bluuebunny/crossref_metadata_2025 huggingface dataset:
3D Simulation of Radiographic Projections to Test and Reduce the Effect of Pelvic Tilt on the Accuracy of Cross-table Lateral Radiography
Authors: Xu Jie , Su Baohua , Zhang Wenhui , Sun Hao , Li Deng , Cai Zhiqing , Chen Meiyi , Qiu Meiling , Ma Ruofan
Published: July 2020

Background:Cross-table lateral (CL) radiography is aconvenientandfeasible method toassess cup version angle (VA) after total hip arthroplasty; however, the pelvic tilt (PT) may contribute to its measurement inaccuracy.We sought (1) to determinethe effect of the PT on cup version measurement on CL radiography and (2) to develop a method for reducing measurement errors caused by the PT.Methods: Two groups of VAswere measured respectively on 3D simulatedCL images and CL radiographs. Based on the data, we created a corrective formula to convert the radiographic measurements into values approximating the actual VA under a natural pelvic position. The corrected valueswere compared with computed tomography (CT) measurements to verified the corrective formula. Results:There was a high correlation between the measurements and PTs. For each 1-degree increased in the PT, the VA decreased by 0.76° (R²=0.995, p<0.001). The VA measurements corrected by our equation was in high agreement with the CT-measured valueswithreferenceto the corresponding PT (intra-class correlation coefficient [ICC]=0.988, p<0.001), which was in sharp contrast to that without PT control (ICC=0.454, p=0.203).Conclusions: ThePT may contribute to cup version measurement inaccuracies on CL radiography. Our mathematical algorithm can serve as a reliable method to improve the accuracy of CL radiography.
Nanopolystyrene Translocation and Fetal Deposition After Acute Lung Exposure During Late-Stage Pregnancy
Authors: Fournier Sara B , D’Errico Jeanine N , Adler Derek S , Kollontzi Stamatina , Goedken Michael J , Fabris Laura , Yurkow Edward J , Stapleton Phoebe A
Published: July 2020

Background: Plastic is everywhere. It is used in food packaging, storage containers, electronics, furniture, clothing, and common single-use disposable items. Microplastic and nanoplastic particulates are formed from bulk fragmentation and disintegration of plastic pollution. Plastic particulates have recently been detected in indoor air and remote atmospheric fallout. Due to their small size, microplastic and nanoplastic particulate in the atmosphere can be inhaled and may pose a risk for human health, specifically in susceptible populations. When inhaled, nanosized particles have been shown to translocate across pulmonary cell barriers to secondary organs, including the placenta. However, the potential for maternal-to-fetal translocation of nanosized-plastic particles and the impact of nanoplastic deposition and accumulation on fetal health remain unknown. In this study we investigated whether nanopolystyrene particles can cross the placental barrier and deposit in fetal tissues after maternal pulmonary exposure.Results: Pregnant Sprague Dawley rats were exposed to 20 nm rhodamine-labeled nanopolystyrene beads (2.64 x 1014 particles) via intratracheal instillation on gestational day (GD) 19. Twenty-four hours later on GD 20, maternal and fetal tissues were evaluated using fluorescent optical imaging. Fetal tissues were fixed for particle visualization with hyperspectral microscopy. Using isolated placental perfusion, a known concentration of nanopolystyrene was injected into the uterine artery. Maternal and fetal effluents were collected for 180 minutes and assessed for polystyrene particle concentration. Twenty-four hours after maternal exposure, fetal and placental weights were significantly lower (7% and 8%, respectively) compared with controls. Nanopolystyrene particles were detected in the maternal lung, heart, and spleen. Polystyrene nanoparticles were also observed in the placenta, fetal liver, lungs, heart, kidney, and brain suggesting maternal lung-to-fetal tissue nanoparticle translocation in late stage pregnancy.Conclusion: These studies confirm that maternal pulmonary exposure to nanopolystyrene results in the translocation of plastic particles to placental and fetal tissues and renders the fetoplacental unit vulnerable to adverse effects. These data are vital to the understanding of plastic particulate toxicology and the developmental origins of health and disease.
Effects of chronic kidney disease on mid- and long-term clinical outcomes after off-pump coronary artery bypass grafting-a retrospective study
Authors: Li Xihui , Song Bo , Dong Shiyong , Zhang Siyu
Published: July 2020

Backgroud: To investigate the effect of chronic kidney disease (CKD) on mid- and long-term clinical outcomes after off-pump coronary artery bypass grafting (CABG).Methods: This was a retrospective analysis of data of 1141 patients discharged from the Department of Cardiac Surgery, Peking University First Hospital from January 2010 to June 2018 after undergoing off-pump CABG. Preoperative baseline, operative, and follow-up data obtained at regular outpatient visits or by telephone calls were collected. Follow-up endpoints included stroke, nonfatal myocardial infarction, heart failure, revascularization, and all-cause death. Patients with preoperative estimated glomerular filtration rate calculated, using the Chronic Kidney Disease Epidemiology equation of≥ 60 mL/min/1.73 m2 and < 60 mL/min/1.73m2, were assigned to normal Group (1, 910 cases) and CKD group (231 cases), respectively. The effects of CKD on selected endpoint events were compared and analyzed.Results: There was a higher proportion of women, more preoperative complications, and a higher incidence of early postoperative complications in patients with CKD than in those with normal renal function. After 1–9 years of follow-up (mean5.0±2.2 years), the incidences of stroke, non-fatal myocardial infarction, and all-cause mortality were significantly higher in the CKD than in the normal renal function group, whereas incidences of revascularization and heart failure were not. Logistic regression analysis showed that preoperative CKD was a risk factor for stroke, non-fatal myocardial infarction, and all-cause death during follow-up. After correcting for common confounding factors, such as sex, age, and left ventricular ejection fraction, preoperative CKD was a risk factor for non-fatal myocardial infarction (OR 2.675, 95% CI 1.023–6.995, P=0.045) and all-cause death (OR 1.833, 95% CI 1.079–3.114, P=0.025).Conclusions: In patients undergoing off-pump CABG, preoperative CKD is associated with increases in the incidences of mid- and long-term non-fatal myocardial infarction and all-cause mortality.
Detection and prevalence of depression among adult type 2 diabetes mellitus patients attending non-communicable diseases clinics in Lilongwe, Malawi
Authors: Udedi Michael , Pence Brian W. , Stewart Robert C. , Muula Adamson S.
Published: July 2020

Background
Depression is associated with chronic physical illnesses and negatively affects health outcomes. However, it often goes undiagnosed and untreated. We investigated the prevalence of depression among adult type 2 diabetes mellitus (T2DM) patients attending non-communicable diseases (NCD) clinics in Lilongwe, Malawi, and estimated the level of routine detection by NCD clinicians. This study set out to determine the prevalence of major depression and its detection among adult type 2 diabetes mellitus (T2DM) patients attending NCD clinics in Lilongwe, Malawi.
Methods
In a cross-sectional study design, 323 T2DM patients aged ≥ 18 years were screened for depression with the Patient Health Questionnare-9 (PHQ-9) followed by diagnostic assessment with the Structured Clinical Interview for DSM-IV (SCID). We analysed the association between presence of major depression and sociodemographic factors using logistic regression.
Results
Three quarters of the participants (76%) were females. The participants’ ages ranged from 21–79 years. Of the 323 participants, 58 (18%) met criteria for DSM-IV major depression. None of the cases of major depression had been identified by the NCD clinicians. Major depression was found not to be significantly associated with any of the sociodemographic factors.
Conclusions
We found that depression is common among NCD clinic attendees with T2DM in Malawi,, and poorly detected by NCD clinicians. Given the high prevalence and challenges in clinical identification, integration of depression screening with a standardized validated tool should be a high priority so as to link patients to appropriate services.
Immediate Bystander Response to Sudden Cardiac Arrest During Sports is Associated with Improved Survival -- A Video Analysis.
Authors: Panhuyzen-Goedkoop Nicole M , Wellens Hein JJ , Verbeek Andre LM , Piek Jan J , Peters Ron JG
Published: July 2020

Background Sudden cardiac arrest (SCA) during sports can be the first symptom of yet undetected cardiovascular conditions. Immediate chest compressions and early defibrillation offer SCA victims the best chance of survival, which requires prompt bystander response.Aims To determine the effect of rapid bystander response to SCA during sports by searching for and analyzing videos of these SCA/SCD events from the internet.Methods We searched images.google.com, video.google.com and YouTube.com, and included any camera-witnessed non-traumatic SCA in athletes and other sports participants at any sports facility. The rapidity of starting bystander chest compressions and defibrillation was classified as <3, 3-5, or >5 minutes. The year SCA occurred was allocated to 1990-2009, 2010-2014 or 2015 onwards, compatible with the current guidelines.ResultsWe identified and included 28 victims of average age 27.9 years (SD=9.8); 27 were males, 22 elite athletes, and 17 participated in soccer. Bystander response <3 minutes (6/28) or 3-5 minutes (1/28) and defibrillation <3 minutes was associated with 100% survival. Not performing chest compressions and defibrillation was associated with death (14/28), and >5 minutes delay of intervention with worse outcome (death 4/28, severe neurologic dysfunction 1/28). Survival was highest between 2010-2014 (71.4%).ConclusionsAnalysis of internet videos showed that immediate bystander response to non-traumatic SCA during sports was associated with improved survival. This suggests that immediate chest compressions and early defibrillation are crucially important in SCA during sport, as they are in other settings. Optimal use of both will most likely result in survival. The observed bystander responses to SCA during sports do not show awareness of current guidelines.
Adjuvant Radiotherapy and Chemoradiation in Elderly Patients with Squamous Cell Carcinoma of the Head and Neck
Authors: Süß Christoph , Ratzisberger Anna , Hipp Matthias , Ettl Tobias , Kuenzel Julian , Krupar Rosemarie , Evert Katja , Steger Felix , Kölbl Oliver , Hautmann Matthias G.
Published: July 2020

Background:Radiotherapy and chemoradiation are well-established therapies for patients with squamous cell carcinoma of the head and neck (SCCHN). In aging societies, also the incidence of SCCHN in elderly patients is rising. Because of the underrepresentation of elderly patients in scientific trials, we evaluated the feasibility of adjuvant radiotherapy and chemoradiation in patients with SCCHN aged >70 years. Methods:All patients had been >70 years at the time of diagnosis and received adjuvant radiotherapy or, if feasible, chemoradiation at the University Medical Centre Regensburg between 2004 and 2018.71 patients -most with SCCHN UICC stage IVa- with a median age of 75 years were included; 9 patients received concomitant chemoradiation. Median follow-up was 27 months (IQR 18 – 62 months).Results:Radiotherapy and chemoradiation was well tolerated. 62 patients (87.3%) underwent treatment without interruption, and 65 patients (91.5%) completed radiotherapy with 95% of the initially prescribed dose. Median dose for all patients was 64 Gy (IQR: 60 – 66 Gy). 6/9 patients received at least 75 % of the planned chemotherapy dose. 37 patients (52.1%) developed acute toxicity CTC grade III or IV.Overall survival was 87 % after 12 months, 67 % after 24 months and 41 % after 60 months. Median overall survival was 51 months (IQR: 19 - 99 months). Local tumour control was 99 % after 12 months, 88 % after 24 months and 76 % after 5 years.Conclusion:Feasibility of adjuvant radiotherapy and chemoradiation in our collective of elderly patients with SCCHN was good. Particularly local tumour control was satisfactory. Overall survival does not seem to differ between elderly and younger patients or patients unselected for age. De-intensification of treatment because of age does not seem justified.
Prognostic Role of Preoperative D-Dimer, Fibrinogen and Platelet Levels in Patients with Oral Squamous Cell Carcinoma
Authors: Liang Yu-jie , Mei Xue-ying , Zeng Bin , Zhang Si-en , Yang Le , Lao Xiao-mei , Liao Gui-qing
Published: July 2020

Background: The relationship between cancer and coagulation have been intensively studied in recent years, however, the effects of coagulation factors on oral squamous cell carcinoma (OSCC) had not been reported. This study aimed to investigate the relationship between preoperative D-dimer (DD), fibrinogen (FIB), platelet (PLT) and OSCC, as well as the prognostic value of them. Methods: We retrospectively investigate a total of 202 OSCC patients treated in Guanghua Hospital of Stomatology, Sun Yat-sen University. Baseline demographic and clinicopathological information as well as both preoperative and postoperative DD, FIB and PLT results were collected from each patient if available, all patients were follow-up to disease progression, death or end of study. The correlations between preoperative DD, FIB, PLT and other clinical features, therapeutic effect and PFS were analyzed statistically, postoperative DD and surgical parameters were also analyzed.Results: Preoperative DD were found significantly correlated with T stage, N stage, Clinical stage and relapse of OSCC (P=0.000, 0.001, 0.000 and 0.000, respectively). Univariate and multivariate Cox regression analysis showed that, high preoperative DD independently predict poor prognosis in patients with OSCC (r=2.1, P=0.033). While FIB and PLT showed no prognostic values. Postoperative DD were found significantly correlated with preoperative DD and surgical type, but not the time consuming of surgery (P=0.005, 0.001 and 0.244, respectively). Conclusion: In this study, for the first time, we reported that, preoperative plasma DD was an independent predictor for OSCC stage and patient survival.
Prognostic significance of surgery after chemotherapy in patients with type 4 gastric cancer
Authors: Arigami Takaaki , Matsushita Daisuke , Okubo Keishi , Tanaka Takako , Sasaki Ken , Noda Masahiro , Kita Yoshiaki , Mori Shinichiro , Kurahara Hiroshi , Yanagita Shigehiro , Uenosono Yoshikazu , Ishigami Sumiya , Ohtsuka Takao
Published: July 2020

Background

The majority of patients with type 4 gastric cancer have distant metastases with extremely poor prognosis. Consequently, considering a therapeutic strategy that improves the prognosis of these patients is clinically important. The present study aimed to assess the clinical indication and prognostic impact of surgery in patients with type 4 gastric cancer who underwent chemotherapy.
Methods

A total of 67 patients with type 4 gastric cancer who underwent chemotherapy were retrospectively enrolled. All patients were grouped into progressive disease (PD) and non-PD groups by tumor response to chemotherapy.
Results

Distant metastases occurred in 58 patients. With regard to tumor response, 16 and 51 patients had PD and non-PD, respectively. The prognosis was significantly poorer in patients with PD than in those with non-PD (p < 0.0001). Among 23 patients who underwent surgery after chemotherapy, 21 had a R0 resection. The presence or absence of surgery was significantly correlated with age, first-line chemotherapeutic regimen, lymph node metastasis, clinical stage, number of distant metastatic sites, peritoneal dissemination, and tumor response (p = 0.0412, p = 0.0096, p = 0.0024, p = 0.0059, p = 0.0128, and p = 0.0020, and p = 0.0066, respectively). Multivariate analysis selected tumor response and surgery as an independent prognostic factor (p = 0.0001 and p = 0.0009, respectively). Moreover, multivariate analysis for the surgery group demonstrated that metastatic nodal status (N0-1 vs N2-3) and residual tumor status (R0 vs R1-2) were significant independent prognostic factors (p = 0.0258 and p = 0.0458, respectively).
Conclusion

Our retrospective study suggests that surgery after chemotherapy for type 4 gastric cancer may improve the prognosis of responders with N0-1 status and a curative R0 resection.
Protein synthesis inhibitors stimulate MondoA transcriptional activity by driving an accumulation of glucose 6-phosphate
Authors: Wilde Blake R , Kaadige Mohan R , Guillen Katrin P , Butterfield Andrew , Welm Bryan E , Ayer Don
Published: July 2020

BACKGROUND Protein synthesis is regulated by the availability of amino acids, the engagement of growth factor signaling pathways and ATP levels sufficient to support translation. Crosstalk between these inputs is extensive, yet other regulatory mechanisms remain to be characterized. For example, the translation initiation inhibitor Rocaglamide A (RocA) induces Thioredoxin Interacting Protein (TXNIP). TXNIP is a negative regulator of glucose uptake, thus its induction by RocA links translation to the availability of glucose. MondoA is the principal regulator of glucose-induced transcription and its activity is triggered by the glycolytic intermediate, glucose 6-phosphate (G6P). MondoA responds to G6P generated by cytoplasmic glucose and mitochondrial ATP (mtATP), suggesting a critical role in the cellular response to these energy sources. TXNIP expression is entirely dependent on MondoA, therefore, we investigated how protein synthesis inhibitors impact its transcriptional activity. METHODS We investigated how translation regulates MondoA activity using cell line models and loss-of-function approaches. We examined how protein synthesis inhibitors effect gene expression and metabolism using RNA-sequencing and metabolomics, respectively. The biological impact of RocA was evaluated using cell lines and Patient-Derived xenograft Organoid (PDxO) models. RESULTS We discovered that multiple protein synthesis inhibitors, including RocA, increase TXNIP expression in a manner that depends on MondoA, a functional electron transport chain and mtATP synthesis. Furthermore, RocA increases mtATP and G6P levels and TXNIP induction depends on interactions between the Voltage-Dependent Anion Channel (VDAC) and hexokinase, which generates G6P. RocA treatment impacts the regulation of ~1200 genes and ~250 of those genes are MondoA-dependent. RocA treatment is cytotoxic to Triple Negative Breast Cancer cell lines and shows preferential cytotoxicity against ER- PDxO breast cancer models. Finally, RocA-driven cytotoxicity is partially-dependent on MondoA or TXNIP. CONCLUSIONS Our data suggest that protein synthesis inhibitors rewire metabolism, resulting in an increase in mtATP and G6P, the latter driving MondoA-dependent transcriptional activity. Further, MondoA is a critical component of the cellular transcriptional response to RocA. Our functional assays suggest that RocA or similar translation inhibitors may show efficacy against ER- breast tumors and that the levels of MondoA and TXNIP should be considered when exploring these potential treatment options.
Cardiovascular Implications of Coronavirus Disease 2019 (COVID-19): A Systematic Review
Authors: Pradhan Ravi Ranjan , Yadav Ajay Kumar , Mandal Shobha
Published: July 2020

Background: World Health Organization has declared Coronavirus disease (COVID-19) as a Public Health Emergency of International Concern. It has killed thousands and millions are infected worldwide. Though COVID-19 is supposed to be primarily a disease of respiratory system, it also has widespread implications on other systems as well. The aim of this systematic review is to summarize the cardiovascular implications of COVID-19. Methods: PubMed, PubMed Central, EMBASE, and Google Scholar were searched for peer-reviewed articles which aimed to delineate the cardiovascular implications of COVID-19.Results: A total of six articles (five original articles and one case report) were included. We found diverse cardiovascular implications of COVID-19 ranging from acute cardiac injury to death. New onset abnormalities in electrocardiogram or echocardiogragram, elevated plasma levels of cardiac troponin, NT-proBNP, and D-dimer have role in early identification of acute cardiac injury in such patients. Additionally, cardiac troponin and NT-proBNP can be used to evaluate prognosis and possible need for intensive care in these patients.Conclusion: Acute cardiac injury is common in patients with COVID-19. Aggressive supportive management based on prognostic indicators along with management of heart failure, arrhythmias, acute coronary syndrome and thrombosis can improve clinical outcomes in such patients.
Long Non-Coding RNA GATA6-AS1 Inhibits Proliferation and Promotes Apoptosis of Lung Adenocarcinoma Through Sponging miR-331-3p and Regulating SOCS1/JAK2/STAT3 Pathway
Authors: Huo Xiaodong , Wang Huixing , Jiang Ning , Yang Kuo , Huo Bin , Wang Lili , Wang Jinhuan , Wang Haitao
Published: July 2020

Background: Accumulating evidence has indicated the remarkable roles of long non-coding RNAs (lncRNAs) as oncogenes or tumor suppressors in many malignancies. The involvement of lncRNA GATA6-AS1 in cancers remains largely undiscovered. Herein, our research was aimed at elucidating the function and mechanism of GATA6-AS1 in lung adenocarcinoma (LUAD).Methods: Gene expression was measured through qRT-PCR and WB. Cell proliferation ratio was determined using CCK-8 and EdU assays. Cell apoptosis ratio was determined using TUNEL and flow cytometry assays. Molecular interactions were examined through RIP, RNA pull-down and luciferase reporter assays.Results: GATA6-AS1 expression was markedly down-regulated in LUAD cell lines. GATA6-AS1 could inhibit LUAD cell proliferation and promote cell apoptosis. Mechanistically, GATA6-AS1 was identified as the molecular sponge for miR-331-3p, whose knockdown in LUAD cells could reinforce the tumor-suppressing effects of GATA6-AS1 overexpression. Moreover, GATA6-AS1 functions as a competing endogenous RNA (ceRNA) through sequestering miR-331-3p to deregulate SOCS1, thus inhibiting JAK2/STAT3 signaling pathway and suppressing LUAD cell viability.Conclusions: These results demonstrate the tumor-suppressing function and mechanism of lncRNA GATA6-AS1 in LUAD cells. The axis of GATA6-AS1/miR-331-3p/SOCS1/JAK2/STAT3 can be adopted as a novel approach for LUAD treatment.
Identification of key genes in head and neck squamous cell carcinoma microenvironment based on gene expression profile
Authors: Xu Lei , Jin Yu , Qin Xing
Published: July 2020

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent malignancy worldwide with high incidence and mortality. Recently, it has been well established that tumor microenvironment (TME) is intimately associated with cancer progression, in which the infiltration of immune and stromal cells could be exploited as effective biomarkers for cancer diagnosis and prognosis. In this study, we aimed to investigate HNSCC microenvironment to identify significant genes involved in carcinogenesis.
Methods: The ESTIMATE algorithm was applied to calculate immune scores and stromal scores based on the gene expression profiles downloaded from The Cancer Genome Atlas (TCGA) database and the correlation of these scores with clinical parameters and prognosis was further analyzed. Differential expression analysis and functional enrichment analysis were performed by R software.
Results: Immune scores and stromal scores were calculated by ESTIMATE algorithm and their correlations with clinicopathological characteristics of HNSCC patients were identified. Differentially expressed genes (DEGs) based on two scores were identified and subjected to functional analysis, demonstrating their close associations with tumor immunity. Hub genes were selected from which CCR2, CCR4, CCR8 and P2RY14 were found to be significantly associated with the survival rate of HNSCC patients.
Conclusions: In summary, we made a comprehensive analysis of HNSCC microenvironment and illustrated several key immune-related genes, which may provide evidences for the development of precision immunotherapy.
Hypoglycemia in older people with diabetes receiving home care: A feasibility-study
Authors: Larsen Annette Bævre , Hermann Monica , Graue Marit
Published: July 2020

Background Hypoglycemic incidents in older people can cause severe health problems, enhance general age-related disabilities and cause frailty. Little is known about incidence of hypoglycemia in older home-dwelling people with diabetes. Thus, the aim of this study was to investigate the feasibility of using continuous glucose monitoring (CGM) and standardized questionnaires on issues associated with increased risk of hypoglycemia among older home dwelling individuals with diabetes type 2 receiving home care. Methods CGM with the Ipro2 blinded monitoring system were performed for five days in six home-dwelling individuals ≥ 75 years diagnosed with diabetes and receiving home care. Demographic (age, gender, living arrangements) and clinical data (diabetes diagnoses and duration, diabetes medication, documented treatment goal, available glycosylated hemoglobin (HbA1c),) were collected from electronic patient records in home care services. Feasibility (ease of use, quality of data, time spent) of standardized questionnaires to identify the risk of hypoglycemia (the McKellar Risk Assessment Tool), risk of malnutrition (the Mini Nutritional Assessment (MNA)), functional status (the Individual-based Statistics for Nursing and Care Services (IPLOS)) and cognitive status (the Mini Mental Status Exam (MMSE)) was also assessed. Questionnaire data were collected by a study nurse in the individuals’ home.Results The practical use of CGM was satisfactory, with no major remarks about discomfort or technical errors, except for one participant with skin reaction (redness). Collecting data with the McKellar Risk Assessment Tool, MNA and IPLOS worked well according to quality of data, time spent and ease of use. The MMSE survey required extensive training of personnel to be conducted. Conclusion The feasibility study inform an upcoming study on the incidence and risk factors of hypoglycemia in home dwelling older individuals, were we will reconsider the use of the MMSE questionnaire. The use of blinded CGM in this population was well tolerated and can be used ‘as is’ for future studies.
In Silico Assessment of 5-FU Therapy via A Mathematical Model with Fuzzy Uncertain Parameters
Authors: Shafiekhani Sajad , Jafari Amir. H. , Jafarzadeh L. , Gheibi N.
Published: July 2020

Background: Ordinary differential equation (ODE) models widely have been used in mathematical oncology to capture dynamics of tumor and immune cells and evaluate the efficacy of treatments. However, for dynamic models of tumor-immune system (TIS), some parameters are uncertain due to inaccurate, missing or incomplete data, which has hindered the application of ODEs that require accurate parameters. Methods: We extended an available ODE model of TIS interactions via fuzzy logic to illustrate the fuzzification procedure of an ODE model. Fuzzy ODE (FODE) models, in comparison with the stochastic differential equation (SDE) models, assigns a fuzzy number instead of a random number (from a specific probability density function) to the parameters, to capture parametric uncertainty. We used FODE model to predict tumor and immune cells dynamics and assess the efficacy of 5-FU. The present model is configurable for 5-FU chemotherapy injection timing and propose testable hypothesis in vitro/ in vivo experiments. Result: FODE model was used to explore the uncertainty of cells dynamics resulting from parametric uncertainty in presence and absence of 5-FU therapy. In silico experiments revealed that the frequent 5-FU injection created a beneficial tumor microenvironment that exerted detrimental effects on tumor cells by enhancing the infiltration of CD8+ T cells, and NK cells, and decreasing that of myeloid-derived suppressor (MDSC) cells. We investigate the effect of perturbation on model parameters on dynamics of cells through global sensitivity analysis (GSA) and compute correlation between model parameters and cell dynamics. Conclusion: ODE models with fuzzy uncertain kinetic parameters cope with insufficient experimental data in the field of mathematical oncology and can predict cells dynamics uncertainty band. In silico assessment of treatments considering parameter uncertainty and investigating the effect of the drugs on movement of cells dynamics uncertainty band may be more appropriate than in crisp setting.
SDG711 is Involved in Rice Seed Development Through Regulation of Starch Metabolism Gene Expression in Coordination With Other Histone Modifications
Authors: Liu Xiaoyun , Luo Junling , Li Tiantian , Yang Huilan , Wang Ping , Su Lufang , Zheng Yu , Bao Chun , Zhou Chao
Published: July 2020

SDG711 is a histone H3K27me2/3 transmethylases in rice, homolog ofCLFin Arabidopsis, that plays key roles in regulating of flowering time and panicle development. In this work, we investigated that the role of SDG711 in rice seed development. Overexpression and down-regulation of SDG711lead to the decrease and increase of the expression level of genes related to starch accumulation, resulting in smaller seed or even seed abortion. ChIP assay showed that SDG711-mediated H3K27me3 changed significantly in genes related to endosperm development and SDG711 can directly bind to the gene body region of several starch synthesis genes and amylase genes. In addition, H3K4me3 and H3K9ac modifications also cooperate with H3K27me3 to regulate the development of endosperm. Our results suggested that the crosstalk of SDG711-mediated H3K27me3 with H3K4me3 and H3K9ac are involved in starch accumulation to control normal seed development.
A Rotor Coupling Fault Mechanism Modeling Based on the Deformation-Motion Vector Analysis Method
Authors: jun hu
Published: July 2020

In view of the limitation of the numerical method for coupling faults of rotating machinery, a modeling method for coupling faults of rotor, Deformation-Motion Vector Analysis Method, is purposed in order to explain the fault mechanism more thoroughly and universally. Firstly, the “Deformation-Motion” is defined by fault and the relationship between fault deformation and periodic signal is established by Fourier series. Secondly, the “Vector Analysis” analyzes the deformation-motion in the dynamic coordinate system, and establishes the relationship between the fault deformation-motion and the periodic excitation force by using the dynamic and static coordinate systems. Thirdly, the analytical solution is obtained by harmonic balance method, and the coriolis acceleration term is first found in the analytical solution of rotating machinery failure. Finally, the validity of the modeling method and the correctness of the analytical solution are verified by engineering practice.
Silencing the Expression of Cyclin G1 Enhances the Radiosensitivity of Hepatocellular Carcinoma in vitro and in vivo by Inducing Apoptosis
Authors: Xu Gang , Bu Shanshan , Wang Xiushen , Ge Hong
Published: July 2020

Background: Radiotherapy plays an important role in the treatment of hepatocellular carcinoma (HCC). Cyclin G1 was a novel member of the cyclin family, and it is abnormally expressed in HCC. The aim of this study was to investigate the role of cyclin G1 in the radiotherapy of HCC cells. Methods: The expression of cyclin G1 was silenced by transfection of cyclin G1-siRNA into HepG2 cells, and the expression of cyclin G1 mRNA and protein was measured by qRT-PCR and western blot analysis. The proliferation was analysed by MTT assay, and the radiosensitivity of HCC cells was detected by using a colony formation assay and a xenograft tumour model. The expression of apoptosis-related proteins (Bcl-2 and Bax) was detected by western blot analysis. Results: The expression of cyclin G1 mRNA and protein in HepG2-cyclin G1-siRNA cells is significantly decreased compared with that in HepG2 cells. Silencing the expression of cyclin G1 inhibits the proliferation of HCC cells and enhances the radiosensitivity of HepG2 cells in vitro and in vivo. HepG2-cyclin G1-siRNA significantly decreases Bcl-2 expression and increases Bax expression in cells.Conclusion: Silencing the expression of cyclin G1 enhances the radiosensitivity of HCC cells in vitro and in vivo, and the mechanism is probably related to the regulation of apoptosis-related proteins.
Role of Liver Enzymes in Patients with Blunt Abdominal Trauma to Diagnose Liver Injury
Authors: Shrestha Anup , Neupane Harish Chandra , Tamrakar Kishor Kumar , Bhattarai Abhishek , Katwal Gaurav
Published: July 2020

Background:The liver is the second most injured organ following blunt abdominal trauma (BAT) after spleen. Although the computed tomography (CT) scan is considered as the gold standard for diagnosing liver injury in BAT, it is not readily available in the hospital. This study was performed to evaluate the role of aspartate transaminase (AST) and alanine transaminase (ALT) in patients with BAT and its significance in predicting the diagnosis and severity of the liver injury.Method:The study was conducted in Chitwan Medical College Teaching Hospital (CMCTH) study from February 2019 to May 2020. During that period 96 patients with BAT presented to the emergency department(ED) of CMCTH.Results:Among the 96 patients admitted with BAT, 38 patients had liver injury and 58 patients had no liver injury. The median length of the intensive care unit (ICU) stay of patients with liver injury was higher than without liver injury. There was a significant difference in the median level of AST and ALT (<0.001) between patients with liver injury and no liver injury. The area under the ROC curve of AST was 0.89(95% Confidence Interval 0.86-0.98) and of ALT was 0.92(95% Confidence Interval 0.83-0.97). The area under the curve demonstrated that the test was a good predictor for the identification of liver injury and also the severity of liver enzymes. The cut-off values for the liver injury were 106 U/l and 80 U/l for AST and ALT respectively. Based on these values, AST ≥ 106 U/l had a sensitivity of 71.7 %, a specificity of 90 %, a positive predictive value of 86.8 %, and a negative predictive value of 77.6 %. The corresponding values for ALT ≥ 80 U/l were 77.8 %, 94.1%, 92.1% and 82.8 %, respectively.ConclusionIn conclusion, we report the optimal cut-off value of AST and ALT for liver injury in BAT as ≥ 106 U/l and 80 U/l respectively. The elevated level of AST and ALT might assist the surgeons to timely refer the suspected patients with the liver to a tertiary center and it might help the surgeons to go for conservative management for minor liver injuries in BAT preventing the exposure hazards of the CT scan.
PD-L1 Polymorphism Can Predict Clinical Outcome of Brazilian Non-Small Cell Lung Cancer Patients After Postoperative Adjuvant Treatment
Authors: Machado-Rugolo Juliana , Prieto Tabatha Gutierrez , Fabro Alexandre Todorovic , Cuentas Edwin Roger Parras , Sá Vanessa Karen , Baldavira Camila Machado , Rainho Claudia Aparecida , Castelli Erick C. , Farhat Cecilia , Takagaki Teresa Yae , Nagai Maria Aparecida , Capelozzi Vera Luiza
Published: July 2020

BackgroundAlthough the incidence and mortality of non-small cell lung cancer (NSCLC) remains high with poor prognosis, programmed death‐1 (PD‐1) and programmed death‐ligand 1 (PD‐L1) pathway are promising prognostic and predictive biomarker of NSCLC. The polymorphisms on PD‐L1 gene may be associated with their protein expressions and affect the adjuvant treatment and outcome of NSCLC patients. The goal of this study was to evaluate the clinicopathologic values of PD-L1 expression and single-nucleotide polymorphisms (SNPs) in the PD-L1 gene in lung adenocarcinoma (ADC), squamous cell carcinoma (SqCC), and large cell carcinoma (LCC). MethodsThe 70 NSCLC samples consisted of 33 samples of ADC, 24 of SqCC and 13 of LCC. All tissue microarray paraffin blocks were used for PD-L1 multiplex immunofluorescence assays with Cell Signaling E1L3N clone. Fifteen polymorphisms in the PD-L1 gene were investigated by deep targeted sequencing.ResultsThe PD-L1 expression was higher in ADC than in SqCC and LCC. Three polymorphisms rs4742098, rs4143815, and rs7041009 were significantly associated with tumor recurrence (P=0.01; P=0.05; P=0.02, respectively). According to the recurrence of the disease, carriers of the G allele were less likely to relapse (P=0.01) compared to the homozygous AA genotype for rs4742098. As in rs4143815, individuals with the C allele were also less likely to relapse (P=0.05). As for rs7041009, individuals with AG or GG genotypes were more likely to relapse. The G allele of rs7041009 also showed a significant correlation with age, younger patients, 16 (41.0%) and status, among 11 (39.3%) compared to carriers of the A allele (P=0.02 and P<0.01, respectively). The rs7041009 AG genotype was inversely associated with E1L3N clone PD-L1 labeling in NSCLCs but did not reach statistical significance. Kaplan-Meier survival curves showed that the prognosis of patients with NSCLC was strongly dependent on the alternative allele G (genotype AG or GG) of rs4742098, alternative allele C (genotype CG or CC) of rs4143815 and individuals with GG genotype of rs7041009 (P=0.02; P=0.05 and P<0.01, respectively). Multivariate analysis by the Cox Regression model showed genotype GG of rs7041009 independently associated with cancer recurrence and patients without adjuvant radiotherapy (hazard ratio [HR] = 7.59, 95% confidence interval [CI] = 1.06-54.03, and HR = 9.24, CI = 1.13-75.16).ConclusionsPD-L1 rs7041009 GG polymorphisms may be useful for the prediction of clinical outcome of radiotherapy in NSCLC. Further studies are needed to confirm our findings and to understand the role of PD-L1 in the radiotherapy outcome of NSCLC patients.
FOXM1D Potentiates PKM2-Mediated Tumor Glycolysis and Angiogenesis
Authors: Zhang Wei , Zhang Xin , Huang Sheng , Chen Jianfeng , Ding Peipei , Wang Qi , Li Luying , Lv Xinyue , Li Ling , Zhang Pingzhao , Zhou Danlei , Wen Wenyu , Wang Yiping , Lei Qunying , Wu Jiong , Hu Weiguo
Published: July 2020

Background: Tumor growth, especially in the late stage, requires adequate nutrients and rich vasculature, in which PKM2 plays a convergent role. It has been reported that PKM2, together with FOXM1D, is upregulated in late stage colorectal cancer and associated with metastasis; however, their underlying mechanism for promoting tumor progression remains elusive. Methods: Western blot, coimmunoprecipitation (Co-IP), glutathione S-transferase (GST)-pull down and Immunofluorescence (IF) were performed to investigate the interaction between FOXM1D with PKM2 and other proteins. Extracellular acidification (ECAR) and oxygen consumption rate (OCR) assays, Protein Cross-linking, Gel chromatography, Pyruvate Kinase (PK) activity assay were used to examine the effect of FOXM1D on glycolysis. The angiogenesis effect was verified by Human umbilical vein endothelial cell (HUVEC) tube formation assay, tumor tissue microangiography, VEGFA Elisa assay and ChIP assay.Results: FOXM1D potentiates PKM2-mediated glycolysis and angiogenesis through multiple protein-protein interactions. In the presence of FBP, FOXM1D binds to tetrameric PKM2 and assembles a heterooctamer, restraining PKM2 metabolic activity by about a half and thereby promoting aerobic glycolysis. Furthermore, FOXM1D interacts with PKM2 and NF-κB and induces their nuclear translocation with the assistance of the nuclear transporter importin 4, which subsequently augments VEGFA transcription that is regulated by the PKM2 and NF-κB complex. The increased VEGFA is secreted extracellularly via exosome, which is potentiated by the interaction of FOXM1 with VPS11, eventually promoting tumor angiogenesis. Conclusion: Our study indicates that FOXM1D plays a crucial role in promoting glycolysis and angiogenesis through its protein-protein interaction. The above findings provide another insight into the role of PKM2 in the regulation of glycolysis and angiogenesis.
EFFECT OF N-ACETYLCYSTEINE ON APOPTOSIS OF P19 CANCER CELLS DURING HYPOXIA
Authors: Nosareva O. L. , Orlov D. S. , Shakhristova E. V. , Stepovaya E. A. , Sadykova A. A.
Published: July 2020

Introduction. Hypoxia in tumor growth contributes to mitochondrial dysfunction and exacerbates oxidative stress in the immortalized cell. The objective of the study was to investigate the molecular mechanisms of the effects of N-acetylcysteine on redox regulation of tumor cell apoptosis under hypoxia.

Material and Methods. P19 cells (mouse teratocarcinoma) cultured under hypoxia served as the material for the study. The redox status was modulated with N-acetylcysteine in the final concentration of 5 mM. The level of reactive oxygen species, concentration of calcium ions, transmembrane potential and the number of CD95-, CD120- and Annexin V-positive cells were determined by flow cytometry. The concentration of glutathione system components as well as the levels of protein SH groups and protein carbonyl derivatives were measured by spectrophotometry.

Results. The use of N-acetylcysteine under hypoxic conditions was accompanied by the increased total glutathione concentration and protein SH groups levels, decreased levels of Са2+ ions, proteinbound glutathione and protein carbonyl derivatives, as well as the production of reactive oxygen species and more appropriate functioning of P19 cells mitochondria. N-acetylcysteine contributed to the development of additional resistance of P19 cells to apoptosis under hypoxia.

Conclusion. The alteration in the state of the glutathione system under hypoxia influences the changes in tumor cell metabolism on the whole and promotes formation of additional mechanisms to escape apoptosis.
THE CHOICE OF THE METHOD OF ENDOSCOPIC STENTING IN PATIENTS WITH UNRESECTABLE ADENOCARCINOMA OF THE PANCREATIC HEAD
Authors: Shabunin A. V. , Tavobilov M. M. , Lebedev S. S. , Korzheva I. Yu. , Karpov A. A. , Lantsynova A. V.
Published: July 2020

The purpose of the study was to comparatively assess the endoscopic plastic or nitinol stenting in patients with unresectable adenocarcinoma of the pancreatic head, who subsequently received systemic chemotherapy.

Material and Methods. Between 2014 and 2018, 64 patients underwent retrograde stenting followed by chemotherapy. All patients were divided into 2 groups. Group I consisted of 21 patients, who underwent nitinol stent implantation. Group II comprised 43 patients, who underwent plastic stent implantation.

Results. The technical success was 91.3 % in group I and 93.5 % in group II (р=0.324); clinical success was 95.2 % in group I and 90.6 % in group II (р=0.218). Complications according to the Clavien–Dindo classification in group I patients: Grade II in 2 (9.5 %), Grade III in 1 (4.5 %), and Grade IV 2 in (9.5 %). In group II patients, these complications were as follows: Grade II in 4 (9.3 %), Grade III in 4 (9.3 %), and Grade IV in 1 (2.3 %). The median duration of chemotherapy was 127.3 days. Stent dysfunction was observed in 5 (23.8 %) patients of group I and in 24 (55.8 %) patients of group II (р=0.026). The median time of stent patency was 108 ± 5.2 days in group I and 64 ± 4.3 days in group II (р=0.034). In group I patients, the median survival time was 100 days in 5 patients, 120 days in 9 patients, and 150 days in 5 patients. Two patients are alive. In group II patients, the median survival time was 100 days in 10, 120 days in 16, and 150 days in 13. Five patients are alive.

Conclusion. Based on the results obtained, it is advisable to recommend the use of nitinol stents for resolving obstructive jaundice in patients with unresectable ductal adenocarcinoma of the pancreatic head, who are scheduled to undergo chemotherapy.
NUCLEAR MEDICINE TECHNIQUES FOR IN VIVO ANIMAL IMAGING
Authors: Finogenova Y. A. , Lipengolts A. A. , Smirnova A. V. , Grigorieva E. Y.
Published: July 2020

The object of the study was to analyze radionuclide detection techniques for in vivo animal imaging. Material and Methods. A total of 49 publications available from Scopus, Web of Science, Google Scholar eLIBRARY and Pubmed and published between 2013 and 2019 were reviewed. Results. The nuclear medicine techniques, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) are the most suitable imaging modalities for in vivo animal imaging. Besides traditional radiopharmaceuticals, such as [18F]-FDG and [99mTc]-MDP, the new radiolabeled tracers, such as [99mTc]-3PRGD2, [ 99mTc]-HisoDGR targeted to integrin, [18F]- tetrafluoroborate, labeled antibodies and others have been used for the noninvasive detection of tumors and for monitoring their response to treatment in mice and rats. 111In and 89Zr –labeled monoclonal antibodies are used to evaluate the expression level of many receptors such as EGFR, HER-2 and others in different tumors. PET imaging has demonstrated a good efficacy in tumor hypoxia imaging with [64Cu]-ATSM, [18F]-FMISO. PET and SPECT can also be used for early evaluation of anticancer therapy response. Nuclear imaging techniques may assist in the vivo assessment of DNA damage (doubleand single-strand brakes) as well as apoptosis intensity in tumor and normal tissues. [99mTc]- duramycin is the most commonly used tracer for imaging of apoptosis. Changes in tumor cell proliferation in response to anticancer therapy can be assessed by PET imaging with [18F]-FLT. Conclusion. Nuclear medicine offers a unique means to study cancer biology in vivo and to optimize cancer therapy.
THE ROLE OF GATA3, FOXA1, ELF5 TRANSCRIPTION FACTORS IN THE PATHOGENESIS AND PROGNOSIS OF BREAST CANCER
Authors: Vasilchenko D. V. , Krakhmal N. V. , Vtorushin S. V. , Zavyalova M. V.
Published: July 2020

Purpose of the study: to review available data on the role and significance of GATA3, FOXA1 and ELF5 transcription factors in the pathogenesis, progression and therapy resistance of breast cancer.

Material and Methods. The Medline and PubMed databases were used to identify all studies that evaluated the structure, functional parameters and participation of the studied transcription factors in the pathogenesis of breast cancer. More than 180 publications were analyzed, of which 76 were included into the review.

Results. The review shows that molecular genetic studies in relation to transcription factors and subsequent comparison of the obtained results with various clinical and morphological characteristics of breast cancer are of great importance. The review also demonstrates the inconsistency of the available data regarding clinical significance in assessing the prognosis of the disease and the sensitivity of the tumor to hormone therapy.

Conclusion. The study of the expression parameters of GATA3, FOXA1, and ELF5 transcription factors, as well as their relationship with tumor progression mechanisms will increase the reliability of immunomorphological studies, most likely suggesting the efficiency of hormone therapy. Therefore, the results of this study can help to plan adequate treatment tactics and predict outcomes in patients with breast cancer.