bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Ultrasound Imaging in the Prediction of TRIM67 in Brain Metastases From Breast Cancer
Authors: Xuan Zhidong , Ma Ting , Qin Yue , Guo Yajie 
Published: June 2022

ObjectivesUltrasound (US) imaging is a relatively novel strategy to monitor the activity of the blood–brain barrier, which can facilitate the diagnosis and treatment of neurovascular-related metastatic tumors. The purpose of this study was to investigate the clinical significance of applying a combination of US imaging outcomes and the associated genes. This was performed to construct line drawings to facilitate the prediction of brain metastases arising from breast cancer.MethodsThe RNA transcript data from The Cancer Genome Atlas (TCGA) database was obtained for breast cancer, and the differentially expressed genes (DEGs) associated with tumor and brain tumor metastases were identified. Subsequently, key genes associated with survival prognosis were subsequently identified from the DEGs.ResultsTripartite motif-containing protein 67 (TRIM67) was identified and the differential; in addition, the survival analyses of the TCGA database revealed that it was associated with brain tumor metastases and overall survival prognosis. Applying independent clinical cohort data, US-related features (microcalcification and lymph node metastasis) were associated with breast cancer tumor metastasis. Furthermore, ultrasonographic findings of microcalcifications showed correlations with TRIM67 expression. The study results revealed that six variables [stage, TRIM67, tumor size, regional lymph node staging (N), age, and HER2 status] were suitable predictors of tumor metastasis by applying support vector machine–recursive feature elimination. Among these, US-predicted tumor size correlated with tumor size classification, whereas US-predicted lymph node metastasis correlated with tumor N classification. The TRIM67 upregulation was accompanied by upregulation of the integrated breast cancer pathway; however, it leads to the downregulation of the miRNA targets in ECM and membrane receptors and the miRNAs involved in DNA damage response pathways.ConclusionsThe TRIM67 is a risk factor associated with brain metastases from breast cancer and it is considered a prognostic survival factor. The nomogram constructed from six variables—stage, TRIM67, tumor size, N, age, HER2 status—is an appropriate predictor to estimate the occurrence of breast cancer metastasis.
The Clustering Analysis of Time Properties in Patients With Cerebral Small Vessel Disease: A Dynamic Connectivity Study
Authors: Yin Wenwen , Zhou Xia , Li Chenchen , You Mengzhe , Wan Ke , Zhang Wei , Zhu Wenhao , Li Mingxu , Zhu Xiaoqun , Qian Yinfeng , Sun Zhongwu 
Published: June 2022

PurposeThis study aimed to investigate the dynamic functional connectivity (DFC) pattern in cerebral small vessel disease (CSVD) and explore the relationships between DFC temporal properties and cognitive impairment in CSVD.MethodsFunctional data were collected from 67 CSVD patients, including 35 patients with subcortical vascular cognitive impairment (SVCI) and 32 cognitively unimpaired (CU) patients, as well as 35 healthy controls (HCs). The DFC properties were estimated by k-means clustering analysis. DFC strength analysis was used to explore the regional functional alterations between CSVD patients and HCs. Correlation analysis was used for DFC properties with cognition and SVD scores, respectively.ResultsThe DFC analysis showed three distinct connectivity states (state I: sparsely connected, state II: strongly connected, state III: intermediate pattern). Compared to HCs, CSVD patients exhibited an increased proportion in state I and decreased proportion in state II. Besides, CSVD patients dwelled longer in state I while dwelled shorter in state II. CSVD subgroup analyses showed that state I frequently occurred and dwelled longer in SVCI compared with CSVD-CU. Also, the internetwork (frontal-parietal lobe, frontal-occipital lobe) and intranetwork (frontal lobe, occipital lobe) functional activities were obviously decreased in CSVD. Furthermore, the fractional windows and mean dwell time (MDT) in state I were negatively correlated with cognition in CSVD but opposite to cognition in state II.ConclusionPatients with CSVD accounted for a higher proportion and dwelled longer mean time in the sparsely connected state, while presented lower proportion and shorter mean dwell time in the strongly connected state, which was more prominent in SVCI. The changes in the DFC are associated with altered cognition in CSVD. This study provides a better explanation of the potential mechanism of CSVD patients with cognitive impairment from the perspective of DFC.
Systematic Review of Pre-injury Migraines as a Vulnerability Factor for Worse Outcome Following Sport-Related Concussion
Authors: Terry Douglas P. , Büttner Fionn , Huebschmann Nathan A. , Gardner Andrew J. , Cook Nathan E. , Iverson Grant L. 
Published: June 2022

BackgroundIndividuals with migraine disorders may be affected differently by concussions compared to individuals without migraine disorders. Prior studies on this topic have had mixed results. The purpose of this study was to systematically examine clinical outcomes following a sport-related concussion in athletes who have a pre-injury history of migraines.MethodsAll studies published prior to 15 May 2021 that examined pre-injury migraines as a possible predictor of clinical recovery from concussion were included. The search included (i) sport/athlete-related terms, (ii) concussion-related terms, and (iii) diverse predictor/modifier terms. After removing duplicates, 5,118 abstracts were screened, 538 full-text articles were reviewed, and 27 articles were included for narrative synthesis without meta-analysis (n = 25 with unique samples). Risk of bias was assessed using the domain-based Quality In Prognosis Studies (QUIPS) tool.ResultsMost studies did not find pre-injury migraines to be associated with concussion outcome, but several of these studies had small or very small sample sizes, as well as other methodological weaknesses. Risk of bias varied greatly across studies. Some of the larger, better-designed studies suggested pre-injury migraines may be a risk factor for worse concussion outcome. Most articles examined pre-injury migraines as an exploratory/secondary predictor of concussion outcome; very few were designed to examine migraine as the primary focus of the study. Migraine history was predominantly based on self-report and studies included minimal information about migraine (e.g., age of onset, frequency/severity, past treatment). Effect sizes were usually not reported or able to be calculated from reported study data.ConclusionThere is some evidence to suggest that pre-injury migraines may be a vulnerability factor for a worse outcome following concussion, with studies having the lowest risk of bias reporting a positive association. Future studies should focus on improving methodological quality when assessing the relationship between pre-injury migraines and concussion outcome and better characterizing pre-injury migraine status.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019128292, identifier: PROSPERO 2019 CRD42019128292.
The Effect of Neurofeedback on the Reaction Time and Cognitive Performance of Athletes: A Systematic Review and Meta-Analysis
Authors: Brito Michele Andrade de , Fernandes José Raimundo , Esteves Natã Sant'Anna , Müller Vanessa Teixeira , Alexandria Daniella Brito , Pérez Diego Ignacio Valenzuela , Slimani Maamer , Brito Ciro José , Bragazzi Nicola Luigi , Miarka Bianca 
Published: June 2022

Our study evaluated the effect of training with neurofeedback (NFB) in improving athletes' reaction time and decision-making. A computerized search in PubMed, PsycINFO, Scielo, Web of Science, EMBASE, Scopus, BVS, and Cochrane databases was performed to identify studies published from 2011 to June 2021. The protocol was registered in PROSPERO. The quality of studies that was peer-reviewed and included was assessed using the Review Manager tool, Cochrane Risk of Bias, and design and reporting quality according to the CRED-nf checklist. Standard mean differences and 95% confidence intervals (CIs) were calculated and combined using a random-effects model. A total of 07 randomized controlled trials (RCTs) (173 athletes) met the inclusion criteria. Significant effects of NFB in the experimental group in relation to reaction time were found, indicating an improvement in sports performance [standardized mean difference (SMD) = −1.08; 95% CI = (−1.90, −0.25),p= 0.0009] and cognitive performance vs. decision-making with moderate effect [SMD = 1.12; 95% CI = (−0.40, 1.85),p= 0.0001]. However, the control group had a very small effect on cognitive performance [SMD = 0.19; 95% CI = (−0.20, 0.59),p= 0.086]. NFB could improve athletes' reaction time and decision-making, effectively increasing their performance in the sports field. Future studies should focus on standardized protocols for NFB training.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021258387.
Citrus Consumption and Risk of Melanoma: A Dose-Response Meta-Analysis of Prospective Cohort Studies
Authors: Fang Xuexian , Han Dan , Yang Jun , Li Fulun , Sui Xinbing 
Published: June 2022

BackgroundEpidemiological studies of citrus consumption in relation to melanoma risk have yielded conflicting results. This meta-analysis was performed to investigate the dose-response association between citrus consumption and risk of melanoma.MethodsRelevant prospective cohort studies were identified by searching PubMed, Embase, Scopus, and Web of Science databases up to February 28th, 2022. Results from individual studies were pooled using a random-effects model.ResultsFive prospective studies, with 8,836 melanoma cases and 977,558 participants, were included in the meta-analysis. A significantly increased risk of melanoma was associated with the highest categories of either total citrus products (RR: 1.20; 95% CI: 1.01–1.42) or citrus fruit consumption (1.15; 1.04–1.28), but consumption of citrus juice was not associated with melanoma risk (1.08; 0.97–1.21). The dose-response analyses revealed that for per 1 serving/day increase in total citrus or citrus fruit consumption, the risk of melanoma increased by 9 and 12%, respectively. An inverted U-shaped curvilinear relationship, but not linear association, was observed between citrus juice consumption and melanoma risk.ConclusionsCitrus consumption was generally associated with a greater risk of malignant melanoma. Our findings may have important public health implications with respect to preventing melanoma.
The Effects of Different Induction Chemotherapy Cycles and Adjuvant Chemotherapy on the Survival Outcomes of Patients With Locally Advanced Nasopharyngeal Carcinoma
Authors: Liao Shu , Diao Yunlian , Ling Qingyuan , Xiong Zhijuan , Deng Wenxin , Zhang Ping , Zhang Congkai , Ying Ying , Zhong Xiaojun , Zhang Wei 
Published: June 2022

ObjectiveThis study investigated whether differences in the induction chemotherapy (IC) cycle number and adjuvant chemotherapy (AC) affect survival outcomes in patients with locally advanced nasopharyngeal carcinoma (LA-NPC).MethodsThe survival outcomes of 386 consecutive LA-NPC patients treated between January 2015 and March 2018 were retrospectively analyzed. Univariate and multivariate analyses were used to compare treatment groups defined by IC&lt; 3 or ≥3 IC cycles followed by radiotherapy with or without AC (i.e., IC&lt;3+AC, IC&lt;3+non-AC, IC≥3+AC, and IC≥3+non-AC groups).ResultsThe median follow-up time was 53 months (range: 2-74 months) and the median number of IC cycles was 2 (range: 1-6 cycles). The 3-year overall survival (OS) rate was significantly higher in patients with IC≥3 cycles compared to IC&lt;3 cycles (95.7% vs. 90.3%, P=0.020). Multivariate analysis indicated that the IC cycle number is an independent factor for OS (hazard ratio=0.326, P=0.007). Furthermore, patients in the IC&lt;3+AC group had a better OS rate than those in the IC&lt;3+non-AC group (91.6% vs. 79.1%, P=0.030), indicating that AC positively affected OS in patients with IC&lt;3. However, no significant difference in the OS rate was found between IC≥3+non-AC and IC≥3+AC groups (92.1% vs. 94.6%, P =0.550).ConclusionThe IC cycle number appears to be an independent prognostic factor for higher OS in LA-NPC patients who received ≥3 cycles. Sequential AC after IC plus radiotherapy may improve OS in patients with IC&lt;3 cycles.
Prognostic Role of Tumor Immune Microenvironment in Pleural Epithelioid Mesothelioma
Authors: Ollila Hely , Mäyränpää Mikko I. , Paavolainen Lassi , Paajanen Juuso , Välimäki Katja , Sutinen Eva , Wolff Henrik , Räsänen Jari , Kallioniemi Olli , Myllärniemi Marjukka , Ilonen Ilkka , Pellinen Teijo 
Published: June 2022

BackgroundPleural mesothelioma (MPM) is an aggressive malignancy with an average patient survival of only 10 months. Interestingly, about 5%–10% of the patients survive remarkably longer. Prior studies have suggested that the tumor immune microenvironment (TIME) has potential prognostic value in MPM. We hypothesized that high-resolution single-cell spatial profiling of the TIME would make it possible to identify subpopulations of patients with long survival and identify immunophenotypes for the development of novel treatment strategies.MethodsWe used multiplexed fluorescence immunohistochemistry (mfIHC) and cell-based image analysis to define spatial TIME immunophenotypes in 69 patients with epithelioid MPM (20 patients surviving ≥ 36 months). Five mfIHC panels (altogether 21 antibodies) were used to classify tumor-associated stromal cells and different immune cell populations. Prognostic associations were evaluated using univariate and multivariable Cox regression, as well as combination risk models with area under receiver operating characteristic curve (AUROC) analyses.ResultsWe observed that type M2 pro-tumorigenic macrophages (CD163+pSTAT1−HLA-DRA1−) were independently associated with shorter survival, whereas granzyme B+ cells and CD11c+ cells were independently associated with longer survival. CD11c+ cells were the only immunophenotype increasing the AUROC (from 0.67 to 0.84) when added to clinical factors (age, gender, clinical stage, and grade).ConclusionHigh-resolution, deep profiling of TIME in MPM defined subgroups associated with both poor (M2 macrophages) and favorable (granzyme B/CD11c positivity) patient survival. CD11c positivity stood out as the most potential prognostic cell subtype adding prediction power to the clinical factors. These findings help to understand the critical determinants of TIME for risk and therapeutic stratification purposes in MPM.
Role of Pneumonectomy in T1–4N2M0 Non-Small Cell Lung Cancer: A Propensity Score Matching Analysis
Authors: Wang Suyu , Wang Qing , Zhu Wanli , Wei Juan , Feng Di , Lv Xin , Liu Meiyun 
Published: June 2022

BackgroundN2 stage disease constitutes approximately 20%–30% of all non-small cell lung cancer (NSCLC). Concurrently, surgery remains the first-choice treatment for patients with N2 NSCLC if feasible. However, the role of pneumonectomy in N2 NSCLC has rarely been investigated and remains controversial.MethodsWe enrolled 26,798 patients with T1–4N2M0 NSCLC (stage IIIA/IIIB) from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. We compared the overall survival (OS) and cancer-specific survival (CSS) between patients who received pneumonectomy and those who did not receive surgery. The Kaplan–Meier method, Cox regression analyses, and propensity score matching (PSM) were applied to demonstrate the effect of pneumonectomy.ResultsPatients receiving pneumonectomy had a significantly better OS and CSS than those without pneumonectomy both before [adjusted-HR (95% CI): 0.461 (0.425–0.501) for OS, 0.444 (0.406–0.485) for CSS] and after PSM [adjusted-HR (95% CI): 0.499 (0.445–0.560) for OS, 0.457 (0.405–0.517) for CSS] with all p-values &lt;0.001. Subgroup analysis demonstrated concordant results stratified by demographic or clinicopathological variables. In sensitivity analysis, no significant difference was observed between patients receiving single pneumonectomy and chemoradiotherapy without surgery in OS and CSS both before [unadjusted-HR (95% CI): 1.016 (0.878–1.176) for OS, 0.934 (0.794–1.099) for CSS, p = 0.832] and after PSM [unadjusted-HR (95% CI): 0.988 (0.799–1.222) for OS, 0.938 (0.744–1.182) for CSS] with all p-values &gt;0.4.ConclusionFor patients with T1–4N2M0 NSCLC (stage IIIA/IIIB), pneumonectomy is an independent protective factor of OS and should be considered when applicable.
Radiomics-Based Machine Learning Models for Predicting P504s/P63 Immunohistochemical Expression: A Noninvasive Diagnostic Tool for Prostate Cancer
Authors: Liu Yun-Fan , Shu Xin , Qiao Xiao-Feng , Ai Guang-Yong , Liu Li , Liao Jun , Qian Shuang , He Xiao-Jing 
Published: June 2022

ObjectiveTo develop and validate a noninvasive radiomic-based machine learning (ML) model to identify P504s/P63 status and further achieve the diagnosis of prostate cancer (PCa).MethodsA retrospective dataset of patients with preoperative prostate MRI examination and P504s/P63 pathological immunohistochemical results between June 2016 and February 2021 was conducted. As indicated by P504s/P63 expression, the patients were divided into label 0 (atypical prostatic hyperplasia), label 1 (benign prostatic hyperplasia, BPH) and label 2 (PCa) groups. This study employed T2WI, DWI and ADC sequences to assess prostate diseases and manually segmented regions of interest (ROIs) with Artificial Intelligence Kit software for radiomics feature acquisition. Feature dimensionality reduction and selection were performed by using a mutual information algorithm. Based on screened features, P504s/P63 prediction models were established by random forest (RF), gradient boosting decision tree (GBDT), logistic regression (LR), adaptive boosting (AdaBoost) and k-nearest neighbor (KNN) algorithms. The performance was evaluated by the area under the ROC curve (AUC) and accuracy.ResultsA total of 315 patients were enrolled. Among the 851 radiomic features, the 32 top features were derived from T2WI, in which the gray-level run length matrix (GLRLM) and gray-level cooccurrence matrix (GLCM) features accounted for the largest proportion. Among the five models, the RF algorithm performed best in general evaluations (microaverage AUC=0.920, macroaverage AUC=0.870) and provided the most accurate result in further sublabel prediction (the accuracies of label 0, 1, and 2 were 0.831, 0.831, and 0.932, respectively). In comparative sequence analyses, T2WI was the best single-sequence candidate (microaverage AUC=0.94 and macroaverage AUC=0.78). The merged datasets of T2WI, DWI, and ADC yielded optimal AUCs (microaverage AUC=0.930 and macroaverage AUC=0.900).ConclusionsThe radiomic-based RF classifier has the potential to be used to evaluate the presurgical P504s/P63 status and further diagnose PCa noninvasively and accurately.
Nomogram for Estimating the Risks of Intestinal Ischemia and Necrosis in Neonates With Midgut Volvulus: A Retrospective Study
Authors: Guan Xisi , Wang Zhe , He Qiuming , Lv Junjian , Yu Jiakang , Zhong Wei 
Published: June 2022

BackgroundDelayed diagnosis and inaccurate judgment of the severity of the disease may be the principal reasons for the poor prognosis associated with neonatal midgut volvulus. We aimed to develop a nomogram model that timely assesses the risks of intestinal ischemia and necrosis in the neonate with midgut volvulus.Materials and MethodsWe retrospectively analyzed the clinical data from neonates with midgut volvulus who were admitted to Guangzhou Women and Children’s Medical Center from January 2009 to December 2019. Univariate and multivariate analyses were used to obtain independent factors to build a predictive model. The independent factors were used to develop the nomogram model.ResultsHeart rate, mean arterial pressure, serum C-reactive protein, serum sodium, serum albumin, and pH levels were independent predictors for intestinal ischemia and necrosis in patients with midgut volvulus. The area under the receiver operating characteristic curve (AUC) of the predictive model was 0.985 (95% confidence interval, 0.966–0.999; P &lt; 0.001). The sensitivity was 90.48%, and the specificity was 93.10%. A nomogram model was established using the six independent predictors, with a C-index of 0.859 and a favorable consistency between the predicted and actual intestinal ischemia and necrosis rates according to the internal validation.ConclusionThe constructed nomogram model could be a superior tool for predicting intestinal ischemia and necrosis in neonates with midgut volvulus.
Application of Pharmacokinetic/Pharmacodynamic Modeling to Bridge Mouse Antitumor Efficacy and Monkey Toxicology Data for Determining the Therapeutic Index of an Interleukin-10 Fc Fusion Protein
Authors: Yang Zheng , Loy James , Poirson Brian , Dai Yanshan , Rajendran Surendran , Xu Shihua , Spires Vanessa , Gururajan Murali , Lin Zheng , Arbanas Jaren , Carl Stephen , Pace Samantha , Wang Yun , Mehl John , Vasudevan Krishna , Spires Thomas , Novosiadly Ruslan , Coker Shodeinde , Perez Raymond , Covello Kelly , Morin Paul , Graziano Robert , Broz Miranda , Lehman-McKeeman Lois 
Published: June 2022

Pharmacokinetic/pharmacodynamic (PK/PD) modeling was performed to quantitatively integrate preclinical pharmacology and toxicology data for determining the therapeutic index (TI) of an interleukin-10 (IL-10) fragment crystallizable (Fc) fusion protein. Mouse Fc fused with mouse IL-10 (mFc-mIL-10) was studied in mice for antitumor efficacy, and the elevation of interleukin-18 (IL-18) was examined as a PD biomarker. The in vivo mFc-mIL-10 EC50 for the IL-18 induction was estimated to be 2.4 nM, similar to the in vitro receptor binding affinity (Kd) of 3.2 nM. The IL-18 induction was further evaluated in cynomolgus monkeys, where the in vivo induction EC50 by a human IL-10 human Fc-fusion protein (hFc-hIL-10) was 0.08 nM vs. 0.3 nM measured as the in vitro Kd. The extent of the IL-18 induction correlated with mouse antitumor efficacy and was used to connect mouse efficacy to that in monkeys. The PD-based efficacious dose projected in monkeys was comparable to the results obtained using a PK-based method in which mouse efficacious exposure was targeted and corrected for affinity differences between the species. Furthermore, PK/PD relationships were developed for anemia and thrombocytopenia in monkeys treated with hFc-hIL-10, with thrombocytopenia predicted to be dose-limiting toxicity. Using quantitative pharmacology and toxicology information obtained through modeling work in the same species, the TI of hFc-hIL-10 in monkeys was determined to be 2.4 (vs. PD-based efficacy) and 1.2–3 (vs. PK-based efficacy), indicating a narrow safety margin. The model-based approaches were proven valuable to the developability assessment of the IL-10 Fc-fusion protein.