bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic and topical administration of spermidine accelerates skin wound healing
Authors: Ito Daisuke , Ito Hiroyasu , Ideta Takayasu , Kanbe Ayumu , Ninomiya Soranobu , Shimizu Masahito
Published: November 2020

Background The skin wound healing process is regulated by various cytokines, chemokines, and growth factors. Recent reports have demonstrated that spermine/spermidine (SPD) promote wound healing through urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) signaling in vitro. Here, we investigated whether the systemic and topical administration of SPD would accelerate the skin wound-repair process in vivo.Methods A skin wound repair model was established using C57BL/6 J mice. SPD was mixed with white petrolatum for topical administration. For systemic administration, SPD mixed with drinking water was orally administered. Changes in wound size over time were calculated using digital photography.Results Systemic and topical SPD treatment significantly accelerated skin wound healing. The administration of SPD promoted the uPA/uPAR pathway in wound sites. Moreover, topical treatment with SPD enhanced the expression of IL-6 and TNF-α in wound sites. Scratch and cell proliferation assays revealed that SPD administration accelerated scratch wound closure and cell proliferation in vitro.Conclusion These results indicate that treatment with SPD promotes skin wound healing through activation of the uPA/uPAR pathway and induction of the inflammatory response in wound sites. The administration of SPD might contribute to new effective treatments to accelerate skin wound healing.
CCNA2 Expression and Its Prognostic Significance in cholangiocarcinoma
Authors: Zhang Jie , Zhang Jingjun , Liu Hairong , Chen Qinyang , Li Pengcheng , Chen Taiyu , Xu Lei , Ren Tao
Published: November 2020

Background: Cholangiocarcinoma（CCA）is a rare malignancy and it has become a significant health burden worldwide. An increasing number of studies have demonstrated the crucial correlation of immunophenotypic characteristics modifications in resected specimen of CCA. However, the accurate prognostic markers is still lacking in the prognosis of CCA. Methods: Gene expression profiles and clinical data of CCA were downloaded from the Gene Expression Omnibus（GEO）database. GO and KEGG analysis were applied for differentially expressed genes in cholangiocarcinoma, and PPI network was constructed in Cytoscape software. The expression difference of Cyclin A2 (CCNA2) in CCA tissues and adjacent noncancerous tissues was analyzed by R software and verified by comprehensive analysis. The relationship between CCNA2 expression and immune infiltration was assessed in the the Cancer Genome Atlas (TCGA) database. Kaplan–Meier survival analysis were chosen to assess the effect of CCNA2 expression on survival. Gene set enrichment analysis (GSEA) was used to screen the signaling pathways involved in CCA between the low and the high CCNA2 expression group.Results: The expression of CCNA2 in CCA was significantly higher than that in adjacent cancerous tissues (P < 0.001) from the GEO database. The top 10 hub genes were mined by the Degree, MCC, and Closeness method​ based on the PPI network. CCNA2 was screened as the candidates to be further analyzed and validated. The Kaplan–Meier curves suggested that patients with high CCNA2 expression had a poor prognosis. Multivariate analysis showed that a high expression of CCNA2 was an important independent predictor of poor overall survival (P = 0.033). Cibersort analysis showed that the fraction of T cells CD4 (naive, P < 0.0001), T cells CD4 (memory, P = 0.0055), T cells (follicular, P = 0.0063), NK cells ( P = 0.0149), dendritic cells ( P = 0.029), neutrophils ( P = 0.0113) is significantly correlated with the expression of CCNA2, which highlighted the CCNA2 expression in immune infiltrates. GSEA indicated that 12 signaling pathways were evidently enriched in samples with the high-CCNA2 phenotype.Conclusions: CCNA2 might act as an oncogene in the progression of CCA and could be regarded as a potential prognostic indicator and therapeutic target for CCA.
Frailty as a Predictor for Mortality Among Patients With COVID-19: A Systematic Review and Meta-Analysis
Authors: Zhang Xiaoming , Jiao Jing , Cao Jing , Huo Xiao-Peng , Zhu Chen , Wu Xinjuan , Xie Xiao-Hua
Published: November 2020

BackgroundA great number of studies have explored the association between frailty and mortality among COVID-19 patients, suggesting inconsistent results. The aim of this meta-analysis was to synthesize the evidence on this issue. MethodsThree databases, including PubMed, Embase, and Cochrane Library from inception to 20th October, 2020 were conducted to search for relevant literature. The Newcastle–Ottawa Scale (NOS) was used to assess quality bias, and STATA was employed to pool the effect size. Additionally, potential publication bias and sensitivity analysis was performed.ResultsThere are 11 studies that were included, with a total of 22105 COVID-19 patients for quantitative analysis. Overall, the pooled prevalence of frailty was 51% (95%CI:42%-60%). Patients infected with COVID-19 with frailty had an increased risk of mortality, compared to those without frailty, and the pooled HR was 2.27 (95%CI:1.79-2.89). In addition, subgroup analysis based on population showed that the pooled HR for hospitalized patients and nursing home residents was 2.24 (95%CI:1.74-2.89) and 2.95 (95%CI:1.19-7.32), respectively. Subgroup analysis using the frailty assessment tool indicated that this association still existed when using the clinical frailty scale (CFS)(HR=2.41;95%CI:1.60-3.62), frailty index(HR=2.95;95%CI:1.19-7.32), hospital frailty risk score (HR=1.96;95%CI:1.79-2.15) and palliative performance scale (HR= 2.89;95%CI:1.42-5.87). Conclusion﻿Our study indicates that frailty was an independent predictor for mortality among patients with COVID-19. Thus, frailty could be a prognostic factor for clinicians to stratify high-risk groups, and remind doctors and nurses to perform early screening and corresponding interventions urgently needed to reduce mortality rates in patients infected by SARS-CoV-2.
A Case of a Male Patient with Frontotemporal Dementia with Behavioral and Psychological Symptoms Responding to a Low Dose of Escitalopram
Authors: Ikenouchi Atsuko , Seki Issei , Takaoka Kei , Murakami Sayuri , Okamoto Naomichi , Yoshimura Reiji
Published: November 2020

Background: Frontotemporal dementia (FTD) is a common type of early-onset dementia. It is characterized by insidious onset and gradual progression, early decline in social interpersonal conduct and regulation of personal conduct, early emotional blunting and loss of insight. Behavioral disorder, speech and language are supportive features in FTD. Here, we present a case of a patient with FTD with behavioral and psychological symptoms of dementia (BPSD) responding to escitalopram treatment.Case presentation: A 60-year-old Japanese man had been treated for early-onset Alzheimer-type dementia with galantamine (24 mg/day) for 5 years. He developed behavioral, executive and semantic deficits. He had stereotypical, compulsive behavior, eating habit changes, disinhibition, excitement, irritability and anxiety. His diagnosis changed to FTD based on clinical features and MRI and SPECT. Galantamine was tapered off, and escitalopram 5 mg/day was started and increased to 10 mg/day. The symptoms of FTD, including behavioral and psychological symptoms, were decreased.Conclusion: This case is the first report demonstrating that escitalopram might be effective for BPSD that accompany FTD.
Surge Effects and Survival to Hospital Discharge in Critical Care Patients with COVID-19 During the Early Pandemic: A Cohort Study
Authors: Dale Christopher , Starcher Rachael , Chang Shu Ching , Robicsek Ari , Parsons Guilford , Goldman Jason , Vovan Andre , Hotchkin David , Gluckman Ty
Published: November 2020

BackgroundThe early months of the COVID-19 pandemic were fraught with much uncertainty and some resource constraint. We assessed the change in survival to hospital discharge over time for intensive care unit patients with COVID-19 during the first three months of the pandemic and the presence of any surge effects on patient outcomes.MethodsRetrospective cohort study with electronic medical record data of all patients with laboratory-confirmed COVID-19 admitted to intensive care units from February 25, 2020 to May 15, 2020 admitted to intensive care units of 26 hospitals of an integrated delivery system in the Western United States. Patient demographic, comorbidity and severity of illness were measured along with exposure to pharmacologic and medical therapies and hospital outcomes over time. Multivariable logistic regression models were constructed to assess the change in survival to hospital discharge over time during the study period.ResultsOf 620 patients with COVID-19 admitted to the study ICUs (mean age 63.5 years (SD 15.7) and 69% male), 403 (65%) survived to hospital discharge and 217 (35%) died in hospital. Survival to hospital discharge increased over the study period from 60.0% in the first two weeks of patient admission to 67.6% in the last two weeks. In a multivariable logistic regression analysis, the risk-adjusted odds of survival to hospital discharge increased over time (bi-weekly change, adjusted odds ratio [aOR] 1.22, 95%CI 1.04-1.40, P = 0.02). Additionally, an a priori-defined explanatory model showed that after adjusting for both hospital occupancy and COVID positive/PUI percent hospital capacity, and the same set of covariates, the temporal trend in risk-adjusted patient survival to hospital discharge remained the same (bi-weekly change, aOR 1.18, 95% CI 1.00 to 1.38, P = 0.04) and a greater COVID positive/PUI percentage of hospital capacity remained significantly and inversely associated with survival to hospital discharge (aOR 0.95, 95% CI 0.92 to 0.98, P < 0.01).ConclusionsDuring the the early COVID-19 pandemic, risk-adjusted survival to hospital discharge increased over time for critical care patients. This may have been partially explained by surge affects, as measured by a greater COVID positive/PUI percentage of hospital capacity.
Caregiver Burden and Emotional Wellbeing in Informal Caregivers to ICU Survivors: A Prospective Cohort Study
Authors: Milton Anna , Schandl Anna , Larsson Ing-Marie , Wallin Ewa , Savilampi Johanna , Meijers Katarina , Joelsson-Alm Eva , Bottai Matteo , Sackey Peter
Published: November 2020

BackgroundInformal caregivers to intensive care unit (ICU) survivors may develop post-intensive care syndrome family (PICS-F), including psychological problems such as depression, anxiety and post-traumatic stress (PTS). Our primary aim was to investigate associations between caregiver burden in informal caregivers cohabiting with ICU survivors and patients’ physical and psychological outcomes.MethodsWe conducted a prospective, multicentre cohort study in four ICUs in Sweden. Adults cohabiting with ICU patients included in a previous study were eligible for inclusion. Three months post-ICU, informal caregivers received questionnaires assessing perceived caregiver burden, health-related quality of life (HRQL) and symptoms of depression, anxiety and PTS. In parallel, patients reported their physical and psychological status via validated questionnaires. The primary outcome was to compare caregiver burden in informal caregivers to patients with and without adverse physical and psychological outcomes three months post-ICU. Secondary outcomes were correlations between caregiver burden and informal caregivers’ psychological status and mental HRQL.ResultsAmong 62 included informal caregivers, 55 (89%) responded to the follow-up questionnaires. Caregiver burden was higher in informal caregivers to patients with an adverse psychological or physical outcome, compared to informal caregivers to patients without an adverse outcome, caregiver burden scale score mean (±standard deviation) 52 (11) and 41 (13) respectively (p=0.003). There was strong negative correlation between caregiver burden and informal caregivers’ mental HRQL (rs -0.74, p<0.001). ConclusionInformal caregivers to ICU survivors with an adverse physical or psychological outcome experience a higher caregiver burden. A higher caregiver burden correlates with worse caregiver mental HRQL. ICU follow-up programs should consider screening and follow-up of informal caregivers for mental health problems.Trial registrationThe study was registered at clinicaltrials.gov, NCT02712541 on March 18 2016.
Pulmonary Dysfunction in Patients Recovered from COVID-19 Pneumonia: A 6-Month Follow-up Study
Authors: Meng Xianglin , Kang Kai , Gao Yang , Fei Dongsheng , Yang Wei , Yang Songlin , Zhang Meiling , Lu Baitao , Meng Shishuai , Li Xianyong , Liu Wen , Jin Songgen , Kong Weilan , Chong Yang , Liu Yan , Wu Haolan , Sun Chongyang , Guan Xue , Wang Changsong , Zhao Mingyan , Yu Kaijiang
Published: November 2020

Objectives: This study investigates the clinical features and pulmonary functions of COVID-19 pneumonia survivors at 3 or 6 months after diagnosis in the Heilongjiang Province, China.Methods: Forty-six patients with COVID-19 pneumonia diagnosed since February 2020 were enrolled in this study for follow-up in July 2020. These patients were categorized into three groups: Group A (n=24) and Group B (n=11) who were diagnosed with moderate or severe pneumonia and followed up at three months after diagnosis; Group C (n=11) who were diagnosed with severe pneumonia and followed up at six months after diagnosis. Data on pulmonary function, arterial blood gas analysis, chest CT, blood test, antibody test, and health-related quality of life during hospitalization and at the follow-up visits were collected and analyzed. Results: Abnormal PO2 (A-a) was more prevalent in severe cases (Group B and C) than in moderate cases (Group A). Pulmonary dysfunction was common in this cohort. Abnormal CT scores of severe cases (Group B and C) were significantly higher than that of moderate cases (Group A). During the follow-up, lung abnormalities gradually resolved in the first 3 months (Group A and B), however, further resolution was not significant from 3 months to 6 months (Group B and C). Conclusion: Although pulmonary interstitial changes due to COVID-19 pneumonia gradually reverse over time, pulmonary dysfunction is common and appears to persist at least up to 6 months in patients recovered from COVID-19 pneumonia.
Abdominal Tuberculosis With Pancreatic Head Involvement Mimicking Pancreatic Malignancy in a Young Man: A Case Report
Authors: Wang Lie-zhi , Jiang Hao , Jin Chong , Wen Yu , Zou Heng , Wang Kunpeng
Published: November 2020

Background：Pancreatic tuberculosis is a rare disease, even in immuocompentent hosts. Abdominal tuberculosis involving the pancreatic head and peripancreatic areas may simulate pancreatic head carcinoma.Case presentation: We herein present the case of a 32-year-old man who was admitted to our hospital for intermittent epigastric pain and weight loss. Computed tomography scan and magnetic resonance imaging revealed a mass in the head of the pancreas.The lesion was initially diagnosed as pancreatic head carcinoma on abdominal imaging. Laparotomy confirmed the diagnosis of pancreatic tuberculosis, while he test for acid-fast bacilli was negative before operation and the patient fully recovered after six month of standard anti-tuberculosis treatment.Conclusions: The present case is reported to emphasize the importance of including pancreatic tuberculosis in the differential diagnosis of pancreatic lesions, under the premise of safety, we recommend endoscopic ultrasound-guided fine needle aspiration biopsy for diagnosis.
Efficacy of upfront hepatectomy without neoadjuvant chemotherapy for resectable colorectal liver metastasis
Authors: Ono Kosuke , Abe Tomoyuki , Ohshita Akihiko , Sumi Yusuke , Yano Takuya , Okuda Hiroshi , Kurayoshi Manabu , Kobayashi Tsuyoshi , Ohdan Hideki , Noriyuki Toshio , Nakahara Masahiro
Published: November 2020

Background
This study evaluated the impact of neoadjuvant chemotherapy on the prognosis of patients with resectable colorectal liver metastasis and assessed the usefulness of Beppu’s nomogram for predicting prognosis.
Methods
This retrospective study identified 88 consecutive inpatients who underwent primary hepatic resection for colorectal liver metastasis; 58 received neoadjuvant chemotherapy and 30 underwent upfront surgery. Factors associated with recurrence-free survival were identified via univariate and multivariate analysis. Propensity score analysis using inverse probability of treatment weighting was also performed.
Results
On univariate analysis, poor recurrence-free survival was associated with multiple tumors, advanced primary tumor stage, vascular invasion by the primary tumor, a Beppu score ≥ 6, and neoadjuvant chemotherapy. On multivariate analysis, a Beppu score ≥ 6 and neoadjuvant chemotherapy were independent risk factors for recurrence. Neoadjuvant chemotherapy recipients had a higher incidence of lymph node metastasis and vascular invasion than non-recipients. Propensity score analysis revealed no significant difference in the recurrence-free survival rate between these groups.
Conclusions
Our results show the usefulness of Beppu scores for predicting the prognosis of patients with colorectal liver metastasis, but do not support the use of neoadjuvant chemotherapy in these patients.
Correlation and Mechanism Study of Multivoxel 1H-MRS Parameters, Cho / Cr and CHKA
Authors: Yue Fangqian , Zou YouRui , Sun ShengYu , Ma Hui , Wang Zhe , Gao Xinyi , Huang Ling
Published: November 2020

Background Glioma is a common malignant brain tumor with strong invasiveness and poor prognosis. in order to improve the survival rate of patients, there is an urgent need to find the targeted molecular mechanism affecting its invasion and development. Methods In this study, the differential regions of Cho/Cr metabolism of tumor cells were identified by multi-voxel 1H-MRS and the tumor tissues of Cho/Cr high metabolism group and Cho/Cr low metabolism group were accurately obtained by combining neuronavigation system. The expression of CHKA in different Cho/Cr metabolic groups was verified by Real-timePCR and Western-blot. Then we used CHKA inhibitor MN58b and short hairpin RNA to study the role of CHKA in the proliferation and invasion of U251 glioma cells, and the relationship between CHKA and EMT in nude mice.Results We found that the expression of CHKA in Cho/Cr high metabolism group was significantly higher than that in Cho/Cr low metabolism group. Decreased CHKA activity can inhibit the proliferation and invasion of glioma cells and slow down the process of EMT.Conclusion CHKA may be an oncogenic gene, which affects the invasion and development of glioma cells by regulating the process of tumor EMT, and is expected to become a molecular target for glioma therapy, and multi-voxel 1H-MRS parameter Cho/Cr may become an important clinical index for detecting CHKA expression.
A Well-differentiated Liposarcoma of the Prevertebral Space: A Case Report
Authors: Yang Tianming , Xiao Lin , Ren Huijun
Published: November 2020

Background: Liposarcoma is common in adults. However, its occurrence in the retropharyngeal space is extremely rare, and no cases of liposarcoma in the prevertebral space have been reported before.Case presentation: A 78-year-old man presented to the Otolaryngology Department with a 1-year history of progressive dysphagia and a 1-month history of dyspnea and dysphonia. A computed tomography scan of his neck demonstrated a large retropharyngeal mass. Magnetic resonance imaging was performed to further characterize this mass. Based on the above examinations, retropharyngeal liposarcoma was first made. The patient underwent transoral surgical excision with the help of nasal endoscope. During surgery, the tumor was found to lie in the prevertebral space. Combine with histological examination, the diagnosis was modified to liposarcoma of the prevertebral space. Conclusions: It’s difficult to distinguish the enormous retropharyngeal tumors and prevertebral tumors using imaging. Complete excision via transoral approach maybe enough for these tumors.
Mechanism of Hydrogen Gas Promoted Apoptosis of Lung Adenocarcinoma A549 cells through XIAP and BIRC3
Authors: Zhang Yu , Chen Gang , Yan Feng Zhen , Wang Fei Li , Wang Chang Dong
Published: November 2020

Background/AIMLung cancer is the most common reason of cancer-related death in worldwide. Hydrogen gas has been found to have effects on a variety of diseases. At present, it is not reported that the effect of hydrogen gas on lung cancer domestic and overseas. Therefore, we designed this experiment to test the differences in the expression of XIAP, BIRC3 and BAX In vivo and in vitro. Materials and methodsA549 cells in logarithmic phase were treated by 20%, 40%, 60% hydrogen gas respectively. Then the apoptosis of different groups were detected by Flow cytometry. We identify the differential expressed genes(DEGs) by transcriptional. The protein expression of XIAP, BIRC3 and BAX were detected by western blot and immunohistochemistry. ResultThe results demonstrated that hydrogen gas can significantly induce apoptosis compared with the control group. The expression of XIAP and BIRC3 were downregulated in hydrogen group. Conclusion﻿Hydrogen gas may promote the apoptosis of lung cancer A549 cells by reducing the expression of XIAP and BIRC3 protein.
Bioinformatic Analysis: Screening and Identification of Differentially Expressed Genes Modified by m6A in Ovarian Cancer
Authors: Liu Huidong , Zhang Wen-wen , Lou Ge
Published: November 2020

Background: N6-methyladenosine(m6A) is one of the most common RNA modifications that occurs at the nitrogen-6 position of adenine. Emerging evidence has revealed that regulatory functions of m6A play an essential role in the development of cancer. However the study of m6A in ovarian cancer(OC) is still in our infancy. In this work ,we aimed to identify and analysis the differentially expressed genes(DEGs） modified by m6A which can provide new therapeutic targets and key biomarkers in OC.Methods: We downloaded Microarray datasets GSE146553 and GSE124766 from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by GEO2R analysis tools. Subsequently, The DAVID database was used to construct Enrichment analysis of GO and KEGG pathways. Next, the DEGs modified by m6A were identified by m6AVar database. Finally, the functional analysis and clinical sample validation of these genes were verified by ONCOMINE, GEPIA, cBioPortal online platform and Kaplan-Meier Plotter.Results:152 DEGs were selected ,and the DEGs were mainly enriched in extracellular exosome, spindle microtubule, response to hypoxia and cell cycle .And we identified 15 DEGs which were modified by m6A:MAPK10、MXRA5、CHD7、MECOM、SCN7A、GREB、PRUNE2、MX2、TOP2A、JAM2、DST、LAPTM5、CDKN2A、GATM and ANGPTL1. After statistical analysis, two DEGs (SCN7A and GAMT) were selected for detailed study. We revealed that SCN7A and GAMT were expressed at a low level in OC. Afterwards, Survival analysis showed that SCN7A and GAMT expression were correlated with OC overall survival. And the expression of SCN7A and GAMT mRNA decreasing in different TNM stages. Finally, we presumed that the modification of m6A spongs GAMT via EIF4A3 or FUS to participate in the occcurrence and the development of OC.Conclusion: Altogether, the current study identified and analysised the DEGs modified by m6A in OC. It will help us to investigate the underlying mechanism and progression of OC. In addition, it can provide new diagnostic markers and potential therapeutic targets in OC.
The Short-Term Efficacy of Novel No-Touch Combined Directional Perfusion Radiofrequency Ablation in the Treatment of Small Hepatocellular Carcinoma With Cirrhosis.
Authors: Qu Chengming , Li Xin-Qian , Xia Feng , Feng Kai , Ma Kuansheng
Published: November 2020

BackgroundNo-touch combined directed perfusion radiofrequency ablation (NTDP-RFA) is a new technique for the treatment of hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the short-term efficacy of this new technique for the treatment of small HCC with cirrhosis.MethodsFrom January 2017 to March 2018, 56 consecutive patients treated with NTDP-RFA at our center were enrolled in this retrospective study. All NTDP-RFA procedures involved the use of internally cooled wet electrodes with a directional injection function, which can perform both intraelectrode cooling and extraelectrode saline perfusion. Survival curves were analyzed using Kaplan-Meier methods, and Cox proportional hazards regression analyses were used to assess predictors of tumor progression and overall survival. Operative characteristics and complications were also assessed.ResultsNo technical failure occurred, and the complete ablation rate after single NTDP-RFA treatment was 98.2%. The median ablation time was only 8 (6-8) min. Only 5 patients (8.9%) experienced mild complications postoperation, and the median hospital stay was only 4 (3-5) days. In the 18 patients (32.1%) with poor liver function reserve (indocyanine green retention rate at 15 min > 15%), their liver function returned to normal on the third day after the postoperation. The 1-year and 2-year local and distant progression rates were 1.7%, 7.1%, 3.5% and 10.7%, respectively.ConclusionsNTDP-RFA in the treatment of small HCC with cirrhosis has a low incidence of complications and provides a high survival rate without local tumor progression. Further prospective randomized controlled studies are needed to investigate the long-term results.
Associations Between Dynamic Contrast Enhanced Magnetic Resonance Imaging and Clinically Relevant Histopathological Features in Breast Cancer. A Multicenter Analysis
Authors: Surov Alexey , Pech Maciej , Kim Jin You , Aiello Marco , Huang Wei , Yankeelov Thomas E. , Wienke Andreas
Published: November 2020

Background: To provide evident data regarding relationships between quantitative dynamic contrast enhanced magnetic resonance imaging (DCE MRI) and prognostic factors in breast cancer (BC).Methods: Data from 4 centers (200 female patients, mean age, 51.2 ± 11.5 years) were acquired. The following data were collected: histopathological diagnosis, tumor grade, stage, hormone receptor status, KI 67, and DCE MRI values including Ktrans (volume transfer constant), Ve (volume of the extravascular extracellular leakage space (EES) and Kep (diffusion of contrast medium from the EES back to the plasma). DCE MRI values between different groups were compared using the Mann–Whitney U test and by the Kruskal-Wallis H test. The association between DCE MRI and Ki 67 values was calculated by Spearman’s rank correlation coefficient. Results: DCE MRI values of different tumor subtypes overlapped significantly. There were no statistically significant differences of DCE MRI values between different tumor grades. All DCE MRI parameters correlated with KI 67: Ktrans, r = 0.44, p=0.0001; Ve, r = 0.34, p=0.0001; Kep, r = 0.28, p=0.002. ROC analysis identified a Ktrans threshold of 0.3 min-1 for discrimination of tumors with low KI 67 expression (<25%) and high KI 67 expression (≥25%): sensitivity, 75.5%, specificity, 73.0%, accuracy, 74.0%, AUC, 0.78. DCE MRI values overlapped between tumors with different T and N stages.Conclusion: Ktrans, Kep, and Ve cannot be used as reliable a surrogate marker for hormone receptor status, tumor stage and grade in BC. Ktrans may discriminate lesions with high and lower proliferation activity.
The Expression of CLDN11 in Invasive Ductal and Invasive Lobular Breast Cancer and Multivariate Prognostic Analysis
Authors: Cui Yu , Du Qiupei , Zhang Zhanhong , Feng Haojie , Hu Wang , Jin Guoquan , Fan Haining
Published: November 2020

Background: Breast cancer (BRCA) remains the most common malignancy among women worldwide. Invasive ductal (IDC) and invasive lobular breast cancer (ILC) are the most frequent histological subtypes. Many genetic heterogeneities are related to the carcinogenesis of breast cancer, but exact reasons are still unclear. The study aimed to perform a clinical multivariate analysis of CLDN11 in ILC and IDC. Methods: Datasets analyzed CLDN11 expression in IDC and ILC from The Cancer Genome Atlas (TCGA) database, and the multiple analysis of stratification in terms of clinical pathologic features and CLDN11 was using the Chi-square test. Results: CLDN11 expression was significantly decreased in IDC and ILC data of GEO and TCGA compared to the normal breast tissues. Besides, CLDN11 is negatively correlated with pro-oncogene IKBKE expression and positively correlated with tumor suppressor ETS1 expression in IDC and ILC samples. Multiple factors, including age, clinical stage, subtype, and mutation status, indicated that the expression of CLDN11 is positively associated with the progression of IDC and ILC.Conclusions: CLDN11 acted as a tumor suppressor in IDC and ILC patients and serves as a drug-gable target against IDC and ILC.
Nephron-sparing Surgery Versus Radical Nephroureterectomy in the Treatment of Organ-localized Upper Urinary Tract Urothelial Carcinoma: A Population-based Study of 1581 Patients
Authors: Qiu Jianhui , Liu Hua , Wang Zixin , Zhou Jingcheng , Gong Yanqing , Cai Lin , Gong Kan
Published: November 2020

Purpose: Nephron-sparing surgeries (NSS) have been widely used for patients with low-risk upper tract urothelial carcinoma (UTUC). We compared the prognosis of patients with organ-localized UTUC after NSS and radical nephroureterectomy (RN) through a population-based study and a propensity score matching (PSM) method. We further developed prognostic models for these patients using the Cox analysis and the competing-risk models.Materials and methods: The follow-up dataset of 1580 patients with organ-localized UTUC were screened out from the Surveillance, Epidemiology, and End Results (SEER) registry. A PSM process with a caliper width of 0.05 was performed to match the patients accepting NSS with those accepting RN. The Cox analysis was used for overall survival (OS) and competing-risks models based on Fine-Gray regression for cancer-specific survival (CSS). A forward stepwise selection process was applied to select independent predictors for OS and CSS. After selecting the predictors, two nomograms were developed based on the Cox analysis and the competing-risk model and internal validations were performed using 1000 bootstrap resamples.Results: Before PSM, RN was associated with better OS compared with NSS in the overall cohort (5-year OS rate: 65.1% vs. 55.6%, p<0.001) and the patients with renal pelvic lesions (5-year OS rate: 68.6% vs. 52.8%, p=0.001). Baseline variables were well balanced using the PSM method. After PSM, there was no significant difference in OS between the RN and NSS groups. Competing-risks models revealed that NSS was associated with poorer CSS compared with RN in the post-PSM cohort (n=766; subdistribution hazard ratio/ SHR=1.39, 95% confidence interval/ CI 1.03-1.89, p=0.033) and in patients with ureteral lesions from the post-PSM cohort. Four independent predictors, which were age at diagnosis, AJCC T stage, histologic grade, and surgery methods, were selected out for OS and CSS through forward stepwise selection methods. Two nomograms for OS and CSS were respectively developed. Conclusions: Patients accepting RN had a comparative or better outcome in each sample group. NSS achieved a similar prognosis for selective patients with organ-localized UTUC. Two nomograms were developed to predict OS and CSS with C-indexes of 0.672 and 0.643.
The Association of Sex-biased ATRX Mutation in Female Gastric Cancer Patients With Enhanced Immunotherapy-related Anticancer Immunity  
Authors: Ge You , Wei Feiran , Du Guoping , Fei Gaoqiang , Li Wei , Li Xiaoshan , Chu Jinjin , Wei Pingmin
Published: November 2020

Background: Genetic alterations have been proven to be the promising biomarkers for ICI response. However, sex biases in genetic alterations have been often ignored in the field of immunotherapy, which might specially influence the anticancer immunity and immunotherapy efficacy in male or female patients. Here, we have systematically evaluated the effect of the sex biases in somatic mutation of gastric cancer (GC) patients on the anticancer immunity and clinical benefit to immunotherapy. Methods: Genomic and transcriptomic data of gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). We also obtained the genomic and clinical data of a MSKCC ICI-treated cohort from cbioportal database. GC male and female-derived tumor somatic mutation profiles were compared by maftools R package. Single sample gene set enrichment analysis (ssGSEA) was conducted to calculate the score of the anticancer immunity indicators including IFN-γ signaling, cytolytic activity (CYT) and antigen presenting machinery (APM). Results: ATRX was found to mutate more frequently in female GC patients compared to male patients (FDR = 0.0108). Female GC patients with ATRX mutation manifested significantly more MSI-high subtypes, increased TMB and PDL1 expression as well as higher scores of IFN-γ signaling, CYT and APM. Gene set enrichment analysis (GSEA) has shown that ATRX mutation might enhance the immunogenicity and anticancer immunity through affecting DNA damage repair pathways. In the ICI-treated cohort from MSKCC, GC patients with ATRX mutation were associated with prolonged overall survival. When stratifying the entire ICI-treated cohort by sex, female patients with ATRX mutation obtained significantly better survival benefits than that of ATRX mutant male patients (Female patients, HR of ATRX MT vs WT = 0.636, 95%CI = 0.455-0.890, P = 0.023; Male patients, HR of ATRX MT vs WT = 0.929, 95%CI = 0.596-1.362, P = 0.712). Conclusions: ATRX mutation might serve as a potential predictive biomarker for favorable clinical benefit to ICI in female GC patients. ATRX mutation could be applied in combination with other biomarkers of ICI response to better identify the female GC patients who will derive greater benefits from ICI therapy.
The Safety and Efficacy of the Interleukin-1 Antagonist Anakinra in Severe Cases of COVID-19- A Systematic Review and Meta-analysis.
Authors: Somagutta Manoj Kumar Reddy , Pormento Maria Kezia Lourdes , Hamid Pousette , Hamdan Alaa , Khan Muhammad Adnan , Desir Rockeven , Vijayan Rupalakshmi , Shirke Saloni , Jeyakumar Rishan , Dogar Zeryab , Makkar Sarabjot Singh , Guntipalli Prathima , Ngaba Neguemadji Ngardig , Nagineni Manasa Sindhura , Paul Trissa , Luvsannyam Enkhmaa , Riddick Chala
Published: November 2020

This study aims to assess anakinra's safety and efficacy for treating severe coronavirus disease in 2019 (COVID-19). PubMed, Google Scholar, Cochrane Library, Embase, Scopus, medRxiv, and bioRxiv were searched. Three retrospective studies and five case series involving 3,274 adult patients with severe COVID-19 were included, 621 treated with anakinra (whether administered alone or in combination with other drugs) and 1,565 in the control group arm. All-cause mortality of severe COVID-19 patients among the anakinra group was 20% (16/81), which was lower than that in the control group (65%; 39/60). The difference was statistically significant [hazard ratio (HR) = 0.13, 95% confidence interval (CI) 0.06–0.29, I2= 0%]. The mechanical ventilation requirement with OR 0.57 (0.11-2.84, I2=87%) was not significantly better compared to the control group. For the safety of anakinra, we evaluated thromboembolism risk and liver enzyme elevation. Thromboembolism risk with OR: 1.48 (0.55- 3.99, I2=0%) and elevation in liver transaminases with OR 0.67 (0.11-3.93, I2=66%) were not statistically significant over the control group. However, these non-significant differences between the anakinra and control groups may have been the result of baseline characteristics of the intervention group, and further studies are essential in evaluating anakinra's safety profile.
The Safety and Efficacy of the Interleukin-1 Antagonist Anakinra in Severe Cases of COVID-19- A Systematic Review and Meta-analysis.
Authors: Somagutta Manoj Kumar Reddy , Pormento Maria Kezia Lourdes , Hamid Pousette , Hamdan Alaa , Khan Muhammad Adnan , Desir Rockeven , Vijayan Rupalakshmi , Shirke Saloni , Jeyakumar Rishan , Dogar Zeryab , Makkar Sarabjot Singh , Guntipalli Prathima , Ngaba Neguemadji Ngardig , Nagineni Manasa Sindhura , Paul Trissa , Luvsannyam Enkhmaa , Riddick Chala , Pagad Sukrut , Sanchez-Gonzalez Marcos
Published: November 2020

This study aims to assess anakinra's safety and efficacy for treating severe coronavirus disease in 2019 (COVID-19). PubMed, Google Scholar, Cochrane Library, Embase, Scopus, medRxiv, and bioRxiv were searched. Three retrospective studies and five case series involving 3,274 adult patients with severe COVID-19 were included, 621 treated with anakinra (whether administered alone or in combination with other drugs) and 1,565 in the control group arm. All-cause mortality of severe COVID-19 patients among the anakinra group was 20% (16/81), which was lower than that in the control group (65%; 39/60). The difference was statistically significant [hazard ratio (HR) = 0.13, 95% confidence interval (CI) 0.06–0.29, I2= 0%]. The mechanical ventilation requirement with OR 0.57 (0.11-2.84, I2=87%) was not significantly better compared to the control group. For the safety of anakinra, we evaluated thromboembolism risk and liver enzyme elevation. Thromboembolism risk with OR: 1.48 (0.55- 3.99, I2=0%) and elevation in liver transaminases with OR 0.67 (0.11-3.93, I2=66%) were not statistically significant over the control group. However, these non-significant differences between the anakinra and control groups may have been the result of baseline characteristics of the intervention group, and further studies are essential in evaluating anakinra's safety profile.
Upregulation of ACE2 and TMPRSS2 by particulate matter and idiopathic pulmonary fibrosis: A potential role in severe COVID-19
Authors: Li Hsin-Hsien , Liu Chen-Chi , Hsu Tien-Wei , Lin Jiun-Han , Hsu Jyuan-Wei , Li Anna Fen-Yau , Yeh Yi-Chen , Hsu Han-Shui , Hung Shih-Chieh
Published: November 2020

Background: Air pollution and idiopathic pulmonary fibrosis (IPF) cause a poor prognosis after COVID-19 infection, but the underlying mechanisms are not well exploited. Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the keys to the entry of SARS-CoV-2. We measured their expression levels in lung tissues of control non-IPF and IPF patients, and used murine animal models to study the deterioration of IPF caused by particulate matter (PM) and the molecular pathways involved in the expression of ACE2 and TMPRSS2.Results: In non-IPF patients, cells expressing ACE2 and TMPRSS2 were limited to human alveolar cells. ACE2 and TMPRSS2 were largely upregulated in IPF patients, and were co-expressed by fibroblast specific protein 1 (FSP-1)+ lung fibroblasts in human pulmonary fibrotic tissue. In animal models, PM exposure increased the severity of bleomycin-induced pulmonary fibrosis. ACE2 and TMPRSS2 were also expressed in FSP-1+ lung fibroblasts in bleomycin-inuced pulmonary fibrosis, and when combined with PM exposure, they were further upregulated. The severity of pulmonary fibrosis and the expression of ACE2 and TMPRSS2 caused by PM exposure were blocked by deletion of KC, a murine homologue of IL‐8, or treatment with reparixin, an inhibitor of IL‐8 receptors CXCR1/2.Conclusions: These data suggest that poor prognosis after COVID-19 infection caused by air pollution and IPF is mediated through upregulation of ACE2 and TMPRSS2 in pulmonary fibroblasts, which can be prevented by blocking the IL-8/CXCR1/2 pathway.
Autistic traits and gender modulate emotion changes before and during the COVID-19 outbreak: a preliminary evidence based on quasi-experimental design
Authors: Zhao Xudong , Zhao Binglei , Li Wenrui , Cai Yang , Shi Wendian , Li Chunbo
Published: November 2020

Individuals with autism spectrum disorder (ASD) show an enhanced response to stressors, and gender plays an important role in stress response. Thus, autistic traits (ATs) in the general population and gender may regulate the emotion changes before and during the outbreak of COVID-19. The present study addressed this issue through a participants between quasi-experimental design, in which the epidemic status (before, during), gender (male, female), and AT groups (high ATs, low ATs) were independent variables, and positive and negative emotions were dependent variables. We used generalized linear models to estimate the effects of the independent variables and their interactions on emotions. The results showed that the COVID-19 outbreak reduced positive emotions and increased fear and anger. Furthermore, compared with before the COVID-19 outbreak, individuals with high ATs and females experienced stronger anger and fear than individuals with low ATs and males during the epidemic. The present study revealed the emotional impacts of COVID-19 and greater emotional susceptibility to COVID-19 pandemic among individuals with high ATs and females. Our findings provide prospective evidence for understanding the ASD/ATs-related enhanced response to pathogen threat-related stressors and have implications for COVID-19 crisis interventions.
Candida tropicalis distribution and drug resistance is correlated with ERG11 and UPC2 expression
Authors: Wang Dan , An Na , Yang Yuwei , Yang Xianggui , Fan Yingzi , Feng Jiafu
Published: November 2020

Background: Candida tropicalis (C. tropicalis) is an important opportunistic pathogenic Candida species that can cause nosocomial infection. In this study, we analyzed the distribution and drug susceptibility of C. tropicalis and the relationship between ERG11 and UPC2 expression and resistance to azole antifungal agents.Methods: C. tropicalis was cultured and identified by Sabouraud Agar Medium, CHROM Agar Candida and ATB tests (Bio-Mérieux, France). Total RNA was extracted from the collected strains, and the ERG11 and UPC2 mRNA expression levels were analyzed by quantitative real-time PCR.Results: In total, 2872 clinical isolates of Candida, including 319 strains of C. tropicalis, were analyzed herein; they were mainly obtained from the Departments of Respiratory Medicine and ICU. The strains were predominantly isolated from airway secretion samples, and the detection trend in four years was mainly related to the type of department and specimens. The resistance rates of C. tropicalis to fluconazole, itraconazole and voriconazole had been increasing year by year. The mRNA expression levels of ERG11 and UPC2 in the fluconazole-resistant group were significantly higher than they were in the susceptible group. In addition, there was a significant positive linear correlation between these two genes in the fluconazole-resistant group.Conclusions: Overexpression of the ERG11 and UPC2 genes in C. tropicalis could increase resistance to azole antifungal drugs. The routine testing for ERG11 and UPC2 in high-risk patients in key departments would provide a theoretical basis for the rational application of azole antifungal drugs.
Exploring health-seeking behaviour among adolescent mothers during the Ebola epidemic in Western rural district of Freetown, Sierra Leone
Authors: Massaquoi Hamida , Atuhaire Catherine , Chinkonono Gorgeous Sarah , Christensen Betty Nyawira , Bradby Hannah , Cumber Samuel Nambile
Published: November 2020

Background: From 2014-2016, the largest Ebola outbreak in history threatened Sierra Leone and its neighbouring countries, Guinea and Liberia. The Ebola outbreak impacted pregnant adolescent girl’s access to prenatal care during the pandemic. The aim of the study is to understand health-seeking behaviour among adolescent mothers who were pregnant during the Ebola epidemic in Waterloo, Sierra Leone. Methods: The present qualitative study uses the “Three Delay” model, as a theoretical framework to understand and explore adolescent mother’s health-seeking behaviour through four focus group discussions with five participants in each discussion group. The data were analysed using thematic analysis. Results: A multitude of challenges were identified following the Ebola epidemic. The fear of contracting Ebola was a common reason for not seeking care or utilising services. This notion was perpetuated by perceptions in the community and participants personal experiences. Quarantines, national lockdowns, roadblocks, loss of income and extreme poverty were also identified as barriers to accessing health facilities during Ebola. The different encounters with health workers and the challenges that arose at the health facilities were subsequently additional discouraging factors influencing participant’s decision not to seek health care. Conclusion: Many of the pre-existing maternal health, societal and social-economic challenges were exacerbated during the Ebola. The epidemic also contributed new challenges such as public fear, mistrust towards health professionals and the health system. Greater emphasis needs to be placed on improving maternal care in general, but also improving preparedness for maternal care in case of future outbreaks, especially for the most vulnerable groups such as adolescent mothers.
Host reproductive cycle influences the pouch microbiota of wild Southern Hairy-nosed Wombats (Lasiorhinus latifrons)
Authors: Weiss Sesilje , Taggart David , Smith Ian , Helgen Kristofer M , Eisenhofer Raphael
Published: November 2020

Background: Marsupials are born much earlier than placental mammals, with most crawling from the birth canal to the protective marsupium (pouch) to further their development. However, little is known about the microbiology of the pouch and how it changes throughout a marsupial’s reproductive cycle. Here, using stringent controls, we characterized the microbial composition of multiple body sites from 26 wild Southern Hairy-nosed Wombats (SHNWs), including pouch samples from animals at different reproductive stages. Results: Using qPCR of the 16S rRNA gene we found higher concentrations of microbial DNA in the pouch than in negative controls. We observed significant differences in microbial composition and diversity between the body sites tested, as well as between pouch samples from different reproductive stages. The pouches of reproductively active females had drastically lower microbial diversity (mean richness 19) compared to reproductively inactive females (mean richness 941), and were dominated by gram positive bacteria from the Actinobacteriota phylum (81.7-90.6%), with the dominant families classified as Brevibacteriaceae, Corynebacteriaceae, Microbacteriaceae, and Dietziaceae. Three of the five most abundant sequences identified in reproductively active pouches had closest matches to microbes previously isolated from tammar wallaby pouches. Conclusions: This study represents the first contamination controlled investigation into the marsupial pouch microbiota, and sets a rigorous framework for future pouch microbiota studies. Our results suggest that SHNW pouches contain communities of microorganisms that are substantially altered by the host reproductive cycle. We recommend further investigation into the roles that pouch microorganisms may play in marsupial reproductive health and joey survival.