bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Tumor Mutation Burden, Microsatellite Instability, and Somatic Copy Number Alteration Derived Nine Gene Signatures to Predict Clinical Outcomes in STAD
Authors: Chen Chuanzhi , Chen Yi , Jin Xin , Ding Yongfeng , Jiang Junjie , Wang Haohao , Yang Yan , Lin Wu , Chen Xiangliu , Huang Yingying , Teng Lisong 
Published: April 2022

Genomic features, including tumor mutation burden (TMB), microsatellite instability (MSI), and somatic copy number alteration (SCNA), had been demonstrated to be involved with the tumor microenvironment (TME) and outcome of gastric cancer (GC). We obtained profiles of TMB, MSI, and SCNA by processing 405 GC data from The Cancer Genome Atlas (TCGA) and then conducted a comprehensive analysis though “iClusterPlus.” A total of two subgroups were generated, with distinguished prognosis, somatic mutation burden, copy number changes, and immune landscape. We revealed that Cluster1 was marked by a better prognosis, accompanied by higher TMB, MSIsensor score, TMEscore, and lower SCNA burden. Based on these clusters, we screened 196 differentially expressed genes (DEGs), which were subsequently projected into univariate Cox survival analysis. We constructed a 9-gene immune risk score (IRS) model using LASSO-penalized logistic regression. Moreover, the prognostic prediction of IRS was verified by receiver operating characteristic (ROC) curve analysis and nomogram plot. Another independent Gene Expression Omnibus (GEO) contained specimens from 109 GC patients was designed as an external validation. Our works suggested that the 9‐gene‐signature prediction model, which was derived from TMB, MSI, and SCNA, was a promising predictive tool for clinical outcomes in GC patients. This novel methodology may help clinicians uncover the underlying mechanisms and guide future treatment strategies.
Network Reconfiguration Among Cerebellar Visual, and Motor Regions Affects Movement Function in Spinocerebellar Ataxia Type 3
Authors: Chen Hui , Dai Limeng , Zhang Yuhan , Feng Liu , Jiang Zhenzhen , Wang Xingang , Xie Dongjing , Guo Jing , Chen Huafu , Wang Jian , Liu Chen 
Published: April 2022

BackgroundSpinocerebellar ataxia type 3 (SCA3) is a rare movement disorder characterized with ataxia. Previous studies on movement disorders show that the whole-brain functional network tends to be more regular, and these reconfigurations correlate with genetic and clinical variables.MethodsTo test whether the brain network in patients with SCA3 follows a similar reconfiguration course to other movement disorders, we recruited 41 patients with SCA3 (mean age = 40.51 ± 12.13 years; 23 male) and 41 age and sex-matched healthy individuals (age = 40.10 ± 11.56 years; 24 male). In both groups, the whole-brain network topology of resting-state functional magnetic resonance imaging (rs-fMRI) was conducted using graph theory, and the relationships among network topologies, cytosine-adenine-guanine (CAG) repeats, clinical symptoms, and functional connectivity were explored in SCA3 patients using partial correlation analysis, controlling for age and sex.ResultsThe brain networks tended to be more regular with a higher clustering coefficient, local efficiency, and modularity in patients with SCA3. Hubs in SCA3 patients were reorganized as the number of hubs increased in motor-related areas and decreased in cognitive areas. At the global level, small-worldness and normalized clustering coefficients were significantly positively correlated with clinical motor symptoms. At the nodal level, the clustering coefficient and local efficiency increased significantly in the visual (bilateral cuneus) and sensorimotor (right cerebellar lobules IV, V, VI) networks and decreased in the cognitive areas (right middle frontal gyrus). The clustering coefficient and local efficiency in the bilateral cuneus gyrus were negatively correlated with clinical motor symptoms. The functional connectivity between right caudate nucleus and bilateral calcarine gyrus were negatively correlated with disease duration, while connectivity between right posterior cingulum gyrus and left cerebellar lobule III, left inferior occipital gyrus and right cerebellar lobule IX was positively correlated.ConclusionOur results demonstrate that a more regular brain network occurred in SCA3 patients, with motor and visual-related regions, such as, cerebellar lobules and cuneus gyrus, both forayed neighbor nodes as “resource predators” to compensate for normal function, with motor and visual function having the higher priority comparing with other high-order functions. This study provides new information about the neurological mechanisms underlying SCA3 network topology impairments in the resting state, which give a potential guideline for future clinical treatments.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [ChiCTR1800019901].
The Correlation of Prediabetes and Type 2 Diabetes With Adiposity in Adults
Authors: Sun Juan , Liu Zhen , Zhang Zimu , Zeng Ziyang , Kang Weiming 
Published: April 2022

BackgroundFat metabolism is associated with prediabetes and type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the detailed correlation of diabetes status with adiposity among adults.MethodsBriefly, 28,429 adults aged ≥18 years from both sexes in the National Health and Nutrition Examination Survey (NHANES) 1999–2018 were included in this study. Multivariable linear regression models were used to examine associations of prediabetes and diabetes status, disease duration of T2DM, serum glucose, glycohemoglobin (HbA1c) with total percent fat (TPF), and fat mass distribution.ResultsAfter adjusting for sociodemographic covariates, health behaviors, hypertension, hypercholesterolemia, there were direct associations of prediabetes and T2DM status with TPF, trunk fat mass, android fat mass, gynoid fat mass and android to gynoid ratio compared with non-diabetes. But the fat mass decreased with the increase of the disease duration in patients with T2DM. Besides, when stratifying by diabetes status, we found direct associations of serum glucose and HbA1c with TPF, trunk fat mass, android fat mass, gynoid fat mass, and android to gynoid ratio in non-diabetic and prediabetic participants. But in patients with T2DM, inverse associations of serum glucose and HbA1c with fat mass were observed.ConclusionsThis study indicated that adults with prediabetes and T2DM had significantly higher TPF, trunk fat mass, android fat mass, gynoid fat mass, and android to gynoid ratio compared with those without diabetes. Moreover, fat mass decreased as the disease duration increased in patients with T2DM. The associations of serum glucose and HbA1c with TPF and fat mass distribution in patients with T2DM were opposite to the relationships observed in non-diabetic and prediabetic participants.
Conformal Dose Modulator for Proton Beam Therapy Part 1: A Simulation Study
Authors: Zhang Zhexuan , Zhao Weizhao , Butkus Michael , Wu Xiaodong 
Published: April 2022

PurposeConformal dose deliveries in proton therapy utilize either a passive scattering system with a modulator or a pencil beam scanning (PBS) system. Efforts have been made to achieve conformal dose delivery by scanning a single energy layer of pencil beams through a 3D conformal modulator (3DCM), which combines a spread-out Bragg peak (SOBP) modulator consisting of a micro-pyramid array and a range compensator. The current published approach of designing such 3DCM relies on forward calculation methods to determine the geometry of the modulator. This study presents an alternative designing algorithm that inversely generates the geometry of a 3DCM paired with a corresponding fluence map, customized to patient-specific clinical indications.MethodsCritical spacing governing the size and separation between neighboring micro-pyramids was first determined, under which the dose homogeneity at desired depths could be achieved. We designed an adaptive ring optimization method using a modified gradient descent algorithm to inversely calculate the geometry of the 3DCM. This method includes several stages that progressively optimize both target coverage and dose conformity. The output contains the geometry of the 3DCM and its corresponding proton fluence map. Monte Carlo (MC) simulation was used to validate the results.ResultsThe critical size and spacing of Lucite pyramids was determined to be 0.5 cm for a 184-MeV pristine proton beam. Using MATLAB (R2020a), the inverse designing algorithm generated an optimized 3DCM geometry and a fluence distribution achieving 100% target coverage with the 90% isodose surface and a corresponding conformity index of 1.057 on a spherical target. The resulting geometry was pruned to accommodate the MC simulation software and a currently accessible 3D printing service. The pruned geometry gave 95% target coverage by 90% isodose surface with a conformity index of 1.09 by ray-tracing dose computation. The MC simulation validated the 3DCM with 95% target coverage by 87% isodose surface and a conformity index of 1.12.ConclusionWe have demonstrated the feasibility of using a novel inverse optimization algorithm to generate 3DCM geometry and its corresponding proton beam fluence/intensity map, which could deliver highly conformal dose distribution with pencil beam scanning system using a single energy layer.
A Novel Nomogram for Prediction and Evaluation of Lymphatic Metastasis in Patients With Renal Cell Carcinoma
Authors: Li Wenle , Wang Bing , Dong Shengtao , Xu Chan , Song Yang , Qiao Ximin , Xu Xiaofeng , Huang Meijin , Yin Chengliang 
Published: April 2022

BackgroundLymphatic metastasis is an important mechanism of renal cell carcinoma (RCC) dissemination and is an indicator of poor prognosis. Therefore, we aimed to identify predictors of lymphatic metastases (LMs) in RCC patients and to develop a new nomogram to assess the risk of LMs.MethodsThis study included patients with RCC from 2010 to 2018 in the Surveillance, Epidemiology, and Final Results (SEER) database into the training cohort and included the RCC patients diagnosed during the same period in the Second Affiliated Hospital of Dalian Medical University into the validation cohort. Univariate and multivariate logistic regression analysis were performed to identify risk factors for LM, constructing a nomogram. The receiver operating characteristic (ROC) curves were generated to assess the nomogram’s performance, and the concordance index (C-index), area under curve value (AUC), and calibration plots were used to evaluate the discrimination and calibration of the nomogram. The nomogram’s clinical performance was evaluated by decision curve analysis (DCA), probability density function (PDF) and clinical utility curve (CUC). Furthermore, Kaplan-Meier curves were performed in the training and the validation cohort to evaluate the survival risk of the patients with lymphatic metastasis or not. Additionally, on the basis of the constructed nomogram, we obtained a convenient and intuitive network calculator.ResultsA total of 41837 patients were included for analysis, including 41,018 in the training group and 819 in the validation group. Eleven risk factors were considered as predictor variables in the nomogram. The nomogram displayed excellent discrimination power, with AUC both reached 0.916 in the training group (95% confidence interval (CI) 0.913 to 0.918) and the validation group (95% CI 0.895 to 0.934). The calibration curves presented that the nomogram-based prediction had good consistency with practical application. Moreover, Kaplan-Meier curves analysis showed that RCC patients with LMs had worse survival outcomes compared with patients without LMs.ConclusionsThe nomogram and web calculator (https://liwenle0910.shinyapps.io/DynNomapp/) may be a useful tool to quantify the risk of LMs in patients with RCC, which may provide guidance for clinicians, such as identifying high-risk patients, performing surgery, and establishing personalized treatment as soon as possible.
Metformin Regulates TET2 Expression to Inhibit Endometrial Carcinoma Proliferation: A New Mechanism
Authors: Zhang Jingbo , Kuang Lei , Li Yanyu , Wang Qing , Xu Hui , Liu Jianwei , Zhou Xueyan , Li Yang , Zhang Bei 
Published: April 2022

ObjectivesTo investigate the relationship between TET2 expression and endometrial cancer’s clinicopathological features and prognosis, and the effect of metformin on TET2 and 5hmC levels in endometrial cancer cells.MethodsThe clinical significance of TET2 expression in endometrial carcinoma was analyzed from TCGA public database. Eighty-eight patients with endometrial cancer and 20 patients with normal proliferative endometrium were enrolled in this study. TET2 and 5hmC were respectively detected by Immunohistochemistry and ELISA in endometrial tissues. Kaplan-Meier and Cox proportional hazard regression models were used to analyze relationships between TET2 and 5hmC and the overall survival of EC patients. Endometrial cell proliferation was assessed after TET2 gene knockdown. Western blotting and real-time PCR were used to detect the effect of metformin on TET2 expression and to explore whether AMPK is involved in metformin-mediated TET2 regulation.ResultsThe clinical significance of expression of TET2 in endometrial cancer from TCGA public database confirmed that TET2 expression was significantly down-regulated in cancer samples and TET2 expression was also significantly different among different histopathological samples and TET2 is down-regulated in advanced, high-grade, and relapsed endometrial carcinoma tissues(P&lt;0.05). Immunohistochemical analysis showed that TET2 and 5hmC levels were significantly lower in endometrial adenocarcinoma(P&lt;0.05). TET2 expression was correlated with the degree of EC differentiation (P &lt; 0.05). 5hmC levels were associated with clinical stage, differentiation, the depth of myometrial invasion, and lymph node metastasis (P &lt; 0.05). The mean survival time of patients with negative staining for TET2 and 5hmC was shorter than that of patients with positive staining for both markers (P&lt;0.05). Multivariate Cox regression analysis showed that TET2 expression was an independent risk factor for prognosis in patients with endometrial adenocarcinoma (HR = 14.520, 95% CI was 1.From 060 to 198.843, P = 0.045). siRNA-mediated TET2 knockdown increased the proliferation of EC cells. Metformin increased the levels of TET2 and 5hmC in EC cells. AMPK was involved in the regulation of TET2 by metformin.ConclusionsTET2 may play an important role in EC development and may be a prognostic marker. Moreover, TET2 may be involved in a novel mechanism by which metformin inhibits EC cell proliferation.
A Dual-Polarized Horn Antenna Covering Full Ka-Band Using Turnstile OMT
Authors: Xiao Jun , Teni Geer , Li Hongmei , Ding Tongyu , Ye Qiubo 
Published: April 2022

This article presents a dual-polarized corrugated horn antenna incorporated a turnstile orthomode transducer (OMT) covering the full Ka-band (26.5–40 GHz). A three-stepped cylindrical tuning stub scattering element is designed in the turnstile junction to combine/split the two linearly polarized waves with high isolation. The proposed turnstile OMT shows a good simulated return loss better than 20 dB and a high isolation higher than 57 dB within the whole Ka-band. Then, a corrugated horn antenna with five-stage choke rings is designed. Finally, the proposed horn antenna incorporated in the turnstile OMT is fabricated and measured. The measured impedance bandwidth for |S11/22|≤ −15 dB is 50.7% from 25 to 42 GHz. The measured peak gain is 11.9 dBi. The proposed antenna system is a promising candidate for the 5G millimeter-wave applications.
Supplementation of Specific Collagen Peptides Following High-Load Resistance Exercise Upregulates Gene Expression in Pathways Involved in Skeletal Muscle Signal Transduction
Authors: Centner Christoph , Jerger Simon , Mallard Alistair , Herrmann Anna , Varfolomeeva Eugenia , Gollhofer Sandra , Oesser Steffen , Sticht Carsten , Gretz Norbert , Aagaard Per , Nielsen Jakob L. , Frandsen Ulrik , Suetta Charlotte , Gollhofer Albert , König Daniel 
Published: April 2022

Previous evidence suggests that resistance training in combination with specific collagen peptides (CP) improves adaptive responses of the muscular apparatus. Although beneficial effects have been repeatedly demonstrated, the underlying mechanisms are not well understood. Therefore, the primary objective of the present randomized trial was to elucidate differences in gene expression pathways related to skeletal muscle signal transduction following acute high-load resistance exercise with and without CP intake. Recreationally active male participants were equally randomized to high-load leg extension exercise in combination with 15 g CP or placebo (PLA) supplementation. Muscle biopsies from the vastus lateralis muscle were obtained at baseline as well as 1, 4 and 24 h post exercise to investigate gene expression using next generation sequencing analysis. Several important anabolic pathways including PI3K-Akt and MAPK pathways were significantly upregulated at 1 and 4 h post-exercise. Significant between-group differences for both pathways were identified at the 4 h time point demonstrating a more pronounced effect after CP intake. Gene expression related to the mTOR pathway demonstrated a higher visual increase in the CP group compared to PLA by trend, but failed to achieve statistically significant group differences. The current findings revealed a significantly higher upregulation of key anabolic pathways (PI3K-Akt, MAPK) in human skeletal muscle 4 h following an acute resistance training combined with intake of 15 g of specific collagen peptides compared to placebo. Further investigations should examine potential relationships between upregulated gene expression and changes in myofibrillar protein synthesis as well as potential long-term effects on anabolic pathways on the protein level.
School Refusal in Immigrants and Ethnic Minority Groups: A Qualitative Study of Adolescents' and Young Adults' Experiences
Authors: Brault Camille , Thomas Isaiah , Moro Marie Rose , Benoit Laelia 
Published: April 2022

BackgroundSchool refusal is one cause of school absenteeism along with truancy, and the two can be difficult to distinguish. School absenteeism behaviors among students in transcultural situations (immigrants or children of immigrants) and from ethnic minority groups are subject to misdiagnosis and decreased access to care. To improve the care provided, this exploratory study addresses the experience of adolescents and young adults engaging in school refusal, from immigrant and ethnic minority groups.MethodsSixteen participants between the ages of 16 and 20 years old presenting with school refusal were interviewed for this qualitative study. All participants were either immigrants, children of immigrants, or from an ethnic minority group. We conducted a qualitative analysis based on Interpretative Phenomenological Analysis.ResultsParticipants experienced school refusal as a loss of identity and as a failure to achieve what was perceived as parental expectations of success, which triggered feelings of worthlessness, shame, and guilt. The loss of a peer group, namely their classmates, as a result of school absenteeism was experienced as a marginalization from the larger society. Although participants denied having personally experienced racism, some of them recalled their parents experiencing racism at school.ConclusionSchool refusal complicates identity construction, autonomy, and integration into society. For adolescents and young adults from immigrant and ethnic minority backgrounds, it also triggers guilt, transgenerational traumatic memories, and the fear of marginalization. In addition to validated therapies for school refusal, sociological, intersectional, and cross-cultural tools would be a valuable addition to treatment.
Emotional Dysregulation and Adaptive Functioning in Preschoolers With Autism Spectrum Disorder or Other Neurodevelopmental Disorders
Authors: Davico Chiara , Marcotulli Daniele , Cudia Valentina Francesca , Arletti Luca , Ghiggia Ada , Svevi Barbara , Faraoni Chiara , Amianto Federico , Ricci Federica , Vitiello Benedetto 
Published: April 2022

AimEmotional dysregulation (ED), defined by deficits in the ability to monitor and modulate the valence, intensity, and expression of emotions, is typically expressed with irritability, tantrums, mood fluctuations, and self-harm in young children with autism spectrum disorder (ASD). Although ED does not represent a diagnostic feature of ASD, its manifestations are an important contributor to functional impairment and clinical referral. This study aims to examine the relationship between ED and adaptive functioning in preschoolers clinically referred for ASD or other neurodevelopmental disorders.MethodsA sample of 100 children (74% males, mean age 39.4 ± 12.3 months), consecutively referred to a university clinic for neurodevelopmental disorders, received clinical assessments of psychopathology with the CBCL and the Autism Diagnostic Interview-Revised, of ED- with the CBCL-Attention, Anxious/Depressed, and Aggression index (CBCL-AAA), of autism symptom severity with the ADOS-2 Calibrated Severity Score (ADOS-CSS), and of global developmental/cognitive delay (GDD) with the WPPSI-IV or other age-appropriate standardized scales. Adaptive functioning was measured with the ABAS-II. Sixty-five children met DSM-5 criteria for ASD. Multivariate regression models were applied to evaluate the relative contribution of ED, ASD severity and GDD to the ABAS-II general (GAC), conceptual (CAD), social (SAD), and practical (PAD) adaptive functioning domains.ResultsOverall (n = 100), lower adaptive functioning was associated with higher CBCL-AAA (p = 0.003), higher ADOS-CSS (p &lt; 0.001), and presence of GDD (p = 0.023). In the ASD group (n = 65), worse CAD was predicted by GDD (p = 0.016), and worse SAD and PAD by higher ADOS-CSS (p = 0.032) and ED (p = 0.002). No sex differences were detected in the study variables.ConclusionTogether with the severity of global developmental delay and of autism symptoms, ED is a significant contributor to impairment in adaptive functioning among young children with a neurodevelopmental disorder and, in particular, with ASD. ED could represent a specific target for early interventions aimed at enhancing adaptive functioning in early childhood.