bluuebunny/crossref_metadata_2025_split huggingface dataset:
m6A Regulator-Based Methylation Modification Patterns Characterized by Distinct Tumor Microenvironment Immune Profiles in Rectal Cancer
Authors: Liao Kaili , Hu Jialing , Huang Yu , Yu Siji , Yang Qijun , Sun Fan , Wu Chengfeng , Cheng Yunqi , Zhang Wenyige , Zhang Xue , Li Hongyu , Wang Xiaozhong 
Published: July 2022

BackgroundPrevious studies reported the related role of RNA n6-methyladenosine (m6A) modification in tumorigenesis and development. However, it is not clear whether m6A modification also plays a potential role in the immune regulation of rectal cancer (RC) and the formation of tumor microenvironment.MethodsIn this study, we screened 23 m6A regulatory factors from 369 rectal cancer specimens, further determined the modification patterns of m6A in RC, and systematically linked these modification patterns with the characteristics of TME cell infiltration. The principal component analysis (PCA) algorithm was used to evaluate the m6A modification pattern of a single tumor related to immune response.ResultsThree different m6A modification patterns were found in the measurement results, which are related to different clinical results and biological pathways. TME identification results show that the identified m6A pattern is closely related to immune characteristics. According to the m6Ascore extracted from m6A-related signature genes, RC patients were divided into high and low score subgroups combined with tumor mutation burden. Patients with high tumor mutation burden and higher m6Ascore have a significant survival advantage and enhanced immune infiltration. Further analysis showed that patients with higher m6Ascore had higher PD-L1 expression levels and showed better immune response and lasting clinical benefits.ConclusionsM6A modification plays a crucial role in the formation of TME diversity and complexity. The evaluation of the m6A modification mode will help us to enhance our understanding of the characteristics of TME infiltration and provide new insights for more effective immunotherapy strategies.
The Potential Value of Gastric Histopathology for Predicting Colorectal Adenomatous Polyps Among the Chinese Population: A Retrospective Cross-Sectional Study
Authors: Li Weiwei , Zhang Lin , Jing Yuanming , Yang Yanfei , Wang Yulong 
Published: July 2022

BackgroundIt remains unknown whether gastric histopathology is associated with the occurrence of colonic neoplasms. We aimed to clarify the association between gastric histopathology and different types of colorectal polyps (CP) and colorectal cancer (CRC), and whether various gastric histopathologies are risk factors for different types of CP and CRC.MethodsA retrospective cross-sectional study was conducted on 5,986 patients who underwent gastroscopy and colonoscopy simultaneously at Shaoxing People’s Hospital from August 1, 2019, to May 31, 2020. The Pearson χ2 test was used to analyze the occurrence of various gastric histopathologies in different types of CP and CRC, and logistic regression was used to determine whether various gastric histopathologies were risk factors for different types of CP and CRC.ResultsFor the Chinese population, male sex (odds ratio [OR] 1.67, 95% confidence interval [CI] 1.41–1.97, P &lt; 0.001) and old age (OR 1.03, 95% CI 1.02–1.04, P &lt; 0.001) were risk factors for non-adenomatous polyps (NAP), but Helicobacter pylori (H. pylori) and various gastric histopathologies were not significant in the NAP compared with the normal group. Nevertheless, it is noteworthy that, similar to male sex and old age, H. pylori (OR 1.22, 95% CI 1.08–1.38, P = 0.002), low-grade intraepithelial neoplasia (LGIN) (OR 1.79, 95% CI 1.21–2.66, P = 0.004), gastric fundus gland polyps (FGPs) (OR 1.44, 95% CI 1.11–1.87, P = 0.007), hyperplastic/inflammatory gastric polyps (GHP or GIP) (OR 1.50, 95% CI 1.06–2.12, P = 0.022), and atrophy/intestinal metaplasia (AG or IM) (OR 1.27, 95% CI 1.13–1.43, P &lt; 0.001) were all risk factors for colorectal adenomatous polyps (AP). However, the results of CRC showed that old age (OR 1.13, 95% CI 1.10–1.16, P &lt; 0.001) and H. pylori (OR 1.67, 95% CI 0.99–2.75, P &lt; 0.05) were risk factors for CRC (OR 1.67, 95% CI 0.99–2.75, P &lt; 0.05), but not sex and various gastric histopathologies (P &gt; 0.05).ConclusionGastric histopathology, such as AG or IM, LGIN, FGP, and GHP or GIP, were risk factors for AP, but not for NAP and CRC, indicating that gastric histopathology has potential predictive value for AP in the Chinese population.
Increased ASF1B Expression Correlates With Poor Prognosis in Patients With Gliomas
Authors: Zhu Huaxin , Ouyang Hengyang , Pan Xinyi , Zhang Zhixiong , Tan Jiacong , Yu Nianzu , Li Meihua , Zhao Yeyu 
Published: July 2022

BackgroundSeveral studies have suggested that anti-silencing function 1 B (ASF1B) can serve as a good potential marker for predicting tumor prognosis. But the values of ASF1B in gliomas have not been elucidated and further confirmation is needed.MethodsTranscriptomic and clinical data were downloaded from The Cancer Genome Atlas database (TCGA), genotypic tissue expression (GTEx), and the Chinese Gliomas Genome Atlas database (CGGA). Univariate and multivariate Cox regression analyses were used to investigate the link between clinical variables and ASF1B. Survival analysis was used to assess the association between ASF1B expression and overall survival (OS). The relationship between ASF1B expression and OS was studied using survival analysis. To investigate the probable function and immunological infiltration, researchers used gene ontology (GO) analysis, gene set enrichment analysis (GSEA), and single-sample GSEA (ssGSEA).ResultsIn glioma tissues, ASF1B expression was considerably higher than in normal tissues. The survival analysis found that increased ASF1B expression was linked with a poor prognosis in glioma patients. ASF1B demonstrated a high diagnostic value in glioma patients, according to a Receiver Operating Characteristic (ROC) analysis. ASF1B was found to be an independent predictive factor for OS in a Cox regression study (HR = 1.573, 95% CI: 1.053–2.350, p = 0.027). GO, KEGG, and GSEA functional enrichment analysis revealed that ASF1B was associated with nuclear division, cell cycle, m-phase, and cell cycle checkpoints. Immuno-infiltration analysis revealed that ASF1B was positively related to Th2 cells, macrophages, and aDC and was negatively related to pDC, TFH, and NK CD56 bright cells.ConclusionA high level of ASF1B mRNA expression was correlated with a poor prognosis in glioma patients in this study, implying that it could be a reliable prognostic biomarker for glioma patients.
Preoperative Prediction of Lymph Node Metastasis of Pancreatic Ductal Adenocarcinoma Based on a Radiomics Nomogram of Dual-Parametric MRI Imaging
Authors: Shi Lin , Wang Ling , Wu Cuiyun , Wei Yuguo , Zhang Yang , Chen Junfa 
Published: July 2022

PurposeThis study aims to uncover and validate an MRI-based radiomics nomogram for detecting lymph node metastasis (LNM) in pancreatic ductal adenocarcinoma (PDAC) patients prior to surgery.Materials and MethodsWe retrospectively collected 141 patients with pathologically confirmed PDAC who underwent preoperative T2-weighted imaging (T2WI) and portal venous phase (PVP) contrast-enhanced T1-weighted imaging (T1WI) scans between January 2017 and December 2021. The patients were randomly divided into training (n = 98) and validation (n = 43) cohorts at a ratio of 7:3. For each sequence, 1037 radiomics features were extracted and analyzed. After applying the gradient-boosting decision tree (GBDT), the key MRI radiomics features were selected. Three radiomics scores (rad-score 1 for PVP, rad-score 2 for T2WI, and rad-score 3 for T2WI combined with PVP) were calculated. Rad-score 3 and clinical independent risk factors were combined to construct a nomogram for the prediction of LNM of PDAC by multivariable logistic regression analysis. The predictive performances of the rad-scores and the nomogram were assessed by the area under the operating characteristic curve (AUC), and the clinical utility of the radiomics nomogram was assessed by decision curve analysis (DCA).ResultsSix radiomics features of T2WI, eight radiomics features of PVP and ten radiomics features of T2WI combined with PVP were found to be associated with LNM. Multivariate logistic regression analysis showed that rad-score 3 and MRI-reported LN status were independent predictors. In the training and validation cohorts, the AUCs of rad-score 1, rad-score 2 and rad-score 3 were 0.769 and 0.751, 0.807 and 0.784, and 0.834 and 0.807, respectively. The predictive value of rad-score 3 was similar to that of rad-score 1 and rad-score 2 in both the training and validation cohorts (P &gt; 0.05). The radiomics nomogram constructed by rad-score 3 and MRI-reported LN status showed encouraging clinical benefit, with an AUC of 0.845 for the training cohort and 0.816 for the validation cohort.ConclusionsThe radiomics nomogram derived from the rad-score based on MRI features and MRI-reported lymph status showed outstanding performance for the preoperative prediction of LNM of PDAC.
Survival Outcomes of Patients With Stage IB3 Cervical Cancer Who Undergo Abdominal Radical Hysterectomy Versus Radiochemotherapy
Authors: Li Zhiqiang , Yang Qing , Guo Jianxin , Liang Guoqiang , Duan Hui , Wang Shaoguang , Hao Min , Liang Wentong , Li Donglin , Zhan Xuemei , Xie Qinghuang , Lang Jinghe , Liu Ping , Chen Chunlin 
Published: July 2022

ObjectiveThis study aimed to compare the survival outcomes among stage IB3 cervical cancer patients who undergo abdominal radical hysterectomy (ARH)+pelvic lymphadenectomy ± para-aortic lymph node dissection versus radiochemotherapy (R-CT).MethodsBased on the large number of diagnoses and treatments for cervical cancer in the Chinese database, propensity score matching (PSM) was used to compare the 5-year overall survival (OS) and disease-free survival (DFS) rates of the ARH group and R-CT group.ResultsThere were 590 patients with stage IB3 cervical cancer according to the FIGO 2018 staging system, with 470 patients in the ARH group and 120 patients in the R-CT group. The ARH and R-CT groups showed different 5-year OS and DFS rates in the total study population, and the 5-year OS and DFS rates in the R-CT group (n = 120) were lower than those in the ARH group (n = 470) (OS: 78.1% vs. 92.1%, p &lt; 0.001; DFS: 71.6% vs. 90.3%, p &lt; 0.001). R-CT was associated with a worse 5-year OS rate (hazard ratio [HR] = 3.401; 95% confidence interval [CI] = 1.875–6.167; p &lt; 0.001) and DFS rate (HR = 3.440; 95% CI = 2.075–5.703; p &lt; 0.001) by Cox multivariate analysis. After 1:3 PSM, the 5-year OS and DFS rates in the R-CT group (n = 108) were lower than those in the RH group (n = 280) (OS: 76.4% vs. 94.0%, p &lt; 0.001; DFS: 69.3% vs. 92.6%, p &lt; 0.001, respectively). R-CT was associated with a worse 5-year OS rate (HR = 4.071; 95% CI = 2.042–8.117; p &lt; 0.001) and DFS rate (HR = 4.450; 95% CI = 2.441–8.113; p &lt; 0.001) by Cox multivariate analysis.ConclusionOur study found that for FIGO 2018 stage IB3 cervical cancer patients, ARH resulted in better OS and DFS than R-CT.
Nomogram Based on CT Radiomics Features Combined With Clinical Factors to Predict Ki-67 Expression in Hepatocellular Carcinoma
Authors: Wu Cuiyun , Chen Junfa , Fan Yuqian , Zhao Ming , He Xiaodong , Wei Yuguo , Ge Weidong , Liu Yang 
Published: July 2022

ObjectivesThe study developed and validated a radiomics nomogram based on a combination of computed tomography (CT) radiomics signature and clinical factors and explored the ability of radiomics for individualized prediction of Ki-67 expression in hepatocellular carcinoma (HCC).MethodsFirst-order, second-order, and high-order radiomics features were extracted from preoperative enhanced CT images of 172 HCC patients, and the radiomics features with predictive value for high Ki-67 expression were extracted to construct the radiomic signature prediction model. Based on the training group, the radiomics nomogram was constructed based on a combination of radiomic signature and clinical factors that showed an independent association with Ki-67 expression. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to verify the performance of the nomogram.ResultsSixteen higher-order radiomic features that were associated with Ki-67 expression were used to construct the radiomics signature (AUC: training group, 0.854; validation group, 0.744). In multivariate logistic regression, alfa-fetoprotein (AFP) and Edmondson grades were identified as independent predictors of Ki-67 expression. Thus, the radiomics signature was combined with AFP and Edmondson grades to construct the radiomics nomogram (AUC: training group, 0.884; validation group, 0.819). The calibration curve and DCA showed good clinical application of the nomogram.ConclusionThe radiomics nomogram developed in this study based on the high-order features of CT images can accurately predict high Ki-67 expression and provide individualized guidance for the treatment and clinical monitoring of HCC patients.
Co-development and Usability Testing of Research 101: A Patient-Oriented Research Curriculum in Child Health (PORCCH) E-Learning Module for Patients and Families
Authors: Walsh Catharine M. , Jones Nicola L. , McCreath Graham A. , Connan Veronik , Pires Linda , Chen Autumn Q. H. , Karoly Aliza , Macarthur Colin 
Published: July 2022

BackgroundEngaging patients and families as research partners increases the relevance, quality, and impact of child health research. However, those interested in research engagement may feel underequipped to meaningfully partner. We sought to co-develop an online learning (e-learning) module, “Research 101,” to support capacity-development in patient-oriented child health research amongst patients and families.MethodsModule co-development was co-led by a parent and researcher, with guidance from a diverse, multi-stakeholder steering committee. A mixed-methods usability testing approach, with three iterative cycles of semi-structured interviews, observations, and questionnaires, was used to refine and evaluate the e-learning module. Module feedback was collected during testing and a post-module interview, and with the validated System Usability Scale (SUS), and satisfaction, knowledge, and self-efficacy questionnaires. Transcripts and field notes were analyzed through team discussion and thematic coding to inform module revisions.ResultsThirty participants fully tested Research 101, and another 15 completed confirmatory usability testing (32 caregivers, 6 patients, and 7 clinician-researchers). Module modifications pertaining to learner-centered design, content, aesthetic design, and learner experience were made in each cycle. SUS scores indicated the overall usability of the final version was “excellent.” Participants' knowledge of patient-oriented research and self-efficacy to engage in research improved significantly after completing Research 101 (p &lt; 0.01).ConclusionsCo-development and usability testing facilitated the creation of an engaging and effective resource to support the scaling up of patient-oriented child health research capacity. The methods and findings of this study may help guide the integration of co-development and usability testing in creating similar resources.
Universal Newborn Screening for Congenital Cytomegalovirus Infection – From Infant to Maternal Infection: A Prospective Multicenter Study
Authors: Chiereghin Angela , Pavia Claudia , Turello Gabriele , Borgatti Eva Caterina , Baiesi Pillastrini Federico , Gabrielli Liliana , Gibertoni Dino , Marsico Concetta , De Paschale Massimo , Manco Maria Teresa , Ruscitto Antonia , Pogliani Laura , Bellini Marta , Porta Alessandro , Parola Luciana , Scarasciulli Maria Luisa , Calvario Agata , Capozza Manuela , Capretti Maria Grazia , Laforgia Nicola , Clerici Pierangelo , Lazzarotto Tiziana 
Published: July 2022

Introduction:Most infants at risk for cytomegalovirus (CMV)-associated sensorineural hearing loss (SNHL) are unrecognized because of the absence of a universal neonatal CMV screening. The search of CMV-DNA by molecular methods in salivary swabs was demonstrated to be a reliable approach. This study describes the results obtained by carrying out a universal screening for congenital CMV (cCMV) infection including all live-born newborns in three Italian sites, as well as the therapeutic interventions and clinical outcome of the CMV-infected neonates. Moreover, CMV maternal infection's characteristics were evaluated.MethodsTo confirm or exclude cCMV infection, a CMV-DNA-positive result on a first salivary swab was followed by repeated saliva and urine samples collected within 21 days of age. Breast milk samples were also collected. The search of CMV-DNA was performed with a single automated quantitative commercial real-time PCR assay, regardless of the type of samples used.ResultsA total of 3,151 newborns were enrolled; 21 (0.66%) of them were congenitally infected (median saliva viral load at screening, 6.65 [range, 5.03–7.17] log10 IU/ml). Very low/low viral load in screening saliva samples (median value, 1.87 [range, 1.14–2.59] log10 IU/ml) was associated with false-positive results (n = 54; 1.7%). CMV-DNA was detected in almost half of the breast milk samples of mother–infant pairs with a false-positive result, suggesting that contamination from breast milk may not be the only explanation in the study population. cCMV infection confirmation with the search of CMV-DNA in a urine sample proved to be the gold standard strategy, since false-positive results were observed in 4/54 (7.5%) of the repeated saliva samples. Symptomatic cCMV infection was observed in 3/21 (14.3%) infants; notably, one (4.7%) developed moderate unilateral SNHL at 5 months after birth. Finally, two symptomatic cCMV infections were associated with primary maternal infection acquired in the first trimester of gestation; one newborn with severe cCMV symptoms was born to a mother with no CMV checkups in pregnancy.ConclusionWithout universal neonatal CMV screening, some infected infants who develop late neurological sequelae may not be recognized and, consequently, they are not able to benefit early from instrumental and therapeutic interventions to limit and/or treat CMV disease.
Ultrasonographic Evaluation of the Hypospadiac Penis in Children
Authors: Abbas Tariq O. 
Published: July 2022

IntroductionIdentifying key anatomical features of the hypospadiac penis is crucial to better understanding this pathology and guiding surgical reconstruction plans, thereby achieving superior functional and cosmetic outcomes.ObjectiveTo Assess the feasibility and precision of penile ultrasonography (PUG) in determining key structural features for hypospadias cases (including distal extent of the spongiosal component of the urethral plate, to elucidate the healing process following tubularised incised-plate urethroplasty).Patients and MethodsTwenty-five children with hypospadias were assessed using PUG prior to surgical repair and then again under general anesthesia. Preoperative images were acquired using ultrasonography in sagittal and transverse planes, then later compared with anatomical findings obtained during surgical repair of urethral hypoplasia.ResultsMedian patient age was 1.2 years (range 0.5–12) and hypospadias types included coronal 17/25 (68%), mid-penile 5/25 (20%), and proximal penile 3/25 (12%). Distinct layers of the corpus spongiosa and mucosal layer, Buck fascia, tunica albuginea, glans, corpora cavernosa, and penile skin were delineated so that their spatial inter-relationship could be assessed. Distal extent of the spongiosal component of the urethral plate was determined by the mid-glans B-B line. The extent of urethral hypoplasia identified by PUG was relatively similar to measurements obtained intraoperatively.ConclusionPUG is a feasible and accurate approach to evaluating penile configuration in children with hypospadias. Distal extent of the spongiosal component of the urethral plate was accurately determined, hence PUG could potentially be used to improve surgical planning and appraisal of current repair procedures.
Toxicological Properties of 7-Methylguanine, and Preliminary Data on its Anticancer Activity
Authors: Kirsanov Kirill , Fetisov Timur , Antoshina Elena , Trukhanova Lubov , Gor’kova Tatiana , Vlasova Olga , Khitrovo Irina , Lesovaya Ekaterina , Kulbachevskaya Nataliya , Shcherbakova Tatiana , Belitsky Gennady , Yakubovskaya Marianna , Švedas Vytas , Nilov Dmitry 
Published: July 2022

7-Methylguanine (7-MG) competitively inhibits the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) and RNA-modifying enzyme tRNA-guanine transglycosylase (TGT) and represents a potential anticancer drug candidate. Furthermore, as a natural compound, it could escape the serious side effects characteristic for approved synthetic PARP inhibitors. Here we present a comprehensive study of toxicological and carcinogenic properties of 7-MG. It was demonstrated that 7-MG does not induce mutations or structural chromosomal abnormalities, and has no blastomogenic activity. A treatment regimen with 7-MG has been established in mice (50 mg/kg per os, 3 times per week), exerting no adverse effects or changes in morphology. Preliminary data on the 7-MG anticancer activity obtained on transplantable tumor models support our conclusions that 7-MG can become a promising new component of chemotherapy.
Population Pharmacokinetics and Initial Dosage Optimization of Tacrolimus in Pediatric Hematopoietic Stem Cell Transplant Patients
Authors: Liu Xiao-Lin , Guan Yan-Ping , Wang Ying , Huang Ke , Jiang Fu-Lin , Wang Jian , Yu Qi-Hong , Qiu Kai-Feng , Huang Min , Wu Jun-Yan , Zhou Dun-Hua , Zhong Guo-Ping , Yu Xiao-Xia 
Published: July 2022

Background: There is a substantial lack of tacrolimus pharmacokinetic information in pediatric hematopoietic stem cell transplant (HSCT) patients. This study aimed to develop population pharmacokinetics (PopPK) of tacrolimus in pediatric HSCT patients and to devise model-guided dosage regimens.Methods: A retrospective analysis was performed on 86 pediatric HSCT patients who received tacrolimus intravenously or orally. A total of 578 tacrolimus trough concentrations (C0) were available for pharmacokinetic analysis using a non-linear mixed-effects modeling method. Demographic and clinical data were included and assessed as covariates via the stepwise method. Bayesian estimators were used to devise pediatric dosage regimens that targeted C0 of 5–15 ng mL−1.Results: A one-compartment model with first-order absorption adequately described the tacrolimus pharmacokinetics. Clearance (CL), volume of distribution (V), and typical bioavailability (F) in this study were estimated to be 2.42 L h−1 (10.84%), 79.6 L (16.51%), and 19% (13.01%), respectively. Body weight, hematocrit, post-transplantation days, and caspofungin and azoles concomitant therapy were considered significant covariates for tacrolimus CL. Hematocrit had a significant impact on the V of tacrolimus. In the subgroup cohort of children (n = 24) with CYP3A5 genotype, the clearance was 1.38-fold higher in CYP3A5 expressers than in non-expressers. Simulation indicated that the initial dosage optimation of tacrolimus for intravenous and oral administration was recommended as 0.025 and 0.1 mg kg−1 d−1 (q12h), respectively.Conclusion: A PopPK model for tacrolimus in pediatric HSCT patients was developed, showing good predictive performance. Model-devised dosage regimens with trough tacrolimus concentrations provide a practical strategy for achieving the therapeutic range.