bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of a Fortified Dairy-Based Drink on Micronutrient Status, Growth, and Cognitive Development of Nigerian Toddlers- A Dose-Response Study
Authors: Senbanjo Idowu Odunayo , Owolabi Adedotun J. , Oshikoya Kazeem Adeola , Hageman Jeske H. J. , Adeniyi Yetunde , Samuel Folake , Melse-Boonstra Alida , Schaafsma Anne
Published: April 2022

Malnutrition results in a high prevalence of stunting, underweight, and micronutrient deficiencies. This study investigated the effect of a multi-nutrient fortified dairy-based drink on micronutrient status, growth, and cognitive development in malnourished [height-for-age z-score (HAZ) and/or weight-for-age z-score (WAZ) < -1 SD and >−3 SD] Nigerian toddlers (n = 184, 1–3 years). The product was provided in different daily amounts (200, 400, or 600 ml) for 6 months. At baseline and endline, venous blood and urine samples were collected to determine micronutrient status. Bodyweight, height, waist, and head circumference were measured, and corresponding Z-scores were calculated. The Bayley-III Screening Test was used to classify the cognitive development of the children. In a modified per-protocol (PP) population, the highest prevalence's of micronutrient deficiencies were found for vitamin A (35.5%) and selenium (17.9%). At endline, there were no significant improvements in iodine, zinc, vitamin B12, and folate status in any of the three groups. Regarding vitamin D status (25OHD), consumption of 600 and 400 ml resulted in an improved status as compared to baseline, and in a difference between the 600- and 200-ml groups. Consumption of 600 ml also increased vitamin A and selenium status as compared to baseline, but no differences were found between groups. Within the groups, WAZ, weight-for-height z-score (WHZ), and BMI-for-age z-score (BAZ) improved, but without differences between the groups. For HAZ, only the 600 ml group showed improvement within the group, but it was not different between groups. For the absolute weight, height, and head circumference only trends for differences between groups were indicated. Cognition results did not differ between the groups. Within groups, all showed a decline in the per cent of competent children for receptive language. To study the effects of a nutritional intervention on linear growth and cognition, a longer study duration might be necessary. Regarding the improvement of micronutrient status, 600 ml of fortified dairy-based drink seems most effective.

Clinical Trial Registration:

https://clinicaltrials.gov/ct2/show/NCT03411590?term=NCT03411590.&draw=2&rank=1, identifier: NCT03411590.
Hypermethylated CDO1 and ZNF454 in Cytological Specimens as Screening Biomarkers for Endometrial Cancer
Authors: Wang Lei , Dong Lanlan , Xu Jun , Guo Lin , Wang Yiran , Wan Kangkang , Jing Wei , Zhao Lanbo , Feng Xue , Zhang Kailu , Guo Miao , Zou Yuliang , Zhang Lianglu , Li Qiling
Published: April 2022

We aimed to estimate the diagnostic value of DNA methylation levels in cytological samples of endometrial cancer (EC) and atypical hyperplasia (AH). Two hypermethylated genes, namely, cysteine dioxygenase type 1 (CDO1) and zinc finger protein 454 (ZNF454), in patients with EC were identified from The Cancer Genome Atlas database. In 103 endometrial histological specimens (the training set), the methylation levels of candidate genes were verified by quantitative methylation-specific polymerase chain reaction (qMSP). The methylation levels of another 120 cytological specimens (the testing set) were evaluated. Sensitivity (Se), specificity (Sp), accuracy, and area under the curve (AUC) were determined, with diagnosis verified by histopathological results. CDO1 and ZNF454 verified hypermethylation in histological specimens of patients with EC and AH compared with those with benign and normal endometrium (P < 0.001). In cytological specimens, hypermethylated CDO1 showed 86.36% Se and 90.79% Sp with the cutoff value of 6.0 to distinguish between malignant and benign groups; ZNF454 showed 79.55% Se and 93.42% Sp with the cutoff value of 7.1. When the two genes were combined, Se increased to 90.91% and Sp was 86.84%. AUC reached 0.931 (95% CI: 0.885–0.976). The diagnostic accuracy with cytology had no significant difference with endometrial tissue (P = 0.847 for CDO1, P = 0.108 for ZNF454, and P = 0.665 for their combination). Hypermethylated CDO1 and ZNF454 in endometrial cytology showed high Se, Sp, and AUC to detect EC and AH. Methylation analysis of endometrial cytology is promising biomarker for the screening of EC and AH.
Tumor Suppressive Role of MUC6 in Wilms Tumor via Autophagy-Dependent β-Catenin Degradation
Authors: Liu Bai-Hui , Liu Gong-Bao , Zhang Bin-Bin , Shen Jian , Xie Lu-Lu , Liu Xiang-Qi , Yao Wei , Dong Rui , Bi Yun-Li , Dong Kui-Ran
Published: April 2022

Wilms tumor is the most common renal malignancy in children. Known gene mutations account for about 40% of all wilms tumor cases, but the full map of genetic mutations in wilms tumor is far from clear. Whole genome sequencing and RNA sequencing were performed in 5 pairs of wilms tumor tissues and adjacent normal tissues to figure out important genetic mutations. Gene knock-down, CRISPR-induced mutations were used to investigate their potential effects in cell lines and in-vivo xenografted model. Mutations in seven novel genes (MUC6, GOLGA6L2, GPRIN2, MDN1, MUC4, OR4L1 and PDE4DIP) occurred in more than one patient. The most prevalent mutation was found in MUC6, which had 7 somatic exonic variants in 4 patients. In addition, TaqMan assay and immunoblot confirmed that MUC6 expression was reduced in WT tissues when compared with control tissues. Moreover, the results of MUC6 knock-down assay and CRISPR-induced MUC6 mutations showed that MUC6 inhibited tumor aggression via autophagy-dependent β-catenin degradation while its mutations attenuated tumor-suppressive effects of MUC6. Seven novel mutated genes (MUC6, GOLGA6L2, GPRIN2, MDN1, MUC4, OR4L1 and PDE4DIP) were found in WT, among which MUC6 was the most prevalent one. MUC6 acted as a tumor suppressive gene through autophagy dependent β-catenin pathway.
Prognostic Factors for the Therapeutic Performance of Cisplatin in Head and Neck Malignancies
Authors: Jungbauer Frederic , Huber Lena , Ludwig Sonja , Rotter Nicole , Walter Beatrice , Zaubitzer Lena , Lammert Anne
Published: April 2022

Introduction

For squamous cell carcinoma of the head and neck (HNSCC), cisplatin is used as primary or adjuvant (radio)chemotherapy. In terms of dosage, two main regimens are used, weekly 40mg/m2 or 3-weekly 100mg/m2. For an optimal outcome, the highest possible cumulative total dose of cisplatin is aimed for. The selection of the scheme is patient-specific, but the factors for the selection of the optimal scheme have not yet been conclusively researched. The aim of this study was to find correlations between initial laboratory values and the cumulative total dose of cisplatin, as well as any correlations between early laboratory values or their dynamics and later laboratory values or their dynamics to provide support in the selection of the chemo regimen.

Material and Methods

In this retrospective study, the clinical data and laboratory values, namely glomerular filtration rate (GFR), hemoglobin, albumin, leucocyte, erythrocyte and platelet count, over the course of time of 79 patients with HNSCC who had received chemotherapy with cisplatin in our clinic between 2018 and 2021 were evaluated.

Results

Patients on 3-weekly regimens achieved a higher mean cumulative total dose of cisplatin than patients on weekly regimens (214.18 ± 65.95 vs 183.33 ± 65.2 mg/m2). Significant positive correlations were seen for total cumulative dose of cisplatin with initial GFR (p=0.001, Pearson’s r=0.364), initial hemoglobin (p=0.035, r=0.237), initial erythrocyte (p=0.002, r=0.337), and initial albumin (p=0.002, r=0.337). There were no significant correlations for initial leucocyte or platelets. Regarding the dynamics of the laboratory values under the first chemo administration, no correlation was found with later laboratory values or dynamics.

Discussion and Conclusion

As in other prospective studies, our retrospective analysis found a higher cumulative total dose in the 3-weekly regimen. As this seems to correlate positively with patient outcome, superiority of the 3-weekly regimen over the weekly regimen can be assumed. Functioning organ systems, especially of the bone marrow and kidneys, are associated with an increased cumulative total dose and can therefore be regarded as predictive factors. Regular monitoring of laboratory values is nevertheless essential throughout the entire course of chemotherapy.
Improved Clinical Workflow for Whole-Body Patlak Parametric Imaging Using Two Short Dynamic Acquisitions
Authors: Wang Hui , Miao Ying , Yu Wenjing , Zhu Gan , Wu Tao , Zhao Xuefeng , Yuan Guangjie , Li Biao , Xu Huiqin
Published: April 2022

Objective

We sought to explore the feasibility of shorter acquisition times using two short dynamic scans for a multiparametric PET study and the influence of quantitative performance in shortened dynamic PET.

Methods

Twenty-one patients underwent whole-body dynamic 18F-FDG PET/CT examinations on a PET/CT (Siemens Biograph Vision) with a total scan time of 75 min using continuous bed motion for Patlak multiparametric imaging. Two sets of Patlak multiparametric images were produced: the standard MRFDG and DVFDG images (MRFDG-std and DVFDG-std) and two short dynamic MRFDG and DVFDG images (MRFDG-tsd and DVFDG-tsd), which were generated by a 0–75 min post injection (p.i.) dynamic PET series and a 0–6 min + 60–75 min p.i. dynamic PET series, respectively. The maximum, mean, and peak values of the standard and two short dynamic multiparametric acquisitions were obtained and compared using Passing–Bablok regression and Bland–Altman analysis.

Results

High correlations were obtained between MRFDG-tsd and MRFDG-std, and between DVFDG-tsd and DVFDG-std for both normal organs and all lesions (0.962 ≦ Spearman’s rho ≦ 0.982, p < 0.0001). The maximum, mean, and peak values of the standard and two short dynamic multiparametric acquisitions were also in agreement. For normal organs, the Bland–Altman plot showed that the mean bias of MRFDG-max, MRFDG-mean, and MRFDG-peak was -0.002 (95% CI: -0.032–0.027), -0.002 (95% CI: -0.026–0.023), and -0.002 (95% CI: -0.026–0.022), respectively. The mean bias of DVFDG-max, DVFDG-mean, and DVFDG-peak was -3.3 (95% CI: -24.8–18.2), -1.4 (95% CI: -12.1–9.2), and -2.3 (95% CI: -15–10.4), respectively. For lesions, the Bland–Altman plot showed that the mean bias of MRFDG-max, MRFDG-mean, and MRFDG-peak was -0.009 (95% CI: -0.056–0.038), -0.004 (95% CI: -0.039–0.031), and -0.004 (95% CI: -0.036–0.028), respectively. The mean bias of DVFDG-max, DVFDG-mean, and DVFDG-peak was -8.4 (95% CI: -42.6–25.9), -4.8 (95% CI: -20.2–10.6), and -4.0 (95% CI: -23.7–15.6), respectively.

Conclusions

This study demonstrates the feasibility of using two short dynamic scans that include the first 0–6 min and 60–75 min scans p.i. for Patlak multiparametric images, which can increase patient throughout for parametric analysis.
CSF2RB Is a Unique Biomarker and Correlated With Immune Infiltrates in Lung Adenocarcinoma
Authors: Zhu Ningning , Yang Yueyang , Wang Haitong , Tang Peng , Zhang Hongdian , Sun Haiyan , Gong Lei , Yu Zhentao
Published: April 2022

Background

The tumor microenvironment plays an important role in the occurrence and development of tumors. However, there are gaps in understanding the molecular and cellular interactions between tumor cells and the immune tumor microenvironment (TME). The aim of this study was to identify a novel gene that played an important role in the tumor microenvironment of lung adenocarcinoma (LUAD).

Methods

The gene expression profile and clinical data for LUAD were downloaded from TCGA database. First, we used the ESTIMATE algorithm to evaluate the immune and stromal scores accordingly. Also, we analyzed differentially expressed immune-related genes (IRGs) in the high and low immune/stromal score groups. Then, we used the protein–protein interaction network (PPI network) and a univariate Cox regression analysis to identify the hub gene. After that, we analyzed the relationship between CSF2RB expression and TNM stage/prognosis. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathway regulated by CSF2RB and the Pearson correlation analysis method was used to analyze the correlation between the CSF2RB and immune cells. Finally, we used Western blot, real-time quantitative PCR (RT-qPCR), and immunohistochemistry (IHC) to validate CSF2RB expression in cancer and para-cancerous tissues.

Results

We identified that CSF2RB played an important role in the tumor microenvironment of LUAD. The expression of CSF2RB in tumor tissues was lower than that in normal tissues. Furthermore, the Kaplan–Meier plotter showed that a low CSF2RB expression was associated with poor survival and multivariate COX regression analysis revealed that the CSF2RB gene was an independent risk factor for prognosis, independent of whether patients received chemotherapy or radiotherapy. More importantly, a high expression of CSF2RB was related to early T, N, and clinical stages. GSEA analysis revealed that CSF2RB associated with diverse immune-related pathways, including T-cell receptor signaling pathway, Toll-like receptor signaling pathway, and B-cell receptor signaling pathway. CSF2RB expression levels were also positively related with the levels of infiltrating CD4+ T cells, macrophages, NK cells, and monocytes in LUAD. Finally, tumor tissues from LUAD patients were used for the assessment of CSF2RB expression. It was significantly lower in tumor sites than in adjacent normal tissues, which was consistent with data analysis.

Conclusion

CSF2RB effectively predicted the prognosis of patients with lung adenocarcinoma which could also be a potential target for cancer treatment and prevention. However, further studies are required to elucidate the function and regulatory mechanisms of CSF2RB and to develop some novel treatment strategies.
A Nomogram to Predict Recurrence-Free Survival Following Surgery for Vestibular Schwannoma
Authors: Zhang Zehan , Zhang Ding , Shi Xudong , Tao Bingyan , Liu Yuyang , Zhang Jun
Published: April 2022

Background

Vestibular schwannoma (VS) is the most common benign tumor of the posterior fossa. The recurrence of VS has always received widespread attention. This study aimed to develop a nomogram to predict Recurrence-free survival (RFS) following resection of VS.

Methods

A total of 425 patients with VS who underwent resection at the Department of Neurosurgery in Chinese PLA General Hospital between January 2014 and December 2020 were enrolled in this retrospective study. The medical records and follow-up data were collected. Cox regression analysis was used to screen prognostic factors and construct the nomogram. The predictive accuracy and clinical benefits of the nomogram were validated using the area under the curve (AUC), calibration curves, and decision curve analysis (DCA).

Results

The Cox regression analysis revealed that age (HR = 0.96; 95% CI 0.94 - 0.99; p < 0.01), EOR (HR = 4.65; 95% CI 2.22 - 9.74; p < 0.001), and Ki-67 (HR = 1.16; 95% CI 1.09 - 1.23; p < 0.001) were all significantly correlated with recurrence, and they were finally included in the nomogram model. The concordance index of the nomogram was 0.86. The areas under the curve (AUCs) of the nomogram model of 3-, 4- and 5-year were 0.912, 0.865, and 0.809, respectively. A well-fitted calibration curve was also generated for the nomogram model. The DCA curves also indicated that the nomogram model had satisfactory clinical utility compared to the single indicators.

Conclusions

We developed a nomogram that has high accuracy in predicting RFS in patients after resection of VS. All of the included prognostic factors are easy to obtain. The nomogram can improve the postoperative management of patients and assist clinicians in individualized clinical treatment. Furthermore, we generated a web-based calculator to facilitate clinical application: https://abc123-123.shinyapps.io/VS-RFS/.
Efficacy and Safety of Recombinant Human Adenovirus Type 5 (H101) in Persistent, Recurrent, or Metastatic Gynecologic Malignancies: A Retrospective Study
Authors: Zhang Jing , Zhang Qiying , Liu Zi , Wang Juan , Shi Fan , Su Jin , Wang Tao , Wang Fei
Published: April 2022

Background

To assess the efficacy and safety of recombinant human adenovirus type 5 (H101) in patients with persistent, recurrent, or metastatic gynecologic malignancies.

Methods

The study retrospectively enrolled patients with persistent/recurrent/metastatic gynecologic malignancies who received H101-containing treatment at The First Affiliated Hospital of Xi’an Jiaotong University from September 1, 2019 to September 30, 2021. H101 was injected intratumorally into target lesions and dosage was calculated based on tumor diameter once a day for five consecutive days. The primary endpoint was local control (LC) rate. Secondary endpoints included objective response rate (ORR), duration of response (DOR) and progression-free survival (PFS). Safety was the exploratory endpoint. Depending on prior treatment, patients received H101 either as monotherapy or as a combination therapy.

Results

Totally, 29 patients were enrolled in the study. Median follow-up was 6.3 months (range: 3.2-27.9) from data analysis cut-off on December 31, 2021. The LC rate at 3 months was 44.8%, while ORR was 72.4%. Median DOR and PFS rates were not determined. The DOR rate, PFS rate at 6 and 12 months were 88.1%, 74.6% and 70.5%, 62.2%, respectively. Responses were observed in all four cancer types. Most treatment-related adverse events (90.5%) were grade 1 or 2, with the most common being fever (70%). Clinically significant adverse events were uncommon (7.9% in grade 3 and 1.6% in grade 4). No treatment-related deaths occurred.

Conclusion

Our study showed that H101 (either monotherapy or combination therapy) has promising efficacy and favorable safety in patients with persistent, recurrent, metastatic gynecologic malignancies.
Short-Term Outcomes and Clinical Efficacy of Stereotactic Body Radiation Therapy (SBRT) for Oligometastases of Prostate Cancer in China
Authors: Xu Chenyang , Zhao Xianzhi , Ju Xiaoping , Shen Yuxin , Qu Min , Ye Yusheng , Wang Xiaoyan , Yu Chunshan , Gao Xu , Zhang Huojun
Published: April 2022

Objective

To assess the efficacy and safety of stereotactic body radiation therapy (SBRT) in managing oligometastases of prostate cancer. Moreover, it is the largest-to-date study in China to report the safety and efficacy of SBRT by CyberKnife for oligometastases of prostate cancer.

Methods

In this retrospective study, 75 patients with 108 oligometastases were treated by SBRT from May 2012 to February 2021. Among these patients, 43 patients were treated with the intention to control all known metastatic lesions and 32 were treated for palliative care. Patients received regular follow-up evaluations every 3 months. Efficacy was assessed based on local control (LC) rates, biochemical progression-free survival (bPFS), progression-free survival (PFS), and overall survival (OS). Safety was assessed based on clinical adverse events.

Results

Median follow-up time was 23.2 months (1.2-106.9 months). The complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) rates were 63.0%, 10.2%, 21.3% and 5.6%, respectively. The 6-month, 1-, and 2-year LC rates were 100%, 97.5%, and 96.0% respectively while the 6-month, 1-, and 2-year bPFS rates were 74.6%, 53.3%, and 47.9%, respectively. Additionally, 6-month, 1-, and 2-year PFS rates were 77.5%, 50.8%, and 47.2%, respectively. The 6-month, 1-, and 2-year OS rates were 97.0%, 88.8%, and 87.0%, respectively. For the 15 metastatic castration-resistant prostate cancer (mCRPC) patients with 23 lesions, the 2-year LC rates were 93.8%, while for 60 metastatic hormone-sensitive prostate cancer (mHSPC) patients with 85 lesions, the 2-year LC rates were 96.7%. No predictors of LC were found after univariate analysis. In those not on androgen deprivation therapy (ADT; n = 27), the 2-year freedom from ADT was 44.0%. All of the 24 patients with oligmetastase-induced complications experienced varying degrees of alleviation after SBRT. The treatment was well tolerated. No grade 3 or higher toxicity was observed.

Conclusion

SBRT is a safe and effective treatment modality in the management of oligometastases of mHSPC and mCRPC with high LC rates and acceptable toxicity. SBRT could provide a treatment choice for mCRPC, as well as an alternative to delay the start of ADT for mHSPC.
Epidemiology of Cardiopulmonary Arrest and Outcome of Resuscitation in PICU Across China: A Prospective Multicenter Cohort Study
Authors: Ding Xin , Liu Gang , Qian Suyun , Zeng Jiansheng , Wang Ying , Chu Jianping , Chen Qing , Chen Jianli , Duan Yuanyuan , Jin Danqun , Huang Jiaotian , Lu Xiulan , Guo Yanmei , Shi Xiaona , Huo Ximin , Su Jun , Cheng Yibing , Yin Yi , Xin Xiaowei , Sun Zhengyun , Zhao Shaodong , Miao Hongjun , Lou Zixuan , Li Jun , Jiang Jinghui , Dong Shengying
Published: April 2022

Objective

To investigate the epidemiology and the effectiveness of resuscitation from cardiopulmonary arrest (CPA) among critically ill children and adolescents during pediatric intensive care unit (PICU) stay across China.

Methods

A prospective multicenter study was conducted in 11 PICUs in tertiary hospitals. Consecutively hospitalized critically ill children, from 29-day old to 18-year old, who had suffered from CPA and required cardiopulmonary resuscitation (CPR) in the PICU were enrolled (December 2017–October 2018). Data were collected and analyzed using the “in-hospital Utstein style.” Neurological outcome was assessed with the Pediatric Cerebral Performance Category (PCPC) scale among children who had survived. Factors associated with the return of spontaneous circulation (ROSC) and survival at discharge were evaluated using multivariate logistic regression.

Results

Among 11,599 admissions to PICU, 372 children (3.2%) had CPA during their stay; 281 (75.5%) received CPR, and 91 (24.5%) did not (due to an order of “Do Not Resuscitate” requested by their guardians). Cardiopulmonary disease was the most common reason for CPA (28.1% respiratory and 19.6% circulatory). The most frequent initial dysrhythmia was bradycardia (79%). In total, 170 (60.3%) of the total children had an ROSC, 91 had (37.4%) survived till hospital discharge, 28 (11.5%) had survived 6 months, and 19 (7.8%) had survived for 1 year after discharge. Among the 91 children who were viable at discharge, 47.2% (43/91) received a good PCPC score (1–3). The regression analysis results revealed that the duration of CPR and the dose of epinephrine were significantly associated with ROSC, while the duration of CPR, number of CPR attempts, ventricular tachycardia/ventricular fibrillation (VT/VF), and the dose of epinephrine were significantly associated with survival at discharge.

Conclusion

The prevalence of CPA in critically ill children and adolescents is relatively high in China. The duration of CPR and the dose of epinephrine are associated with ROSC. The long-term prognosis of children who had survived after CPR needs further improvement.
Clinical Profile and Risk Factors for Cardiac Death in Pediatric Patients With Primary Dilated Cardiomyopathy at a Tertiary Medical Center in China
Authors: Wang Yan , Han Bo , Fan Youfei , Yi Yingchun , Lv Jianli , Wang Jing , Yang Xiaofei , Jiang Diandong , Zhao Lijian , Zhang Jianjun , Yuan Hui
Published: April 2022

Aim

We sought to identify the clinical characteristics and risk factors for cardiac mortality in pediatric patients with primary dilated cardiomyopathy (DCM) in China.

Methods

A total of 138 pediatric patients who were consecutively diagnosed with primary DCM from January 2011 to December 2020 were included. We assessed patients’ clinical symptoms and performed laboratory examinations, electrocardiography, and echocardiography.

Results

Of these patients, 79 (57%) had severe systolic dysfunction (left ventricular ejection fraction of < 30%), 79 (57.2%) developed DCM before 12 months of age, 62 (45%) were male, 121 (87.7%) presented with advanced heart failure (cardiac functional class III/IV), and 54 (39.1%) presented with arrhythmia. At a median follow-up of 12 months, the overall cardiac mortality rate was 33%, and 40 of 46 deaths occurred within 6 months following DCM diagnosis. A multivariate Cox regression analysis identified several independent cardiac death predictors, including an age of 12 months to 5 years [hazard ratio (HR) 2.799; 95% confidence interval (CI) 1.160–6.758; P = 0.022] or 10–15 years (HR 3.617; 95% CI 1.336–9.788; P = 0.011) at diagnosis, an elevated serum alanine aminotransferase (ALT) concentration (≥ 51.5 U/L) (HR 2.219; 95% CI 1.06–4.574; P = 0.031), and use of mechanical ventilation (HR 4.223; 95% CI 1.763–10.114; P = 0.001).

Conclusion

The mortality rate of primary DCM without transplantation is high. Age, an elevated serum ALT concentration, and the need for mechanical ventilation predict mortality in patients with primary DCM, providing new insights into DCM risk stratification.
Identification and Validation of Autophagy-Related Genes in Necrotizing Enterocolitis
Authors: Tian Yuxin , Mao Mengjia , Cao Xuqing , Zhu Haitao , Shen Chun
Published: April 2022

Background

Autophagy plays an essential role in the occurrence and progression of necrotizing enterocolitis (NEC). We intend to carry out the identification and validation of the probable autophagy-related genes of NEC via bioinformatics methods and experiment trials.

Methods

The autophagy-related differentially expressed genes (arDEGs) of NEC were identified by analyzing the RNA sequencing data of the experiment neonatal mouse model and dataset GSE46619. Protein–protein interactions (PPIs), Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used for the arDEGs. Then, co-expressed autophagy-related genes in two datasets were identified by Venn analysis and verified by qRT-PCR in experimental NEC.

Results

Autophagy increased in experimental NEC and 47 arDEGs were identified in experimental NEC by RNA-sequencing. The PPI results proclaimed those genes interplayed with each other. The GO and KEGG enrichment results of arDEGs reported certain enriched pathways related to autophagy and macroautophagy. Furthermore, 22 arDEGs were identified in human NEC from dataset GSE46619. The GO and KEGG enrichment analysis of these genes showed similar enriched terms with the results of experimental NEC. Finally, HIF-1a, VEGFA, ITGA3, ITGA6, ITGB4, and NAMPT were identified as co-expressed autophagy-related genes by Venn analysis in human NEC from dataset GSE46619 and experimental NEC. The result of quantified real-time PCR (qRT-PCR) revealed that the expression levels of HIF-1a and ITGA3 were upregulated, while VEGFA and ITGB4 were downregulated in experimental NEC.

Conclusion

We identified 47 arDEGs in experimental NEC and 22 arDEGs in human NEC via bioinformatics analysis. HIF-1a, ITGA3, VEGFA, and ITGB4 may have effects on the progression of NEC through modulating autophagy.
Considerations for Balance Between Fundamental Treatment and Improvement of Quality of Life of Pediatric Thyroid Cancer Patient: Comparative Analysis With Adult Using Propensity Score Matching
Authors: You Ji Young , An Se-Woong , Kim Hoon Yub , Park Da Won , Byeon Hyung Kwon , Patroniti Serena , Dionigi Gianlorenzo , Tufano Ralph P.
Published: April 2022

Background

Thyroid cancer is very rarely observed in children and adolescents, some reports have shown that the long-term outcome of treatment is better than that of adult patients, despite many treatment failures or a high risk of recurrence. This study considers whether it is appropriate to treat pediatric thyroid cancer patients aggressively, as per the ATA guidelines, based on the balance between the fundamental treatment of thyroid cancer and the improvement of the long-term quality of life of pediatric patients.

Methods

A total of 1,950 patients were recruited, including 83 pediatric and 1,867 adult patients, who were diagnosed with thyroid cancer and underwent surgical treatment at one of our medical center hospitals from March 2000 to January 2020.

Results

Sixty-nine pairs of pediatric and adult patients were matched in a ratio of 1:2 through propensity score matching. When compared through propensity score matching, there was no significant difference in prognosis such as recurrence rate in children and adults at the same stage.

Conclusion

This study showed that the prognosis of both pediatric and adult patients who underwent a total thyroidectomy and lobectomy was not significantly different. If more pediatric patients can be considered for the less-aggressive lobectomy than a total thyroidectomy through various preoperative examinations and meticulous pre-diagnosis, it may be possible to properly determine the balance between improving long-term quality of life while providing fundamental cancer treatment.
Case Report: A Case of a Child With Facial Foreign Body Abscess and Facial Artery Pseudoaneurysm
Authors: Kuang Rong , Zhou Jing , Deng Jiaqi , Xia Tian , Li Mingxing
Published: April 2022

Facial artery pseudoaneurysms are rare and mostly a result of blunt injury. Since the facial arteries are well protected by facial soft tissue and the lumen of the facial artery is thin and small in diameter, a sharp injury usually leads to complete transection rather than partial laceration of the blood vessel. As a non-invasive method, ultrasound does not involve radiation and sedation. Diagnosis of facial artery pseudoaneurysms is most commonly made with ultrasound, and Doppler ultrasound is essential. On grayscale imaging, facial artery pseudoaneurysms often appearanced of a fluid collection, Color Doppler imaging often show a well-defined swirl pattern named “yin and yang sign,” the Spectral Doppler showed a diagnostic “to and fro” two-phase bidirectional arterial blood flow spectrum. It’s particularly for the examination of facial artery pseudoaneurysms in children. Here, we report a case of facial foreign body abscess and facial artery pseudoaneurysm in a 19-month-old child 1 week after a sharpness injury that was diagnosed by ultrasound.
Co-Crystal of Rosiglitazone With Berberine Ameliorates Hyperglycemia and Insulin Resistance Through the PI3K/AKT/TXNIP Pathway In Vivo and In Vitro
Authors: He Qichen , Chen Bo , Wang Gang , Zhou Duanfang , Zeng Hongfang , Li Xiaoli , Song Yi , Yu Xiaoping , Liang Wenxin , Chen Huiling , Liu Xu , Wu Qiuya , Wu Lihong , Zhang Limei , Li Huizhen , Hu Xiangnan , Zhou Weiying
Published: April 2022

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by insulin resistance and hyperglycemia. This study examined the effect and elucidated the mechanism of improvement of hyperglycemia and insulin resistance by a co-crystal of rosiglitazone with berberine (RB) in high-sugar high-fat diet (HSHFD)-induced diabetic KKAy mice.

Methods: Diabetic KKAy mice were randomly divided into seven groups: KKAy model control group (DM control) treated with 3% sodium carboxymethyl cellulose; RB groups, administered daily with RB 0.7 mg/kg (RB-L), 2.11 mg/kg (RB-M), or 6.33 mg/kg (RB-H); positive control groups, administered daily with rosiglitazone 1.04 mg/kg (RSG), berberine 195 mg/kg (BBR), or combination of 1.04 mg/kg RSG and 1.08 mg/kg BBR (MIX). Test compounds were administered orally for 8 weeks. Non-diabetic C57BL/6J mice were used as normal control (NC). Blood glucose, food intake, body weight, glucose-lipid metabolism, and pathological changes in the pancreas and liver were examined. We further evaluated the mechanism of action of RB in C2C12 and HepG2 cells stimulated with high glucose and palmitate.

Results: RB treatment improved glucolipid metabolism and insulin resistance in diabetic KKAy mice. RB reduced blood glucose levels, white fat index, plasma triglyceride (TG), low-density lipoprotein (LDL), gastric inhibitory peptide (GIP), and insulin levels, increased the levels of plasma glucagon-like peptide-1 (GLP-1), high-density lipoprotein (HDL), and glycogen content in the liver and muscle; and improved oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and pathological changes in the pancreas and liver of KKAy mice. Moreover, RB upregulated p-PI3K and p-AKT levels and reduced TXNIP expression in KKAy mice and in HepG2 and C2C12 cells.

Conclusion: These data indicate that RB ameliorates insulin resistance and metabolic disorders, and the mechanism might be through regulating the PI3K/AKT/TXNIP signaling pathway . Thus, the co-crystal drug RB may be considered as a potential antidiabetic agent for future clinical therapy.
Stevens-Johnson Syndrome Following Vancomycin and Linezolid: A Real-World Analysis of Post-Marketing Surveillance Data
Authors: Ni Ming , Yin Xue-Dong , Hu Wen-Juan , Zeng Na , Zhao Bin , Li Zhi-Ling
Published: April 2022

Background: Stevens-Johnson syndrome (SJS) has been reported as a serious adverse effect in patients treated with vancomycin or linezolid, and there is currently a lack of real-world studies comparing specific differences in adverse effects of SJS.

Methods: According to the FDA’s Adverse Event Reporting System (FAERS), from January 2004 to July 2021, the data of suspected SJS after the use of vancomycin and linezolid were analyzed by imbalance and Bayesian analysis. The onset time, fatality rate and hospitalization rate of vancomycin-associated SJS and linezolid-associated SJS were also investigated.

Results: 276 cases of vancomycin-related SJS reports and 63 cases of linezolid-related SJS reports were identified. These two drugs are more common in middle-aged patients (45–64 years) than other age groups, and less common in underage children (<18). Among them, linezolid-related SJS is more common in middle-aged and elderly patients (45–74 years old) than other groups. Except for unspecified data, in vancomycin-associated SJS cases, there are more men than women (49.28% vs 43.84%), while in linezolid-associated SJS cases, the proportion of men and women is almost equal (44.44%). From the point of view of the areas where adverse reactions were reported, about 1/2 of the reports on Vancomycin-related SJS came from North America, and 1/3 of the reports came from Europe. The median onset time of Linezolid-related SJS was 5 days (interquartile range [IQR] 2–7.75), which was significantly earlier than that of Vancomycin-related SJS (12 days, IQR 4–20) (Mann-Whitney test, p < 0.0001). There were no significant differences in mortality and hospitalization rates after vancomycin and linezolid caused SJS.

Conclusion: The analysis of faers data provides a comprehensive overview of the adverse reactions of SJS caused by the use of vancomycin and linezolid, and can warn clinical workers to timely intervene and continuously monitor the patients at risk of SJS when using such drugs.
Modulation of Tumor Immune Microenvironment and Prognostic Value of Ferroptosis-Related Genes, and Candidate Target Drugs in Glioblastoma Multiforme
Authors: Zhang Xudong , Jin Shengnan , Shi Xin , Liu Shengyu , Li Kunhang , Liu Guojun , Zhong Shiyu , Liu Tao , Li Lishuai , Tao Shanwei , Zhai Qingqing , Bao Nan , Ren Lijie , Wu Ying , Bao Yijun
Published: April 2022

Glioblastoma multiforme (GBM) is the most common type of malignant brain tumor, among which IDH1-wild type GBM has a poor prognosis. Recent studies have shown that ferroptosis-related genes (FRGs) are correlated with the development and progression of cancer. In GBM, the role of FRGs associated with IDH1 status as biological indicators and therapeutic targets remains to be clarified. Ten of FRGs (STEAP3, HSPB1, MAP1LC3A, SOCS1, LOX, CAPG, CP, GDF15, CDKN1A, and CD44) associated with IDH1 status in GBM were identified as key genes through screening by survival analysis and Random Forest using The Cancer Genome Atlas (TCGA) datasets, and the protein expressions of key genes were verified. Transwell and qPCR results showed that ferroptosis promoted the migration of glioblastoma cells and affected the expression of key genes. Our study established the ferroptosis-related prognostic model for GBM patients based on ten key genes by a different modeling method from previous study, the GSVA algorithm. Further, we took the methods of functional enrichment analysis, clinical characteristics, immune cell infiltration, immunomodulator, ESTIMATE and single nucleotide variant (SNV) analysis to study the molecular mechanisms of prognostic model and key genes. The results showed that ten key genes were strongly associated with immune-related factors and were significantly involved in the p53 signaling pathway, senescence and autophagy in cancer, and in the negative regulation of protein kinase activity. Moreover, potential therapeutic drugs were identified by Virtual Screening and Molecular Docking. Our study indicated that the novel ferrotosis-related prognostic model for GBM patients and key genes possessed the prognostic and therapeutic values.
Mass-Conservation Increases Robustness in Stochastic Reaction-Diffusion Models of Cell Crawling
Authors: Moreno Eduardo , Alonso Sergio
Published: April 2022

The process of polarization determines the head and tail of single cells. A mechanism of this kind frequently precedes the subsequent cell locomotion and it determines the direction of motion. The process of polarization has frequently been described as a reaction-diffusion mechanism combined with a source of stochastic perturbations. We selected a particular model of amoeboid cell crawling for the motion of Dictyostelium discoideum and studied the interplay between pattern formation and locomotion. Next, we integrated the model in a two-dimensional domain considering the shape deformations of the cells in order to characterize the dynamics. We observed that the condition of pattern formation is finely tuned and we propose a modification based on the use of a mass-conservation constraint to substantially increase the robustness of the mathematical model.
Animal Models of Temporomandibular Joint Osteoarthritis: Classification and Selection
Authors: Zhao Yuqing , An Yanxin , Zhou Libo , Wu Fan , Wu Gaoyi , Wang Jing , Chen Lei
Published: April 2022

Temporomandibular joint osteoarthritis (TMJOA) is a common degenerative joint disease that can cause severe pain and dysfunction. It has a serious impact on the quality of lives of patients. Since mechanism underlying the pathogenesis of TMJOA is not fully understood, the development of effective tools for early diagnosis and disease-modifying therapies has been hindered. Animal models play a key role in understanding the pathological process of diseases and evaluating new therapeutic interventions. Although some similarities in disease processes between animals and humans are known, no one animal model is sufficient for studying all characteristics of TMJOA, as each model has different translatability to human clinical conditions. For the past 4 decades, TMJOA animal models have been studied by numerous researchers and can be broadly divided into induced, naturally occurring, and genetically modified models. The induced models can be divided into invasive models (intra-articular injection and surgical induction) or non-invasive models (mechanical loading, high-fat diet, and sleep deprivation). Different types of animal models simulate different pathological expressions of TMJOA and have their unique characteristics. Currently, mice, rats, and rabbits are commonly used in the study of TMJOA. This review sought to provide a general description of current experimental models of TMJOA and assist researchers in selecting the most appropriate models for different kinds of research.
Low Omega-3 Levels in the Diet Disturbs Intestinal Barrier and Transporting Functions of Atlantic Salmon Freshwater and Seawater Smolts
Authors: Sundell Kristina , Berge Gerd Marit , Ruyter Bente , Sundh Henrik
Published: April 2022

Due to a limited access to marine raw materials from capture fisheries, Atlantic salmon feeds are currently based on mainly plant ingredients (75%) while only 25% come from traditional marine ingredients including marine fish meal and fish oil. Thus, current feeds contain less of the essential omega-3 fatty acids. The aim of the study was to assess the impact of different omega-3 levels in fish feed on intestinal barrier and transporting functions of Atlantic salmon freshwater and seawater smolts. Atlantic salmon were fed three levels of omega-3 (2, 1 and 0.5%) and fish performance was followed through smoltification and the subsequent seawater acclimation. Intestinal barrier and transporting functions were assessed using Ussing chamber methodology and combined with transcript analysis of tight junction related proteins and ion transporters. A linear decrease in growth was observed with decreasing omega-3 levels. Low (0.5%) inclusion of omega-3 impaired the barrier function of the proximal intestine compared to 2% inclusion. Further, low levels of omega-3 decrease the transepithelial electrical potential across the epithelium indicating disturbed ion transport. It can be concluded that low dietary levels of omega-3 impair somatic growth and intestinal function of Atlantic salmon.
Evaluation of Ecological Suitability and Quality Suitability of Panax notoginseng Under Multi-Regionalization Modeling Theory
Authors: Yue JiaQi , Li ZhiMin , Zuo ZhiTian , Wang YuanZhong
Published: April 2022

Panax notoginseng is an important medicinal plant in China, but there are some limitations in the ecological suitability study, such as incomplete investigation of species distribution, single regionalization modeling, and lack of collaborative evaluation of ecological suitability, and quality suitability. In this study, the maximum entropy model was used to analyze the ecological suitability of P. notoginseng under current and future climates. The multi-source chemical information of samples was collected to evaluate the uniformity between quality and ecology. The results showed that the current suitable habitat was mainly in southwest China. In the future climate scenarios, the high suitable habitat will be severely degraded. Modeling based on different regionalization could predict larger suitable habitat areas. The samples in the high suitable habitat had both quality suitability and ecological suitability, and the accumulation of chemical components had different responses to different environmental factors. Two-dimensional correlation spectroscopy combined with deep learning could achieve rapid identification of samples from different suitable habitats. In conclusion, global warming is not conducive to the distribution and spread of P. notoginseng. The high suitable habitat was conducive to the cultivation of high-quality medicinal materials. Actual regionalization modeling had more guiding significance for the selection of suitable habitats in a small area. The multi-regionalization modeling theory proposed in this study could provide a new perspective for the ecological suitability study of similar medicinal plants. The results provided a reference for the introduction and cultivation, and lay the foundation for the scientific and standardized production of high-quality P. notoginseng.
Genetic Variability in Balkan Paleoendemic Resurrection Plants Ramonda serbica and R. nathaliae Across Their Range and in the Zone of Sympatry
Authors: Lazarević Maja , Siljak-Yakovlev Sonja , Sanino Agathe , Niketić Marjan , Lamy Françoise , Hinsinger Damien D. , Tomović Gordana , Stevanović Branka , Stevanović Vladimir , Robert Thierry
Published: April 2022

The genusRamondaincludes three Paleoendemic and Tertiary relict species that survived in refugial habitats of the Balkan Peninsula (R. nathaliaeandR. serbica) and the Iberian Peninsula (R. myconi). They are all “resurrection plants,” a rare phenomenon among flowering plants in Europe.Ramonda myconiandR. nathaliaeare diploids (2n = 2x = 48), whileR. serbicais a hexaploid (2n = 6x = 144). The two Balkan species occur in sympatry in only two localities in eastern Serbia, where tetraploid potential hybrids (2n = 4x = 96) were found. This observation raised questions about the existence of gene flow between the two species and, more generally, about the evolutionary processes shaping their genetic diversity. To address this question, genetic markers (AFLP) and an estimate of genome size variation were used in a much larger sample and at a larger geographic scale than previously. The combination of AFLP markers and genome size results suggested ongoing processes of interspecific and interploidy hybridization in the two sites of sympatry. The data also showed that interspecific gene flow was strictly confined to sympatry. Elsewhere, bothRamondaspecies were characterized by low genetic diversity within populations and high population differentiation. This is consistent with the fact that the two species are highly fragmented into small and isolated populations, likely a consequence of their postglacial history. Within sympatry, enormous variability in cytotypes was observed, exceeding most reported cases of mixed ploidy in complex plant species (from 2xto >8x). The AFLP profiles of non-canonical ploidy levels indicated a diversity of origin pathways and that backcrosses probably occur between tetraploid interspecific hybrids and parental species. The question arises whether this diversity of cytotypes corresponds to a transient situation. If not, the question arises as to the genetic and ecological mechanisms that allow this diversity to be maintained over time.
Cytoplasmic Linker Protein-Associating Protein at the Nexus of Hormone Signaling, Microtubule Organization, and the Transition From Division to Differentiation in Primary Roots
Authors: Halat Laryssa Sophia , Bali Breanne , Wasteneys Geoffrey
Published: April 2022

The transition from cell division to differentiation in primary roots is dependent on precise gradients of phytohormones, including auxin, cytokinins and brassinosteroids. The reorganization of microtubules also plays a key role in determining whether a cell will enter another round of mitosis or begin to rapidly elongate as the first step in terminal differentiation. In the last few years, progress has been made to establish connections between signaling pathways at distinct locations within the root. This review focuses on the different factors that influence whether a root cell remains in the division zone or transitions to elongation and differentiation using Arabidopsis thaliana as a model system. We highlight the role of the microtubule-associated protein CLASP as an intermediary between sustaining hormone signaling and controlling microtubule organization. We discuss new, innovative tools and methods, such as hormone sensors and computer modeling, that are allowing researchers to more accurately visualize the belowground growth dynamics of plants.