bluuebunny/crossref_metadata_2025_split huggingface dataset:
m6A Regulator Expression Segregates Meningiomas Into Biologically Distinct Subtypes
Authors: Chen Jiawei , Sun Shuchen , Ren Leihao , Hua Lingyang , Wang Daijun , Xie Qing , Wirsching Hans-Georg , Deng Jiaojiao , Weller Michael , Gong Ye 
Published: December 2021

BackgroundMeningiomas are the most common primary intracranial tumors in adults. According to the 2021 World Health Organization (WHO) classification of central nervous system tumors, approximately 80% of meningiomas are WHO grade 1, that is, histopathologically benign, whereas about 20% are WHO grade 2 or grade 3, showing signs of atypia or malignancy. The dysregulation of N6-methylation (m6A) regulators is associated with disorders of diverse critical biological processes in human cancer. This study aimed to explore whether m6A regulator expression was associated with meningioma molecular subtypes and immune infiltration.MethodsWe evaluated the m6A modification patterns of 160 meningioma samples based on 19 m6A regulators and correlated them with immune infiltration characteristics. Novel molecular subtypes were defined based on prognostic hub gene expression.ResultsTwo meningioma clusters were identified based on the expression of 19 m6A regulators. In cluster 1, 607 differentially expressed genes (DEGs) were upregulated and 519 were downregulated. A total of 1,126 DEGs comprised three gene expression modules characterized by turquoise, blue, and gray. Functional annotation suggested that the turquoise module was involved in Wnt-related and other important cancer-related pathways. We identified 32 hub genes in this module by constructing a protein–protein interaction network. The meningioma samples were divided into two molecular subtypes. EPN1, EXOSC4, H2AX, and MZT2B not only showed significant differences between meningioma molecular subtypes but also had the potential to be the marker genes of specific meningioma subtypes.Conclusionm6A regulator gene expression may be a novel prognostic marker in meningioma.
A Retrospective Study on Spinal Dissemination of Supratentorial Glioma
Authors: Chen Jianxin , Yang Fan , Shi Qi , Zhao Yuze , Huang Hongyan 
Published: December 2021

ObjectiveMetastatic spinal dissemination (MSD) of supratentorial glioma is very rare and there is no established standard of care. The current study investigates the clinical characteristics and course of spinal dissemination of supratentorial glioma.MethodsA retrospective analysis of adult patients with MSD of supratentorial glioma treated in the Department of Oncology in Beijing Shijitan Hospital, Capital Medical University from June 2012 until August 2021 was performed. The time to event was estimated using Kaplan–Meier analysis. Univariate analyses were performed using log-rank test and multivariate analysis was performed using the Cox proportional hazards model.ResultsThirty-four adult patients with MSD of supratentorial glioma were enrolled in this retrospective study. The median time to MSD (TTMSD) and overall survival (OS) were 5 months (range: 0–78 months) and 15 months (range: 0.7–85 months), respectively, in the entire cohort. Univariate analysis demonstrated that the patients who had received TMZ therapy had a longer TTMSD than those who did not (mTTMSD: 15 vs. 3 months, log-rank P = 0.0004). Furthermore, a protracted duration of salvage chemotherapy of &gt;6 months after MSD was associated with longer OS of the patients with MSD of supratentorial glioma (mOS: 13 vs. 5 months, log-rank P = 0.0163) and reduced the death risk by 64.3% (hazard ratio: 0.357, 95% CI: 0.141–0.901, P = 0.029) compared with a duration ≤6 months.ConclusionPatients with MSD of supratentorial glioma experienced poor prognosis and adjuvant chemotherapy may delay the occurrence of MSD. The protracted duration of systemic salvage chemotherapy may favor survival after spinal dissemination.
A Study of the Lipidomic Profiles of the CAL-27 and HOK Cell Lines Using EMS Spectra
Authors: Wang Xue-ying , Zhang Ting , Guan Wei-qun , Li Hua-zhu , Lin Ling 
Published: December 2021

ObjectiveThe aim of this study was to explore the lipidomic profiles of the CAL-27 human tongue cancer cell line and the human oral keratinocyte (HOK) cell line.MethodsThe lipidomic differences between the CAL-27 and the HOK cell lines were investigated using non-targeted high-performance liquid chromatography–mass spectrometry lipidomic analysis. The resulting data were then further mined via bioinformatics analysis technology and metabolic pathway analysis was conducted in order to map the most affected metabolites and pathways in the two cell lines.ResultsA total of 711 lipids were identified, including 403 glycerophospholipids (GPs), 147 glycerolipids, and 161 sphingolipids. Comparison of the enhanced MS (EMS) spectra of the two cell lines in positive and negative ionization modes showed the lipid compositions of HOK and CAL-27 cells to be similar. The expressions of most GP species in CAL-27 cells showed an increasing trend as compared with HOK, whereas a significant increase in phosphatidylcholine was observed (p &lt; 0.05). Significant differences in the lipid composition between CAL-27 and HOK cells were shown as a heatmap. Through principal component analysis and orthogonal partial least squares discriminant analysis, noticeably clear separation trends and satisfactory clustering trends between groups of HOK and CAL-27 cells were identified. The numbers of specific lipid metabolites that could distinguish CAL-27 from HOK in positive and negative modes were 100 and 248, respectively. GP metabolism was the most significantly altered lipid metabolic pathway, with 4 metabolites differentially expressed in 39 hit products.ConclusionThis study demonstrated the potential of using untargeted mass spectra and bioinformatics analysis to describe the lipid profiles of HOK and CAL-27 cells.
Geometrical Comparison and Quantitative Evaluation of 18F-FDG PET/CT- and DW-MRI-Based Target Delineation Before and During Radiotherapy for Esophageal Squamous Carcinoma
Authors: Li Huimin , Li Jianbin , Li Fengxiang , Zhang Yingjie , Li Yankang , Guo Yanluan , Xu Liang 
Published: December 2021

Background and PurposeThis study aimed to evaluate the geometrical differences in and metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG PET-CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) performed before and during radiotherapy (RT) for patients with esophageal cancer based on the three-dimensional CT (3DCT) medium and explore whether the high signal area derived from DW-MRI can be used as a tool for an individualized definition of the volume in need of dose escalation for esophageal squamous cancer.Materials and MethodsThirty-two patients with esophageal squamous cancer sequentially underwent repeated 3DCT, 18F-FDG PET-CT, and enhanced MRI before the initiation of RT and after the 15th fraction. All images were fused with 3DCT images through deformable registration. The gross tumor volume (GTV) was delineated based on PET Edge on the first and second PET-CT images and defined as GTVPETpre and GTVPETdur, respectively. GTVDWIpre and GTVDWIdur were delineated on the first and second DWI and corresponding T2-weighted MRI (T2W-MRI)-fused images. The maximum, mean, and peak standardized uptake values (SUVs; SUVmax, SUVmean, and SUVpeak, respectively); metabolic tumor volume (MTV); and total lesion glycolysis(TLG) and its relative changes were calculated automatically on PET. Similarly, the minimum and mean apparent diffusion coefficient (ADC; ADCmin and ADCmean) and its relative changes were measured manually using ADC maps.ResultsThe volume of GTVCT exhibited a significant positive correlation with that of GTVPET and GTVDWI (both p &lt; 0.001). Significant differences were observed in both ADCs and 18F-FDG PET metabolic parameters before and during RT (both p &lt; 0.001). No significant correlation was observed between SUVs and ADCs before and during RT (p = 0.072–0.944) and between ∆ADCs and ∆SUVs (p = 0.238–0.854). The conformity index and degree of inclusion of GTVPETpre to GTVDWIpre were significantly higher than those of GTVPETdur to GTVDWIdur (both p &lt; 0.001). The maximum diameter shrinkage rate (∆LDDWI) (24%) and the tumor volume shrinkage rate (VRRDWI) (60%) based on DW-MRI during RT were significantly greater than the corresponding PET-based ∆LDPET (14%) and VRRPET (41%) rates (p = 0.017 and 0.000, respectively).ConclusionBased on the medium of CT images, there are significant differences in spatial position, biometabolic characteristics, and the tumor shrinkage rate for GTVs derived from 18F-FDG PET-CT and DW-MRI before and during RT for esophageal squamous cancer. Further studies are needed to determine if DW-MRI will be used as tool for an individualized definition of the volume in need of dose escalation.
A Prediction Model Using Alternative Splicing Events and the Immune Microenvironment Signature in Lung Adenocarcinoma
Authors: Zhu Liping , Wang Zhiqiang , Sun Yilan , Giamas Georgios , Stebbing Justin , Yu Zhentao , Peng Ling 
Published: December 2021

BackgroundAlternative splicing (AS) is a gene regulatory mechanism that drives protein diversity. Dysregulation of AS is thought to play an essential role in cancer initiation and development. This study aimed to construct a prognostic signature based on AS and explore the role in the tumor immune microenvironment (TIME) in lung adenocarcinoma.MethodsWe analyzed transcriptome profiling and clinical lung adenocarcinoma data from The Cancer Genome Atlas (TCGA) database and lists of AS-related and immune-related signatures from the SpliceSeq. Prognosis-related AS events were analyzed by univariate Cox regression analysis. Gene set enrichment analyses (GSEA) were performed for functional annotation. Prognostic signatures were identified and validated using univariate and multivariate Cox regression, LASSO regression, Kaplan–Meier survival analyses, and proportional hazards model. The context of TIME in lung adenocarcinoma was also analyzed. Gene and protein expression data of Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A) were obtained from ONCOMINE and Human Protein Atlas. Splicing factor (SF) regulatory networks were visualized.ResultsA total of 19,054 survival-related AS events in lung adenocarcinoma were screened in 1,323 genes. Exon skip (ES) and mutually exclusive exons (ME) exhibited the most and fewest AS events, respectively. Based on AS subtypes, eight AS prognostic signatures were constructed. Patients with high-risk scores were associated with poor overall survival. A nomogram with good validity in prognostic prediction was generated. AUCs of risk scores at 1, 2, and 3 years were 0.775, 0.736, and 0.759, respectively. Furthermore, the prognostic signatures were significantly correlated with TIME diversity and immune checkpoint inhibitor (ICI)-related genes. Low-risk patients had a higher StromalScore, ImmuneScore, and ESTIMATEScore. AS-based risk score signature was positively associated with CD8+ T cells. CDKN2A was also found to be a prognostic factor in lung adenocarcinoma. Finally, potential functions of SFs were determined by regulatory networks.ConclusionTaken together, our findings show a clear association between AS and immune cell infiltration events and patient outcome, which could provide a basis for the identification of novel markers and therapeutic targets for lung adenocarcinoma. SF networks provide information of regulatory mechanisms.
Bridging the Gap for Children With Compound Health Challenges: An Intervention Protocol
Authors: Elgen Irene , Heggestad Torhild , Tronstad Rune , Greve Gottfried 
Published: December 2021

Background: During the last decades, there is a major shift in the panorama of diseases in children and adolescents. More children are referred to the specialized health care services due to less specific symptoms and more complex health challenges. These children are particularly difficult to care for in a “single-disease” oriented system. Our objective was to develop an alternative and more holistic approach better tailored to the complex needs of these children.Method: The target patient population is children between 6 and 13 years with three or more referrals including both the pediatric department and the mental health services. Furthermore, to be included in the project, the child's actual complaints needed to be clinically considered as an unclear or compound condition in need of an alternative approach. This paper describes the process of developing an intervention where a complementary professional team meets the patient and his/her family altogether for 2.5 h. The consultation focus on clarifying the complex symptomatology and on problem solving. The bio-psycho-social model is applied, emphasizing the patient's story as told on the whiteboard. In the dynamic processes of development, piloting, evaluating, and adjusting the components, feed-back from the patients, their families, professional team members, and external team coaches is important.The professional teams include pediatricians, psychologists and physiotherapists. Achieving the transformation from a logistic oriented team where members act separately toward a real complementary team, seems to be a success factor.Discussion: Composing multi-disciplinary and complementary teams was an essential part of the re-designed intervention. Team interaction transforming the professionals from working as a logistic team to act as a complementary team, was one of the important requirements in the process. When re-designing the specialist health service, it is mandatory to anchor all changes among employees as well as the hospital leadership. In addition, it is important to include patient experiences in the process of improvement. Evaluation of long-term outcomes is needed to investigate possible benefits from the new intervention.Trial Registration: Transitioning Young Patients' Health Care Trajectories, NCT04652154. Registered December 3rd, 2020–Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04652154?term=NCT04652154&amp;draw=2&amp;rank=1.
Inhibition of Brain GTP Cyclohydrolase I Attenuates 3-Nitropropionic Acid-Induced Striatal Toxicity: Involvement of Mas Receptor/PI3k/Akt/CREB/ BDNF Axis
Authors: Mustafa Aya M. , Rabie Mostafa A. , Zaki Hala F. , Shaheen Aya M. 
Published: December 2021

GTP cyclohydrolase I (GTPCH I) is the rate-limiting enzyme for tetrahydrobiopterin (BH4) biosynthesis; the latter is an essential factor for iNOS activation that contributes neuronal loss in Huntington’s disease (HD). The aim of the study was to investigate the neuroprotective effect of 2,4-diamino-6-hydroxypyrimidine (DAHP), GTPCH I enzyme inhibitor, against neuronal loss in 3-nitropropinic acid (3-NP)-induced HD in rats and to reveal the possible involved mechanisms mediated through PI3K/Akt axis and its correlation to Mas receptor (MasR). Rats received 3-NP (10 mg/kg/day; i.p.) with or without administration of DAHP (0.5 g/kg/day; i.p.) or wortmannin (WM), a PI3K inhibitor, (15 μg/kg/day; i.v.) for 14 days. DAHP improved cognitive, memory, and motor abnormalities induced by 3-NP, as confirmed by striatal histopathological specimens and immunohistochemical examination of GFAP. Moreover, DAHP treatment inhibited GTPCH I activity, resulting in decreased BH4 levels and iNOS activation. Also, DAHP upregulated the protein expression of survival protein; p85/p55 (pY458/199)-PI3K and pS473-Akt that, in turn, boosted the activation of striatal neurotrophic factors and receptor, pS133-CREB, BDNF and pY515-TrKB, which positively affect MasR protein expression and improve mitochondrial dysfunction, as indicated by enhancing both SDH and PGC-1α levels. Indeed, DAHP attenuates oxidative stress by increasing SOD activity and Nrf2 expression in addition to reducing neuro-inflammatory status by inhibiting NF-κB p65 and TNF-α expression. Interestingly, all the previous effects were blocked by co-administration of WM with DAHP. In conclusion, DAHP exerts neuroprotective effect against neuronal loss induced by 3-NP administration via inhibition of GTPCH I and iNOS activity and activation of MasR/PI3K/Akt/CREB/BDNF/TrKB axis besides its antioxidant and anti-inflammatory effect.
Moving Toward and Through Trauma: Participant Experiences of Multi-Modal Motion-Assisted Memory Desensitization and Reconsolidation (3MDR)
Authors: Hamilton Tristin , Burback Lisa , Smith-MacDonald Lorraine , Jones Chelsea , Brown Matthew R. G. , Mikolas Cynthia , Tang Emily , O'Toole Kaitlin , Vergis Priyanka , Merino Anna , Weiman Kyle , Vermetten Eric H. G. J. M. , Brémault-Phillips Suzette 
Published: December 2021

Introduction:Military members and Veterans are at risk of developing combat-related, treatment-resistant posttraumatic stress disorder (TR-PTSD) and moral injury (MI). Conventional trauma-focused therapies (TFTs) have shown limited success. Novel interventions including Multi-modal Motion-assisted Memory Desensitization and Reconsolidation therapy (3MDR) may prove successful in treating TR-PTSD.Objective:To qualitatively study the experiences of Canadian military members and Veterans with TR-PTSD who received the 3MDR intervention.Methods:This study explored qualitative data from a larger mixed-method waitlist control trial testing the efficacy of 3MDR in military members and veterans. Qualitative data were recorded and collected from 3MDR sessions, session debriefings and follow-up interviews up to 6 months post-intervention; the data were then thematically analyzed.Results:Three themes emerged from the data: (1) the participants' experiences with 3MDR; (2) perceived outcomes of 3MDR; and (3) keys to successful 3MDR treatment. Participants expressed that 3MDR provided an immersive environment, active engagement and empowerment. The role of the therapist as a coach and “fireteam partner” supports the participants' control over their therapy. The multi-modal nature of 3MDR, combining treadmill-walking toward self-selected trauma imagery with components of multiple conventional TFTs, was key to helping participants engage with and attribute new meaning to the memory of the traumatic experience.Discussion:Preliminary thematic analysis of participant experiences of 3MDR indicate that 3MDR has potential as an effective intervention for combat-related TR-PTSD, with significant functional, well-being and relational improvements reported post-intervention.Conclusion:Military members and Veterans are at risk of developing TR-PTSD, with worse outcomes than in civilians. Further research is needed into 3MDR and its use with other trauma-affected populations.
The Clinical Consistency and Utility of ICD-11 Diagnostic Guidelines for Gaming Disorder: A Field Study Among the Chinese Population
Authors: Ma Chenyi , Wang Zhe , Li Chuanwei , Lu Jing , Long Jiang , Li Ruihua , Wu Qianying , Jiang Haifeng , Du Jiang , Li Runji , Wang Peiyan , Ma Limin , Li Hongwei , Hui Shuqin , Zhao Wenli , Zhong Na , Zhao Min 
Published: December 2021

Purpose: As a new category proposed in the International Classification of Diseases (11th Revision) (ICD-11), the reliability and clinical utility of ICD diagnostic guidelines for gaming disorder (GD) in the Chinese population have not been studied. The purpose of this field study is to clarify the reliability, clinical utility, and cultural applicability of ICD diagnostic guidelines for GD in China and its comparability with Internet GD (IGD) in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5).Methods: Participants included 21 paired clinical raters consisting of seven psychiatrists and 200 gaming players aged from 15 to 18 years with different risk levels of Internet addiction based on the scores of Young's Internet Addiction Test. Each participant received a semi-structured face-to-face interview by paired clinical raters at the same time. Then clinical raters made the diagnosis and filled the clinical utility questionnaire independently according to the diagnostic guidelines for GD in both ICD-11 and DSM-5.Results: The diagnostic consistency coefficient (kappa value) between the paired clinical raters was 0.545 (0.490–0.600, p &lt; 0.001) and 0.622 (0.553–0.691, p &lt; 0.001) for ICD-11 and DSM-5 diagnostic guidelines, respectively, for GD. The diagnostic consistency was 0.847 (0.814–0.880, p &lt; 0.001) between GD in ICD-11 and IGD in DSM-5. Meanwhile, 86.7% of responses that agreed with the ICD-11 diagnostic guidelines for GD provided enough detailed implementation characteristics and showed good overall clinical applicability (86.0%), specificity (94.4%), usefulness (84.1%), and acceptable cultural adaptation (74.8%). GD in ICD-11 was slightly more accepted than IGD in DSM-5 (p &lt; 0.001), while the clinical efficiency of ICD-11 was inferior to that of DSM-5 (p &lt; 0.001).Conclusion: This study indicates that the ICD-11 diagnostic guidelines for GD have acceptable clinical reliability and high consistency with IGD in DSM-5. Their clinical applicability and cultural adaption are comparable with those of DSM-5. Although the guidelines still need to be adjusted for better implementation in China, this is already a great step committed to reducing the serious consequences caused by excessive gaming behaviors through effective identification and normative diagnosis, especially for adolescents.
An Internet Based Intervention for Adults With Autism Spectrum Disorder—A Qualitative Study of Participants Experiences
Authors: Westerberg Britta , Bäärnhielm Sofie , Giles Clover , Hylén Ulrika , Holländare Fredrik , Bejerot Susanne 
Published: December 2021

Background: Adults with autism spectrum disorder face several barriers to accessing evidence-based care, including difficulties in communicating needs, social anxiety or in traveling to a health care unit. In recent years, several forms of internet-based treatments have shown to be effective for a variety of psychiatric conditions. Internet-based treatment alternatives allow convenient and flexible formats, and therefore have the potential to increase access to health care for individuals with autism spectrum disorder. However, knowledge about how internet-based treatment features may suit the needs of individuals with autism is limited. The aim of this study was to explore the participant experiences of an internet-based intervention for adults with autism spectrum disorder. The primary focus of the investigation was on autism-specific needs in relation to the features unique to the online format.Methods: In this qualitative study, semi-structured telephone interviews were conducted with 14 participants who had completed a text-based internet-based intervention for adults with autism spectrum disorder. We used an inductive approach and analyzed the data using qualitative content analysis.Results: Five main categories were identified: (1) implications of the online format, (2) the fixed non-individualized model, (3) therapist interaction, (4) interacting with other participants, and (5) making use of the treatment content. Overall, participants appreciated the availability and that they could work on their treatment independent of time or location. Among those participating in group-based chat-sessions with the other participants, it was considered a generally positive experience. Furthermore, most participants felt safe and relaxed in relation to the therapist and appreciated the text-based format. However, several participants felt that the format and content of the treatment was not sufficiently adapted to their individual life situation.Conclusion: In conclusion, this internet-based treatment constitutes an accessible and energy-saving treatment alternative for adults with autism. Further, integrating group-based components seems feasible in an otherwise individual internet-based treatment for individuals with autism. However, group-based components do require a clear purpose and rationale. Future studies should develop and evaluate treatment adaptations tailored to individual needs.