bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of an Immune Cell Infiltration Score to Evaluate the Prognosis and Therapeutic Efficacy of Ovarian Cancer Patients
Authors: Liu Jinhui , Wang Yichun , Yuan Shuning , Wei Junting , Bai Jianling 
Published: October 2021

BackgroundOvarian cancer (OC) is an immunogenetic disease that contains tumor-infiltrating lymphocytes (TILs), and immunotherapy has become a novel treatment for OC. With the development of next-generation sequencing (NGS), profiles of gene expression and comprehensive landscape of immune cells can be applied to predict clinical outcome and response to immunotherapy.MethodsWe obtained data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and applied two computational algorithms (CIBERSORT and ESTIMATE) for consensus clustering of immune cells. Patients were divided into two subtypes using immune cell infiltration (ICI) levels. Then, differentially expressed genes (DEGs) associated with immune cell infiltration (ICI) level were identified. We also constructed ICI score after principle-component analysis (PCA) for dimension reduction.ResultsPatients in ICI cluster B had better survival than those in ICI cluster A. After construction of ICI score, we found that high ICI score had better clinical OS and significantly higher tumor mutation burden (TMB). According to the expression of immune checkpoints, the results showed that patients in high ICI group showed high expression of CTLA4, PD1, PD-L1, and PD-L2, which implies that they might benefit from immunotherapy. Besides, patients in high ICI group showed higher sensitivity to two first-line chemotherapy drugs (Paclitaxel and Cisplatin).ConclusionICI score is an effective prognosis-related biomarker for OC and can provide valuable information on the potential response to immunotherapy.
Impact of the COVID-19 Pandemic on Survival in the Patients With the Intra-Abdominal Infections
Authors: Gálvez-Benítez Lydia , Rodríguez-Villodres Ángel , Álvarez-Marín Rocío , Jiménez-Rodríguez Rosa , Lepe-Jiménez José Antonio , Pachón Jerónimo , Smani Younes 
Published: October 2021

Objective: To analyze the availability and access to the hospital for the patients with intra-abdominal infections (IAIs) by Escherichia coli (E. coli) as a result of the coronavirus disease 2019 (COVID-19) pandemic and the impact of these changes in the diagnosis and their effects on the death of these patients.Methods: Two prospective observational cohorts of the patients with IAI by E. coli were conducted in 2016 (the pre-COVID-19, n = 108) and in 2020 (during the COVID-19, n = 96) at the University Hospital of Seville, Spain. The demographic and clinical variables of the patients were collected and analyzed. The patients were followed-up for 120 days, until the hospital discharge or death. The bivariate and multivariate analyses were performed.Results: Both the cohorts were homogeneous according to age, sex, emergency surgery cause, immunosuppression, neutropenia, acquisition type, and previous intervention. The patients attended during the COVID-19 had significantly higher Charlson comorbidity index and the more McCabe score, required more emergency surgery, had more severe infections with the higher rates of septic shock and sepsis, and the presence of additional care support such as a nasogastric tube. They were diagnosed later; the time intervals between the symptoms onset (SO) to the first medical contact or surgical intervention (SI) and between the first medical contact to the admission or SI were significantly higher. The death rates during the COVID-19 and the pre-COVID-19 were 16.7 and 6.5%, respectively (p = 0.02). Finally, the multivariate analysis in both the cohorts together identified the patients diagnosed during the COVID-19, the longer period from SO to SI, septic shock, and the Charlson comorbidity index as the independent factors associated with death.Conclusion: This study showed the impact of the COVID-19 pandemic on the clinical outcome and death due to IAI with an extension of the time between SO and SI.
Voxel-Based Analysis of [18F]-FDG Brain PET in Rats Using Data-Driven Normalization
Authors: Proesmans Silke , Raedt Robrecht , Germonpré Charlotte , Christiaen Emma , Descamps Benedicte , Boon Paul , De Herdt Veerle , Vanhove Christian 
Published: October 2021

Introduction: [18F]-FDG PET is a widely used imaging modality that visualizes cellular glucose uptake and provides functional information on the metabolic state of different tissues in vivo. Various quantification methods can be used to evaluate glucose metabolism in the brain, including the cerebral metabolic rate of glucose (CMRglc) and standard uptake values (SUVs). Especially in the brain, these (semi-)quantitative measures can be affected by several physiological factors, such as blood glucose level, age, gender, and stress. Next to this inter- and intra-subject variability, the use of different PET acquisition protocols across studies has created a need for the standardization and harmonization of brain PET evaluation. In this study we present a framework for statistical voxel-based analysis of glucose uptake in the rat brain using histogram-based intensity normalization.Methods: [18F]-FDG PET images of 28 normal rat brains were coregistered and voxel-wisely averaged. Ratio images were generated by voxel-wisely dividing each of these images with the group average. The most prevalent value in the ratio image was used as normalization factor. The normalized PET images were voxel-wisely averaged to generate a normal rat brain atlas. The variability of voxel intensities across the normalized PET images was compared to images that were either normalized by whole brain normalization, or not normalized.To illustrate the added value of this normal rat brain atlas, 9 animals with a striatal hemorrhagic lesion and 9 control animals were intravenously injected with [18F]-FDG and the PET images of these animals were voxel-wisely compared to the normal atlas by group- and individual analyses.Results: The average coefficient of variation of the voxel intensities in the brain across normal [18F]-FDG PET images was 6.7% for the histogram-based normalized images, 11.6% for whole brain normalized images, and 31.2% when no normalization was applied. Statistical voxel-based analysis, using the normal template, indicated regions of significantly decreased glucose uptake at the site of the ICH lesion in the ICH animals, but not in control animals.Conclusion: In summary, histogram-based intensity normalization of [18F]-FDG uptake in the brain is a suitable data-driven approach for standardized voxel-based comparison of brain PET images.
Diagnostic Efficacy and Decision-Making Role of Preoperative Endoscopic Ultrasonography in Early Gastric Cancer
Authors: Li Xiao , Zhu Min , Wang Yongjun , Niu Yinglin , Ji Ming , Li Peng , Zhang Shutian 
Published: October 2021

Objectives: Endoscopic ultrasonography (EUS) is the most commonly used method for T staging of early gastric cancer (EGC). However, the studies pertaining to EUS for staging EGC reported widely varied sensitivities and specificities. This study aimed to estimate the overall diagnostic accuracy of EUS for staging the depth of EGCs and to explore the influential factors.Methods: We retrospectively reviewed data from 208 consecutive patients with EGC, and all patients underwent EUS for estimating tumor invasion depth, followed by either curative surgery or endoscopic submucosal dissection (ESD). The diagnostic accuracy of EUS was evaluated by comparing the final histologic results of resected specimens. The correlation between accuracy of EUS and characteristics of EGC lesion was analyzed.Results: A total of 211 EGC lesions in 208 patients were included. The overall diagnostic accuracy of EUS in assessing the tumor invasion depth of EGC was 55.9%. Multivariate analysis showed that submucosal invasion (OR 2.615; 95% CI 1.203–5.684, P = 0.015) was independently associated with misdiagnosis of the depth of EGC and 0-III type lesions (OR 31.495; 95% CI 2.083–476.256, P = 0.013) were an independent risk factor for over-diagnosis of invasion depth by EUS. However, EUS was only suitable for lesions within absolute indications for endoscopic resection.Conclusions: The overall accuracy of EUS in diagnosing invasion depth of EGC was relatively low. Thus, EUS is not necessary routinely for determining the therapeutic strategy for EGC.
Aberrant Methylation and Immune Microenvironment Are Associated With Overexpressed Fibronectin 1: A Diagnostic and Prognostic Target in Head and Neck Squamous Cell Carcinoma
Authors: Sheng Surui , Guo Bing , Wang Zhentao , Zhang Zhihua , Zhou Jieyu , Huo Zirong 
Published: October 2021

Background: Fibronectin 1 (FN1) is involved in cell adhesion and migration processes such as metastasis, wound healing, embryogenesis, blood coagulation, and host defense. However, the role of FN1 in the diagnosis and prognosis of head and neck squamous cell carcinoma (HNSCC) is far from understood.Methods: FN1 expression profiles and clinical parameters from multiple HNSCC datasets were applied to evaluate the association between FN1 expression and HNSCC survival. We also identified FN1 expression in the mRNA and protein levels in 20 pairs of clinical samples by quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Receiver operator characteristic (ROC) analysis was used to demonstrate the potential diagnostic value of FN1 in HNSCC. Aberrant methylation PPI networks were established using multiple bioinformatic tools based on TCGA database. The immune microenvironment and levels of immune checkpoints were investigated between groups with high and low FN1 expression.Results: FN1 was significantly upregulated in HNSCC compared with para-carcinoma tissues on the basis of TCGA database and our clinical samples. Univariate and multivariate Cox regression analysis revealed that FN1 could be an independent indicator for prognosis of HNSCC. GO enrichment and KEGG pathway analysis demonstrated that cell adhesion, focal adhesion, and the PI3K-Akt signaling pathway might be involved in the potential mechanisms of FN1’s prognostic performance in HNSCC. Methylation of FN1 was also higher and closely associated with poorer survival in HNSCC. In addition, FN1 expression was positively correlated with three DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B). Furthermore, FN1 was positively associated with CD4+ T cells, endothelial cells, macrophages, and NK cells and negatively correlated with CD8+ T cellsConclusion: FN1 might be an independent prognostic biomarker for HNSCC patients. Hypermethylation, the aberrant proportions of immune cells, and the PI3K/Akt signaling pathway might be involved in the mechanism of FN1’s oncogene role in HNSCC.
Personalized Motor-Cognitive Exergame Training in Chronic Stroke Patients—A Feasibility Study
Authors: Huber Simone K. , Held Jeremia P. O. , de Bruin Eling D. , Knols Ruud H. 
Published: October 2021

Purpose: Exergame training may be beneficial for improving long-term outcome in stroke patients. Personalized training prescription applying progression rules, is missing. We adapted a theory-based taxonomy for a rehabilitation approach using user-centered exergames. The aims were primarily to investigate the feasibility of this rehabilitation approach, and secondarily to evaluate its performance of personalizing training progression, as well as explore the effects on secondary outcomes.Methods: Chronic stroke patients (≥ 18 years) were included, who were able to walk 10 meters and stand for 3 min. The rehabilitation approach was administered twice per week for 8 weeks. As primary outcome, feasibility was evaluated by comparing achieved rates of inclusion, adherence, compliance, attrition, motivation, and satisfaction to pre-defined thresholds for acceptance. Secondary outcomes were (1) perceived motor and cognitive task difficulty throughout the intervention; (2) measures collected during baseline and post-measurements—a gait analysis, the Timed-up-and-go test (TUG), several cognitive tests assessing attentional, executive, and visuospatial functions.Results: Thirteen patients [median: 68.0 (IQR: 49.5–73.5) years, median: 34.5 (IQR: 12.25–90.75) months post-stroke] were included, of whom ten completed the study. Rates for inclusion (57%), adherence (95%), compliance (99%), motivation (77%), and satisfaction (74%) were acceptable, however, the attrition rate was high (23%). The perceived motor and cognitive task difficulty predominantly moved below the targeted range. We found a significant change in the TUG (p = 0.05, r = 0.46) and medium-to-large effect sizes (p &gt; 0.05) for swing time of the affected leg, the asymmetry index, time needed for the Trail-making test (TMT) A and accuracy for the TMT B and the Mental Rotation Test (MRT; 0.26 ≤ r ≤ 0.46).Discussion: The intervention was feasible with minor modifications necessary, which warrants a larger trial investigating the effects of the rehabilitation approach following the adapted taxonomy on mobility, gait and cognitive functions. Two main limitations of the rehabilitation approach were; (1) the taxonomy decoupled motor and cognitive progression, which may be improper as motor and cognitive learning is coupled; (2) separate subjective ratings were used to guide the progression. Future studies should develop an instrument to objectively assess motor-cognitive task difficulty for monitoring the progression of an exergame-based training.
The Relationship of APOE ε4, Race, and Sex on the Age of Onset and Risk of Dementia
Authors: Powell Danielle S. , Kuo Pei-Lun , Qureshi Riaz , Coburn Sally B. , Knopman David S. , Palta Priya , Gottesman Rebecca , Griswold Michael , Albert Marilyn , Deal Jennifer A. , Gross Alden L. 
Published: October 2021

Objective: To investigate whether APOE ε4 genotype—an established risk factor for dementia—is associated with earlier age at diagnosis in addition to increased risk overall and in secondary analysis by race and sex.Methods: We followed up 13,782 dementia-free individuals (n = 10,137 White, n = 3,645 Black, baseline age 60–66 years) in the Atherosclerosis Risk in Communities study for up to 30 years. Dementia was operationalized using standardized algorithms incorporating longitudinal cognitive change, proxy report, and hospital or death certificate dementia codes. We used a mixture of generalized gamma distributions to simultaneously estimate time to dementia, time to dementia-free death, and the proportion of individuals with dementia, by APOE ε4 status (≥1 vs. no alleles).Results: Median age of dementia onset among APOE ε4 carriers was 81.7 (Blacks) and 83.3 years (Whites) compared with 82.6 (Blacks) and 85.7 years (Whites) in non-APOE ε4 carriers (p &gt; 0.05 Blacks; p &lt; 0.01 Whites). Age of dementia diagnosis did not differ by sex in ε4 carriers, but among non-carriers, average age was earlier in males than females regardless of race. APOE ε4 carriers had on average a higher proportion of diagnoses; results did not differ by race or sex.Conclusions:APOE ε4 carrier status is associated with earlier age of dementia diagnosis with differences across race and sex. These findings clarify the causal role of APOE in dementia etiology, which could help better identify at-risk subgroups and may help facilitate better research trial recruitment and design.
The Efficacy and Tolerability of Selective Serotonin Reuptake Inhibitors for Motor Recovery in Non-depressed Patients After Acute Stroke: A Meta-Analysis
Authors: Su Ning , Wen Changming , Guo Shiqian , Yu Yang , Wang Chenglin 
Published: October 2021

Objective: To explore the efficacy and tolerability of selective serotonin reuptake inhibitors (SSRIs) for motor recovery in non-depressed patients after acute stroke.Methods: According to the predefined retrieval strategy, multiple electronic databases were searched for randomized controlled trials (RCTs) that met the inclusion criteria. The primary efficacy outcome was measured by Fugl-Meyer Motor Scale (FMMS) score and the indicators of tolerability included withdrawal rate and the incidence of adverse events (AEs).Results: 10RCTs were included, the pooled analyses showed patients who received fluoxetine (endpoint: MD = 21.17, 95% CI 14.13–28.21, P &lt; 0.00001; mean change: MD = 16.27, 95% CI 10.05–22.50, P &lt; 0.00001) and citalopram (endpoint: MD = 22.93, 95% CI 11.13–34.73, P = 0.0001; mean change: MD = 24.06, 95% CI 10.47–37.65, P = 0.0005) experienced greater improvement in FMMS score. There was no evident difference in total withdrawal rate (fluoxetine: OR = 1.11, 95% CI 0.90–1.27, P = 1.38; citalopram: OR = 0.94, 95% CI 0.69–1.28, P = 0.71; escitalopram: OR = 0.87, 95% CI 0.58–1.28, P = 0.47) between two groups. Besides, the incidence of hyponatremia (OR = 2.01, 95% CI 1.16–3.50, P = 0.01), seizure (OR = 1.46, 95% CI 1.03–2.08, P = 0.04) and fracture (OR = 2.34, 95% CI 1.61–3.40, P &lt; 0.00001) in the fluoxetine group was higher than in the placebo group.Conclusions: Fluoxetine and citalopram can promote motor recovery in non-depressed patients with acute stroke, but it is necessary to pay attention to the possible AEs of fluoxetine, such as hyponatremia, seizure and fracture.Systematic Review Registration: PROSPERO, identifier [CRD42021227452].
Sentinel Lymph Node in Aged Endometrial Cancer Patients “The SAGE Study”: A Multicenter Experience
Authors: Cianci Stefano , Rosati Andrea , Vargiu Virginia , Capozzi Vito Andrea , Sozzi Giulio , Gioè Alessandro , Gueli Alletti Salvatore , Ercoli Alfredo , Cosentino Francesco , Berretta Roberto , Chiantera Vito , Scambia Giovanni , Fanfani Francesco 
Published: October 2021

ObjectiveThe incidence of endometrial cancer is increasing in elderly people. Considering that aging progressively affects lymphatic draining function, we aimed to define its impact on IGC uptake during SLN mapping.MethodsA multicenter retrospective cohort of endometrial cancer patients with apparently early-stage endometrial cancer undergoing complete surgical staging with SLN dissection was identified in four referral cancer centers from May 2015 to March 2021. Patients were classified in Group 1 (&lt;65 years old) and Group 2 (≥65 years old). The primary endpoint was the assessment of the overall, bilateral, and unsuccessful SLN mapping in the two groups. Secondary outcomes were the evaluation of SLN anatomical distribution and the identification of predictors for mapping failure applying a logistic regression.ResultsA total of 844 patients were enrolled in the study (499 in Group 1 and 395 in Group 2). The overall detection rate, the successful bilateral mapping, and the mapping failure rate of the SLN were 93.8% vs. 87.6% (p = 0.002), 77.1% vs. 66.8% (p = 0.001), and 22.9% vs. 33.2% (p = 0.001), respectively, in Group 1 vs. Group 2. The advanced age affects the anatomical distribution of the SLN leading to a stepwise reduction of “unexpected” mapping sites (left hemipelvis: p &lt; 0.001; right hemipelvis: p = 0.058). At multivariate analysis age ≥ 65 (OR: 1.495, 95% CI: 1.095–2.042, p = 0.011), BMI (OR: 1.023, 95% CI: 1.000–1.046, p = 0.047), non-endometrioid histotype (OR: 1.619, 95% CI: 1.067–2.458, p = 0.024), and LVSI (OR: 1.407, 95% CI: 1.010–1.961, p = 0.044) represent independent predictors of unsuccessful mapping. Applying binomial logistic regression analysis, there was a 1.280-fold increase in the risk of failed mapping for every 10-year-old increase in age (OR: 1.280, 95% CI: 1.108–1.479, p = 0.001). A higher rate of surgical under-staging (0.9% vs. 3.3%, p = 0.012) and adjuvant undertreatment (p = 0.018) was reported in Group 2.ConclusionsOld age represents a risk factor for SLN mapping failure both intrinsically and in relation to the greater incidence of other independent risk factors such as LVSI, non-endometrioid histotype, and BMI. Surgeons should target the usual uptake along UPP during the SLN dissection in this subgroup of patients to minimize mapping failure and the consequent risk of surgical under-staging and adjuvant undertreatment.
The Mediating Effects of Diabetes Distress, Anxiety, and Cognitive Fusion on the Association Between Neuroticism and Fear of Hypoglycemia in Patients With Type 2 Diabetes
Authors: Huang Jing , Ding Shenglan , Xiong Shuyuan , Liu Zhiping 
Published: October 2021

Purpose:To explore the relationship between neuroticism and fear of hypoglycemia (FoH) among patients with type 2 diabetes (T2D), as well as the mediating effects of diabetes distress, anxiety, and cognitive fusion on the relationship between neuroticism and FoH.Methods:A total of 494 patients with T2D (39.9% females,n= 197) were analyzed using the neuroticism scale of the Eysenck Personality Questionnaire-Revised Short Scale (EPQ-RS), the Fear of Hypoglycemia-15 Scale (FH-15), the Diabetes Distress Scale (DDS), the Self-Rating Anxiety Scale (SAS), and the Cognitive Fusion Questionnaire (CFQ). The bootstrapping method was used to test the separate and parallel mediation models.Results:FoH was noted in 17.4% (n= 86) of patients. The correlations between neuroticism, diabetes distress, anxiety, cognitive fusion, and FoH were positive. Diabetes distress, anxiety, and cognitive fusion were significant mediators in the association between neuroticism and FoH in both separate and parallel mediation models. In the parallel mediation model, the mediating effect of anxiety was the highest, and the mediating effect of diabetes distress was the lowest, but no significant differences were found in the comparison of these three indirect effects.Conclusion:This study indicated that neuroticism not only directly affected FoH, but also indirectly influenced FoHviathe increase of diabetes distress, anxiety, and cognitive fusion in patients with T2D. The results provide a theoretical basis for the development of intervention programs to ameliorate patients’ FoH directly and indirectly. Healthcare providers should be encouraged to develop appropriate programs based on improving diabetes distress, anxiety, and cognitive fusion to help patients with T2D improve FoH.