bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-World Effectiveness of Natalizumab in Korean Patients With Multiple Sclerosis
Authors: Kim Ki Hoon , Kim Su-Hyun , Park Na Young , Hyun Jae-Won , Kim Ho Jin 
Published: July 2021

Background and Purpose: Natalizumab is a highly efficacious disease-modifying therapy for relapsing-remitting multiple sclerosis (MS). Data on the efficacy and safety profile of natalizumab in Asian patients with MS are limited. This study assessed the efficacy and safety of natalizumab in Korean patients with MS in a real-world setting.Methods: This study enrolled consecutive Korean patients with active relapsing-remitting MS who were treated with natalizumab for at least 6 months between 2015 and 2021. To evaluate the therapeutic outcome of natalizumab, we used the Expanded Disability Status Scale (EDSS) scores and brain magnetic resonance imaging; adverse events were assessed at regular intervals. No evidence of disease activity (NEDA) was defined as no clinical relapse, no worsening of EDSS score, and no radiological activities.Results: Fourteen subjects with MS were included in the study. The mean age at initiation of natalizumab therapy was 32 years. All patients were positive for anti-John Cunningham virus antibodies before natalizumab administration. The mean annual relapse rate was markedly reduced from 2.7 ± 3.2 before natalizumab therapy to 0.1 ± 0.4 during natalizumab therapy (p = 0.001). Disability was either improved or stabilized after natalizumab treatment in 13 patients (93%). During the 1st year and 2 years after initiating natalizumab, NEDA-3 was achieved in 11/12 (92%) and 9/11 (82%) patients, respectively. No progressive multifocal leukoencephalopathy or other serious adverse events leading to the discontinuation of natalizumab were observed.Conclusions: Natalizumab therapy showed high efficacy in treating Korean patients with active MS, without unexpected safety problems.
Texture Analysis of DCE-MRI Intratumoral Subregions to Identify Benign and Malignant Breast Tumors
Authors: Zhang Bin , Song Lirong , Yin Jiandong 
Published: July 2021

PurposeTo evaluate the potential of the texture features extracted from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) intratumoral subregions to distinguish benign from malignant breast tumors.Materials and MethodsA total of 299 patients with pathologically verified breast tumors who underwent breast DCE-MRI examination were enrolled in this study, including 124 benign cases and 175 malignant cases. The whole tumor area was semi-automatically segmented on the basis of subtraction images of DCE-MRI in Matlab 2018b. According to the time to peak of the contrast agent, the whole tumor area was partitioned into three subregions: early, moderate, and late. A total of 467 texture features were extracted from the whole tumor area and the three subregions, respectively. Patients were divided into training (n = 209) and validation (n = 90) cohorts by different MRI scanners. The least absolute shrinkage and selection operator (LASSO) method was used to select the optimal feature subset in the training cohort. The Kolmogorov-Smirnov test was first performed on texture features selected by LASSO to test whether the samples followed a normal distribution. Two machine learning methods, decision tree (DT) and support vector machine (SVM), were used to establish classification models with a 10-fold cross-validation method. The performance of the classification models was evaluated with receiver operating characteristic (ROC) curves.ResultsIn the training cohort, the areas under the ROC curve (AUCs) for the DT_Whole model and SVM_Whole model were 0.744 and 0.806, respectively. In contrast, the AUCs of the DT_Early model (P = 0.004), DT_Late model (P = 0.015), SVM_Early model (P = 0.002), and SVM_Late model (P = 0.002) were significantly higher: 0.863 (95% CI, 0.808–0.906), 0.860 (95% CI, 0.806–0.904), 0.934 (95% CI, 0.891–0.963), and 0.921 (95% CI, 0.876–0.954), respectively. The SVM_Early model and SVM_Late model achieved better performance than the DT_Early model and DT_Late model (P = 0.003, 0.034, 0.008, and 0.026, respectively). In the validation cohort, the AUCs for the DT_Whole model and SVM_Whole model were 0.670 and 0.708, respectively. In comparison, the AUCs of the DT_Early model (P = 0.006), DT_Late model (P = 0.043), SVM_Early model (P = 0.001), and SVM_Late model (P = 0.007) were significantly higher: 0.839 (95% CI, 0.747–0.908), 0.784 (95% CI, 0.601–0.798), 0.890 (95% CI, 0.806–0.946), and 0.865 (95% CI, 0.777–0.928), respectively.ConclusionThe texture features from intratumoral subregions of breast DCE-MRI showed potential in identifying benign and malignant breast tumors.
Clinicopathological Features of Low-Grade Appendiceal Mucinous Neoplasms Confined to the Appendix
Authors: Lu Yiyan , Li Fang , Ma Ruiqing , Fang Lan , Qi Changhai 
Published: July 2021

ObjectiveTo investigate the clinicopathological features and follow-up of low-grade appendiceal mucinous neoplasms (LAMNs) confined to the appendix.MethodsThe clinicopathological features, pathological primary tumor (pT) staging and follow-up of 22 patients with LAMNs confined to the appendix were analyzed retrospectively.ResultsOf 22 patients with LAMNs, 14 were pTis (eight pTism and six pTisf), six were pT3, and two were pT4a. The appendiceal diameter was significantly larger for pTisf than for pTism. The interval between first symptoms and surgery was longer for pTisf than for pTism, but not significantly different. No significant differences were found between the pT stages and appendiceal diameter or in the interval between the first symptoms and surgery. Pathomorphologically, the epithelial structures were mainly flat (100%), undulating or scalloped (82%); a few showed filiform villous hyperplasia (46%), and seven (32%) had serrated lesions in the background. Diverticula may be associated with LAMNs, and the location of acellular mucin caused by diverticula affected the pT stage of the LAMNs. The immunohistochemistry information showed the same pattern with cytokeratin 7 (CK7) negative, cytokeratin 20 (CK20) positive and caudal type homeobox 2 (CDX-2) positive. No lymph node metastasis was found. The lack of treatment guidelines for LAMNs confined to the appendix and different acceptances of patients of preventive intervention led to varied clinical treatments. However, we found no short-term benefits of prophylactic extended resection or hyperthermic intraperitoneal chemotherapy.ConclusionLAMNs confined to the appendix are rare and must be differentiated from serrated lesions and diverticula. LAMNs with different pT stages have inert biological behavior. Determining the long-term effects of preventive treatment on survival and recurrence requires more data and a longer follow-up.
Role of Sex in the Therapeutic Targeting of p53 Circuitry
Authors: Mancini Francesca , Giorgini Ludovica , Teveroni Emanuela , Pontecorvi Alfredo , Moretti Fabiola 
Published: July 2021

Sex profoundly affects cancer incidence and susceptibility to therapy, with sex hormones highly contributing to this disparity. Various studies and omics data suggest a relationship between sex and the oncosuppressor p53 circuitry, including its regulators MDM2 and MDM4. Association of this network with genetic variation underlies sex-related altered cancer risk, age of onset, and cancer sensitivity to therapy. Moreover, sex-related factors, mainly estrogenic hormones, can affect the levels and/or function of the p53 network both in hormone-dependent and independent cancer. Despite this evidence, preclinical and clinical studies aimed to evaluate p53 targeted therapy rarely consider sex and related factors. This review summarizes the studies reporting the relationship between sex and the p53 circuitry, including its associated regulators, MDM2 and MDM4, with particular emphasis on estrogenic hormones. Moreover, we reviewed the evaluation of sex/hormone in preclinical studies and clinical trials employing p53-target therapies, and discuss how patients’ sex and hormonal status could impact these therapeutic approaches.
Auxiliary Structures-Assisted Radiotherapy Improvement for Advanced Left Breast Cancer
Authors: Lei Runhong , Zhang Xile , Li Jinna , Sun Haitao , Yang Ruijie 
Published: July 2021

BackgroundTo improve the quality of plan for the radiation treatment of advanced left breast cancer by introducing the auxiliary structures (ASs) which are used to spare the regions with no intact delineated structures adjacent to the target volume.MethodsCT data from 20 patients with left-sided advanced breast cancer were selected. An AS designated as A1 was created to spare the regions of the aorta, pulmonary artery, superior vena ava, and contralateral tissue of the upper chest and neck, and another, designated as A2, was created in the regions of the cardia and fundus of the stomach, left liver lobe, and splenic flexure of the colon. IMRT and VMAT plans were created for cases with and without the use of the AS dose constraints in plan optimization. Dosimetric parameters of the target and organs at risk (OARs) were compared between the separated groups.ResultsWith the use of AS dose constraints, both the IMRT and VMAT plans were clinically acceptable and deliverable, even showing a slight improvement in dose distribution of both the target and OARs compared with the AS-unused plans. The ASs significantly realized the dose sparing for the regions and brought a better conformity index (p &lt; 0.05) and homogeneity index (p &lt; 0.05) in VMAT plans. In addition, the volume receiving at least 20 Gy (V20) for the heart (p &lt; 0.05), V40 for the left lung (p &lt; 0.05), and V40 for the axillary-lateral thoracic vessel juncture region (p &lt; 0.05) were all lower in VMAT plans.ConclusionThe use of the defined AS dose constraints in plan optimization was effective in sparing the indicated regions, improving the target dose distribution, and sparing OARs for advanced left breast cancer radiotherapy, especially those that utilize VMAT plans.
Afatinib in EGFR TKI-Naïve Patients with Locally Advanced or Metastatic EGFR Mutation-Positive Non-Small Cell Lung Cancer: A Pooled Analysis of Three Phase IIIb Studies
Authors: Passaro Antonio , de Marinis Filippo , Tu Hai-Yan , Laktionov Konstantin K. , Feng Jifeng , Poltoratskiy Artem , Zhao Jun , Tan Eng Huat , Gottfried Maya , Lee Victor , Kowalski Dariusz , Yang Cheng Ta , Srinivasa BJ , Clementi Laura , Jalikop Tejaswini , Huang Dennis Chin Lun , Cseh Agnieszka , Park Keunchil , Wu Yi-Long 
Published: July 2021

BackgroundAfatinib is approved for first-line treatment of patients with epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC). Here, we report findings from a combined analysis of three phase IIIb studies of afatinib in EGFR tyrosine kinase inhibitor (TKI)-naïve patients.MethodsEGFR-TKI-naïve patients withEGFRm+ NSCLC received afatinib 40 mg/day. Dose reductions were permitted for adverse events (AEs). Efficacy endpoints included progression-free survival (PFS), time to symptomatic progression (TTSP), and tumor response. Subgroup analyses were performed by Eastern Cooperative Oncology Group performance status (ECOG PS), presence of brain metastasis, age and common/uncommonEGFRmutations (plus other factors).Results1108 patients were treated. Median age was 61 years (range, 25–89); 19.2% had baseline brain metastases, 4.4% had ECOG PS ≥2, and 17.9% had tumors harboring uncommon mutations. Treatment-related AEs (TRAEs) were reported in 97.2%, most commonly diarrhea and rash. 41.6% had AEs leading to dose reduction. Median PFS was 13.0 months [95% confidence interval (CI): 12.0–13.8]; median TTSP was 14.8 months (95% CI: 13.9–16.1). Objective response rate (ORR) was 55.0%. Age, presence of baseline brain metastases, major (G719X, L861Q, S768I) or compound uncommon mutations had little/no effect on PFS, TTSP, or ORR, while outcomes were poorer in patients with ECOG PS 2 or exon 20 insertion/T790M mutations.ConclusionsAfatinib was tolerable with no new safety signals. Afatinib demonstrated encouraging efficacy in a broad patient population, including those with brain metastases or uncommonEGFRmutations.
Inflammatory Myofibroblastic Tumors in Children: A Clinical Retrospective Study on 19 Cases
Authors: Da Min , Qian Bo , Mo Xuming , Xu Cheng , Wu Haiyan , Jiang Bin , Peng Wei , Qi Jirong , Sun Jian , Wu Kaihong 
Published: July 2021

Background: Inflammatory myofibroblastic tumor (IMFT) is a rare neoplasm mainly affecting children and young adults. We conducted a retrospective study to evaluate the clinical features and treatment alternatives of childhood inflammatory myofibroblastic tumors.Methods: A total of 19 patients who were pathologically diagnosed with IMT between December 2008 and October 2018 were included. Collected data were demographic information, main complaints, tumor characteristics, treatment, pathological results, immunohistochemical analysis, and prognosis.Results: The male/female ratio was 13:6. The mean age at disease onset was 44.9 ± 33.9 months (range 4 to 111 months). The mean tumor size was 6.5 ± 4.0 cm (range 1.2 to 17.0 cm). The most common site was the abdomen (13/19). The most commonly used detection tool was CT. Eleven patients (57.9%) had aggressive tumor growth, including eight receiving extensive resection and three receiving palliative resection due to high local invasiveness and postoperative chemotherapy. Eight cases whose tumors were completely enveloped received complete resection. Immunohistochemistry was performed for 17 patients and ALK positivity was found in 11 patients. Despite three children lost to follow-up, sixteen patients were followed up for 6 to 132 months (average 63.9 months, median 66 months). Of which, twelve children survived with no evidence of IMT, and four cases (21%) showed local recurrences (two of them died). No distant metastasis was detected.Conclusions: IMT is rare in children with various locations, mostly appearing in the abdomen. Whether the tumor could be completely removed, the location and the invasiveness of surrounding tissues might be highly prognosis-related.
Circulating MIF Associated With Disease Severity and Clinical Response of Sublingual Immunotherapy in House Dust Mite–Induced Allergic Rhinitis
Authors: Xie Shaobing , Zhang Hua , Wang Fengjun , Xie Zhihai , Jiang Weihong , Gao Kelei 
Published: July 2021

Background: Macrophage migration inhibitory factor (MIF) is described as a pro-inflammatory cytokine involved in many inflammatory and allergic disorders, but the role of MIF in allergic rhinitis (AR) remains poorly clarified. The aim of this study was to investigate the association between circulating MIF levels and house dust mite (HDM)-induced AR, and evaluate MIF as a potential biomarker in reflecting disease severity and predicting the clinical response of sublingual immunotherapy (SLIT) in HDM-induced AR patients.Methods: In this study, we enrolled 160 persistent HDM-induced AR patients (AR group), including 48 mild AR patients (MAR group) and 112 moderate–severe AR patients (MSAR group), and 77 healthy controls (HC group). Circulating levels of MIF were measured by ELISA, and the relationship between MIF concentrations and disease severity was assessed. In the MSAR group, 106 patients were assigned to receive SLIT for 3 years. At the end of the study, patients were categorized into good response group and poor response group, and associations between clinical variables or biomarkers and clinical response were analyzed by the multivariate regression analysis.Results: The concentrations of serum MIF were significantly higher in AR patients than in HCs, especially in those with MSAR. Moreover, circulating MIF levels were positively correlated with TNSS, VAS, serum HDM–specific IgE, total IgE, blood eosinophil count, and blood eosinophil percentage (all p &lt; 0.05). Eighty MSAR patients finally completed SLIT, 45 patients obtained good response, and 35 patients resulted in poor response. The serum levels of MIF were significantly lower in the good-response group than in the poor-response group (p &lt; 0.001). The receiver operating characteristic analysis for MIF showed good accuracy for predicting clinical response of SLIT (area under the curve = 0.877, p &lt; 0.001). The multivariate regression analysis demonstrated that serum MIF was an independent factor for SLIT responsiveness.Conclusion: Serum MIF appeared to be an important biological indicator in reflecting disease severity and an independent predictor for clinical responsiveness of SLIT in HDM-induced AR patients.
Mindfulness-Based Versus Story Reading Intervention in Public Elementary Schools: Effects on Executive Functions and Emotional Health
Authors: Milaré Claudete A. R. , Kozasa Elisa H. , Lacerda Shirley , Barrichello Carla , Tobo Patricia R. , Horta Ana Lucia D. 
Published: July 2021

IntroductionIn this study we compared the effects of a mindfulness-based intervention (MBI) with a story reading intervention (SI) on the executive functions and psychological profile of children in two different public schools in São Paulo, Brazil.MethodsIn this controlled clinical trial, 207 children aged 8 to 9 years old responded to the Five-Digit Test (FDT), stress levels, depression, anxiety, positive and negative affect, at baseline (T0) and 8 weeks later (T1). From T0 to T1, school 1 participated in MBI classes and school 2 in IS classes.ResultsIn school 1 (MBI), children improved their scores on all tests except reading (errors) and counting (errors) compared with school 2. No differences were observed between groups in terms of emotional health.ConclusionIt is feasible to implement MBI or SI in Brazilian public schools. Students in the MBI group presented broader effects in executive functions, while students in the SI group showed a trend toward reduced negative affect and depression symptoms.
Emotion and Psychophysiological Responses During Emotion–Eliciting Film Clips in an Eating Disorders Sample
Authors: French Melanie N. , Chen Eunice Y. 
Published: July 2021

Background: Greater vulnerability to negative emotions appears associated with the development and maintenance of eating disorders (EDs). A systematic review of psychophysiological studies using emotion-eliciting film clips reveals that there are no studies examining the effect of standardized validated film clips on psychophysiological response across a range of EDs.Methods: Using standardized validated film clips without ED-specific content, the present study examined self-reported emotions and psychophysiological responses of women with Binge-Eating Disorder (BED; n = 57), Anorexia Nervosa (AN; n = 16), Bulimia Nervosa (BN; n = 34), and Healthy Controls (HCs; n = 26) at Baseline, during Neutral, Sad, Happy, and Fear-inducing film clips, and at Recovery.Results: Throughout the protocol, the ED groups reported significantly greater sadness and anxiety than HCs. Additionally, the AN group reported more fear, the BED group more frustration, and the BED and BN groups more tension than HCs. Compared to HCs, the BED group reported stronger urges to binge throughout the protocol, whereas BN group reported stronger urges to binge relative to the HC group only at Baseline and Recovery. The BN and BED groups experienced decreased urges to binge during all film clips compared to Baseline. Respiratory Sinus Arrhythmia levels were significantly lower in the BED group compared to HCs and the BN group throughout the protocol.Discussion: Standardized validated film clips can be used to elicit expected self-reported emotion and skin conductance responses in ED groups, although individuals with EDs compared HCs report greater negative emotions. Interestingly, film clips appeared to reduce urges to binge in binge-eating groups.
Serum Metabolic Profiling of Late-Pregnant Women With Antenatal Depressive Symptoms
Authors: Mao Qiang , Tian Tian , Chen Jing , Guo Xunyi , Zhang Xueli , Zou Tao 
Published: July 2021

Background: Antenatal depression (AD) is a major public health issue worldwide and lacks objective laboratory-based tests to support its diagnosis. Recently, small metabolic molecules have been found to play a vital role in interpreting the pathogenesis of AD. Thus, non-target metabolomics was conducted in serum.Methods: Liquid chromatography—tandem mass spectrometry—based metabolomics platforms were used to conduct serum metabolic profiling of AD and non-antenatal depression (NAD). Orthogonal partial least squares discriminant analysis, the non-parametric Mann–Whitney U test, and Benjamini–Hochberg correction were used to identify the differential metabolites between AD and NAD groups; Spearman's correlation between the key differential metabolites and Edinburgh Postnatal Depression Scale (EPDS) and the stepwise logistic regression analysis was used to identify potential biomarkers.Results: In total, 79 significant differential metabolites between AD and NAD were identified. These metabolites mainly influence amino acid metabolism and glycerophospholipid metabolism. Then, PC (16:0/16:0) and betaine were significantly positively correlated with EPDS. The simplified biomarker panel consisting of these three metabolites [betaine, PC (16:0/16:0) and succinic acid] has excellent diagnostic performance (95% confidence interval = 0.911–1.000, specificity = 95%, sensitivity = 85%) in discriminating AD and NAD.Conclusion: The results suggested that betaine, PC (16:0/16:0), and succinic acid were potential biomarker panels, which significantly correlated with depression; and it could make for developing an objective method in future to diagnose AD.
Altered Cerebral Blood Flow in Alzheimer's Disease With Depression
Authors: Li Runzhi , Zhang Yanling , Zhuo Zhizheng , Wang Yanli , Jia Ziyan , Sun Mengfan , Zhang Yuan , Li Wenyi , Duan Yunyun , Yao Zeshan , Weng Haoyi , Wei Juan , Liu Yaou , Xu Jun 
Published: July 2021

Background: Depression is common in Alzheimer's disease (AD) with an unclear neural mechanism. This study aimed to investigate the underlying cerebral perfusion associated with depression in AD and evaluate its clinical significance.Method: Twenty-one AD patients and 21 healthy controls (HCs) were enrolled in this study. The depressive symptom was defined according to the Hamilton Depression Rating Scale (HAMD). Nine patients were diagnosed as AD with depression symptoms (HAMD &gt;7). Three-dimensional pseudocontinuous arterial spin labeling MR imaging was conducted to measure regional cerebral blood flow (CBF). Neuropsychological tests covered cognition and depressive scores. Between-group comparisons on clinical variables and regional CBFs, relationship between regional CBF and depressive score, and identification of AD patients with depression were performed using covariance analysis, linear regression, and receiver operating characteristic (ROC) analysis, respectively.Results: Compared with HCs, AD patients without depression exhibited lower gray matter CBF (p = 0.016); compared with AD patients without depression, AD patients with depression had higher CBF in the right supplementary motor area (39.23 vs. 47.91 ml/100 g/min, p = 0.017) and right supramarginal gyrus (35.54 vs. 43.85 ml/100 g/min, p = 0.034). CBF in the right supplementary motor area was correlated with depressive score (β = 0.46, p = 0.025). The combination of CBF in the right supplementary motor area and supramarginal gyrus and age could identify AD patients with depression from those without depression with a specificity of 100%, sensitivity of 66.67%, accuracy of 85.71%, and area under the curve of 0.87.Conclusions: Our findings suggested that hyperperfusion of the right supplementary motor area and right supramarginal gyrus were associated with depression syndrome in AD, which could provide a potential neuroimaging marker to evaluate the depression state in AD.