bluuebunny/crossref_metadata_2025 huggingface dataset:
A Study on Liner-Reaction Speed based on the Aging of a Curing System
Authors: Park Sungjun , Choi Sunghan , Park Jungho
Published: January 2021

In this study, the hardening reaction speed of a rocket motor liner based on the aging of a curing system comprised of a hardener and hardening catalyst was observed. It was indicated that as the aging time of the curing system increased, the liner viscosity build-up was accelerated. The raw material having the biggest impact on the hardening reaction of the curing system’s liner was triphenylbismuth (TPB). Stirring isophorone diisocyanate and TPB forms activated complex, and the activated complex facilitates urethane reaction. If TPB is ligand bound with isocyanate, it forms TPB-isocyanate complex. This is a type of TPB’s oxide, and the formation of activated complex through changes in its color. In addition, lining hardening time can be adjusted by the aging period of the curing system through this study, and adhesive strength with the liner and propellant can be improved.
Comparison of Statistical Methods for Estimating Continuous Paediatric Reference Intervals: A Simulation Study
Authors: Hoq Monsurul , Donath Susan , Monagle Paul , Carlin John
Published: January 2021

Background: Reference intervals (RIs), which are used as an assessment tool in laboratory medicine, change with age for most biomarkers in children. Addressing this, RIs that vary continuously with age have been developed using a range of curve-fitting approaches. The choice of statistical method may be important as different methods may produce substantially different RIs. Hence, we developed a simulation study to investigate the performance of statistical methods for estimating continuous paediatric RIs.Methods: We compared four methods for estimating age-varying RIs. These were Cole’s LMS, the Generalised Additive Model for Location Scale and Shape (GAMLSS), Royston’s method based on fractional polynomials and exponential transformation, and a new method applying quantile regression using power variables in age selected by fractional polynomial regression for the mean. Data were generated using hypothetical true curves based on five biomarkers with varying complexity of association with age, i.e. linear or nonlinear, constant or nonconstant variation across age, and for four sample sizes (100, 200, 400 and 1000). Root mean square error (RMSE) was used as the primary performance measure for comparison. Results: Regression-based parametric methods performed better in most scenarios. Royston’s and the new method performed consistently well in all scenarios for sample sizes of at least 400, while the new method had the smallest average RMSE in scenarios with nonconstant variation across age. Conclusions: We recommend methods based on flexible parametric models for estimating continuous paediatric RIs, irrespective of the complexity of the association between biomarkers and age, for at least 400 samples.
A Method of Calculating the Bearing Capacity of Sand Pile Composite Foundations in a Mucky Soil Layer Considering Consolidation
Authors: Chen Peishuai , Luo Huiwu , Li Dejie , Liu Enlong , Yang Benliang
Published: January 2021

In engineering practice, the measured bearing capacity of a sand pile composite foundation in a mucky soil layer is much larger than the design value. Based on the sand pile construction and the load application process, a method of calculating the bearing capacity of the foundation based on the effective stress was proposed. Cavity diameter expansion in sand pile construction was simplified into a planar problem, and the cavity expansion theory was used to establish the expression of the rate of displacement and the horizontal stress increase. Based on the e–p curve and the calculation of the degree of consolidation, the relationships between the horizontal and vertical effective stress and the void ratio were obtained. According to the close relationship between the bearing capacity of the foundation in a mucky soil layer and the water content, an expression describing the relationships between the bearing capacity of the foundation, effective stress, void ratio, and water content was established. For the temporary engineering foundation treatment project, which needs a high bearing capacity but allows large foundation deformation, the design of sand pile composite foundations uses these relationships to take the consolidation effect of mucky soil into consideration, thereby reducing the replacement rate and lowering the construction cost.
A Qualitative Study of Home Care Client and Caregiver Experiences With a Complex Cardio-respiratory Management Model
Authors: Schumacher Connie , Dash Darly , Mowbray Fabrice , Klea Lindsay , Costa Andrew
Published: January 2021

BackgroundHome care clients are typically older and have some degree of medical, physical, cognitive or social conditions that require formal or informal support to promote healthy aging in the community. Home care clients contribute a significant proportion of health service use, including emergency department visits. The DIVERT-CARE trial introduced a cardio-respiratory management model to improve patient motivation, symptoms and rates of unwarranted health service use. Our objective was to explore the perceptions and experiences of individuals who participated in the DIVERT-CARE self-management support and education intervention.MethodsA qualitative study was nested within a pragmatic randomized control trial and conducted following a 15-week multicomponent cardio-respiratory intervention. A phenomenological descriptive design was employed using thematic analysis. Post-intervention, clients and their caregivers were invited to participate in a semi-structured telephone interview. Interview questions were designed to elicit the experience with the intervention components.ResultsA total of 29 interviews were completed from June 2018 to March 2020 from participants in Ontario, Newfoundland, and British Columbia. Five themes were identified; self-care trajectory and responsibility, learning and behaviour change, pre-emptive connection to care providers, connection to information and the health system, and connection through therapeutic relationships.ConclusionsHome care clients experience unique challenges in managing chronic disease. Home-based interventions fostered a therapeutic relationship of connectedness while equipping clients with necessary knowledge and skills. These results inform recommendations for community nursing, and home-based self-management supports for older community-residing individuals.
Study on cement based composite board of wire mesh and straw fibers in severe cold area of Northeast China
Authors: Liu Jie , Lv Chun
Published: January 2021

There is a large amount of residual straw fibers resources in Northeast China. Rice straw fibers was chosen to make steel-wire-net mortar roof-board composed of straw fibers in different sizes. Cold-drawn and low-carbon steel-wire-nets, whose diameter was 3mm and whose size of mesh opening was 60mm×60mm ,were set on both upper and lower sides. Vertical tied cold-drawn low-carbon wires were set between the upper and lower cold-drawn and low-carbon steel-wire-lath for spot welding. The distance between two vertical tied steel wires was 120mm. After the mortar was squirted on the steel-wire-nets, outbound alkali resistance fiber glass mesh and thin floated finish make the alkali resistance fiber glass mesh and thin plastering mortar and horizontal wire mesh mortar and compressed straw fibers slab straw fibersboard work together. The deformation characteristics that studies roof-board composed of straw fibers boards; the fracture distribution and the feature of crack developing that studies the boards; the strain distribution and its change law were summarized, the loading mechanism of roof-board composed of straw fibers boards had been studied; by observing the failure form and destruction feature of test specimen, the factors affecting the flexural property of roof-board composed of straw fibers boards had been studied, preparation points of roof-board composed of straw fibers boards had been put forward. The advantages of grass steel-wire-net thin plastering roof-board composed of straw fibers boards reside in cheap materials, moderate carrying capacity and it was easy to be applied.
Endometrial Polyps Effect on Pregnancy Outcomes in Infertile Women with Minimal/Mild Endometriosis: A Retrospective Study
Authors: Xiang Yingchun , Zhu Huili , Long Ying , Huang Xin , Ouyang Yunwei , Huang Wei
Published: January 2021

Background: The infertile patients with endometriosis had a higher prevalence of endometrial polyps. The effect of endometrial polyps on pregnancy outcomes in endometriosis-associated infertility patients is unclear. This study assessed the pregnancy outcomes and associated influencing factors of pregnancy after hysteroscopy combined with laparoscopy treatment in infertile patients with minimal/mild endometriosis. Methods: We enrolled 898 infertile women who underwent both hysteroscopy and laparoscopy treatment. Based on the existence of endometrial polyps confirmed by hysteroscopy and pathologic examination, patients were divided into polyps group and non-polyps group, and their pregnancy outcomes were compared. Results: After removal of 136 subjects who were lost to follow-up, underwent assisted reproduction techniques, or postponed plans to become pregnant. A total of 271 women were included in polyps group and 491 in non-polyps group. The pregnancy rate of polyps group was not statistically significant compared with non-polyp group (60.15% VS. 58.25%). The pregnancy rate was higher among patients with polyps ≥ 1 cm (76.06%, 54/71) than patients with polyps < 1 cm (54.50%, 109/200) or patients without polyps (58.25%, 286/491) (p = 0.006). The pregnancy rate was higher for patients with multiple polyps (67.86%, 95/140) than for patients with single polyp (51.91%, 68/131) or without polyps (p = 0.025). Conclusions: Compared with those without endometrial polyps, single polyp, and size of polyp < 1 cm, hysteroscopic polypectomy did significantly increase fertility in infertile patients with multiple polyps or size of polyp ≥ 1cm. The size and number of polyps were independently associated with the reproductive ability of women with minimal/mild endometriosis.
Data Augmentation Using Generative Adversarial Networks (GANs) For GAN-Based Detection Of Pneumonia And COVID-19 In Chest X-Ray Images
Authors: Motamed Saman , Rogalla Patrik , Khalvati Farzad
Published: January 2021

Successful training of convolutional neural networks (CNNs) requires a substantial amount of data. With small datasets networks generalize poorly. Data Augmentation techniques improve the generalizability of neural networks by using existing training data more effectively. Standard data augmentation methods, however, produce limited plausible alternative data. Generative Adversarial Networks (GANs) have been utilized to generate new data and improve the performance of CNNs. Nevertheless, data augmentation techniques for training GANs are under-explored compared to CNNs. In this work, we propose a new GAN architecture for augmentation of chest X-rays for semi-supervised detection of pneumonia and COVID-19 using generative models. We show that the proposed GAN can be used to effectively augment data and improve classification accuracy of disease in chest X-rays for pneumonia and COVID-19. We compare our augmentation GAN model with Deep Convolutional GAN and traditional augmentation methods (rotate, zoom, etc) on two different X-ray datasets and show our GAN-based augmentation method surpasses other augmentation methods for training a GAN in detecting anomalies in X-ray images.
First Report of X-Linked Hypohidrotic Ectodermal Dysplasia with a Hemizygous c.1142G >C in the EDA Gene: Variant of Uncertain Significance or New Pathogenic Variant?
Authors: Tumminello Mario , Gangemi Antonella , Matina Federico , Guardino Melania , Giuffrè Bianca Lea , Corsello Giovanni
Published: January 2021

BackgroundHypohidrotic Ectodermal Dysplasia (HED) is a genetic disorder which affects structures of ectodermal origin. X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of disease. XLHED Is characterized by hypotrichosis, hypohydrosis and hypodontia. The cardinal features of classic HED become obvious during childhood. Identification of a hemizygous EDA pathogenic variant in an affected male confirms the diagnosis. Case PresentationWe report on a male newborn with the main clinical characteristics of the X-linked HED including hypotrichosis, hypodontia and hypohidrosis. Gene panel sequencing identified a new hemizygous missense variant of uncertain significance (VUS) c.1142G >C (p.Gly318A1a) in the EDA gene, located on the X chromosome and inherited from the healthy mother. ConclusionDespite the potential functional impact of VUS remains uncharacterized, our goal is to evaluate the clinical potential consequences of missense VUS on EDA gene. Given the proband’s phenotype compatibility with classic HED, it is reasonable to attribute a causative role to the variant found in hemizygosis in the gene EDA. The present case demonstrates that this novel VUS could broaden the spectrum of genes mutations involved in the HED phenotype.
Autophagy R Educes B Acterial T Ranslocation by Attenuating Oxidative Stress in Hypervirulent Klebsiella Pneumoniae-Caused Liver Abscesses Mice
Authors: Lu Xing , Wang Xianlong , Xu Jie , Yin Chengfen , Zhang Peng , Mao Daqing , Xu Lei , Wang Fengmei
Published: January 2021

Background Translocation of intestinal flora can cause liver abscesses.The epidemiological data were mainly Kebsiella pneumoniae infection.It is usually associated with changes in mucosal autophagy and oxidative stress.Objective The aim of this study was to investigate the correlation between autophagy and oxidative stress on the intestinal mucosal barrier of hypervirulent Klebsiella pneumoniae-caused liver abscesses(hvKp-cla) mice model. And the genes that might be involved.Methods C57BL/6J mice were used as study subjects to induce liver abscesses model by hypervirulent Klebsiella pneumoniae gavage. Bacterial translocation (BT) was detected by 16S rDNA sequencing analysis.Morphological alterations in the liver and gut were assessed by hematoxylin–eosin staining.Oxidative stress status was determined by measuring the level of intestinal malondialdehyde (MDA),superoxide dismutase (SOD) and glutathione peroxidase (GPx).In situ hybridization was used to determine whether the bacteria had migrated to the liver.Western blot, RT-PCR,and immunofuorescent staining were preformed to analyze the expression of tight junction and autophagy proteins. The ultrastructural changes of liver were examined by electron microscopy.RNA-seq was used to detect the possible involved genes. Results According to the sequencing analysis, mice were divided into BT (+) group (n = 7) and BT (-) group(n = 7).The damage of intestinal mucosa and liver in BT(+) group was more serious than that in BT(-) group. The translocated Klebsiella pneumoniae was observed in the intestinal mucosa lamina propria and liver.The content of MDA was clearly elevated, and SOD as well as GPx activities were decreased in BT (+) group as compared with BT (-) group.The expression of LC3II and Beclin1 in BT (-) group was higher than that observed in BT (+). In contrast, BT (+)group had a lower level of Zonulin-1 (ZO-1) and claudin-2. RNA-seq found 1912 genes were up-regulated and 1,911 genes down-regulated. Those genes of mTOR,Atg4b and SERPINA3 were involved. Conclusion Autophagy reduces intestinal hypervirulent Klebsiella pneumoniae translocation by reducing oxidative stress levels. Those genes of mTOR,Atg4b and SERPINA3 were involved.
Predictive value of qSOFA score for death in emergency department resuscitation room among adult trauma patients：a retrospective study
Authors: Huang Wenjuan , Yang Peng , Xu Feng , Chen Du
Published: January 2021

Background To explore the predictive value of quick Sequential Organ Failure Assessment (qSOFA) score for death in emergency department (ED) resuscitation room among adult trauma patients.Methods During the period November 1, 2016 to November 30, 2019, we retrospectively collected data of adult trauma patients triaged to ED resuscitation room of the First Affiliated Hospital of Soochow University. Take death occurred in ED resuscitation room as the study endpoint. Univariate and multivariate analyses were performed to explore the association between qSOFA score and death. Receiver operating characteristic (ROC) curve analysis was also performed for death.Results A total of 1739 trauma victims were admitted, including 1695 survivors and 44 non-survivors. The death proportion raised with qSOFA score: 0.60% for qSOFA=0, 3.28% for qSOFA༝1, 12.06% for qSOFA༝2, and 15.38% for qSOFA༝3, p < 0.001. Subgroup of qSOFA = 0 was used as a reference. In univariate analysis, crude OR for death with qSOFA = 1 was 5.65 [95% CI 2.25 to 14.24, p < 0.001], qSOFA = 2 was 22.85 [95% CI 8.84 to 59.04, p < 0.001], and qSOFA = 3 was 30.30 [95% CI 5.50 to 167.05, p < 0.001]. In multivariate analysis, with an adjusted OR (aOR) of 2.87 (95% CI 0.84 to 9.87, p༝0.094) for qSOFA༝1, aOR 6.80 (95% CI 1.79 to 25.90, p = 0.005) for qSOFA༝2, and aOR 24.42 (95% CI 3.67 to 162.27, p = 0.001) for qSOFA༝3. The Area Under the Curve (AUC) for predicting death in ED resuscitation room among trauma patients was 0.78 [95% CI, 0.72–0.85].Conclusions qSOFA score can assess the severity of emergency trauma patients and has good predictive value for death in ED resuscitation room.
Association between Deep White Matter Hyperintensities and Right-to-left Shunt in Migraine (CAMBRAIN): A Cross-sectional Multicenter Study
Authors: Xing Yingqi , Zhang YiShui , Zhao HongLing , Wang SiBo , Cui YingHua , Fang YaLang , Guo Rong , Li YaJie , Wan Qi , Zhang Kaili , Cui Yan , Wei HuiXing , Lin Pan , You Yong , Huang Hong , Su Yan
Published: January 2021

BackgroundDeep white matter hyperintensities (DWMHs), often identified by hyperintense lesions on T2-weighted magnetic resonance imaging (MRI), were discovered to have a higher prevalence in migraine patients. A right-to-left shunt (RLS), which is also prevalent in migraineurs, could potentially contribute to the formation of DWMHs by induction of controversial embolism and endothelial dysfunction. In this cross-sectional study, we aim to evaluate the association between RLS and the prevalence of DWMHs in patients with migraine.MethodsIn this study, we consecutively enrolled patients with migraine aged between 18 and 50 years from the 14 headache clinics of participating hospitals. DWMHs were rated using Scheltens scale on digital MRI images obtained from 1.5T scanners, and RLS was detected via contrast-enhanced transcranial Doppler. Analyses on DWMH prevalence and loads by RLS grading or subtype were performed. A logistic regression analysis on DWMH prevalence was also performed.ResultsIn all, 237 migraine patients (age: 39.3 ± 11.7, 78.1% women, 13% migraine with aura) were enrolled. RLS was detected in 48.5% of the subjects and DWMHs were identified in 138 (58.2%) patients. Prevalence of DWMHs did not differ significantly between RLS+ (57.4%) and RLS− patients (59.0%, p = 0.74). No statistical difference in DWMH loads was found between different RLS grades or subtypes. Instead of RLS grades (p = 0.75), age (OR 1.067; 95%CI 1.034–1.101; p < 0.001) and aura (OR 4.063; 95%CI 1.492–11.061; p = 0.006) were statistically significant independent risk factors for increased DWMH prevalence in migraine patients.ConclusionsOur findings do not support an association between RLS and DWMHs in migraine patients, regardless of RLS grades or subtypes.Clinical Trial Registration: NCT 03418766; Date of registration: February 1, 2018
The Pathological Features of Leukaemic Cells Infiltrating Renal Interstitium in Chronic Lymphocytic Leukaemia/small Lymphocytic Lymphoma Within 10 Years in a Large Single Chinese Centre
Authors: Wang Hui , Yu Xiaojuan , Zhang Xu , Wang Suxia , Zhao Minghui
Published: January 2021

Background Chronic lymphocytic leukemia/Small Lymphocytic Lymphoma (CLL/SLL) was rare in Asians and patients with CLL/SLL rarely undergo kidney biopsy. Little information is available on the histopathological features and clinical relevance of CLL/SLL tubulointerstitial injury. Hence, we attempted to describe the clinical characteristics, renal pathology and clinical outcome of a well characterized population of CLL/SLL patients with CLL infiltration in renal interstitium from a large single center in China.Methods Between January 1st, 2010 to September 31st, 2020, 31946 reanl biopsy pathology were performed at Peking University First Hospital and 10 patients with CLL infiltration in renal interstitium were included. Complete clinical data were collected from these 10 patients and the renal specimens were examined by routine light microscopy, immunonuorescence and electron microscopy examination.Results The extent of infiltrating CLL cells was diverse between different patients, from 10% to 90%. Five patients presented interstitial infiltration with the percent of infiltrate CLL cells≥50%. Proliferation centers were formed in the renal interstitium of 6 patients (6/10, 60%). Intrestingly, we found three patients (3/10, 30%) expressed monoclonal immunoglobulin in infiltrating CLL cells and special crystal structures were found in these cells in two of the three patients for the first time. Conclusions The finding confirmed CLL cells infiltrating in renal interstitium can secret monoclonal immunoglobulins directly, indicating that CLL cells in renal interstitium probably directly involved in local lesion injurys by secrecting monoclonal immunoglobulin. This finding will help understanding the mechanism of renal injury with CLL infiltration, thereby improving our current therapeutic efforts.
Co-Modification With Mesenchymal Stem Cells Membrane and PDA Prevents Fe3O4-Induced Pulmonary Toxicity in Micevia AMPK-ULK1 Axis
Authors: Yao Hua , Yan Jun , Shao Pu , Wang Yuzhuo , Liu Tianxin , Jiang Jinlan , Liu Te
Published: January 2021

Background: Fe3O4 nanoparticles are widely used in the diagnosis and treatment of diseases, but the toxicity should not be ignored. It has been reported that PDA modification can reduce the toxicity of Fe3O4 and increase the biocompatibility. However, a better modification method is still worth studying. We have developed a new method to coat Fe3O4@PDA nanoparticles with mesenchymal stem cells membrane (MSCM) and evaluated the lung toxicity of the modified particles to mice.Result: We found that MSCM modification significantly reduced the lung injury induced by Fe3O4 nanoparticles in mice. Compared with Fe3O4@PDA nanoparticles, co-modification with MSCM and PDA modification significantly reduced autophagy and apoptosis of mouse lung tissue, and reduced the activation of autophagy pathway AMPK-ULK1 axis. Thus, co-modification with MSCM and PDA prevents Fe3O4-induced pulmonary toxicity in mice by inhibiting the AMPK-ULK1 derived autophagy.Conclusion: MSCM coated Fe3O4@PDA nanoparticles were demonstrated to prevent lung damage from autophagy and reduce the toxicity of iron oxide nanomaterials. The co-modification of PDA and MSCM can improve the biocompatibility and facilitate their further bioapplication.
Preliminary Efficacy of Tocilizumab Treatment in The Patients With COVID-19.
Authors: Chen Yu , Zhang Xijing
Published: January 2021

Background: Interleukin-6 (IL-6) was considered to be with the severity and mortality in COVID-19 patients, which implies a potential therapeutic target for treatment. We aimed to evaluate the safety and initial efficacy of Tocilizumab treatment for COVID-19 patients.Methods: In the retrospective study, sixty-one patients with COVID-19 with the mean age of 69 were enrolled from Feb 27 to Mar 14, 2020 in Wuhan Huoshenshan Hospital. Twenty-nine of them received one dose (400 mg) of add-on Tocilizumab treatment as the treated group and remaining 32 cases served as control group. The clinical manifestations and laboratory examinations were compared between the two groups.Results: The average duration of symptoms to admission was 28.2 days. Compared with the cases in control group, the treated cases exhibited a significant increase of serum IL-6 on the seventh day since Tocilizumab injection, however, there were no differences in whole blood white cell count, circulating lymphocyte count, serum C-reactive protein, and respiratory parameters or other clinical manifestations between the treated and control groups. There were no adverse events associated with Tocilizumab treatment in the treated COVID-19 patients.Conclusions: In the elder moderate and severe patients with COVID-19, one dose of Tocilizumab treatment was safe but no clinical benefit was observed on the seventh day in this study.Trial registration: Chinese Clinical Trail Registry, ChiCTR2000033705. Registered June 10, 2020 - Retrospectively registered, http://www.chictr.org.cn/showprojen.aspx?proj=54989.
A Region Within the Third Extracellular Loop of Rat AQP6 Precludes Its Trafficking to Plasma Membrane in a Heterologous Cell Line.
Authors: Soler David , Kowatz Thomas , Sloan Andrew , McCormick Thomas , Cooper Kevin , Stepanyan Ruben , Engel Andreas , Vahedi-Faridi Ardi
Published: January 2021

The inability to over-express AQP6 in the plasma membrane of heterologous cells has hampered efforts to further characterize the function of this aquaglyceroporin membrane protein at atomic detail. Using the AGR reporter system we have identified a region within loop C of AQP6 that is responsible for severely hampering its plasma membrane localization. Serine substitution corroborated that amino acids present within AQP6194-213 of AQP6 loop C contribute to intracellular retention. This intracellular retention signal may preclude proper plasma membrane trafficking and severely curtail expression of AQP6 in heterologous cells.
Deep Learning Method for Prediction of Patient-Specific Dose Distribution in Breast Cancer
Authors: Ahn Sang Hee , Kim EunSook , Kim Chankyu , Cheon Wonjoong , Kim Myeongsoo , Lee Se Byeong , Lim Young Kyung , Kim Haksoo , Shin Dongho , Kim Dae Yong , Jeong Jong Hwi
Published: January 2021

BackgroundPatient-specific dose prediction improves the efficiency and quality of radiation treatment planning and reduces the time required to find the optimal plan. In this study, a patient-specific dose prediction model was developed for a left-sided breast clinical case using deep learning and its performance was compared with that of conventional knowledge-based planning using RapidPlan™.MethodsPatient-specific dose prediction was performed using a contour image of the planning target volume (PTV) and organs at risk (OARs) with a U-net-based modified dose prediction neural network. A database of 50 volumetric modulated arc therapy (VMAT) plans for left-sided breast cancer patients was utilized to produce training and validation datasets. The dose prediction deep neural network (DpNet) feature weights of the previously learned convolution layers were applied to the test on a cohort of 10 test sets. With the same patient data set, dose prediction was performed for the 10 test sets after training in RapidPlan. The 3D dose distribution, absolute dose difference error, dose-volume histogram, 2D gamma index, and iso-dose dice similarity coefficient were used for quantitative evaluation of the dose prediction.ResultsThe mean absolute error (MAE) and one standard deviation (SD) between the clinical and deep learning dose prediction models were 0.02 ± 0.04%, 0.01 ± 0.83%, 0.16 ±0.82%, 0.52 ± 0.97% -0.88 ± 1.83%, -1.16 ± 2.58%, and -0.97 ± 1.73% for D95%, Dmean in the PTV, and the OARs of the body, left breast, heart, left lung, and right lung, respectively, and those measured between the clinical and RapidPlan dose prediction models were 0.02 ± 0.04%, 0.87 ± 0.63%, -0.29 ± 0.98%, 1.30 ± 0.86%, -0.32 ± 1.10%, 0.12 ± 2.13, and -1.74 ±1.79%, respectively.ConclusionsIn this study, a deep learning method for dose prediction was developed and was demonstrated to predict patient-specific doses for left-sided breast cancer accurately. Using the deep learning framework, the efficiency and accuracy of the dose prediction were compared to those of RapidPlan. The doses predicted by deep learning were superior to the results of the RapidPlan-generated VMAT plan. The proposed model will be able to maintain treatment plan quality and increase efficiency through patient dose prediction.
Assessment of Toxicity After 68Ga-PSMA-PET-Imaging Based Treatment Planning and Dose-Escalation in Radiation Therapy in Prostate Cancer Patients
Authors: Schiller Kilian , Dewes Sabrina , Pfetsch Lisa , Vogel Marco MME , Devecka Michal , Sage Eva , Eiber Matthias , Gschwend Jürgen E , Combs Stephanie E
Published: January 2021

PURPOSE: Effective tumor control in prostate cancer demands elevated radiation doses given its low alpha/beta ratio. We investigated in primary and recurrent prostate cancer whether dose-escalated-radiation therapy (DE-RT) based on 68Ga-PSMA-PET positive lesions yields increased toxicity. METHODS: We evaluated 90 patients (salvage DE-RT: 67 patients, DE-re-RT: 11 patients, definite DE-RT: 12 patients) who were treated based on a pre-treatment hybrid 68Ga-PSMA. Findings from pre-treatment hybrid 68Ga-PSMA-PET could result in an adaption of radiation planning. Common Toxicity Criteria of Adverse Effects (Version 4.03) were used to assess toxicity, this was done before the initiation and at the end of DE-RT, as well as at the first and last follow-up (F/U) examination. We evaluated the change in toxicity for each interval for the collective as well as in a per-patient analysis.RESULTS: Findings in 68Ga-PSMA-PET-imaging resulted in a change of TNM-stage in 61.1% and an adapted treatment concept in 71.1% of patients. When comparing overall toxicity before DE-RT and at the last follow-up, 5.9% treatment-related side effects (grade 1-3) occurred with 1.7% of them being severe (grade 3). In a patient-centered approach we examined the intra-individual changes in toxicity before and after DE-RT. At the last F/U, the majority out of 80 patients (range: 61.3-93.8%) stated unchanged toxicity rates compared to the toxicity examined at the initiation of RT.CONCLUSION: The rate of treatment-related toxicity (grade 1-2) due to DE-RT in our cohort is 4.2%. For grade 3 toxicity it is 1.7%, respectively. The overall level of toxicity is highest during and shortly after completion of DE-RT (+7.4%) and improves over time until the last reported F/U (+5.9%). Compared to historical data, the toxicity profile of DE-RT is not increased. Therefore it is possible to apply DE-RT with the aim to increase tumor control by precisely treating all involved areas according to PSMA-PET-imaging.
The Impact of the Fidelity of Simulation on Medical Undergraduate Education: A Meta-Analysis
Authors: Hua Yan , Cen Xiao-yan , Niu Sha , Yu Tao
Published: January 2021

Background: With the development of science and technology, simulation-based education has also developed rapidly. However, whether the fidelity level of simulators has a positive correlation with medical students' learning outcomes is controversial. This study aims to compare the theoretical knowledge, skill performance and confidence of undergraduate medical students through meta-analysis according to the fidelity level of the simulator.Methods: Two researchers independently searched the PubMed database, the Cochrane Library, and the Embase database through October 20, 2020, to retrieve articles on the differences in effectiveness between high-fidelity simulators and low-fidelity simulators in undergraduate medical education. The Cochrane risk of bias tool was used to evaluate all included literature. Quantitative meta-analysis of the included literature was performed with Review Manager 5.3.Results: Fifteen studies met the inclusion criteria, 11 of which were meta-analysed. Meta-analysis showed whether there were differences in students’ theoretical knowledge [standardized mean difference -0.51; 95% CI -1.30～0.29，P=0.21], skill performance [standardized mean difference -0.26; 95% CI -0.87～0.35, P = 0.40], and confidence [standardized mean difference 2.53; 95% CI -1.05～6.10, P = 0.17]: there were no significant differences between high-fidelity simulators and low-fidelity simulators.Conclusions: In medical undergraduate education, students who experience low-fidelity simulator training are not inferior to students who learn from high-fidelity simulators in their theoretical knowledge, skill performance, or confidence.
Using Markov Chain Model to Evaluate Medical Students’ Trajectory on Progress Tests and Predict USMLE Step 1 Scores
Authors: Wang Ling , Laird-Fick Heather S. , Parker Carol J. , Solomon David
Published: January 2021

Medical students must meet curricular expectations and pass national licensing examinations to become physicians. The Michigan State University College of Human Medicine implemented progress testing in place of discipline-specific examinations as its primary assessment of knowledge in 2016. Ideally this innovative assessment strategy will characterize students’ growth in basic science knowledge over time and predict licensing examination performance.Markov chain method was employed to: 1) identify latent states of acquiring scientific knowledge based on progress tests, 2) estimate students’ transition probabilities between states, and 3) predict United States Medical Licensing Examination Step 1 results based on the students’ predicted probabilities in each state. A total of 358 students were included in the analysis. Four latent states were identified based on students’ progress test results: Novice, Advanced Beginner I, Advanced Beginner II and Competent States. At the end of the first year, students predicted to remain in the Novice state had lower mean Step 1 scores compared to those in the Competent state (209, SD = 14.8 versus 255, SD = 10.8 respectively) and had more first attempt failures (11.5% versus 0%). On regression analysis, it is found that at the end of the first year, if there was 10% higher chance staying in Novice State, Step 1 scores will be predicted 2.0 points lower (P< .01); while 10% higher chance in Competent State, Step 1scores will be predicted 4.3 points higher (P< .01). Similar findings were also found at the end of second year medical school.Using the Markov chain model to analyze longitudinal progress test performance offers a flexible and effective estimation method to identify students’ transitions across latent stages for acquiring scientific knowledge. The results can help identify students who are at-risk for licensing examination failure and may benefit from targeted academic support.
Systemic Sclerosis Patients With Negative Antinuclear Antibodies Have Distinctive Clinical Manifestations: a Multicenter CRDC Cohort in China
Authors: Hui Min , Zhou Jiaxin , Zhang Liyun , Duan Xinwang , Li Mengtao , Wang Qian , Zhao Jiuliang , Hou Yong , Xu Dong , Zeng Xiaofeng
Published: January 2021

Objective: The presence of circulating antinuclear antibodies (ANAs) is a hallmark of immune dysregulation in patients with systemic sclerosis (SSc). A variety of ANAs are associated with unique sets of disease manifestations and are widely used in clinical practice for diagnosis, clinical subgrouping, and prediction of future organ involvement and prognosis in SSc. This study aimed to investigate the clinical features of SSc patients negative for ANAs in a Chinese Rheumatism Data Center (CRDC) multicenter cohort in China.Methods: Based on the CRDC database, patients were prospectively recruited between April 2008 and June 2019 from 154 clinical centers nationwide, and all cases fulfilled the 2013 ACR/EULAR classification criteria for systemic sclerosis. Results for antinuclear antibodies were intensively collected. Demographic, clinical, and laboratory data were compared between ANA-positive SSc patients and those negative for ANAs.Results: Antinuclear antibodies were detected in 2129 of 2809 patients enrolled in the study; 4.2% patients were negative. There was a significant difference between patients negative and positive for ANAs based on sex (29/60 vs 294/1746, p＜0.001). The presence of Raynaud’s phenomenon was less common (71.8% vs 91.8%, p＜0.001) in the ANA-negative patients. In addition, the incidence of certain critical organ involvement, including gastroesophageal reflux (5.6% vs 18.5%, p=0.002), interstitial lung disease (65.2% vs 77.9%, p=0.015) and pulmonary arterial hypertension (11.5% vs 29.0%, p=0.006), was significantly lower in ANA-negative patients than in ANA-positive patients. The proportion of abnormal ESR (32.4% vs 47.6%, p=0.013) and IgG elevation (14.3% vs 37.0%, p=0.003), an indicator of disease activity, was significantly lower in ANA-negative patients than in ANA-positive patients.Conclusion: Antinuclear antibodies are strongly associated with the clinical manifestations of systemic sclerosis, with ANA-negative SSc patients tending to exhibit relatively milder disease.
Molecular detection of Epstein-Barr virus in paraffin-embedded tissue samples of patients suffering gastric cancer in Ahvaz, Iran: a case-control study
Authors: Gharibzadeh Mehdi , Azaran Azarakhsh , Jalilian Shahram , Seyedian Seyed Saeid , Makvandi Manoochehr
Published: January 2021

Background

Gastric cancer (GC) is the third most common cause of cancer-related mortality. Epstein-Barr virus (EBV) is associated with gastric cancer. The present research was performed to investigate the prevalence of EBV-associated gastric cancer (EBVaGC) among Iranian patients.
Materials and Methods

Seventy formalin-fixed paraffin-embedded (FFPE) cases of gastric cancer and 30 FFPE cases of gastric ulcer were studied from 2011–2018 in the case-control study. The specimens were investigated for the presence of the EBV genome by Nested-PCR for EBNA1. The positive samples for the EBNA1 region were again tested for the EBER gene by the PCR method. Positive samples were sequenced and aligned to construct the EBV phylogenetic tree.
Results

Five out of 70 cases (7%) indicated positive results for EBV by EBNA1, while all EBNA1 positive samples were negative for EBER. Additionally, EBV was detected in none of the gastric ulcer patients. The mean age for patients with EBV-positive gastric carcinomas was 64.5 years. Three (60%) male patients and 2 (40%) female cases were positive for EBV. Three out of 24 (60%) diffuse-type cases were EBV associated, and 2 out of 46(40%) intestinal-type were EBV positive. most cases of EBVaGC were seen in grade Ⅰ.
Conclusion

The present study shows that the frequency of EBVaGC in Iran is low. Differences in EBVaGC incidence in different countries may represent epidemiologic factors and dietary habits. Further analysis of clinical pathology characteristics of EBVaGC using a greater number of cases will offer useful insights into its etiology.
Lovastatin Inhibits EMT and Metastasis of Triple-Negative Breast Cancer Stem Cells Through Dysregulation of Cytoskeleton-Associated Proteins
Authors: Zheng Chanjuan , Yan Shichao , Lu Lu , Yao Hui , He Guangchun , Chen Sisi , Li Ying , Peng Xiaojun , Cheng Zhongyi , Wu Mi , Zhang Qiuting , Li Guifei , Fu Shujun , Deng Xiyun
Published: January 2021

Background

Triple-negative breast cancer (TNBC) is more aggressive and has poorer prognosis compared to other subtypes of breast cancer. Epithelial-to-mesenchymal transition (EMT) is a process in which epithelial cells transform into mesenchymal-like cells capable of migration, invasion, and metastasis. Recently, we have demonstrated that lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor and a lipid-lowering drug, could inhibit stemness properties of cancer stem cells (CSCs) derived from TNBC cell in vitro and in vivo. This study is aimed at investigating whether lovastatin inhibits TNBC CSCs by inhibiting EMT and suppressing metastasis and the mechanism involved.
Methods

LC-MS/MS was used to identify differentially regulated lysine acylation between TNBC and non-TNBC CSCs. In vivo, two nude mouse models were used to study the tumor growth, EMT phenotype, and metastasis of breast CSCs. The effect of lovastatin on EMT-related proteins was examined by immunohistochemistry, western blot and immunofluorescence-confocal microscopy. TGF-β1-challenged immortalized mammary epithelial cells MCF10A were treated with lovastatin and the change of cell morphology were detected by microscopic examination. Cell migration was detected by wound-healing assay. The formation of pseudopodia and the distribution of F-actin were investigated by transmission electron microscopy (TEM) and immunofluorescence-confocal microscopy, respectively. Bioinformatics analysis was used to evaluate the correlation between the expression of cytoskeleton-associated genes and overall survival of breast cancer patients.
Results

Lovastatin dysregulated lysine succinylation of cytoskeleton-associated proteins in CSCs derived from TNBC MDA-MB-231 cell. Lovastatin inhibited EMT as demonstrated by down-regulation of the protein levels of Vimentin and Twist in MDA-MB-231 CSCs in vitro and vivo and by reversal of TGF-β1-induced morphological change in MCF10A cells. Combination of lovastatin with doxorubicin synergistically inhibited liver metastasis of MDA-MB-231 CSCs. Lovastatin also inhibited the migration of MDA-MB-231 CSCs. The disruption of cytoskeleton in TNBC CSCs by lovastatin was demonstrated by the reduction of the number of pseudopodia and the relocation of F-actin cytoskeleton. Bioinformatics analysis revealed that higher expression levels of cytoskeleton-associated genes were characteristic of TNBC and predicted poorer overall survival in breast cancer patients.
Conclusions

Lovastatin could inhibit the EMT and metastasis of TNBC CSCs in vitro and in vivo through dysregulation of cytoskeleton-associated proteins.
PNO1 promotes human cholangiocarcinoma tumorigenesis and chemosensitivity
Authors: Chen Chuang , Huang Shan , Wu Guobin , Wang Zongyu , Lin Dongyi , He Jianbo , Li Kezhi , Han Zhiwei , Chen Xinxin , Qiu Wenxia , Wang Yu , Zhao Shulei , Gong Wei , Xu Shifeng
Published: January 2021

Background

The partner of NOB1 homolog (PNO1) is important for ribosome biogenesis and serves as an oncogene in several cancers. However, the role of PNO1 in cholangiocarcinoma (CHOL) remains largely unknown.
Methods

The method of mRNA microarray analysis, high-throughput screening technologies, on-line databases analysis, PDXs models, biochemistry and molecular biology have been utilized to reveal the role of PNO1 in the progression of CHOL.
Results

PNO1 was significantly upregulated in CHOL tissues and predicted poor prognosis. PNO1 could induce cell proliferation and metastasis in vitro and in vivo. In CHOL cells expressing wild-type p53, PNO1 knockdown increased expression of p53 and its downstream gene p21 and decreased cell viability; these effects were blocked by p53 knockout and attenuated by the p53 inhibitor PFT-a. Furthermore, PNO1 knockdown reduced global protein synthesis and inhibiting MDM2-mediated ubiquitination and p53 degradation. Moreover, PNO1 overexpression enhanced the sensitivity to bortezomib treatment in CHOL. In addition, MYC overexpression promoted PNO1 promoter activity while MYC knockdown decreased PNO1 mRNA and protein, which led to decreased cell viability and clone formation. The expression of MYC was found positively correlated with PNO1 in CHOL patients.
Conclusions

Collectively, upregulation of PNO1 by MYC promotes cholangiocarcinoma tumorigenesis through suppressing p53 signaling pathway and enhanced the sensitivity to bortezomib treatment. PNO1 serves as a candidate of therapeutic target in CHOL treatment and clinical chemotherapy regimen.
A combined Globo H-OCT4-T7 immunotherapy restrains colorectal tumor growth
Authors: Xu Jiangyao , Liu Maixian , Liu Shikang , Liu Kan , Ouyang Zijun , Jin Guangyi , Lu Desheng , Jiang Wenxiao , Shu Xingsheng , Xu Gaixia , Li Yang , Wu Christina C. N. , Chen Meiyi , Lin Guimiao , Wang Xiaomei
Published: January 2021

Background: Malignant tumors express multiple common markers that might constitute targets for tumor immunotherapy. Methods: Here we performed antigen epitope screening and molecular docking to design a new combination vaccine based on covalently linking Globo H and Oct 4 with a TLR7 agonist. We mainly use flow cytometry to analyze the changes in lymphocyte differentiation after the vaccine is applied. Use Elisa technology to detect the antibodies produced by the vaccine and the changes in lymphokines. In order to supplement the immunological data, RNA sequencing was performed on untreated and vaccine-treated tumors to define the interference of the vaccine on the genome-wide gene expression profile.Results: Our results demonstrated that the Globo H-OCT4-T7 conjugate vaccine effectively induced cellular uptake, maturation and antigen presentation of BMDCs. The combination vaccine enhanced cytokine production, CTLs activity elicited high levels of IgG. Importantly, the tumor immune microenvironment was significantly improved in tumor-bearing mice treated by Globo H-OCT4-T7 conjugate vaccine, demonstrated by increased the ratio of M1 to M2 TAMs, reduced number of Tregs in PBMCs and promoted the infiltration of tumor-specific IFN γ-producing CD8+ T cells. Prophylactic vaccination of Globo H-OCT4-T7 significantly reduced tumor growth by >80 % in both CT26 transplanted mice and in a human PDX mouse model when exposing mice to the combined vaccine compared to control. Our novel, combination vaccine is safe and effective at preventing tumor growth in mice. Conclusions: This combination vaccine is more effective than the single vaccine, and thus has the potential to prevent OCT4 and Globo H from expressing cancer.
Genetic Characterization and Genome-Wide Association Mapping for Stem Rust Resistance in Spring Bread Wheat
Authors: Shewabez Elias , Bekele Endashaw , Alemu Admas , Mugnai Laura , Tadesse Wuletaw
Published: January 2021

Background Emerging wheat stem rust races has become a major threat to global wheat production. Finding additional loci responsible for resistance to these races and incorporating them into currently cultivated varieties is the most economical and environmentally sound strategy to combat this problem. Thus, this study aimed to characterize the genetic diversity of wheat and to identify the genetic loci conferring resistance to stem rust of wheat. To accomplish this study, 245 elite lines introduced from the International Center for Agricultural Research in the Dry Areas (ICARDA) were tested under natural stem rust pressure in the field at the Debre Zeit Agricultural Research Center, Ethiopia. The SNP marker data was retrieved from a 15K SNP wheat array. Association analysis was undertaken between SNP markers and best linear unbiased prediction (BLUP) value of the stem rust coefficient of infection (CI) using a mixed linear model. Results Phenotypic analysis revealed 46% of lines had a coefficient of infection (CI) between 0 to 19. An average 0.38 in Nei’s gene diversity, 0.20 in polymorphism information content, and 0.71 in major allele frequency of the whole genome were identified.A total of 46 marker-trait associations (MTAs) that were encompassed within 13 quantitative trait loci (QTL) on chromosomes 1B, 3A, 3B, 4A, 4B, and 5A were found for CI. Four major QTLs with –log10 (p) ≥ 3 (EWYP1B.1, EWYP1B.3, EWYP1B.4, and EWYP1B.5) were identified on chromosome 1B. Conclusions This study contributes several novel markers associated with stem rust resistance. These can be further facilitating durable rust resistance development through marker-assisted selection. The resistant wheat genotypes identified in this study are recommended to be used in the national wheat breeding programs to improve stem rust resistance. Key words: markers; Puccinia graminis f. sp. tritici; QTL