bluuebunny/crossref_metadata_2025 huggingface dataset:
Wilms Tumor 1 Mutations are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia
Authors: Wang Yin , Weng Wen-Jun , Zhou Dun-Hua , Fang Jian-Pei , Chai Li , Xu Lu-Hong
Published: October 2020

Background: The role of Wilms tumor 1 (WT1) mutations remains controversial for patients with acute myeloid leukemia (AML) with regard to the prognostic impact. Here, we aimed to determine the clinical implication of WT1 mutations in a large cohort of pediatric AML. Methods: The clinical data of 870 pediatric patients with AML were downloaded from the therapeutically applicable research to generate effective treatment (TARGET) dataset. We analyzed the prevalence, clinical profile and prognosis of WT1 mutations in these patients. Results: WT1 mutations were founded in 6.7% of total patients. WT1 mutations were closely associated with normal cytogenetics (P<0.001), FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutations (P<0.001), and low complete remission induction rates (P<0.01). Compared to patients without WT1 mutations, patients with WT1 mutations had worse 5-year event-free survival (21.7±5.5% vs 48.9±1.8%, P<0.001) and overall survival (41.4±6.6% vs 64.3±1.7%, P<0.001). Moreover, patients with both WT1 and FLT3/ITD mutations had a dismal prognosis. Compared to chemotherapy alone, hematopoietic stem cell transplantation had a tendency to improve prognoses of WT1-mutated patients. In multivariate analysis, WT1 mutations conferred an independent adverse impact on event-free survival (hazard ratio 1.910, P = 0.001) and overall survival (hazard ratio 1.709, P = 0.020). Conclusion: Our findings demonstrate that WT1 mutations are independent poor prognostic factors in pediatric AML.
A Novel Modular Disassembly Design Method for CNC Machine Tools based on PSOA and TOPSIS
Authors: Feng Yi-Xiong , Wu Xuan-Yu , Zhai Xing , Zheng Hao , Lou Shan-He , Tan Jian-Rong
Published: October 2020

Disassembly is one of the crucial issues for the green remanufacturing of obsolete CNC machine tools. Meanwhile, modular design method is the guarantee of disassembly rationality, which can maximize economic and environmental benefits. However, modular disassembly processes of CNC machine tools are more uncertainty in system structures and component conditions. On the basis of summarizing the existing research, disassembly module modeling of CNC machine tools is implemented. For one advantage, the rough set theory is utilized to cluster the parts into different disassembly modules. For another, disassembly information model is constructed by the disassembly multi-constrained graph. Secondly, multi-objective mathematical model which contains disassembly time, disassembly benefit and disassembly complexity is built. A novel particle swarm optimization algorithm (PSOA) improved by niche technology is applied to the disassembly sequence planning. Last but not least, this work also evaluates the disassembly scheme of CNC machine tools based on the technology for order preference by similarity to an ideal solution (TOPSIS). Evaluation indicator system is established and the comprehensive weight of evaluation indicators is determined by the respective advantages of entropy weight method (EWM) and analytic hierarchy process (AHP). A case study is conducted to illustrate the feasibility of the proposed models and methods. The results of this work can contribute to the selection of the optimal modular disassembly scheme of CNC machine tools.
A Digital Twin of the Powder Metallurgical Manufacturing Chain of High Strength Sintered Gears
Authors: Rajaei Ali , Deng Yuanbin , Schenk Oliver , Rooein Soheil , Bezold Alexander , Broeckmann Christoph
Published: October 2020

This paper presents a digital twin of the powder metallurgical (PM) production chain of high-performance sintered gears based on an integrated computational materials engineering (ICME) platform. Discrete and finite element methods (DEM and FEM) were combined to describe the macroscopic material response to the thermomechanical loads and process conditions during the entire production process. The microstructural evolution during the sintering process was predicted on then meso-scale using a Monte-Carlo Model. The effective elastic properties were determined by a homogenization method based on modelling a representative volume element (RVE). The results were subsequently used for the FE modelling of the heat treatment process. Through the development of multi-scale models, it was possible on the one hand to obtain characteristics of the microstructural features and on the other hand the predicted hardness and residual stress distributions allow the calculation of the tooth root load bearing capacity of the heat-treated sintered gears.
Theoretical and Experimental Study on Normal Contact Stiffness of Joint Surfaces with Surface Texturing
Authors: Yin Chao-Chao , Huang Hai-Hong , Zhou Dan , Liu Zhi-Feng
Published: October 2020

Effects of surface texturing on the normal contact stiffness of joint surfaces had been investigated by experiments in many previous researches; however, there are relatively few theoretical models in this regard. The rough surface with surface texturing can be divided into two parts: the textured zone and the remaining zone, and their theoretical models are established respectively in this research. For the textured zone, the texture is modeled theoretically based on the three-dimensional topographic data obtained via a 3D-CCMP1 type laser profilometer from TRIMOS. For the remaining zone, the model of normal contact stiffness is established based on the fractal theory for the surface topography description and elastic-plastic deformation of surface asperities, and the structure function method is used to calculate the fractal dimension of rough surface profiles. In the experiment, the normal contact stiffness of specimens is obtained under different normal loads, and the test results are compared with the theoretical predictions. The result shows that the predictions of proposed theoretical model are in good agreement with the experimental data. For the joint surfaces with Sa>2.69 μm, the normal contact stiffness can be effectively increased through proper surface texturing.
Feed-forward, feed-back, and distributed feature representation during visual word recognition revealed by human intracranial neurophysiology
Authors: Long Laura , Yang Minda , Kriegeskorte Nikolaus , Jacobs Joshua , Remez Robert , Sperling Michael , Sharan Ashwini , Lega Bradley , Burks Alexis , Worrell Gregory , Gross Robert , Jobst Barbara , Davis Kathryn , Zaghloul Kareem , Sheth Sameer , Stein Joel , Das Sandhitsu , Gorniak Richard , Wanda Paul , Kahana Michael , Mesgarani Nima
Published: October 2020

Scientists debate where, when, and how different visual, orthographic, lexical, and semantic features are involved in visual word recognition. In this study, we investigate intracranial neurophysiology data from 151 patients engaged in reading single words. Using representational similarity analysis, we characterize the neural representation of a hierarchy of word features across the entire cerebral cortex. We find evidence of both feed-forward and feedback processing, with early representation of visual and lexical information in lingual gyrus followed by lexical representation in fusiform gyrus and semantic sensitivity in inferior frontal gyrus, with letter representation emerging later in fusiform gyrus. Furthermore, we observed a variety of anatomically heterogeneous temporal response shapes, and these functional populations had significant feature sensitivity. Taken together, our results demonstrate the early influence of lexical, phonological, and semantic features in visual word recognition and reveal feed-forward, feed-back, and anatomically distributed processing mechanisms that contribute to visual word recognition.
EP3 Receptor Deficiency Attenuates Vascular Remodeling and Cognitive Impairment in a Cerebral Small Vessel Disease Model
Authors: Liu Na , Tang Jie , Xue Yang , Zhang Miaoyi , Ren Xue , Mok Vincent , Wang Yilong , Fu Jianhui
Published: October 2020

BackgroundAnti-hypertensive therapy has achieved effective but not complete results in treating cerebral small vessel disease (CSVD), suggesting the necessity for additional treatments. Targeting abnormal inflammatory responses has become a research interest. Inhibition of E-prostanoid 3(EP3) receptor has been shown to attenuate vascular remodeling in peripheral organs, but little is known about its role in CSVD. Here, we investigated whether the deletion of EP3 attenuates the development of CSVD.MethodsStroke-prone renovascular hypertensive rat (RHRsp) was used as an animal model of CSVD. The effect of EP3 deletion on the expression of extracellular matrix (ECM) in cerebral small arteries of RHRsp was detected by immunofluorescence. Changes in cognitive function and cerebral blood flow (CBF) of RHRsp were evaluated using the Morris water maze test and MRI. In vitro experiments with primary rat brain microvascular smooth muscle cells were used to confirm whether the transforming growth factor beta 1 (TGF-β1) signal takes part in the processResultsCerebral small arteries of RHRsp exhibited increased EP3 expression. Despite no alleviation in hypertension, the deletion of EP3 still reduced the overexpression of ECM in the cerebral small arteries of RHRsp. In vitro experiments indicated that EP3 deletion regulated the expression of ECM by downregulating TGF-β1/Smad signaling. EP3 knockout further attenuated the cognitive impairment of the RHRsp possibly through increased CBF. ConclusionTogether, our results indicate that the deletion of EP3 attenuates the vascular remodeling and vascular cognitive impairment induced by hypertension, and blockade of the EP3 receptor may be a promising strategy for the treatment of CSVD.
A Narrative Account of Nottingham University Hospitals NHS Trust Critical Care Response to the COVID-19 Pandemic, and Analysis of Outcomes
Authors: Javaid Amar , Swindin Joel , Greenhow Richard , Chikhani Marc
Published: October 2020

BackgroundThe novel coronavirus SARS-CoV-2 and associated multisystem disease COVID-19 originated in Wuhan, China in December 2019. The resultant pandemic has resulted in an unprecedented strain on healthcare services around the world, including the greatest challenge seen by critical care medicine in modern times. This narrative illustrates the response of Nottingham University Hospitals NHS Trust critical care department to the crisis, including resource allocation and clinical management strategies and illustrates patient outcome for those admitted to critical care during the first pandemic wave.MethodsPatients admitted to critical care whom tested positive for SARS-CoV-2 between March-May 2020 were identified for retrospective case review as part of service evaluation. Clinical, laboratory and radiological data was collected. This included patient level data on ventilation and fluid balance.ResultsDuring the three period March-May 2020, retrospective case review showed 109 patients admitted to critical care with COVID-19. 88 (80.7%) of the 109 patients received mechanical ventilation, 21 (19.3%) patients received renal replacement therapy. Critical care mortality was 26 (23.9%) patients and hospital mortality was 27 (24.8%) of the 109 patients.ConclusionThis mortality rate was an unexpected finding based on early literature and help to provide a baseline for comparison hereafter. Commentary is provided for several aspects of care that may account for the low mortality rate and warrant further investigation in the future.
A Prognostic Nomogram and Web-based Real-Time Calculator for Predicting CSS and OS of Primary Rectal Adenocarcinoma Patients
Authors: Wang Zhenshuang , Yang Yi , Jing Jingjing , Yuan Yuan , Xing Chengzhong
Published: October 2020

BackgroundThe purpose of this study was to construct a clinical prognostic model of primary rectal adenocarcinoma (RAC) to assist in clinical diagnosis and treatment. MethodsPrimary RAC patients from 2010 to 2015 were selected from the surveillance, epidemiology and end results (SEER). The relevant significant variables were used to develop the prognosis model. A score was determined for each prognostic factor in the model. The Kaplan–Meier method and the log-rank test were used to establish and distinguish the survival curves. The accuracy of predictive model was assessed by receiver operating characteristics (ROCs) curve, concordance index (C-index), and decision curve analysis (DCA). ResultsA total of 8069 primary RAC were retrieved in this study. The overall survival（OS）model was established based on 14 variables. The CSS nomogram were constructed using 12 variables. The C-indexes for the training set of OS and CSS were 0.769 (95% confidence interval (CI) 0.761–0.777) and 0.793 (95% CI 0.784–0.802) respectively. The C-indexes for the validation set of OS and CSS were 0.776 (95% CI 0.768–0.784) and 0.794 (95% CI 0.785–0.803) respectively. High-quality calibration plots were observed and the model displayed a favorable outcome compared with (TNM) stage and SEER stage of primary RAC based on DCA curve. We then divided the patients into low-risk, medium-risk, and high-risk groups, showing that patients with primary RAC in the high-risk group had a poor prognosis. A primary RAC prognosis prediction model has been shown by a predicted nomogram for 3 or 5 years and a real-time web-based calculator. ConclusionsIn conclusion, we established a clinical prognosis model for primary RAC for the first time based on a variety of risk factors including individual differences, tumor-related factors, and diagnostic and therapeutic factors, which is more effective than TNM stage in predicting the prognosis of patients. The clinical prediction model visualized by the nomogram for 3 and 5 years and the web-based real-time calculator are helpful to optimize clinical work, facilitate patient consultation and clinical individualized treatment.
Value of Machine Learning with CE-MRI Radiomics for Early Prediction of Pathological Complete Response to Neoadjuvant Therapy in HER2-positive Invasive Breast Cancer
Authors: Li Qin , Xiao Qin , Li Jianwei , Wang Zhe , Wang He , Gu Yajia
Published: October 2020

Backgrouds To assess the value of radiomics based on multiphases contrast-enhanced magnetic resonance imaging(CE-MRI) for early prediction of pathological complete response(pCR) to neoadjuvant therapy(NAT) in patients with human epithelial growth factor receptor 2(HER2) positive invasive breast cancer.Methods A total of 127 patients with newly diagnosed primary HER2 positive invasive breast cancer underwent CE-MRI before NAT and performed surgery after NAT. Radiomic features were extracted from the 1st postcontrast CE-MRI phase(CE1) and multi-phases CE-MRI(CEm). With selected features using a forward stepwise regression, 23 machine learning classifiers based on CE1 and CEm were constructed respectively. The performence of classifiers were assessed and compared. Results For the task of pCR classification, 6 radiomic features from CE1 and 6 from CEm were selected for the final machine learning models respectively. The linear SVM based on CEm outperformed the Logistic regression model using CE1 with an AUC of 0.84 vers 0.69. In mass and non-mass enhancement groups, the accuracy of linear SVM achieved 76% and 84%. Whereas in unifocal and unilateral multifocal cases, 79% and 75% accuracy were achieved by linear SVM. Conclusion Multiphases CE-MRI imaging may offer more heterogeneity information in the tumor and provide a non-invasive approach for early prediction of pCR to NAT in patients with HER2 positive invasive breast cancer.
Gene Mutation Characteristics and Clinical Prognosis of Head and Neck Mucosal Melanoma
Authors: Yin Gaofei , Guo Wei , Liu Hongfei , Duan Hanyuan , Cui Chuanliang , Kong Yan , Huang Zhigang , Chen Xiaohong
Published: October 2020

Background: As a highly malignant tumor type, the mucosal type is the second most common pathological subtype in China. In this study, we analyzed the results and clinical data for C-KIT, NRAS, PDGFRA and BRAF genotypes in patients, to explore the characteristics of gene mutation in head and neck mucosal melanoma and the correlation between the four common gene mutation types and prognosis.Methods: C-KIT (exons 9, 11, 13, 17 and 18), NRAS (exons 1 and 2), PDGFRA (exons 12, 14 and 18) and BRAF (exons 11 and 15) were analyzed by PCR amplification and Sanger sequencing in patients. The Chi-squared test, Log rank test and Cox regression model were used to analyze the risk factors. Results: In total, 96 patients were included in the study. 14 (14.58%) patients had the C-KIT mutation, 6 (6.25%) had the BRAF mutation, 23 (23.96%) had the PDGFRA mutation, and 12 (12.50%) had the NRAS mutation. The NRAS mutation (P = 0.037, 95%CI: 1.050–4.572) was an independent factor affecting postoperative distant metastasis. The mutation types of different primary tumor sites were different. The BRAF mutation was more common in the nasopharynx and other sites (P = 0.008), whereas the NRAS mutation was more common in the nasal cavity/sinus (P = 0.043).Conclusion: The specificity of this genotype may have some guiding significance for treatment of patients with head and neck mucosal melanoma, but this study did not find any correlation with survival time, and this needs further analysis with a larger dataset.
Clinical Analysis of Suction Drainage in Cementless Hip Replacement: A Prospective Randomised Study
Authors: Bartosz Pawel , Marczynski Wojciech , Para Marcin , Kogut Maciej , Białecki Jerzy
Published: October 2020

Background: Several studies have suggested that the use of drains did not improve surgical outcomes after hip replacement. There is still a lack of strict recommendations for drainage use.Methods: Prospective, randomised study was performed. The analysis included 100 patients. Inclusion criteria: idiopathic hip osteoarthritis. Exclusion criteria: secondary coxarthrosis, autoimmune disease, coagulopathy, venous/arterial thrombosis, hepatic/renal insufficiency, cement, or hybrid endoprostheses. Results: We found smaller haematomas in the no-drainage group (9.76 mm vs. 10.33 mm, p = 0.653). The visual analogue scale score was lower in the no-drainage group (5 vs. 6). Less bloodloss in the no-drainage group (1,124 ml vs 1,224 ml, p = 0.59). Two patients had a deep joint infection in the no-drainage group, none in the drainage group.Conclusion: It is noteworthy that two cases of early infections were observed in the no-drainage group, whereas there were no such complications in the drainage group. Further research is warranted to validate our findings.Trial registration: The study was successfully retrospectively registered in Clinicaltrial.gov with identification number: NCT04333264 (03/04/2020). https://clinicaltrials.gov/ct2/show/NCT04333264?term=NCT04333264&draw=2&rank=1
A Wnt5a-Cdc42 axis controls aging and rejuvenation of hair-follicle stem cells
Authors: Tiwari Rajiv , Mishra Pratibha , Martin Nicola , George Nikhil , Sakk Vadim , Soller Karin , Nalapareddy Kodandaramireddy , Nattamai Kalpana , Kochanek Karin , Florian Maria , Geiger Hartmut
Published: October 2020

Normal hair growth occurs in cycles, comprising growth (anagen), cessation (catagen) and rest (telogen). Upon aging, the initiation of anagen is significantly delayed, which results in impaired hair regeneration. Hair regeneration is driven by hair follicle stem cells (HFSCs). We show here that aged HFSCs present with a decrease in canonical Wnt signaling and a shift towards non-canonical Wnt5a driven signaling which antagonizes canonical Wnt signaling. Elevated expression of Wnt5a in HFSCs upon aging results in elevated activity of the small RhoGTPase Cdc42 as well as a change in the spatial distribution of Cdc42 within HFSCs. Treatment of aged HFSC with a specific pharmacological inhibitor of Cdc42 activity termed CASIN to suppress the aging-associated elevated activity of Cdc42 restored canonical Wnt signaling in aged HFSCs. Treatment of aged mice in vivo with CASIN induced anagen onset and increased the percentage of anagen skin areas. Aging-associated functional deficits of HFSCs are at least in part intrinsic to HFSCs and can be restored by rational pharmacological approaches.
Long-chain Saturated Fatty Acid Species Are Not Toxic to Human Pancreatic Β-cells and May Offer Protection Against Pro-inflammatory Cytokine Induced β-cell Death
Authors: Thomas Patricia , Leslie Kaiyven A , Welters Hannah J , Morgan Noel G
Published: October 2020

Obesity is a major risk factor for type 2 diabetes (T2D) although the causal links remain unclear. A feature shared by both conditions however is systemic inflammation and raised levels of circulating fatty acids (FFA). It is widely believed that in obese individuals genetically prone to T2D, elevated levels of plasma FFA may contribute towards the death and dysfunction of insulin-producing pancreatic β-cells in a process of (gluco)lipotoxicity. In support of this, in vitro studies have shown consistently that long-chain saturated fatty acids (LC-SFA) are toxic to rodent β-cells during chronic exposure (>24h). Conversely, shorter chain SFA and unsaturated species are well tolerated, suggesting that toxicity is dependent on carbon chain length and/or double bond configuration. Despite the wealth of evidence implicating lipotoxicity as a means of β-cell death in rodents, the evidence that a similar process occurs in humans is much less substantial. Therefore, the present study has evaluated the effects of chronic exposure to fatty acids of varying chain length and degree of saturation, on the viability of human β-cells in culture. We have also studied the effects of a combination of fatty acids and pro-inflammatory cytokines. Strikingly, we find that LC-FFA do not readily promote the demise of human β-cells and that they may even offer a measure of protection against the toxic effects of pro-inflammatory cytokines. Therefore, these findings imply that a model in which elevated circulating LC-FFA play a direct role in mediating β-cell dysfunction and death in humans, may be overly simplistic.
Percutaneous Transluminal Stenting for Superior Vena Cava Syndrome Caused by Malignant Tumors : A Single Center Retrospective Study
Authors: Liu Haitao , Li Yahua , Wang Yang , Yan Lei , Zhou Pengli , Han Xinwei
Published: October 2020

Objectives：To evaluate the efficacy of percutaneous stent placement in the treatment of superior vena cava syndrome caused by malignant tumors.Methods：To retrospectively analyze the clinical data of 32 patients with superior vena cava syndrome who underwent percutaneous endovascular stent treatment in our department from 2015 to 2019 due to malignant tumors, and summarize the patient’s gender, age, tumor type, endovascular treatment plan, complications and postoperative follow-up.Results：All patients successfully underwent percutaneous intraluminal stent placement with digital subtraction angiography (DSA). Thirty seven endovascular stents were implanted in 32 patients, including 21 Eluminexx stents, 12 Wallstent stents, and 4 covered stents..The technical success rate was 100%, and there were no serious surgery-related complications.The remission rate of clinical symptoms was 53.1% (17 / 32) in 24 hours and 84.4% (27 / 32) in 48 hours. The follow-up period was 1.5-24 months, with an average follow-up period of 6.5 months. During the follow-up, 3 patients had re-stenosis and 1 patient had secondary thrombosis in the stent. The symptoms were relieved after the second treatment.Conclusion: For superior vena cava syndrome caused by malignant tumors, percutaneous endoluminal stent therapy can quickly and effectively relieve the clinical symptoms of patients, and the incidence of complications is low. It should be used as a first-line treatment.
Association of Body Mass Index With Postoperative Early Adverse Outcomes in Acute Type a Aortic Dissection Patients in Fujian Province, China: A Retrospective Study
Authors: Lin Lingyu , Lin Yanjuan , Chen Qiong , Peng Yanchun , Li Sailan , Chen Liangwan , Huang Xizhen
Published: October 2020

Background: Abnormal body mass index (BMI) has been related to a higher risk of adverse perioperative outcomes in patients undergoing cardiac surgery. However, the effects of BMI in patients with acute type A aortic dissection (AAAD) on postoperative outcomes remain unclear. The aims of this study were to explore the relationships of BMI and postoperative early adverse outcomes in AAAD patientsMethods: Patients who underwent AAAD surgery at Fujian Province Cardiac Medical Research Center from June 2013 to March 2020 were retrospectively evaluated. They were divided into three groups on the basis of Chinese BMI classification established by the World Health Organization: normal group (BMI 18.5-23.9 kg/m2), overweight group (BMI 24-27.9 kg/m2), and obesity group (BMI > 28kg/m2). Preoperative, intraoperative, and postoperative data were collected. Multivariable and univariable logistic regression analysis models were performed to identify whether BMI was independently associated with postoperative adverse outcomes.Results: Of 777 cases, 31.9% were normal weight, 52.5% were overweight, and 15.6% were obese. The percentage of prolonged mechanical ventilation (44.9% vs 55.8% vs 66.1%, respectively; P<0.001) and the median duration of intensive care unit stays (8.1 vs 9.5 vs 12.0 days, respectively; P<0.001) were higher and longer in the overweight and obese group. Multivariable logistic regression analysis demonstrated that a higher risk of postoperative early adverse outcomes in the overweight (odds ratio [OR]: 2.374, 95%CI: 1.647–3.422), and obese patients (OR: 3.659, 95%CI: 2.122–6.308) with reference to the normal BMI patients, and age, heart rate, and surgery duration were also associated with postoperative early adverse outcomes (P<0.05).Conclusion: Overweight and obese patients are independently associated with higher postoperative early adverse outcomes in patients who underwent AAAD surgery.
Whole Exome Sequencing of Simultaneous Primary Multifocal Lung Cancer (SMPLC): Case Report and Bioinformatics Analysis
Authors: Zhu Donglin , Shen Minghong , Lv Jinghuan
Published: October 2020

Background: To understand the molecular mechanism of synchronous multifocal lung cancer (SMLC) is of great significance for the differential diagnosis of intrapulmonary metastasis (IM) and synchronous multiple primary lung cancer (SMPLC). Recently, next-generation sequencing (NGS) has become a useful tool for understanding SMLC. Case presentation: In this study, two lesions of a 61-year-old man with lung cancer were detected by whole exome sequencing (WES) and the correlation between different lesions was analyzed at the molecular level. Lesion 1 was adenocarcinoma and lesion 2 was squamous cell carcinoma. Gene mutation and copy number variation (CNV) are different in the two lesions. The genome of lesion 2 is more unstable. The clonal evolution analysis showed that there was no obvious evolutionary relationship between the two lesions, and both lesions were independent double primary lesions. Bioinformatics analysis revealed that the alternate genes of the two lesions were inconsistent in function and pathway. PCA analysis was performed using the Cancer Genome Atlas (TCGA) database and the GTEx database, and it was found that the changed genes in these two lesions were significantly separated from the control group, and the changes of TP53 and EGFR genes in the TCGA database were further described. Conclusions: These results indicate that NGS may provide new ideas for SMLC classification.
A Comprehensive Ultrastructure and Transcriptome Analyses of Early Regeneration in Ophryotrocha Xiamen Sp. Nov. (Annelida: Dorvilleidae)
Authors: Chen Ruanni , Mukhtar Irum , Wei Shurong , Wu Siyi , Chen Jianming
Published: October 2020

BackgroundIn recent years, significant progress has been made using powerful genetic approaches with newly developed models for understanding on regeneration, however, the molecular and cellular basis of early regeneration remains unclear. Annelids of the genus Ophryotrocha have long been subjects of research use as model species in ecological, toxicological, reproductive, and regenerative investigations. Although, Ophryotrocha spp., are amenable to molecular, cellular, and functional analyses, still in need to explore new model organisms in this genus to understand regeneration mechanisms. Here, we focus on a newly identified Ophryotrocha species for its early regeneration developmental mode.ResultsBased on detailed morphological (K-maxillae, rosette gland, and chromosome number) and molecular analyses, we present, O. xiamen as a new suitable model species to investigate the early regeneration mechanism. The comparative transcriptome analysis showed the gene expression patterns were related to transcriptional regulation, energy metabolism profiles and structure and signal transduction during early stages of regeneration. Data also exhibited that genes such as neurotrypsin, Nos2, DMBT1, SCO spondin, and endotubin associated to regulate inflammation, enterocyte differentiation, apoptosis, and neuroepithelial, were up-regulated during early regeneration stages (wound healing and blastema formation). Additionally, most of the known regeneration-related genes of annelids were also identified in O. xiamen which enabled to explore the precise functions of genes involved in regeneration process.ConclusionsThis study enriches the identification of genus Ophryotrocha in Chinese coastal zones, an area with high abundances of annelids. The comparative transcriptome analysis provided the whole expression changes during early regeneration process. Morphology and molecular shred of evidences in O. xiamen revealed similar features of early regeneration with other invertebrates. Information on potential candidate genes associated with early regeneration in O. xiamen, will be useful for further studies.
A Rare Case of Bilateral Malignant Brenner Tumors of the Ovaries Associated with Peritoneal Effusion
Authors: Tong Jianing , Niu Jianmin , Li Qiaoyun , Hu Li , Zhang Hui
Published: October 2020

Background: Malignant ovarian Brenner tumors are extremely rare worldwide, accounting for only 1% of malignant ovarian tumors. Their clinical symptoms and pathology are complex and erratic, and the images are mostly non-specific. This poses difficulties in preoperative diagnosis and distinguishing them from other cystic solid ovarian tumors. Here this study has reported on a case of bilateral malignant ovarian Brenner tumor with peritoneal effusion. Case presentation: A 54-year-old woman presented with intermittent vaginal bleeding for more than two months and abdominal pain for one month. Two hard mass of five centimeters with poor movement could be touched at each side of the ovarian areas. The CT findings indicated the presence of two large cystic and solid masses in both adnexal regions. The operation had watched the size of the masses in the bilateral ovarian was both 6cmx6cmx5cm and their surface ulceration showed rotten fleshy tissue. After the operation, combined with morphological and immunohistochemical features, the ovarian specimens were consistent with bilateral ovarian malignant Brenner tumors.Conclusions: Although the incidence of bilateral malignant OBT is extremely low and this disease is extremely rare clinically, the gynecologists should be more informed of its diagnosis and treatment.
Chondromyxoid Fibroma-Like Osteosarcoma in Thoracic Spine with Azygos Tumor Thrombosis, A Case Report
Authors: Du Chuanchao , Liu Shanshan , Liu Yu , Liu Xiaoguang , Wei Feng
Published: October 2020

Background: Chondromyxoid fibroma-like osteosarcoma (CMF-OS) is extremely rare subtype of osteosarcoma, its clinical data is scarce, understanding of it is far from enough. Besides, it is short of typical imaging manifestations, it is not uncommon to be misdiagnosed clinically. Meantime azygos vein thrombosis is also a rare entity, and there is a big controversy over treatments for it.Case presentation: Herein, we report a case of CMF-OS that occurred in spine, coincidently, azygos vein thrombosis was found. A young male patient came to our clinic because of continuous back pain, then neoplastic lesion was suspected in thoracolumbar vertebrae. The pathological results of the biopsy showed low grad of osteosarcoma, and chondromyxoid fibroma-like osteosarcoma was the primary diagnosis. Since the tumor cannot be en-bloc resected, he received palliative decompression surgery, followed by radio and chemotherapy. Azygos vein tumor thrombosis was not intervened, unfortunately, he died of heart failure caused by the thrombus migrated from azygos vein to right atrium. Before the palliative decompression surgery, both the patient and the clinical team were trapped in the dilemma of how big surgery should be done to maximize the benefits of this patient. Conclusions: CMF-OS is indeed more aggressive than its pathological sections look like. Guidelines for osteosarcoma should be followed. Besides, it is important to recognize the danger of tumor thrombosis in azygos vein. Preventive measures have to be done timely to avoid catastrophic results.
Non-Small Cell Lung Cancer Causing Atraumatic Splenic Rupture Without Splenic Metastasis: A Case Report
Authors: Pepe Russel J. , Parekh Akshat , Butts Christopher , Ehsani-Nia Hamid , Amro Chris
Published: October 2020

BackgroundWhile atraumatic splenic rupture is rare phenomenon, its potential lethality emphasizes its clinical importance. Disseminated neoplastic disease is a known mechanism of atraumatic splenic rupture. Case PresentationThis case report discusses a patient presenting with tension hydrothorax and atraumatic splenic rupture in the setting of non-small cell lung carcinoma requiring emergent chest tube insertion and splenectomy. This patient’s presentation represents only the second documented case of atraumatic splenic rupture secondary to metastatic lung carcinoma without pathological evidence of splenic metastasis. ConclusionsThis unique case emphasizes the importance of assessing structural integrity of the spleen in patients with metastatic non-small cell lung carcinoma, as neoplastic atraumatic splenic rupture conveys a significant mortality risk.
Effect of Ulceration on the Therapeutic Benefit of Surgery in Patients with Stage IV Melanoma: A Surveillance, Epidemiology, and End Results Analysis from 2004–2015
Authors: Zhao Qiqi , Gao Zeyun , Xu Xuezhu
Published: October 2020

Background: The effects of various surgical options and ulcerations on the survival of patients with stage IV skin malignant melanoma are unknown. Therefore, we evaluated the potential of these factors as prognostic markers in patients with stage IV malignant melanoma. Methods: We included 5760 patients from 2004–2015 who are screened from the SEER datasets in the study. The patients were divided into four groups: the R 0 group, the primary tumor resection group, the metastasectomy group, and the no-resection group. The median follow-up survival time and overall survival were compared between the four groups as primary outcomes. Result: The R0 , primary tumor resection, metastasectomy, and no-resection groups had median survival times of 11, 13, 20, and 4 months, respectively ( p <0.001). Cox (proportional hazards) regression models estimated that patients in the R 0 , primary tumor resection, and metastasectomy groups had longer survival benefits, with hazard ratios of 0.396 (95% confidence interval [CI], 0.347–0.453), 0.509 (95% CI, 0.465–0.556), and 0.481 (95% CI, 0.447–0.519), respectively. Conclusion: We highlight the importance of surgery in metastatic melanoma; each surgical group in this study is independently correlated with increased survival. In addition, the patient’s ulceration status is able to predict surgical treatment; however, in the ulcerated melanoma cases, caution should be exercised when considering a metastasectomy.
One Case Report of Desmoplastic Small Round Cell Tumor of Pleura
Authors: Zhang Xiao-bo , Li Sheng-lin , Su Xin , Zhang Rui-hao , Hu Yi-cun , Wang Ke-Ping , Zhou Hai-yu
Published: October 2020

BACGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive malignancy tumor that often affects the abdomen, especially in males. Extra-abdominal DSRCT is extremely rare. CASE REPORT: Here we report a 33-year-old man diagnosed with DSRCT from pleura without any clinical symptoms. Routine blood examination was normal, and an X-ray examination revealed a chest mass during the routine physical examination. The patient was diagnosed by immunohistochemistry combined with clinical features and imaging examination and finally confirmed by pathology. After the diagnosis, we immediately underwent surgery and postoperative radiotherapy. In the latest follow-up, there was no sign of recurrence. CONCLUSION: Because the disease is asymptomatic at the beginning, it is easy to deteriorate, and there is no specific targeted treatment. Therefore, early diagnosis and treatment are particularly important.
Ruscogenin Alleviates Intestinal Bleeding and Blood Flow Induced by Dasatinib through ROCK/MLC Pathway
Authors: Liu Yuankai , Dai Yujie , Xu Han , Zhou Qianliu , Li Fang , Yu Boyang , Zhang Yuanyuan , Kou Junping
Published: October 2020

BackgroundAs a second-generation broad-spectrum tyrosine kinase inhibitor, Dasatinib has the antitumor effect of inhibiting tyrosine kinases such as BCR-ABL and SRC. It is mainly used to treat chronic and acute patients with chronic myelogenous leukemia. However, Dasatinib has many side effects, including gastrointestinal bleeding, respiratory infections, and renal failure, and effective means to improve the side effects of drugs are lacking.MethodsC57BL/6 mice and HUVECs were used to evaluate the side effects caused by dasatinib, RUS was administered in advance to prevent, protein expression and phosphorylation were measured by western blot, and monitored the intestinal bleeding with Laser Doppler Blood Flow Monitor. ResultsWe found that Ruscogenin (RUS) can improve Side effects caused by Dasatinib. Through the Laser Doppler Blood Flow Monitor, it was found that after Dasatinib was administered, blood flow in mice are decreased, and intestinal Evans blue leakage increased. Western blot results showed that connexin (ZO-1, VE-cadherin, Occludin) is destroyed, the activation of ROCK increases, and the phosphorylation of MLC increases. Ruscogenin can reverse the above phenomenon and improve the side effects of gastrointestinal bleeding caused by Dasatinib. In vitro, giving Ruscogenin in advance can protect the endothelial barrier damage caused by Dasatinib, reduce the remodeling of F-actin, and restore the expression of connexin (ZO-1, VE-cadherin), inhibit the activation of ROCK, and reduce Phosphorylation of MLC. ConclusionsThis study provides a new direction for improving the side effects caused by clinical drugs and confirm that Ruscogenin could improve the side effect from Dasatinib by ROCK/MLC pathway.
Progression of Severity in Coronavirus Disease 2019 Patients Before Treatment and a Self-Assessment Scale to Predict Disease Severity
Authors: Yao Ye , Tian Jie , Meng Xia , Kan Haidong , Zhou Lian , Wang Weibing
Published: October 2020

Background: With the pandemic of Coronavirus Disease 2019, differing case-fatality rates and limited resources have led to adoption of separate management strategies for severe and nonsevere disease. For patients in quarantine in the community, self-assessment of COVID-19 severity risk can guide appropriate medical consultation. Methods: Data from 45,450 patients infected with COVID-19 from January 1 to February 27, 2020 were extracted from the municipal Notifiable Disease Report System in Wuhan, China. T-test and chi-square test were used to investigate the associations of various patient characteristics with disease severity, and multivariable logistic regression models identified strongly correlated variables for inclusion in the scale. Scale accuracy was assessed using receiver operating characteristic analysis. A least absolute shrinkage and selection operator regression cross-validated prediction accuracy.Results: Twelve scale items - age, gender, illness duration, dyspnea, shortness of breath (clinical evidence of altered breathing), hypertension, pulmonary disease, diabetes, cardio/cerebrovascular disease, number of comorbidities, neutrophil percentage, and lymphocyte percentage - were identified and showed good predictive ability (area under the curve =0·72). After excluding the community healthcare laboratory parameters, the remaining model (the final self-assessment scale) showed similar area under the curve (=0·71).Conclusions: Our COVID-19 severity self-assessment scale can be used by patients in the community to predict their risk of developing severe illness and the need for further medical assistance. The tool is also practical for use in preliminary screening in community healthcare settings.
Development and Validation of a Novel Predictive Nomogram for Disease Progression of COVID-19: A Multicenter Retrospective Cohort Study of 4,086 Cases in China
Authors: Li Li , Li Shen , Zhang Xiaohua , Cheng Lixia , Mao Qing , Li Qi , Fang Xiaoyu , Li Zhujun , Wang Bin , Zhao Songtao , Zhou Yi , Liu Kaijun , Li Chuanwei , Hou Chao , Sun Fenfen , Sun Qidi , Li Mengxia , Wang Fusheng , Zhang Sibing , Xu Dixiong , Ma Xiangyu , Cao Guoqiang
Published: October 2020

Aim: Coronavirus disease 2019 (COVID-19) has caused an unprecedented healthcare crisis. We aim to develop and validate a nomogram for predicting disease progression based on a large cohort of hospitalized COVID-19 patients. Methods: This is a multicenter retrospective cohort study, with a total of 4,086 hospitalized COVID-19 patients enrolled from two hospitals in Wuhan, China between February 3rd and Apr 10th. Nomogram was developed based on a cohort of 3, 022 patients from one hospital, and externally validated in another cohort of 1,064 patients from the other hospital. The calibration was assessed by a calibration plot and the HL test to evaluate the goodness of fit, and the Area under the ROC Curve (AUROC) as a measure of discriminative ability.Results: Six independent predictors, including age, dyspnea, platelet count, lactate dehydrogenase, D-dimer and cardiovascular disease, were finally identified for construction of the nomogram for predicting disease progression of COVID-19 patients during hospitalization. The AUROC was 0.877 and 0.817 for development cohort and validation cohort, respectively. The calibration plots AND Hosmer-Lemeshow test showed optimal agreement between nomogram prediction and actual observation. The decision curve analysis showed the performance of the nomograms were better than all univariable models, and had greater net benefit. Next, a predictive nomogram for disease severity on admission was formulated and the six independent factors used were similar to that of the nomogram for disease progression, which indicates that those factors play important roles in determining disease severity and the risk of disease progression. Conclusion: In the current study, a nomogram was developed based on generally readily available variables at hospital admission to help predict disease progression of COVID-19.
Controlling Nutritional Status (CONUT) Score is a Prognostic Marker in III-IV NSCLC Patients Receiving First-line Chemotherapy
Authors: Zhang Yi , Kong Fei-Fei , Zhu Zheng Qiu
Published: October 2020

Background: To investigate the prognostic impact of the controlling nutritional status (CONUT) score in non-small-cell lung cancer (NSCLC) patients receiving first-line chemotherapy.Methods: We retrospectively reviewed 278 consecutive patients undergoing chemotherapy for stage III-IV NSCLC between May 2012 and July 2020. CONUT score was calculated by incorporating serum albumin, total cholesterol, and total lymphocyte count. The clinicopathological features and follow-up data were evaluated to compare the CONUT score with other prognostic indices, such as the systemic immune-inflammation index (SII) and prognostic nutritional index (PNI), in patients with NSCLC. Results: Applying cut-offs of ≥3 (CONUT), ≥443.607 (SII), and ≥49.05 (PNI). The high CONUT group had a significantly shorter progression-free survival and overall survival than the low CONUT group. A high CONUT score was significantly associated with older age, worse ECOG PS, advanced clinical stage, and lower PNI (all P < 0.05). In the univariate analysis, higher SII, higher CONUT, advanced clinical stage and lower PNI were associated with worse PFS (P<0.05). Worse ECOG PS, higher SII, higher CONUT, advanced clinical stage and lower PNI were associated with worse OS (P<0.05). In multivariate analysis, SII and CONUT score were independently correlated with PFS (P<0.05), while PNI and CONUT score were independently correlated with OS (P<0.05).Conclusion: CONUT score is an independent prognostic indicator of poor outcomes for patients with stage III-IV NSCLC and is superior to the SII and PNI in terms of prognostic ability.Trial registration: retrospectively registered.
Frequency and diagnostic reliability of laboratory variables in cows with traumatic reticuloperitonitis and type 1, 2, 3, 4 and 5 abomasal ulcer
Authors: Braun Ueli , Nuss Karl , Warislohner Sonja , Reif Christina , Oschlies Carina , Gerspach Christian
Published: October 2020

Background: A number of laboratory abnormalities occur in cows with traumatic reticuloperitonitis (TRP) as well as in those with abomasal ulcers (AU). This prompted us to compare the frequencies of laboratory abnormalities of healthy cows and cows with TRP and cows with abomasal ulcers and to calculate diagnostic sensitivities and specificities, predictive values and positive likelihood ratios for laboratory findings. The study included 182 healthy control cows, 503 cows with TRP, 94 cows with U1, 145 cows with U2, 60 cows with U3, 87 cows with U4 and 14 cows with U5. Haematocrit, total leukocyte count, concentrations of total protein, fibrinogen, urea, potassium and chloride, base excess and rumen chloride concentration were analysed.Results: Values outside the reference interval occurred in 2 to 24% of control cows (rumen chloride 2%, urea 6%, serum chloride 11%, haematocrit 13%, base excess 18%, fibrinogen 20%, total protein 21%, total leukocyte count 22% and potassium 24%), which made differentiation of healthy and ill cows difficult. Therefore, the variables best suited for distinguishing healthy and ill cows were rumen chloride and blood urea concentration. This was also supported by an LR+ of 14 to 27 for rumen chloride >30 mmol/l and 6 to 15 for blood urea >6.5 mmol/l in cows with ulcers. Urea also had a high diagnostic specificity and like rumen chloride was suited for differentiation of healthy and diseased cows. The urea concentration was >8.5 mmol/l in only 0.5% of controls, and the LR+ for a urea concentration >8.5 mmol/l ranged from 11 in cows with TRP to 128 in cows with U2. Except for cows with TRP, azotaemia was significantly more frequent in ill cows than in controls. Cows with U2 (70%) had urea concentrations >8.5 significantly more often than cows of the other groups, which may have been prerenal azotaemia attributable to hypovolaemia. Even though the groups of ill cows differed significantly with respect to several variables, no variables were identified to reliably differentiate the various groups.Conclusions: Isolated results are not suitable to distinguish among groups of ill cows and instead the history, the clinical findings and results of additional diagnostic techniques such as ultrasonography are required.