bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyroptosis-Related Patterns Predict Tumor Immune Landscape and Immunotherapy Response in Bladder Cancer
Authors: Yan Yilin , Cao Xiangqian , Wang Zeyi , Huang Zhengnan , Cai Jinming , Tang Pengfei , Yang Chenkai , Zhang Fang , Xia Shujie , Shen Bing 
Published: April 2022

Background: Bladder cancer (BC) is a leading cause of death from malignancy, with significant heterogeneity in the immunotherapeutic responsiveness of advanced status. Pyroptosis, a newly discovered inflammatory programmed cell death, is confirmed to play an indispensable role in tumorigenesis and anti-tumor activity. However, the effect of pyroptosis on the tumor-immune landscape remodeling and immunotherapy in BC remains elusive.Methods: We comprehensively evaluated the mRNA expression and genomic alterations of 33 pyroptosis-related genes (PRGs) in BC and evaluated the patterns of pyroptosis in publicly available BC datasets. An unsupervised clustering method was used to classify patients into distinct patterns. Then, we established a pyroptosis-related signature score (PS-score) model to quantify the pyroptosis-related patterns of individual BC patients using principal component analysis. Furthermore, we correlated the patterns with the immune landscape and response efficacy of immunotherapy.Results: Two pyroptosis-related patterns were identified in BC, and distinct patterns showed various immune characteristics. Patterns with a high expression level of PRGs exhibited a survival advantage and showed higher infiltration of cytotoxic lymphocytes. Tumors with a low PS-score were characterized by high tumor-infiltrating lymphocytes and considered “hot.” Further analysis revealed that the PS-score was an independent prognostic factor and could predict the response to immunotherapy for patients with advanced BC. We found a significant positive association between AHNAK2, AHNAK nucleoprotein 2, expression, and PS-score. Functional assays showed that AHNAK2 knockdown was correlated with attenuated invasive ability.Conclusion: This work comprehensively demonstrated the potential function of pyroptosis-related patterns in the bladder tumor-immune landscape and identified their therapeutic liability in immunotherapy. Our study enhanced our understanding of the immune landscape and provided a new approach toward more effective immunotherapy strategies.
A 13-Gene Signature Based on Estrogen Response Pathway for Predicting Survival and Immune Responses of Patients With UCEC
Authors: Li Yimin , Tian Ruotong , Liu Jiaxin , Ou Chunlin , Wu Qihui , Fu Xiaodan 
Published: April 2022

Background: Accumulating evidence suggests that anti-estrogens have been effective against multiple gynecological diseases, especially advanced uterine corpus endometrial carcinoma (UCEC), highlighting the contribution of the estrogen response pathway in UCEC progression. This study aims to identify a reliable prognostic signature for potentially aiding in the comprehensive management of UCEC.Methods: Firstly, univariate Cox and LASSO regression were performed to identify a satisfying UCEC prognostic model quantifying patients’ risk, constructed from estrogen-response-related genes and verified to be effective by Kaplan-Meier curves, ROC curves, univariate and multivariate Cox regression. Additionally, a nomogram was constructed integrating the prognostic model and other clinicopathological parameters. Next, UCEC patients from the TCGA dataset were divided into low- and high-risk groups according to the median risk score. To elucidate differences in biological characteristics between the two risk groups, pathway enrichment, immune landscape, genomic alterations, and therapeutic responses were evaluated to satisfy this objective. As for treatment, effective responses to anti-PD-1 therapy in the low-risk patients and sensitivity to six chemotherapy drugs in the high-risk patients were demonstrated.Results: The low-risk group with a relatively favorable prognosis was marked by increased immune cell infiltration, higher expression levels of HLA members and immune checkpoint biomarkers, higher tumor mutation burden, and lower copy number alterations. This UCEC prognostic signature, composed of 13 estrogen-response-related genes, has been identified and verified as effective.Conclusion: Our study provides molecular signatures for further functional and therapeutic investigations of estrogen-response-related genes in UCEC and represents a potential systemic approach to characterize key factors in UCEC pathogenesis and therapeutic responses.
Evidence That Nine Autistic Women Out of Ten Have Been Victims of Sexual Violence
Authors: Cazalis Fabienne , Reyes Elisabeth , Leduc Séverine , Gourion David 
Published: April 2022

BackgroundResearch indicates that sexual violence affects about 30% of women in the general population and between two to three times as much for autistic women.Materials and MethodsWe investigated prevalence of sexual abuse, autistic traits and a range of symptoms, using an online survey addressed to the women of the French autistic community (n = 225). We assessed victimization through an open question and through a specific questionnaire, derived from the Sexual Experiences Survey-Short Form Victimization.ResultsBoth case identification methods yielded high figures: 68.9% victimization (open question) compared to 88.4% (standardized questionnaire). Two thirds of the victims were very young when they were first assaulted: among 199 victims, 135 were aged 18 or below and 112 participants were aged 15 or below. 75% of participants included in our study reported several aggressions. Analyses indicate that primo-victimization was highly correlated to revictimization and that being young increased that risk. Young victims were also at higher risk of developing post-traumatic stress disorder. A third of the victims reported the assault. 25% of those were able to file a complaint (n = 12) and/or receive care (n = 13). For the remainder 75%, reporting did not lead to action.DiscussionThose findings indicate a very large proportion of victims of sexual assault among autistic women, consistently with previous research. The World Health Organization states unambiguously that sexual violence is systemic and that vulnerable individuals are preferably targeted by offenders. We therefore postulate that it would be erroneous to consider that victimization of autistic women is mainly due to autism. On the contrary, autism seems to be just a vulnerability factor. Some authors propose that educating potential victims to better protect themselves would help preventing abuse. We reviewed this proposition in the light of our results and found it to be impossible to apply since more than half of the victims were below or at the age of consent. Literature about sexual violence is discussed. Large-scale prevention programs proposed by World Health Organization and the Center for Disease Control aim at cultural changes in order to diminish gender inequality, that they identify as the very root of sexual violence.
Acupuncture Modulates the Spontaneous Activity and Functional Connectivity of Calcarine in Patients With Chronic Stable Angina Pectoris
Authors: Lan Lei , Yin Tao , Tian Zilei , Lan Ying , Sun Ruirui , Li Zhengjie , Jing Miaomiao , Wen Qiao , Li Shenghong , Liang Fanrong , Zeng Fang 
Published: April 2022

BackgroundAcupuncture is an effective adjunctive therapy for chronic stable angina pectoris (CSAP), while the underlying mechanism is unclear. This study aimed to investigate the central pathophysiology of CSAP and explore the mechanism of different acupoint prescriptions for CSAP from the perspective of brain-heart interaction.MethodsThirty-seven CSAP patients and sixty-five healthy subjects (HS) were enrolled, and thirty CSAP patients were divided into two acupoint prescriptions groups (Group A: acupoints on the meridian directly related to the Heart; Group B: acupoints on the meridian indirectly related to the Heart). The Magnetic Resonance Imaging data and clinical data were collected at baseline and after treatment. The comparisons of brain spontaneous activity patterns were performed between CSAP patients and HS, as well as between baseline and after treatment in CSAP patients. Then, the changes in resting-state functional connectivity before and after treatment were compared between the two acupoint prescriptions.ResultsChronic stable angina pectoris patients manifested higher spontaneous activity on the bilateral calcarine, left middle occipital gyrus, right superior temporal gyrus, and right postcentral gyrus. After acupuncture treatment, the spontaneous activity of the left calcarine, left cuneus, and right orbitofrontal gyrus was decreased. The left calcarine was identified as region-of-interest for functional connectivity analysis. Compared with group B, CSAP patients in group A had significantly increased functional connectivity between left calcarine and the left inferior temporal gyrus/cerebellum crus 1, left hippocampus, left thalamus, and left middle cingulate cortex after treatment. Thresholds for all comparisons were p &lt; 0.05, Gaussian Random Field corrected.ConclusionRegulating the aberrant spontaneous activity of the calcarine might be an underlying mechanism of acupuncture for CSAP. The multi-threaded modulation of functional connectivity between calcarine and multiple pain-related brain regions might be a potential mechanism for better efficacy of acupuncture at points on the meridian directly related to the Heart.
Association Between Skeletal Muscle Mass and Severity of Steatosis and Fibrosis in Non-alcoholic Fatty Liver Disease
Authors: Guo Wen , Zhao Xin , Miao Mengyuan , Liang Xiuru , Li Xiaona , Qin Pei , Lu Jing , Zhu Wenfang , Wu Juan , Zhu Chen , Xu Nianzhen , Zhang Qun 
Published: April 2022

BackgroundSarcopenia is known to be the risk factor of non-alcoholic fatty liver disease (NAFLD). However, studies evaluating the association of skeletal muscle mass (SMM) with liver fibrosis by transient elastography are limited. Here, we investigated the association of SMM with hepatic steatosis and fibrosis assessed in Chinese adults.MethodsPatients who underwent liver ultrasonography at the Health Promotion Center of the First Affiliated Hospital of Nanjing Medical University between January 2020 to June 2021 were enrolled. We used transient elastography to evaluate the degree of hepatic fat and liver stiffness. Appendicular skeletal muscle mass was determined by bioelectrical impedance and was adjusted for body weight to derive the skeletal muscle mass index (SMI).ResultsOf 3,602 finally enrolled individuals, 1,830 had NAFLD and 1,772 did not have NAFLD. SMI gradually decreased as the severity of hepatic steatosis increased (40.47 ± 3.94% vs. 39.89 ± 3.57% vs. 39.22 ± 3.46% vs. 37.81 ± 2.84%, P &lt; 0.001). Individuals with F3-F4 and F2 liver fibrosis groups had significantly lower SMI than individuals with F0-F1 stages (37.51 ± 3.19% vs. 38.06 ± 3.51% vs. 39.36 ± 3.38%, P &lt; 0.001). As the SMI increased, the percentages of subjects with mild and severe NAFLD, and the percentages of subjects in F2 and F3-F4 stage were gradually decreased. SMI was independently associated with the severity of hepatic steatosis and fibrosis by logistic regression analysis. Moreover, decreased SMI was an independent risk factor for NAFLD and fibrosis.ConclusionSMI is closely associated with liver fat content and liver fibrosis in Chinese adults with NAFLD.
Assessment of Solid Pulmonary Nodules or Masses Using Zero Echo Time MR Lung Imaging: A Prospective Head-to-Head Comparison With CT
Authors: Liu Qianyun , Feng Zhichao , Liu Weiyin Vivian , Fu Weidong , He Lei , Cheng Xiaosan , Mao Zhongliang , Zhou Wenming 
Published: April 2022

ObjectiveThe aim of this study is to determine the potential of zero echo time (ZTE) MR lung imaging in the assessment of solid pulmonary nodules or masses and diagnostic consistency to CT in terms of morphologic characterization.MethodsOur Institutional Review Board approved this prospective study. Seventy-one patients with solid pulmonary nodules or masses larger than 1 cm in diameter confirmed by chest CT were enrolled and underwent further lung ZTE-MRI scans within 7 days. ZTE-MRI and CT images were compared in terms of image quality and imaging features. Unidimensional diameter and three-dimensional volume measurements on both modalities were manually measured and compared using the Wilcoxon signed-rank test, intraclass correlation coefficient (ICC), Pearson’s correlation analysis, and Bland–Altman analysis. Multivariable logistic regression analysis was used to identify the factors associated with significant inter-modality variation of volume.ResultsFifty-four of 71 (76.1%) patients were diagnosed with lung cancer. Subjective image quality was superior in CT compared with ZTE-MRI (p &lt; 0.001). Inter-modality agreement for the imaging features was moderate for emphysema (kappa = 0.50), substantial for fibrosis (kappa = 0.76), and almost perfect (kappa = 0.88-1.00) for the remaining features. The size measurements including diameter and volume between ZTE-MRI and CT showed no significant difference (p = 0.36 for diameter and 0.60 for volume) and revealed perfect inter-observer (ICC = 0.975–0.980) and inter-modality (ICC = 0.942–0.992) agreements. Multivariable analysis showed that non-smooth margin [odds ratio (OR) = 6.008, p = 0.015] was an independent predictor for the significant inter-modality variation of volume.ConclusionZTE lung imaging is feasible as a part of chest MRI in the assessment and surveillance for solid pulmonary nodules or masses larger than 1 cm, presenting perfect agreement with CT in terms of morphologic characterization.
Real-Time Artificial Intelligence-Based Histologic Classifications of Colorectal Polyps Using Narrow-Band Imaging
Authors: Lu Yi , Wu Jiachuan , Zhuo Xianhua , Hu Minhui , Chen Yongpeng , Luo Yuxuan , Feng Yue , Zhi Min , Li Chujun , Sun Jiachen 
Published: April 2022

Background and AimsWith the development of artificial intelligence (AI), we have become capable of applying real-time computer-aided detection (CAD) in clinical practice. Our aim is to develop an AI-based CAD-N and optimize its diagnostic performance with narrow-band imaging (NBI) images.MethodsWe developed the CAD-N model with ResNeSt using NBI images for real-time assessment of the histopathology of colorectal polyps (type 1, hyperplastic or inflammatory polyps; type 2, adenomatous polyps, intramucosal cancer, or superficial submucosal invasive cancer; type 3, deep submucosal invasive cancer; and type 4, normal mucosa). We also collected 116 consecutive polyp videos to validate the accuracy of the CAD-N.ResultsA total of 10,573 images (7,032 images from 650 polyps and 3,541 normal mucous membrane images) from 478 patients were finally chosen for analysis. The sensitivity, specificity, PPV, NPV, and accuracy for each type of the CAD-N in the test set were 89.86%, 97.88%, 93.13%, 96.79%, and 95.93% for type 1; 93.91%, 95.49%, 91.80%, 96.69%, and 94.94% for type 2; 90.21%, 99.29%, 90.21%, 99.29%, and 98.68% for type 3; and 94.86%, 97.28%, 94.73%, 97.35%, and 96.45% for type 4, respectively. The overall accuracy was 93%. We also built models for polyps ≤5 mm, and the sensitivity, specificity, PPV, NPV, and accuracy for them were 96.81%, 94.08%, 95%, 95.97%, and 95.59%, respectively. Video validation results showed that the sensitivity, specificity, and accuracy of the CAD-N were 84.62%, 86.27%, and 85.34%, respectively.ConclusionsWe have developed real-time AI-based histologic classifications of colorectal polyps using NBI images with good accuracy, which may help in clinical management and documentation of optical histology results.
Dissecting the Effects of Aldosterone and Hypokalemia on the Epithelial Na+ Channel and the NaCl Cotransporter
Authors: Kristensen Mathias , Fenton Robert A. , Poulsen Søren B. 
Published: April 2022

Primary hyperaldosteronism (PA) is characterized by aldosterone excess and hypertension. This may be linked to increased renal Na+ reabsorption via the epithelial Na+ channel (ENaC) and the NaCl cotransporter (NCC). The majority of PA patients have normal plasma K+ levels, but a subset of cases are associated with hypokalemia. High NCC levels observed in long-term studies with aldosterone-infused rodents have been attributed to direct effects of aldosterone. Aldosterone can also increase active phosphorylated NCC (pT58-NCC) acutely. However, direct effects of aldosterone on NCC have been contested by recent studies indicating that it is rather an indirect effect of hypokalemia. We therefore set out to determine isolated long-term aldosterone and K+ effects on ENaC and NCC using various in vivo and ex vivo approaches. In mice, aldosterone-induced hypokalemia was prevented by simultaneous amiloride infusion, coupled to increased cleavage of α- and γENaC but no effect on NCC. Regression analyses of in vivo data showed a positive correlation between aldosterone/K+ and αENaC but a negative correlation with NCC and pT58-NCC. Ex vivo, exposure of kidney tubules for 21 h to aldosterone increased cleavage of αENaC and γENaC, but no effects were observed on NCC or pT58-NCC. Exposure of tubules to low K+ media reduced αENaC but increased NCC and pT58-NCC. As hypokalemia can enhance cell proliferation markers in the distal convoluted tubule (DCT), we hypothesized that aldosterone infusion would increase proliferating cell nuclear antigen (PCNA) expression. Infusion of aldosterone in mice for 6 days greatly increased PCNA expression in the DCT. Collectively, in vivo and ex vivo data suggest that both aldosterone and K+ can increase ENaC directly. In contrast, the observed increase in abundance and phosphorylation of NCC in aldosterone-infused mice is likely an indirect effect of enhanced ENaC-mediated K+ secretion and subsequent hypokalemia. Thus, it is possible that NCC may only be increased in PA when the condition is associated with hypokalemia.
Zfp580 Regulates Paracrine and Endocrine Igf1 and Igfbp3 Differently in the Brain and Blood After a Murine Stroke
Authors: Hoffmann Christian J. , Kuffner Melanie T. C. , Lips Janet , Lorenz Stephanie , Endres Matthias , Harms Christoph 
Published: April 2022

Insulin-like growth factor 1 (Igf1) and insulin-like growth factor binding protein 3 (Igfbp3) are endocrine and paracrine factors that influence stroke occurrence, severity, and recovery. Low levels of endocrine Igf1 and Igfbp3 were associated with larger infarct volumes and unfavorable outcomes. Paracrine Igf1 is brain cytoprotective and improves functional recovery after stroke. In this study, we evaluated the effects of zinc finger protein 580 (Zfp580) on endocrine and paracrine Igf1 and Igfbp3 after stroke. Zfp580 suppressed the expression of Igf1 and Igfbp3 in cerebral microvascular endothelial cells (bEnd.3) as determined by real-time RT-PCR. Zfp580 was suppressed by combined oxygen and glucose deprivation (OGD) and mediated the effect of OGD on Igf1 and Igfbp3. In vivo, we evaluated paracrine regulation by real-time RT-PCR of brain lysates and endocrine regulation by ELISA of blood samples. Genomic ablation of Zfp580 did not alter basal paracrine or endocrine Igf1 and Igfbp3 levels. After transient middle cerebral artery occlusion (MCAo), Zfp580 was globally elevated in the brain for up to 3 days. Paracrine Igf1 and Igfbp3 were selectively induced in the ischemic hemisphere from day 2 to day 3 or day 1 to day 7, respectively. In Zfp580 knockout mice, the paracrine regulations of Igf1 and Igfbp3 were attenuated while endocrine Igf1 and the molar Igf1/Igfbp3 ratio were increased. In conclusion, Zfp580 differentially controls paracrine and endocrine Igf1 and Igfbp3 after stroke. Inhibition of Zfp580 might be a new treatment target leading to increased activity of Igf1 to improve stroke outcome.
The Influence of Sense of Place on Elementary School Students’ Creativity During the COVID-19 Pandemic: The Mediating and Buffering Effects of Psychological Resilience
Authors: Xu Yanhua , Wang Qiaoling , Zhang Dongmei , Lin Peiying 
Published: April 2022

PurposeTo understand the relationship between sense of place and creativity and the mechanisms that affect this relationship, the researchers constructed a mediation model to examine the effect of sense of place on creativity and the mediating role of psychological resilience in elementary school students during the COVID-19 pandemic.MethodsA total of 1,711 students in an elementary school in Beijing, China, were surveyed using Chinese-language versions of the Sense of Place Scale, the Psychological Resilience Scale-Short Version, and the Innovative Behavior Inventory. SPSS (version 23) and PROCESS plug-in (version 3.3) were used for correlation and mediation analyses.Results(1) Correlation analysis revealed that sense of place was positively related to psychological resilience (r = 0.445, p &lt; 0.01) and creativity (r = 0.590, p &lt; 0.01). (2) Psychological resilience was also positively correlated with creativity (r = 0.625, p &lt; 0.01). (3) Further, after controlling for gender and grade level, it was found that sense of place directly predicted creativity and that sense of place also indirectly predicted creativity through psychological resilience. The direct effect (0.45) and the mediating effect (0.23) accounted for 65.95 and 34.05% of the total effect, respectively.ConclusionThe results demonstrate that sense of place is a positive predictor of creativity and can play a facilitating role to some extent. Moreover, psychological resilience is a mediating factor, acting as a buffer between sense of place and creativity. These results contribute to a more comprehensive understanding of the mechanisms influencing creativity.
Physical Activity Adherence Related to Body Composition and Physical Fitness in Spanish Older Adults: 8 Years-Longitudinal EXERNET-Study
Authors: Jiménez-Zazo Fabio , Hernández-Martínez Antonio , Romero-Blanco Cristina , Cabanillas Esther , Pérez-Gómez Jorge , Ara Ignacio , Casajús José A. , Vicente-Rodríguez Germán , Gesteiro Eva , González-Gross Marcela , Aznar Susana 
Published: April 2022

IntroductionThe multiple benefits of physical activity (PA) compared to the current lack of adherence to this behavior in older people makes it necessary to identify the factors related to its long-term dropout, therefore, the aim of this study was: (i) to study the evolution of behavior change for PA through stages of change (SoC) after 8 years and, to identify the associated factors related to the worsening of SoC for PA.MethodsA total of 714 Spanish older adults (&gt;65 years) participated in the Longitudinal elderly EXERNET study 8 years follow-up. SoC for PA from Transtheoretical model of behavior change (TTM), body composition [BMI, fat mass, lean mass, waist circumference (WC), and hip circumference (HC)] and physical fitness (EXERNET battery fitness tests) were recorded. A multivariate binary logistic regression model was used to identify the potential predictive factors of worsening SoC for PA.ResultsThree hundred and sixty participants (50.4%) worsening their SoC for PA after 8 years. Predictors factors associated with worsening of SoC were: HC (OR = 1.022; 95% CI: 1.001, 1.044), Lower body strength (OR = 0.940; 95% CI: 0.887, 0.997) and aerobic endurance at the 6 min-walk test (OR = 0.997; 95% CI: 0.995, 0.999).ConclusionThis study highlights that we need to identify adults with high HC, lower body strength and lower aerobic endurance to design a tailored PA program. Identifying the determinants of losing adherence to PA will help in the creation, design, and evaluation of exercise programs with the goal of reducing older adults’ drop-outs rates.