mechanisms have remained unknown by far. To reveal this potential mechanism, we aimed to investigate the difference in miRNA and mRNA expression profiles between common carp fed with high-starch diets containing MS (HS_MS1 and HS_MS2) and common carp fed with high-starch (HS) diets.Results: Through miRNA deep-sequencing, 10 significantly differentially expressed miRNAs in HC and HS_MS1, including one upregulated and nine downregulated miRNAs, were identified, whereas 10 significantly differentially expressed miRNAs in HC and HS_MS2, including four upregulated and six downregulated miRNAs, were identified. These miRNAs may not only be involved in the regulation of insulin signaling pathways and insulin resistance in common carp but also be the markers for liver insulin resistance in MS therapy for the remission of insulin resistance. This study identified 10 potential known miRNAs, namely, ccr-miR-10b, ccr-miR-122, ccr-miR-143, ccr-miR-146a, ccr-miR-155, ccr-miR-16c, ccr-miR-200a, ccr-miR-29a, ccr-miR-34, and ccr-miR-375, as candidates participating in modulating the liver insulin resistance. According to the biopathway enrichment analysis of the 252 target genes using the KEGG classical biopathway database, the relative expression levels of gsk3bb, pik3r1, and pik3r3b were analyzed using RNA-seq. Compared to the HC group, a significant decrease in the relative expression levels of pik3r1 and pik3r3b was observed in HS_MS1 and HS_MS2 groups (p &lt; 0.05). This study raised a presumption of the presence of ccr-miR-29a targeting pik3r1 or ccr-miR-143 targeting pik3r3 playing likely roles in Momordica charantia saponins remitting the liver insulin resistance.Conclusion: The findings will further deepen the understanding of the carbohydrate metabolism of common carp and provide an important scientific basis for the application of Momordica saponins as functional nutrients to alleviate insulin resistance of fish in fish culture.
Comparative study of size exclusion chromatography for isolation of small extracellular vesicle from cell-conditioned media, plasma, urine, and saliva
Authors: Contreras Hector , Alarcón-Zapata Pedro , Nova-Lamperti Estefania , Ormazabal Valeska , Varas-Godoy Manuel , Salomon Carlos , Zuniga Felipe A. 
Published: April 2023

Introduction: Extracellular vesicles (EVs) are secreted from all types of cells and are involved in the trafficking of proteins, metabolites, and genetic material from cell to cell. According to their biogenesis and physical properties, EVs are often classified as small EVs (including exosomes) or large EVs, and large oncosomes. A variety of methods are used for isolated EVs; however, they have several limitations, including vesicle deformation, reduced particle yield, and co-isolate protein contaminants. Here we present an optimized fast and low-cost methodology to isolate small EVs (30–150 nm) from biological fluids comparing two SEC stationary phases, G200/120 and G200/140 columns.Methods: The optimization parameters considered were a) the selection of the stationary phase, b) the eluate volume per fraction, and c) the selection of the enriched 30–150 nm EVs-fractions. The efficiency and separation profile of each UF/SEC fraction was evaluated by Nanoparticle tracking analysis (NTA), flow cytometry, total protein quantification, and Western blot.Results: Both columns can isolate predominantly small EVs with low protein contaminants from plasma, urine, saliva, and HEK293-derived EV from collection medium. Column G200/ 40 offers a more homogeneous enrichment of vesicles between 30 and 150 nm than G200/120 [76.1 ± 4.4% with an average size of 85.9 ± 3.6 nm (Mode: 72.8 nm)] in the EV collection medium. The enrichment, estimated as the vesicle-to-protein ratio, was 1.3 × 1010 particles/mg protein for G200/40, obtaining a more significant EVs enrichment compared to G200/120. The optimized method delivers 0.8 ml of an EVs-enriched-outcome, taking only 30 min per sample. Using plasma, the enrichment of small EVs from the optimized method was 70.5 ± 0.18%, with an average size of 119.4 ± 6.9 nm (Mode: 120.3 nm), and the enrichment of the vesicle isolation was 4.8 × 1011 particles/mg protein. The average size of urine and saliva -EVs samples was 147.5 ± 3.4 and 111.9 ± 2.5 nm, respectively. All the small EVs isolated from the samples exhibit the characteristic cup-shaped morphology observed by Transmission electron microscopy (TEM).Discussion: This study suggests that the combination of methods is a robust, fast, and improved strategy for isolating small EVs.
Elevated red blood cell distribution width levels predict depression after intracerebral hemorrhage: A 3-month follow-up study
Authors: Zhou Xianping , Li Yaqiang , Sun Zhongbo , Mu Li , Ma Yaoyao 
Published: April 2023

ObjectivesInflammation vitally impacts the progression of depression resulting from intracerebral hemorrhage (ICH), while red blood cell distribution width (RDW) marks inflammatory-related diseases. The present study aimed at evaluating how RDW affects depression after ICH.MethodsFrom prospective analyses of patients admitted to our department between January 2017 and September 2022, ICH patients with complete medical records were evaluated. The 17-item Hamilton Depression (HAMD-17) scale was used for measuring the depressive symptoms at 3 months after ICH. Diagnosis of post-ICH depression was conducted for patients based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria.ResultsA total of 438 patients were enrolled in the study, out of which 93 (21.23%) patients had PSD at the 3-month follow-up. Accordingly, patients with depression had higher RDW levels (13.70 [IQR: 13.56–13.89] vs.13.45 [IQR: 12.64–13.75], p &lt; 0.001) at admission compared with those without depression. In multivariate analyses, RDW was used for independently predicting the depression after ICH at 3 months (OR: 2.832 [95% CI: 1.748–4.587], p &lt; 0.001). After adjusting the underlying confounding factors, the odds ratio (OR) of depression after ICH was 4.225 (95% CI: 1.686–10.586, p = 0.002) for the highest tertile of RDW relative to the lowest tertile. With an AUC of 0.703 (95% CI: 0.649–0.757), RDW demonstrated a significantly better discriminatory ability relative to CRP and WBC. RDW as an indicator for predicting depression after ICH had an optimal cutoff value of 13.68, and the sensitivity and specificity were 63.4% and 64.6%, respectively.ConclusionsElevated RDW level predicted post-ICH depression at 3 months, confirming RDW as an effective inflammatory marker for predicting depression after ICH.
A nomogram for predicting the risk of pulmonary embolism in neurology department suspected PE patients: A 10-year retrospective analysis
Authors: Jianling Qiang , Lulu Jin , Liuyi Qiu , Lanfang Feng , Xu Ma , Wenchen Li , Maofeng Wang 
Published: April 2023

ObjectiveThe purpose of this retrospective study was to establish a numerical model for predicting the risk of pulmonary embolism (PE) in neurology department patients.MethodsA total of 1,578 subjects with suspected PE at the neurology department from January 2012 to December 2021 were considered for enrollment in our retrospective study. The patients were randomly divided into the training cohort and the validation cohort in the ratio of 7:3. The least absolute shrinkage and selection operator regression were used to select the optimal predictive features. Multivariate logistic regression was used to establish the numerical model, and this model was visualized by a nomogram. The model performance was assessed and validated by discrimination, calibration, and clinical utility.ResultsOur predictive model indicated that eight variables, namely, age, pulse, systolic pressure, hemoglobin, neutrophil count, low-density lipoprotein, D-dimer, and partial pressure of oxygen, were associated with PE. The area under the receiver operating characteristic curve of the model was 0.750 [95% confidence interval (CI): 0.721–0.783] in the training cohort and 0.742 (95% CI: 0.689–0.787) in the validation cohort, indicating that the model showed a good differential performance. A good consistency between the prediction and the real observation was presented in the training and validation cohorts. The decision curve analysis in the training and validation cohorts showed that the numerical model had a good net clinical benefit.ConclusionWe established a novel numerical model to predict the risk factors for PE in neurology department suspected PE patients. Our findings may help doctors to develop individualized treatment plans and PE prevention strategies.
Investigation of shared genes and regulatory mechanisms associated with coronavirus disease 2019 and ischemic stroke
Authors: Wu Hao , Han Fei 
Published: April 2023

ObjectiveClinical associations between coronavirus disease (COVID-19) and ischemic stroke (IS) have been reported. This study aimed to investigate the shared genes between COVID-19 and IS and explore their regulatory mechanisms.MethodsPublished datasets for COVID-19 and IS were downloaded. Common differentially expressed genes (DEGs) in the two diseases were identified, followed by protein–protein interaction (PPI) network analysis. Moreover, overlapping module genes associated with the two diseases were investigated using weighted correlation network analysis (WGCNA). Through intersection analysis of PPI cluster genes and overlapping module genes, hub-shared genes associated with the two diseases were obtained, followed by functional enrichment analysis and external dataset validation. Moreover, the upstream miRNAs and transcription factors (TFs) of the hub-shared genes were predicted.ResultsA total of 91 common DEGs were identified from the clusters of the PPI network, and 129 overlapping module genes were screened using WGCNA. Based on further intersection analysis, four hub-shared genes in IS and COVID-19 were identified, including PDE5A, ITGB3, CEACAM8, and BPI. These hub-shared genes were remarkably enriched in pathways such as ECM-receptor interaction and focal adhesion pathways. Moreover, ITGB3, PDE5A, and CEACAM8 were targeted by 53, 32, and 3 miRNAs, respectively, and these miRNAs were also enriched in the aforementioned pathways. Furthermore, TFs, such as lactoferrin, demonstrated a stronger predicted correlation with the hub-shared genes.ConclusionThe four identified hub-shared genes may participate in crucial mechanisms underlying both COVID-19 and IS and may exhibit the potential to be biomarkers or therapeutic targets for the two diseases.
Reconsidering the T category for the T3 non-small cell lung cancer with additional tumor nodules in the same lobe: A population-based study
Authors: Cai Jing-Sheng , Yang Fan , Wang Xun 
Published: April 2023

BackgroundThis study aimed to evaluate the prognosis of the T3 non-small cell lung cancer (NSCLC) patients with additional tumor nodules in the same lobe (T3-Add), and externally validate the current T category of this population.MethodsNSCLC data deposited in the Surveillance, Epidemiology, and End Results (SEER) dataset was extracted. Survivals were estimated using the Kaplan-Meier method with a log-rank test. Propensity score matching (PSM) was performed to reduce bias. The least absolute shrinkage and selection operator (LASSO)-penalized Cox model was used to determine the prognostic factors.ResultsA total of 41,370 eligible cases were included. There were 2,312, 20,632, 12,787, 3,374 and 2,265 cases in the T3-Add, T1, T2, T3 and T4 group, respectively. The Kaplan-Meier curves demonstrated that the survivals of the T3-Add patients were superior to those of the T3 patients both before and after PSM. Additionally, the OS of the T3-Add patients were worse than that of the T2 patients, but the CSS differences between these two groups were not statistically significant. In the subset analyses, the survivals of the T3-Add patients were inferior to those of the T2a patients, but were comparable to those of the T2b patients (5-year OS rate: 54.3% vs. 57.2%, P = 0.884; 5-year CSS rate: 76.2% vs. 76.8%, P = 0.370). In the T3-Add &amp; T2b matched pair, multivariable Cox analysis further confirmed that T category was not a prognostic factor for survivals.ConclusionT3-Add and T2b NSCLC patients had similar survivals, and we proposed that it is necessary to reconsider the T category of the patients with additional nodules in the same lobe in the forthcoming 9th edition of TNM staging manual.