bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic Age Acceleration of Stomach Adenocarcinoma Associated With Tumor Stemness Features, Immunoactivation, and Favorable Prognosis
Authors: Hong Chunhong , Yang Shaohua , Wang Qiaojin , Zhang Shiqiang , Wu Wenhui , Chen Jinyao , Zhong Danhui , Li Mingzhe , Li Liang , Li Jianfeng , Yu Hong , Chen Hong , Zeng Qianlin , Zhang Changhua 
Published: March 2021

Background: Abnormal DNA methylation (DNAm) age has been assumed to be an indicator for canceration and all-cause mortality. However, associations between DNAm age and molecular features of stomach adenocarcinoma (STAD), and its prognosis have not been systematically studied.Method: We calculated the DNAm age of 591 STAD samples and 115 normal stomach samples from The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) database using the Horvath’s clock model. Meanwhile, we utilized survival analysis to evaluate the prognostic value of DNAm age and epigenetic age acceleration shift. In addition, we performed weighted gene co-expression network analysis (WGCNA) to identify DNAm age-associated gene modules and pathways. Finally, the association between DNAm age and molecular features was performed by correlation analysis.Results: DNA methylation age was significantly correlated with chronological age in normal gastric tissues (r = 0.85, p &lt; 0.0001), but it was not associated with chronological age in STAD samples (r = 0.060, p = 0.2369). Compared with tumor adjacent normal tissue, the DNAm age of STAD tissues was significantly decreased. Meanwhile, chronological age in STAD samples was higher than its DNAm age. Both DNAm age and epigenetic acceleration shift were associated with the prognosis of STAD patients. By using correlation analysis, we also found that DNAm age was associated with immunoactivation and stemness in STAD samples.Conclusion: In summary, epigenetic age acceleration of STAD was associated with tumor stemness, immunoactivation, and favorable prognosis.
Thalamocortical Functional Connectivity in Patients With White Matter Hyperintensities
Authors: Chen Chen , Wang Xiaojing , Cao Shanshan , Zhang Jun , Wang Zhiqi , Pan Wen , Yang Jinying , Tian Yanghua , Qiu Bensheng , Wei Qiang , Wang Kai 
Published: March 2021

Background: White matter hyperintensities (WMH)s is a very common neuroradiological manifestation in the elderly and is an increased risk of dementia and cognitive decline. As we all know, the thalamocortical circuit plays an important part in cognition regulation. However, the role of this circuit in WMHs and its related cognitive deficits is still unclear.Method: Eighty WMH patients and 37 healthy controls (HCs) were enrolled in the current study. WMH patients were divided into a mild WMH group (n = 33) and moderate-severe WMH group (n = 47) according to Fazekas scores. Resting-state functional magnetic resonance imaging (rs-fMRI) data of all participants were collected for thalamocortical functional connectivity (FC) analysis. The analysis was performed in two steps. First, the whole cerebral cortex was divided into six regions of interest (ROIs), which were used as seeds to investigate the changes of FC with the thalamus. Then, the subregion of the thalamus generated in the previous step was used as the seed for FC analysis with the whole brain.Results: In the first step of FC analysis, it was found that precentral gyrus (PrCG)-interthalamic adhesion (ITA) FC values in moderate-severe WMH group were higher than those in HC and mild WMH groups. However, when compared with the HC group, the increase of PrCG-ITA FC values in mild WMH group was not statistically significant. In the second step of FC analysis, the ITA was set as the seed, and compared with the HC group, the results showed that the FC values of the ITA-medial frontal gyrus (MFG) in mild group and moderate-severe WMH groups were significantly increased. In addition, the FC values in moderate-severe group were significantly higher than those in mild group. Finally, it was also found that FC values (PrCG-ITA and ITA-MFG) were significantly correlated with neuropsychological test results for multiple cognitive functions such as memory, execution and attention in WMH patients.Conclusion: Abnormal thalamocortical FC was closely related with cognitive impairments in WMH patients.
Characteristic Alterations of Network in Patients With Intraoperative Stimulation-Induced Seizures During Awake Craniotomy
Authors: Fang Shengyu , Zhou Chunyao , Wang Lei , Fan Xing , Wang Yinyan , Zhang Zhong , Jiang Tao 
Published: March 2021

Background: The use of electrocorticography (ECoG) to avoid intraoperative stimulation-induced seizure (ISS) during awake craniotomy is controversial. Although a standard direct cortical stimulating (DCS) protocol is used to identify the eloquent cortices and subcortical structures, ISS still occurs. Epilepsy is related to alterations in brain networks. In this study, we investigated specific alterations in brain networks in patients with ISS.Methods: Twenty-seven patients with glioma were enrolled and categorized into the ISS and non-ISS groups based on their history of ISS occurrence. A standard DCS protocol was used during awake craniotomy without ECoG supervision. Graph theoretical measurement was used to analyze resting-state functional magnetic resonance imaging data to quantitatively reveal alterations in the functional networks.Results: In the sensorimotor networks, the glioma significantly decreased the functional connectivity (FC) of four edges in the ISS group, which were conversely increased in the non-ISS group after multiple corrections (p &lt; 0.001, threshold of p-value = 0.002). Regarding the topological properties, the sensorimotor network of all participants was classified as a small-world network. Glioma significantly increased global efficiency, nodal efficiency, and the sigma value, as well as decreased the shortest path length in the ISS group compared with the non-ISS group (p &lt; 0.05).Conclusions: The specific alterations indicating patient susceptibility to ISS during DCS increased global and nodal efficiencies and decreased the shortest path length and FC induced by gliomas. If the patient has these specific alterations, ECoG is recommended to monitor after-discharge current during DCS to avoid ISS.
Correlation of Lipid Ratios With the Severity of Pulmonary Alveolar Proteinosis: A Cross-Sectional Study
Authors: Yan Xin , Gao Yujuan , Zhao Qi , Qiu Xiaohua , Tian Mi , Dai Jinghong , Zhuang Yi 
Published: March 2021

Background: Lipids are known to accumulate abnormally in the alveoli and circulate during pulmonary alveolar proteinosis (PAP). However, the relationship between lipid ratios and PAP is not clear. In this study, we investigated the lipid ratios in PAP patients and explored the relationships between lipid ratios and the severity of PAP.Methods: A total of 122 PAP patients were diagnosed and divided the mild- moderate PAP group (n = 61) and the severe PAP group (n = 61) according to the value of disease severity score (DSS). One hundred thirty healthy volunteers were classified as the control group. Routine blood examination and pulmonary function tests were performed and lipid profile were measured.Results: Compared with the control group, patients with PAP had significantly higher TG, TC/HDL-C, TG/HDL-C, and non-HDL-C, while lower HDL-C (all P &lt; 0.05). Patients with the severe PAP had higher TC, TG, LDL-C, TC/HDL-C, and non-HDL-C, while lower HDL-C than patients with the mild- moderate PAP (all P &lt; 0.05). Binary logistic regression analysis indicated that TC/HDL-C (OR = 2.322, 95% CI 1.621–3.713, P = 0.024) and non-HDL-C (OR = 1.797, 95% CI 1.239–3.109, P = 0.036) were all significantly correlated with the severity of PAP after adjustment for other risk factors. The AUC value of TC/HDL-C for predicting the severity of PAP was larger than that of non-HDL-C. The AUROC for TC/HDL-C was 0.741 (0.654–0.828), and the optimal cut-off point for TC/HDL-C was 5.05 (sensitivity: 73.6%, specificity: 68.1%).Conclusions: Lipid ratios, including TC-HDL-C and non-HDL-C, were independent risk factors for the severity of PAP. TC/HDL-C is a promising biomarker for the severity of PAP.
Correlation Between Dual-Time-Point FDG PET and Tumor Microenvironment Immune Types in Non-Small Cell Lung Cancer
Authors: Zhou Jianyuan , Zou Sijuan , Cheng Siyuan , Kuang Dong , Li Dan , Chen Lixing , Liu Cong , Yan Jianhua , Zhu Xiaohua 
Published: March 2021

PurposeDual-time-point 18F-fluorodeoxyglucose positron emission tomography (DTP 18F-FDG PET), which reflects the dynamics of tumor glucose metabolism, may also provide a novel approach to the characterization of both cancer cells and immune cells within the tumor immune microenvironment (TIME). We investigated the correlations between the metabolic parameters (MPs) of DTP 18F-FDG PET images and the tumor microenvironment immune types (TMITs) in patients with non-small cell lung cancer (NSCLC).MethodsA retrospective analysis was performed in 91 patients with NSCLC who underwent preoperative DTP 18F-FDG PET/CT scans. MPs in the early scan (eSUVmax, eSUVmean, eMTV, eTLG) and delayed scan (dSUVmax, dSUVmean, dMTV, dTLG) were calculated, respectively. The change in MPs (ΔSUVmax, ΔSUVmean, ΔMTV, ΔTLG) between the two time points were calculated. Tumor specimens were analyzed by immunohistochemistry for PD-1/PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TILs). TIME was classified into four immune types (TMIT I ~ IV) according to the expression of PD-L1 and CD8+ TILs. Correlations between MPs with TMITs and the immune-related biomarkers were analyzed. A composite metabolic signature (Meta-Sig) and a combined model of Meta-Sig and clinical factors were constructed to predict patients with TMIT I tumors.ResultseSUVmax, eSUVmean, dSUVmax, dSUVmean, ΔSUVmax, ΔSUVmean, and ΔTLG were significantly higher in PD-L1 positive patients (p = 0.0007, 0.0006, &lt; 0.0001, &lt; 0.0001, 0.0002, 0.0002, 0.0247, respectively), and in TMIT-I tumors (p = 0.0001, &lt; 0.0001, &lt; 0.0001, &lt; 0.0001, 0.0009, 0.0009, 0.0144, respectively). Compared to stand-alone MP, the Meta-Sig and combined model displayed better performance for assessing TMIT-I tumors (Meta-sig: AUC = 0.818, sensitivity = 86.36%, specificity = 73.91%; Model: AUC = 0.869, sensitivity = 77.27%, specificity = 82.61%).ConclusionHigh glucose metabolism on DTP 18F-FDG PET correlated with the TMIT-I tumors, and the Meta-Sig and combined model based on clinical and metabolic information could improve the performance of identifying the patients who may respond to immunotherapy.
Single-Cell RNA-seq Reveals Characteristics of Malignant Cells and Immune Microenvironment in Subcutaneous Panniculitis-Like T-Cell Lymphoma
Authors: Li Zifeng , Wang Hongsheng , Dong Rui , Man Jie , Sun Li , Qian Xiaowen , Zhu Xiaohua , Cao Ping , Yu Yi , Le Jun , Fu Yang , Wang Ping , Jiang Wenjin , Shen Chen , Ma Yangyang , Chen Lian , Xu Yaochen , Shi Jiantao , Zhang Hui , Qian Maoxiang , Zhai Xiaowen 
Published: March 2021

BackgroundSubcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a malignant primary T-cell lymphoma that is challenging to distinguish from autoimmune disorders and reactive panniculitides. Delay in diagnosis and a high misdiagnosis rate affect the prognosis and survival of patients. The difficulty of diagnosis is mainly due to an incomplete understanding of disease pathogenesis.MethodsWe performed single-cell RNA sequencing of matched subcutaneous lesion tissue, peripheral blood, and bone marrow from a patient with SPTCL, as well as peripheral blood, bone marrow, lymph node, and lung tissue samples from healthy donors as normal controls. We conducted cell clustering, gene expression program identification, gene differential expression analysis, and cell-cell interaction analysis to investigate the ecosystem of SPTCL.ResultsBased on gene expression profiles in a single-cell resolution, we identified and characterized the malignant cells and immune subsets from a patient with SPTCL. Our analysis showed that SPTCL malignant cells expressed a distinct gene signature, including chemokines families, cytotoxic proteins, T cell immune checkpoint molecules, and the immunoglobulin family. By comparing with normal T cells, we identified potential novel markers for SPTCL (e.g., CYTOR, CXCL13, VCAM1, and TIMD4) specifically differentially expressed in the malignant cells. We also found that macrophages and fibroblasts dominated the cell-cell communication landscape with the SPTCL malignant cells.ConclusionsThis work offers insight into the heterogeneity of subcutaneous panniculitis-like T-cell lymphoma, providing a better understanding of the transcription characteristics and immune microenvironment of this rare tumor.
Permanent Interstitial Cesium-131 Brachytherapy in Treating High-Risk Recurrent Head and Neck Cancer: A Prospective Pilot Study
Authors: Kharouta Michael , Zender Chad , Podder Tarun , Rezaee Rod , Lavertu Pierre , Fowler Nicole , Thuener Jason , Li Shawn , Clancy Kate , Xu Zhengzheng , Yao Min 
Published: March 2021

Purpose/ObjectivesTo establish the feasibility and safety of intraoperative placement of cesium-131 (Cs-131) seeds for re-irradiation in recurrent head and neck cancer (HNC).MethodsPatients with resectable recurrent HNC who were deemed to have a high risk of second recurrence were eligible. Immediately after tumor extirpation, seeds were implanted in the surgical bed based on the preoperative treatment plan with intraoperative adjustment. The surgical bed and the seeds were covered with a regional flap or microvascular free flap. A CT of the neck was obtained on postoperative day 1 for evaluation of the postoperative dose distribution. Patients were followed 1 and 3 months after surgery, then every 3 months in the first 2 years.ResultsFrom November 2016 to September 2018, 15 patients were recruited and 12 patients received treatment per protocol. For the patients who had implants, the sites of initial recurrence included 10 neck alone, 1 neck and larynx, and 1 neck/peristomal. The median follow-up was 21.4 months. After surgery, patients remained hospitalized for a median of 6 days. There were no high-grade toxicities except two patients with wound complications requiring wound care. Eight patients had recurrences, three locoregional alone, three distant alone, and two with both locoregional and distant recurrences. Only one patient had an in-field failure. Five patients died, with 1- and 2-year overall survival of 75 and 58%.ConclusionsCs-131 implant after surgical resection in recurrent HNC is feasible and safe. There were no unexpected severe toxicities. Most failures were out-of-field or distant.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT02794675.
The Psychological Pathway to Suicide Attempts: A Strategy of Control Without Awareness
Authors: Macintyre Vanessa G. , Mansell Warren , Pratt Daniel , Tai Sara J. 
Published: March 2021

ObjectivesThis paper aims to identify potential areas for refinement in existing theoretical models of suicide, and introduce a new integrative theoretical framework for understanding suicide, that could inform such refinements.MethodsLiterature on existing theoretical models of suicide and how they contribute to understanding psychological processes involved in suicide was evaluated in a narrative review. This involved identifying psychological processes associated with suicide. Current understanding of these processes is discussed, and suggestions for integration of the existing literature are offered.ResultsExisting approaches to understanding suicide have advanced the current knowledge of suicide in various ways. They have guided valuable research in the following areas: motivations for suicide and the psychological distress which influences suicide attempts; ambivalence about suicide; suicidal individuals’ focus of attention; and ways in which individuals who contemplate suicide differ from individuals who attempt suicide. We outline a new theoretical framework as a means to integrating all of these concepts into the three principles of control, conflict, and awareness. Within this framework, suicide is regarded as occurring due to a long standing conflict between an individual’s personal goals, culminating in an episode of acute loss of control. The new framework posits that the individual then strives to regain control through the means of suicide because of a narrowed awareness of consequences of their actions on other valued goals. This psychological mechanism of limited awareness is posited to be the common pathway by which individuals make a suicide attempt, regardless of which risk factors are present.ConclusionThis article introduces a theoretical framework that generates several hypotheses for future research, and focuses on psychological processes occurring during immediate crisis. One of the key hypotheses resulting from our predictions on how individuals progress from contemplating to attempting suicide will be tested in an ongoing program of research: Individuals who attempt suicide have a significantly reduced awareness of consequences of suicide, which would negatively impact on their important life goals, values, principles, or ideals, compared to individuals who contemplate suicide. Therapy guided by the new framework may be more flexible, immediate, and client-focused than other therapies for suicidal individuals.
Mobile Technology Use and Its Association With Executive Functioning in Healthy Young Adults: A Systematic Review
Authors: Warsaw Rachel E. , Jones Andrew , Rose Abigail K. , Newton-Fenner Alice , Alshukri Sophie , Gage Suzanne H. 
Published: March 2021

Introduction: Screen-based and mobile technology has grown at an unprecedented rate. However, little is understood about whether increased screen-use affects executive functioning (EF), the range of mental processes that aid goal attainment and facilitate the selection of appropriate behaviors. To examine this, a systematic review was conducted.Method: This systematic review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A comprehensive literature search was conducted using Web of Science, MEDLINE, PsycINFO and Scopus databases to identify articles published between 2007 and March 2020, examining the use of mobile technologies on aspects of EF in healthy adults aged 18–35 years. In total 6079 articles were screened by title, and 39 screened by full text. Eight eligible papers were identified for inclusion. Our methods were pre-registered on the PROSPERO international prospective register of systematic reviews.Results: A total of 438 participants were included across the eight studies. Five of the eight studies examined more than one EF. Five studies measured inhibition, and four studies measured decision-making. Smartphone use was negatively associated with inhibition and decision-making. Working memory performance was found to be improved by increased time engaging in video games and by refraining from smartphone use prior to bedtime. Quality assessments indicated high risk of methodological biases across the studies and a low quality of evidence for determining the relationship between technology use and executive functioning.Conclusions: This review highlights the scarcity of the literature in this area. It presents a call for rigorous and objective research to further our understanding of the impact of mobile technology on different aspects of executive function.
A Systematic Review of Factors Affecting Mental Health and Well-Being of Asylum Seekers and Refugees in Germany
Authors: Hajak Vivien L. , Sardana Srishti , Verdeli Helen , Grimm Simone 
Published: March 2021

Background: Since the onset of the 2015 European refugee crisis, ~4. 46 million people have sought asylum in the European Union, with Germany logging the largest share of all asylum applications. In addition to the severe adversities before and during flight, the process of settling into a new environment involves stressors that affect psychological well-being and mental health. The aim of this systematic review was to examine contextual factors during post-migration that influence the mental health and well-being of asylum seekers and refugees (ASRs) in Germany.Methods: Following PRISMA guidelines, a systematic review was conducted across multiple databases for English and German studies published between 2015 and 2020 with index keywords.Results: From a total of 303 articles, 156 duplicates were removed and, after title review, another 87 were excluded for not meeting the inclusion criteria. After assessing the abstracts of the remaining 60 articles, 39 were excluded. Full texts of 21 articles were assessed for eligibility and after excluding 8 articles, 13 articles were included in the review. The results demonstrate high rates of psychological distress among ASRs in Germany and the significant influence of contextual factors on their mental health and psychological well-being. The risk factors for poor mental health include an uncertain asylum status, living in shared asylum accommodations, separation from the nuclear family, lack of German language skills, integration issues and discrimination, while employment is a protective factor.Conclusion: Asylum seekers and refugees have high prevalence rates of psychological distress directly influenced by contextual factors in Germany. Based on these findings, policy makers are strongly recommended to apply preventive strategies to reduce mental health problems of ASRs in Germany.
Twist1 in T Lymphocytes Augments Kidney Fibrosis after Ureteral Obstruction
Authors: Ren Jiafa , Lu Xiaohan , Griffiths Robert , Privratsky Jamie R. , Crowley Steven D. 
Published: March 2021

Key Points

The transcription factor Twist1 acts in T lymphocytes to promote kidney fibrogenesis.T-cell Twist1 limits the accumulation of TNF-producing CD8+ T cells in the injured kidney.TNF produced by T lymphocytes limits kidney scar formation after ureteral obstruction.

Background
Twist1 is a basic helix-loop-helix domain–containing transcription factor that participates in diverse cellular functions, including epithelial-mesenchymal transition and the cellular immune response. Although Twist1 plays critical roles in the initiation and progression of kidney diseases, the effects of Twist1 in the T lymphocyte on the progression of renal fibrosis require elucidation.

Methods
129/SvEv mice with a floxed allele for the gene encoding Twist1 or TNFα were bred with CD4-Cre mice to yield CD4-Cre+ Twist1flox/flox (Twist1-TKO) or CD4-Cre+ TNFflox/flox (TNF-TKO) mice with robust, but selective, deletion of Twist1 or TNFα mRNA in T cells, respectively. Twist1 TKO, TNF TKO, and WT controls underwent UUO with assessment of kidney fibrosis and T-cell phenotype at 14 days.

Results
Compared with WT controls, obstructed kidneys from Twist1 TKO mice had attenuated extracellular matrix deposition. Despite this diminished fibrosis, Twist1 TKO obstructed kidneys contained more CD8+ T cells than in WTs. These intrarenal CD8+ T cells exhibited greater activation and higher levels of TNFα expression than those from WT obstructed kidneys. Further, we found that selective deletion of TNFα from T cells exaggerated renal scar formation and injury after UUO, highlighting the capacity of T-cell TNF to constrain fibrosis in the kidney.

Conclusions
Twist1 in T cells promotes kidney fibrogenesis, in part, by curtailing the renal accumulation of TNF-elaborating T cells.