bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytoplasmic MSH2 Related to Genomic Deletions in the MSH2/EPCAM Genes in Colorectal Cancer Patients With Suspected Lynch Syndrome
Authors: Dong Lin , Zou Shuangmei , Jin Xianglan , Lu Haizhen , Zhang Ye , Guo Lei , Cai Jianqiang , Ying Jianming 
Published: May 2021

BackgroundA large proportion of patients with Lynch syndrome (LS) have MSH2 abnormalities, but genotype-phenotype studies of MSH2 mutations in LS are still lacking. The aim of this study was to comprehensively analyze the clinicopathological characteristics and molecular basis of colorectal cancer (CRC) in patients with uncommon MSH2 cytoplasmic expression.MethodsWe retrospectively reviewed 4195 consecutive cases of CRC patients diagnosed between January 2015 and December 2017 at the Cancer Hospital Chinese Academy of Medical Sciences. Of the 4195 patients with CRC, 69 were indicated to have abnormal MSH2 expression through tumor immunohistochemical staining. Genetic tests, such as next-generation sequencing, large genomic rearrangement (LGR) analysis, microsatellite instability status analysis and genomic breakpoint analysis, were performed. Clinicopathological and molecular characteristics and clinical immunotherapy response were analyzed.ResultsForty-five of 69 patients were identified to have LS with pathogenic germline mutations in MSH2 and/or EPCAM. Of these LS patients, 26.7% were confirmed to harbor large genomic rearrangements (LGRs). Of note, three tumors from two unrelated family pedigrees exhibited a rare cytoplasmic MSH2 staining pattern that was found in LS patients with EPCAM/MSH2 deletions. RNA analysis showed that two novel mRNA fusions of EPCAM and MSH2 resulted in the predicted protein fusion with MSH2 cytoplasmic localization. Analyses of genomic breakpoints indicated that two novel deletions of EPCAM and MSH2 originated from Alu repeat-mediated recombination events. Our study also provides clinical evidence for the beneficial effect of the PD-1 inhibitor pembrolizumab for CRC patients that exhibit cytoplasmic MSH2 staining.ConclusionOur study demonstrates that the rare cytoplasmic MSH2 staining pattern should be fully recognized by pathologists and geneticists. Given the specific genotype-phenotype correlation in LS screening, we advocate that all CRC patients with cytoplasmic MSH2 staining in histology should be screened for LGRs of EPCAM and MSH2.
Influence of Urethra Sparing on Tumor Control Probability and Normal Tissue Complication Probability in Focal Dose Escalated Hypofractionated Radiotherapy: A Planning Study Based on Histopathology Reference
Authors: Spohn Simon K. B. , Sachpazidis Ilias , Wiehle Rolf , Thomann Benedikt , Sigle August , Bronsert Peter , Ruf Juri , Benndorf Matthias , Nicolay Nils H. , Sprave Tanja , Grosu Anca L. , Baltas Dimos , Zamboglou Constantinos 
Published: May 2021

PurposeMultiparametric magnetic resonance tomography (mpMRI) and prostate specific membrane antigen positron emission tomography (PSMA-PET/CT) are used to guide focal radiotherapy (RT) dose escalation concepts. Besides improvements of treatment effectiveness, maintenance of a good quality of life is essential. Therefore, this planning study investigates whether urethral sparing in moderately hypofractionated RT with focal RT dose escalation influences tumour control probability (TCP) and normal tissue complication probability (NTCP).Patients and Methods10 patients with primary prostate cancer (PCa), who underwent 68Ga PSMA-PET/CT and mpMRI followed by radical prostatectomy were enrolled. Intraprostatic tumour volumes (gross tumor volume, GTV) based on both imaging techniques (GTV-MRI and -PET) were contoured manually using validated contouring techniques and GTV-Union was created by summing both. For each patient three IMRT plans were generated with 60 Gy to the whole prostate and a simultaneous integrated boost up to 70 Gy to GTV-Union in 20 fractions by (Plan 1) not respecting and (Plan 2) respecting dose constraints for urethra as well as (Plan 3) respecting dose constraints for planning organ at risk volume for urethra (PRV = urethra + 2mm expansion). NTCP for urethra was calculated applying a Lyman-Kutcher-Burman model. TCP-Histo was calculated based on PCa distribution in co-registered histology (GTV-Histo). Complication free tumour control probability (P+) was calculated. Furthermore, the intrafractional movement was considered.ResultsMedian overlap of GTV-Union and PRV-Urethra was 1.6% (IQR 0-7%). Median minimum distance of GTV-Histo to urethra was 3.6 mm (IQR 2 – 7 mm) and of GTV-Union to urethra was 1.8 mm (IQR 0.0 – 5.0 mm). The respective prescription doses and dose constraints were reached in all plans. Urethra-sparing in Plans 2 and 3 reached significantly lower NTCP-Urethra (p = 0.002) without significantly affecting TCP-GTV-Histo (p = p &gt; 0.28), NTCP-Bladder (p &gt; 0.85) or NTCP-Rectum (p = 0.85), resulting in better P+ (p = 0.006). Simulation of intrafractional movement yielded even higher P+ values for Plans 2 and 3 compared to Plan 1.ConclusionUrethral sparing may increase the therapeutic ratio and should be implemented in focal RT dose escalation concepts.
Dual-Energy Computed Tomography-Based Radiomics to Predict Peritoneal Metastasis in Gastric Cancer
Authors: Chen Yong , Xi Wenqi , Yao Weiwu , Wang Lingyun , Xu Zhihan , Wels Michael , Yuan Fei , Yan Chao , Zhang Huan 
Published: May 2021

ObjectiveTo develop and validate a dual-energy computed tomography (DECT) derived radiomics model to predict peritoneal metastasis (PM) in patients with gastric cancer (GC).MethodsThis retrospective study recruited 239 GC (non-PM = 174, PM = 65) patients with histopathological confirmation for peritoneal status from January 2015 to December 2019. All patients were randomly divided into a training cohort (n = 160) and a testing cohort (n = 79). Standardized iodine-uptake (IU) images and 120-kV-equivalent mixed images (simulating conventional CT images) from portal-venous and delayed phases were used for analysis. Two regions of interest (ROIs) including the peritoneal area and the primary tumor were independently delineated. Subsequently, 1691 and 1226 radiomics features were extracted from the peritoneal area and the primary tumor from IU and mixed images on each phase. Boruta and Spearman correlation analysis were used for feature selection. Three radiomics models were established, including the R_IU model for IU images, the R_MIX model for mixed images and the combined radiomics model (the R_comb model). Random forest was used to tune the optimal radiomics model. The performance of the clinical model and human experts to assess PM was also recorded.ResultsFourteen and three radiomics features with low redundancy and high importance were extracted from the IU and mixed images, respectively. The R_IU model showed significantly better performance to predict PM than the R_MIX model in the training cohort (AUC, 0.981 vs. 0.917, p = 0.034). No improvement was observed in the R_comb model (AUC = 0.967). The R_IU model was the optimal radiomics model which showed no overfitting in the testing cohort (AUC = 0.967, p = 0.528). The R_IU model demonstrated significantly higher predictive value on peritoneal status than the clinical model and human experts in the testing cohort (AUC, 0.785, p = 0.005; AUC, 0.732, p &lt;0.001, respectively).ConclusionDECT derived radiomics could serve as a non-invasive and easy-to-use biomarker to preoperatively predict PM for GC, providing opportunity for those patients to tailor appropriate treatment.
A Comprehensive RNA Study to Identify circRNA and miRNA Biomarkers for Docetaxel Resistance in Breast Cancer
Authors: Huang Peide , Li Fengyu , Mo Zongchao , Geng Chunyu , Wen Fang , Zhang Chunyan , Guo Jia , Wu Song , Li Lin , Brünner Nils , Stenvang Jan 
Published: May 2021

To investigate the relationship between non-coding RNAs [especially circular RNAs (circRNAs)] and docetaxel resistance in breast cancer, and to find potential predictive biomarkers for taxane-containing therapies, we have performed transcriptome and microRNA (miRNA) sequencing for two established docetaxel-resistant breast cancer (DRBC) cell lines and their docetaxel-sensitive parental cell lines. Our analyses revealed differences between circRNA signatures in the docetaxel-resistant and -sensitive breast cancer cells, and discovered circRNAs generated by multidrug-resistance genes in taxane-resistant cancer cells. In DRBC cells, circABCB1 was identified and validated as a circRNA that is strongly up-regulated, whereas circEPHA3.1 and circEPHA3.2 are strongly down-regulated. Furthermore, we investigated the potential functions of these circRNAs by bioinformatics analysis, and miRNA analysis was performed to uncover potential interactions between circRNAs and miRNAs. Our data showed that circABCB1, circEPHA3.1 and circEPHA3.2 may sponge up eight significantly differentially expressed miRNAs that are associated with chemotherapy and contribute to docetaxel resistance via the PI3K-Akt and AGE-RAGE signaling pathways. We also integrated differential expression data of mRNA, long non-coding RNA, circRNA, and miRNA to gain a global profile of multi-level RNA changes in DRBC cells, and compared them with changes in DNA copy numbers in the same cell lines. We found that Chromosome 7 q21.12-q21.2 was a common region dominated by multi-level RNA overexpression and DNA amplification, indicating that overexpression of the RNA molecules transcribed from this region may result from DNA amplification during stepwise exposure to docetaxel. These findings may help to further our understanding of the mechanisms underlying docetaxel resistance in breast cancer.
Comparison of Percutaneous Radiofrequency Ablation for Subcapsular and Non-Subcapsular Colorectal Cancer Liver Metastases
Authors: Fan Hongjie , Wang Xiaoyan , Qu Jiali , Lu Wei , Xu Shufeng , Wu Xia , Xia Jingya , Zhang Yanhua , Sun Jihong , Yang Xiaoming 
Published: May 2021

PurposeTo evaluate the efficacy and safety of percutaneous radiofrequency ablation (RFA) for subcapsular colorectal cancer liver metastases (CLMs).Materials and MethodsWith the approval of the Institutional Review Board, the clinical data of CLM patients who underwent percutaneous RFA for the first time from August 2010 to August 2020 were continuously collected. All CLMs were divided into subcapsular and non-capsular groups. Baseline characteristic data, technical effectiveness, minimal ablative margin, complications, local tumor progression (LTP), and overall survival (OS) between the two groups were analyzed using the t-test or chi-square test. A Cox regression model was used to evaluate the prognostic factors of LTP.ResultsOne hundred and ninety-nine patients (124 males; mean age, 60.2 years) with 402 CLMs (221 subcapsular; mean size, 16.0 mm) were enrolled in the study. Technical effectiveness was achieved in 93.5% (376/402) of CLMs, with a major complication rate of 5.5%. Compared with non-subcapsular tumors, the minimal ablative margin achieved in subcapsular CLM was smaller (χ2 = -8.047, P &lt; 0.001). With a median follow-up time of 23 months (range, 3−96 months), 37.1% of the tumors had LTP. The estimated cumulative OS at 1, 3, and 5 years was 96.1%, 66.0%, and 44.2%, respectively. There were no statistically significant differences between the two groups in terms of technical effectiveness (χ2 = 0.484, P = 0.487), major complications (χ2 = 0.082, P = 0.775), local tumor progression-free survival (LTPFS) (χ2 = 0.881, P = 0.348), and OS (χ2 = 2.874, P = 0.090). Minimal ablative margin, tumor size (≥20 mm), and technical effectiveness were predictors of LTP (all P &lt; 0.05).ConclusionRFA is a safe and effective technique for local tumor control of subcapsular CLMs.
Comparison of Two-Step Transient Evoked Otoacoustic Emissions and One-Step Automated Auditory Brainstem Response for Universal Newborn Hearing Screening Programs in Remote Areas of China
Authors: Sheng Haibin , Zhou Qian , Wang Qixuan , Yu Yun , Liu Lihua , Liang Meie , Zhou Xueyan , Wu Hao , Tang Xiangrong , Huang Zhiwu 
Published: May 2021

Objective: To compare the hearing screening results of two-step transient evoked otoacoustic emissions (TEOAE) and one-step automatic auditory brainstem response (AABR) in non-risk newborns, and to explore a more suitable hearing screening protocol for infants discharged within 48 h after birth in remote areas of China.Methods: To analyze the age effect on pass rate for hearing screening, 2005 newborns were divided into three groups according to screening time after birth: &lt;24, 24–48, and 48–72 h. All subjects received TEOAE + AABR test as first hearing screen, and those who failed in any test were rescreened with TEOAE + AABR at 6 weeks after birth. The first screening results of AABR and TEOAE were compared among the three groups. The results of two-step TEOAE screening and one-step AABR screening were compared for newborns who were discharged within 48 h. The time spent on screening was recorded for TEOAE and AABR.Results: The pass rate of TEOAE and AABR increased significantly with the increase of first screening time (P &lt; 0.05), and the false positive rate decreased significantly with the increase of first screening time (P &lt; 0.05). The failure rate of first screening of AABR within 48 h was 7.31%, which was significantly lower than that of TEOAE (9.93%) (P &lt; 0.05). The average time spent on AABR was 12.51 ± 6.36 min, which was significantly higher than that of TEOAE (4.05 ± 1.56 min, P &lt; 0.05). The failure rate of TEOAE two-step screening was 1.59%, which was significantly lower than one-step AABR.Conclusions: Compared with TEOAE, AABR screening within 48 h after birth can reduce the failure rate and false positive rate of first screening. However, compared with TEOAE two-step screening, one-step AABR screening has higher referral rate for audiological diagnosis. In remote areas of China, especially in hospitals with high delivery rate, one-step AABR screening is not feasible, and two-step TEOAE screening protocol is still applicable to UNHS screening as more and more infants discharged within 48 h after birth.
Increased Risk of Kawasaki Disease in Infants Born of Mothers With Immune Disorders
Authors: Chu Hsiao-Wen , Lin Chien-Heng , Lin Ming-Chih , Hsu Ya-Chi 
Published: May 2021

Introduction:Genetic susceptibility and immune dysregulation play important roles in the pathogenesis of Kawasaki disease (KD). However, it is still unclear whether KD causes immune disorder later in life or whether inherited susceptibility to immune disorders causes KD. The aim of this study was to elucidate whether inherited immune disease properties from mothers increase the risk of KD from a population-based perspective.Method:Taiwan's National Health Insurance Research Database was the main data source in this study. Parents and children were linked using the Taiwan Maternal and Child Health Database. Patients diagnosed with KD and younger than 18 years from 2004 to 2015 were enrolled as the study population. The control group was randomly selected from individuals without the diagnosis of KD matched by age, index year, sex, and urbanization level at a ratio of 1 to 10. The prevalence of maternal autoimmune and allergic diseases was compared between groups.Results:In total, 7,178 children were found to have been diagnosed with Kawasaki disease. Then 71,780 children matched by index year, gender, and urbanization were randomly selected to serve as the control group. Children born from mothers with asthma and allergic rhinitis had a higher risk of developing KD. Children of mothers with an autoimmune disorder had a significantly increased tendency to develop KD. Maternal numbers of autoimmune disorders showed a dose-dependent relationship with KD incidence.Conclusion:This is the first population-based study to investigate maternal immune diseases and the risk of KD in their children. Children of mothers with immune disorders tend to have a higher risk of KD.
Arterial Stiffness: Effects of Anticancer Drugs Used for Breast Cancer Women
Authors: Novo Giuseppina , Di Lisi Daniela , Manganaro Roberta , Manno Girolamo , Lazzara Simone , Immordino Federico Angelo , Madaudo Cristina , Carerj Scipione , Russo Antonio , Incorvaia Lorena , Zito Concetta 
Published: May 2021

Purpose: It is well known that anticancer drugs used for treating breast cancer can cause cardiac toxicity, and less is known about vascular toxicity. The aim of this study was to assess subclinical vascular effects of anthracyclines and trastuzumab (TRZ) in women treated for breast cancer.Methods: We enrolled 133 female patients with breast cancer undergoing adjuvant treatment with anthracycline-containing chemotherapy (CT) followed by taxane (paclitaxel/docetaxel) + TRZ. Patients underwent a standard echocardiography including measurement of left ventricular ejection fraction and global longitudinal strain at baseline and at follow-up. Vascular toxicity was evaluated by measuring brachial blood pressure (BP) and arterial stiffness indices (pulse wave velocity and Beta stiffness index) at T0 (baseline), T1 (3 months), T2 (6 months), and T3 (12 months).Results: Arterial stiffness indices were significantly increased at T1 in patients treated with anthracycline-containing CT (PWV 5.5 m/s IQR 5.15–6.4 at T0 vs. PWV 6.7 m/s IQR 5.6–7.2 at T1, p &lt; 0.05; Beta index PWV 6.7 IQR 5.25–6.65 at T0, PWV 8.35 IQR 6.5–10.15 at T1, p &lt; 0.05) but not at T2 and T3, when treatment with anthracyclines was stopped and patients were under treatment with taxane and TRZ. Blood pressure values did not significantly change during follow-up.Conclusion: Changes in arterial stiffness parameters occur early after starting treatment with anthracyclines, and they seem to be reversible if anthracycline treatment is stopped. These changes are not influenced by blood pressure values modifications. Therefore, in breast cancer women, anthracyclines seem to cause early reversible subclinical vascular injury.
Childhood and Adulthood Severe Stressful Experiences and Biomarkers Related to Glucose Metabolism: A Possible Association?
Authors: Tosato Sarah , Bonetto Chiara , Lopizzo Nicola , Cattane Nadia , Barcella Mara , Turco Giorgia , Ruggeri Mirella , Provasi Stefania , Tomassi Simona , Dazzan Paola , Cattaneo Annamaria 
Published: May 2021

Background: No study investigated the association between stress exposure in different stages of life and metabolic dysfunction.Aim: We explore the association between stress exposure and several biomarkers related to glucose metabolism (insulin, c-peptide, GIP, GLP-1, glucagon) in a group of 72 healthy individuals.Method: We used the Childhood Experience of Care and Abuse-Questionnaire (CECA-Q) and a modified version of the Life Events Scale to define exposure to stress, according to four categories: no exposure to childhood trauma (CT) nor to stressful life events (SLEs) (46%), only to CT (25%), only to SLEs (21%), to both (8%).Results: We found that c-peptide (p = 0.006) and insulin (p = 0.002) levels differed among the four categories: 0.77 ng/ml (SD 0.27) and 0.21 ng/ml (SD 0.06) for none, 0.77 (SD 0.37) and 0.20 (SD 0.08) for only SLEs, 0.88 (SD 0.39) and 0.27 (SD 0.12) for only CT, 1.33 (SD 0.57) and 0.40 (SD 0.28) for both, respectively. The highest levels of biomarkers were found in subjects exposed to both CT and SLEs.Conclusion: Our preliminary results seem to suggest that CT might be specifically associated with a dysfunction of glucose metabolism, which might increase the risk of poorer health outcomes in adulthood. This association seems to be even stronger in individuals additionally exposed to SLEs in adulthood. In conclusion, if confirmed in other studies, subjects exposed to both CT and SLEs appear the most vulnerable individuals, for whom preventative interventions, such as healthy lifestyle education programs, might ameliorate the risk of developing metabolic abnormalities.
Cognitive Empathy and Longitudinal Changes in Temporo-Parietal Junction Thickness in Schizophrenia
Authors: Karpouzian-Rogers Tatiana , Cobia Derin , Petersen Julie , Wang Lei , Mittal Vijay A. , Csernansky John G. , Smith Matthew J. 
Published: May 2021

Objective: Deficits in cognitive empathy are well-documented in individuals with schizophrenia and are related to reduced community functioning. The temporoparietal junction (TPJ) is closely linked to cognitive empathy. We compared the relationship between baseline cognitive empathy and changes in TPJ thickness over 24 months between individuals with schizophrenia and healthy controls.Methods: Individuals with schizophrenia (n = 29) and healthy controls (n = 26) completed a cognitive empathy task and underwent structural neuroimaging at baseline and approximately 24 months later. Symmetrized percent change scores were calculated for right and left TPJ, as well as whole-brain volume, and compared between groups. Task accuracy was examined as a predictor of percent change in TPJ thickness and whole-brain volume in each group.Results: Individuals with schizophrenia demonstrated poorer accuracy on the cognitive empathy task (p &lt; 0.001) and thinner TPJ cortex relative to controls at both time points (p = 0.01). In schizophrenia, greater task accuracy was uniquely related to less thinning of the TPJ over time (p = 0.02); task accuracy did not explain changes in left TPJ or whole-brain volume. Among controls, task accuracy did not explain changes in right or left TPJ, or whole-brain volume.Conclusions: Our findings suggest that greater cognitive empathy may explain sustained integrity of the right TPJ in individuals with schizophrenia, suggesting a contributory substrate for the long-term maintenance of this process in psychosis. Cognitive empathy was not related to changes in whole-brain volume, demonstrating the unique role of the TPJ in cognitive empathy.
Under COVID-19 Pandemic: A Quasi-Experimental Trial of Observation on Diabetes Patients' Health Behavior Affected by the Pandemic From a Coaching Intervention Program
Authors: Lin Ching-Ling , Huang Li-Chi , Chang Yao-Tsung , Chen Ruey-Yu , Yang Shwu-Huey 
Published: May 2021

Introduction: The aim of this study was to explore the impact of diabetes self-management and HbA1c affected by the COVID-19 pandemic and the epidemic prevention work.Methods: This quasi-experimental study collected a pooled data from a randomized-control study between February and May 2020 in which 114 participants who presented type 2 diabetes were recruited. The intervention group had health coaching and usual care, whereas the control had usual care only. The main outcome variables of this observation study were the change of HbA1c, physical activity, and eating out behavior within this time interval.Results: We found that the eating out behavior of both groups had decreased, and if a health coach helped the patients set physical activity goals in the two groups, the physical activity behavior will not be impacted due to the pandemic.Conclusions: While every country is focusing on COVID-19 pandemic prevention, especially when strict home quarantine measures and social distancing are adopted, reminding and assisting chronic patients to maintain good self-management behavior may lessen the social and medical system burdens caused by the deterioration of chronic conditions due to the excessive risk prevention behavior and the epidemic prevention work.Trial Registration:www.isrctn.com, identifier number: ISRCTN14167790, date: 12 July, 2019.