bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowdown of lncRNA HOXA-AS2 inhibits proliferation, invasion and migration of oral squamous cell carcinoma
Authors: Zhao Zhen , Xing Yan , Yang Fei , Zhao Zhijun , Shen Yupeng , Song Junjian , Jing Shanghua
Published: April 2020

Background

Oral squamous cell carcinoma (OSSC) is one of the most common cancers in the world. The aim to the study was to evaluated the biological function and partly underlying regulatory mechanism of lncRNA homeobox A cluster antisense RNA2 (HOXA-AS2) on oral squamous cell carcinoma.
Methods

The expression of HOXA-AS2 in OSSC cells was detected by quantitative real time polymerase chain reaction (qRT-PCR). HOXA-AS2 expression was modified by transfection with HOXA-AS2 knockdown into TCA-8113 cells. The biological activity of TCA-8113 cells were detected by Cell Counting Kit-8 (CCK-8), EdU staining, Tunel staining, flow cytometry, wound healing, transwell assasy and western blot. The relationship between HOXA-AS2 and EZH2 was analyzed by RNA immunoprecipitation (RIP).
Results

At first, in this study, HOXA-AS2 expression in TCA-8113 cell line was increased compared with normal oral cells. Furthermore, HOXA-AS2 knockdown could inhibit cell viability, migration and invasion. Besides, EZH2 is the target of HOXA-AS2 in TCA-8113 cells. EZH2 expression was reduced by the HOXA-AS2 knockdown and the expression of P21 was negatively correlated to the expression of HOXA-AS2 in TCA-8113 cells.
Conclusion

In this study, silencing HOXA-AS2 reduced cell viability, invasion and migration capacity and EZH2, as an oncogene, could be downregulated by HOXA-AS2 knockdown in OSSC cells.
AAZTA5-squaramide ester: promising tool for 177Lu-labeling of monoclonal antibodies under mild conditions
Authors: Klasen Benedikt , Moon Euy Sung , Rösch Frank
Published: April 2020

Background

Combining the advantages of both cyclic and acyclic chelator systems, AAZTA (1,4-bis(carboxymethyl)‐6‐[bis(carboxymethyl)]amino‐6‐methylperhydro‐1,4‐diazepine) is well suited for complexation of various diagnostic and therapeutic radiometals such as gallium-68, scandium-44 and lutetium-177 under mild conditions. Due to its specificity for primary amines and pH dependent binding properties, squaric acid (SA) represents an excellent tool for selective coupling of the appropriate chelator to different target vectors. Therefore, the aim of this study was to evaluate radiolabeling properties of the novel bifunctional AAZTA5-SA being coupled to a model antibody (bevacizumab) in comparison to DOTA-SA using the therapeutic nuclide lutetium-177.
Results

As proof-of-concept, bevacizumab was first functionalized with either AAZTA5-SA or DOTA-SA. After purification via fractionated size exclusion chromatography (SEC), the corresponding immunoconjugates were subsequently radiolabeled with lutetium-177 at pH 7 and room temperature (RT) as well as 37 °C. After 90 min, labeling of AAZTA5-SA-mAb resulted in almost quantitative radiochemical yields (RCY) of > 98% and > 99%, respectively. After purification via SEC, the radioconjugate [177Lu]Lu-AAZTA5-SA-mAb could be obtained with a purity of > 99% and an apparent specific activity of 4.5 GBq/µmol. In contrast, 177Lu-labeling of DOTA-SA-mAb showed negligible radiochemical yields of < 2% both at room temperature and 37 °C. In vitro complex stability measurements of [177Lu]Lu-AAZTA5-SA-mAb in human serum at 37 °C indicated > 99% protein bound activity within 15 days. In phosphate buffered saline (PBS), a slightly decreased stability of > 93% intact conjugate was observed over the same period.
Conclusion

Coupling of AAZTA5-SA to the monoclonal antibody bevacizumab allowed for 177Lu-labeling with almost quantitative radiochemical yields both at room temperature and 37 °C. Within 15 days, the resulting radioconjugate indicated very high in vitro complex stability both in human serum and PBS. Therefore, AAZTA5-SA is a promising tool for 177Lu-labeling of sensitive biomolecules such as antibodies for theranostic applications.
Evaluation on Prognostic Ability of Serum Uric Acid for Very Old Acute Coronary Syndrome Patients with Diabetes Mellitus: A Prospective Cohort Study
Authors: Fu Zhenhong , Jiao Yang , Wang Jihang , Xi Qing , Yang Xia , Shen Mingzhi , Xue Hao , Guo Jun , Dong Wei , Chen Yundai
Published: April 2020

Background This study sought to evaluate the prognostic power of serum uric acid (UA) in predicting adverse events of very old acute coronary syndrome (ACS) patients with diabetes mellitus (DM).Methods This analysis involved 718 ACS patients > 80 years old who were collected general clinical data and baseline blood biochemical indicators prospectively from January 2006 to December 2012, and these patients were classified into two groups based on DM, then followed up after discharge. Kaplan–Meier method was performed for major adverse cardiac events (MACE) rates and all-cause mortality. Multivariate Cox regression was performed to analyze the relationship between UA level and long-term clinical prognosis. Receiver operating characteristic (ROC) curve was analyzed to predict the cutoff value of UA of the very old ACS patients with DM.Results There were 242 and 476 patients in groups DM and non-DM(NDM) and the follow-up time after discharge was 40–120 months (median: 63 months; interquartile range: 51–74 months). The differences in all-cause mortality, cardiac mortality and MACE rates in DM and NDM patients between the control group were statistically significant (P = 0.001). All-cause mortality, cardiac mortality and MACE incidence in DM patients with moderate and high UA level were significantly higher than those in control group (P = 0.001). There were statistically significant differences in long-term survival rates among the ACS groups (P = 0.001), and long-term survival rates decreased significantly with the increase of UA level. UA (OR = 2.106, 95%CI = 1.244–3.568, P = 0.006) was found to be an independent risk factor for all-cause mortality and MACE in very old ACS patients with DM. The cutoff value of UA was 353.6 µmol/L (sensitivity: 67.4%; specificity: 65.7%). The elevation of serum UA level play an important role in predicting the development of all-cause mortality in elderly ACS patients with DM.Conclusion Serum UA level is a strong independent predictor of long-term all-cause death and MACE in very old ACS patients with DM.
Neoadjuvant PD-1 Inhibitor combines with Chemotherapy in Resectable Squamous Cell Non-Small Cell Lung Cancer
Authors: Feng Yuan , Sun Wei , Zhang Jie , Wang Yang , Chen Jinfeng , Liu Xinying , Wang Liang , Li Shaolei , LV Chao , Lu Fangliang , Zhang Jianzhi , Hong Yang , Xiao Shanshan , Wang Tao , Jiao Raymond , Wang Ziping , Qi Liping , Li Nan , Yang Yue , Lin Dongmei , Fang Jian
Published: April 2020

Background

Single agent of PD-1 or PD-L1 inhibitor has been explored recently for resectable patients before surgery. However, the effectiveness and safety of neoadjuvant PD-1 blockade combine with platinum-based doublet chemotherapy has not been fully investigated.
Methods

21 patients with squamous cell lung cancer accepted neoadjuvant therapy followed by surgery in Beijing Cancer Hospital were involved. 8 patients accepted two cycles of neoadjuvant platinum-based doublet chemotherapy combine with anti-PD-1 therapy, while 13 patients accepted two cycles of neoadjuvant platinum doublet chemotherapy. Besides baseline tumor staging, chest CT was repeated two to three weeks before surgery. Adverse events were monitored. Peripheral lymphocytes counting was tested during whole treatment. The residual viable tumor cells were counted after surgery to decide a major pathological response (MPR) rate. Selected specimen was sent for immunohistochemical, multiplex immunofluorescence analyses, and T-cell receptor DNA sequencing.
Results

Comparing with neoadjuvant chemotherapy alone, combination with PD-1 blockade and chemotherapy increased the pathological complete response rate (37·5% Vs. 7·69%) and MPR rate (50% Vs. 38·46%). The pathological evaluation is not consistent with that of radiological evaluation. Although peripheral lymphocyte counting was influenced by neoadjuvant therapy, no unknown adverse effects were reported for all the patients. The tumor infiltrating lymphocytes were observed more in patients accepted PD-1 blockade, and seem infiltrated more in relative “non-responders”. No special pathological features associated with PD-1 blockade were found. Multiplexed immunofluorescence analyses revealed potential immune suppression status in the peritumoral spaces around the residual tumor cells. T-cell receptor DNA sequencing found although some amino acids were shared in primary tumor and lymph nodes in single patients, they are hardly shared among different patients.
Conclusions

Neoadjuvant chemotherapy combine with PD-1 blockade is safe and feasible for patients with potentially resectable squamous cell lung cancer, to improve the clinical and pathological outcome. Even with PD-1 blockade, the immune suppressive status around the residual tumor cells still exists. The squamous cell lung cancers, and corresponding immune responses are extremely highly individualized. The treatment needs to be designed accordingly. The combination strategy of traditional neoadjuvant chemotherapy with current anti-PD-1 inhibitor are still need further investigation.
Targeted sequencing on neurodegenerative genes identified novel causal and risk variants of familial Alzheimer's disease
Authors: Zhang Weiwei , Jiao Bin , Xiao Tingting , Liu Xixi , Xiao Xuewen , Liao Xinxin , Guo Lina , Yan Xinxiang , Tang Beisha , Shen Lu
Published: April 2020

Background

Mutations of APP, PSEN1 and PSEN2 only account for a small portion of familial Alzheimer’s disease (AD), leaving the genetic factors for the rest AD families unexplained. Neurodegenerative diseases have some neuropathological, clinical and genetic crossover. The effect of neurodegenerative genes to familial AD remains unknown. We hypothesized that rare variants of neurodegenerative diseases genes may lead to family aggregation of AD. The aim of the study was to investigate the effect of neurodegenerative genes to familial AD.
Methods

Targeted sequencing of 277 neurodegenerative disease genes was performed on probands from 75 AD families of Chinese origin. Rare coding variants segregated in families were tested for association in an independent cohort of 506 patients with sporadic AD and 498 cognitively normal controls. East Asians data from the Exome Aggregation Consortium (ExAC) were used as a reference control.
Results

A novel mutation, P410S of PLD3, and a known causative mutation, I2012T of LRRK2 were identified in two early-onset AD families respectively. The p.P143S, rs192694824 in ABCA7 and rs374551420 in CR1 were significantly associated with familial AD (p = 0.005437, 0.001383, 0.000549), the rs200820365 in TREM2 was significantly associated with AD (p = 0.000396) when compared with the East Asian controls in ExAC database. The p. G223del of FUS was frequent in AD cases and significantly associated with familial AD (p = 0.008).
Conclusions

Our results revealed that rare variants of AD risk genes, FTD/ALS and PD causative genes may lead to family aggregation of AD. We proposed that targeted sequencing on neurodegenerative genes was necessary for genetically unclear AD families.
Prognostic value of an autophagy-related gene expression signature for endometrial cancer patients
Authors: Wang Hui , Ma Xiaoling , Liu Jinhui , Wan Yicong , Jiang Yi , Xia Yankai , Cheng Wenjun
Published: April 2020

Background: Autophagy is associated with cancer development. Autophagy-related genes play significant roles in endometrial cancer (EC), a major gynecological malignancy worldwide, but little was known about their value as prognostic markers. Here we evaluated the value of a prognostic signature based on autophagy-related genes for EC.Methods: First, various autophagy-related genes were obtained via the Human Autophagy Database and their expression profiles were downloaded from The Cancer Genome Atlas. Second, key prognostic autophagy-related genes were identified via univariat, LASSO, and multivariate Cox regression analyses. Finally, a risk score to predict the prognosis of EC was calculated and validated by using the test and the entire data sets. Besides, gene set enrichment and somatic mutation analyses were also used for these prognostic autophagy-related genes. Results: A total of 40 differentially expressed autophagy-related genes in EC were screened and five of them were prognosis-related (CDKN1B, DLC1, EIF4EBP1, ERBB2 and GRID1). A prognostic signature was constructed based on these five genes using the train set, which stratified EC patients into high-risk and low-risk groups (P<0.05). In terms of overall survival, the analyses of the test set and the entire set yielded consistent results (test set: p < 0.05; entire set: p < 0.05). Time-dependent ROC analysis suggested that the risk score predicted EC prognosis accurately and independently (0.674 at 1 year, 0.712 at 3 years and 0.659 at 5 years). A nomogram with clinical utility was built. Patients in the high-risk group displayed distinct mutation signatures compared with those in the low-risk group. Gene set enrichment analysis revealed high risk score was associated with tumor initiation and progression associated pathways.Conclusions: Based on five autophagy-related genes (CDKN1B, DLC1, EIF4EBP1, ERBB2 and GRID1), our model can independently predict the OS of EC patients by combining molecular signature and clinical characteristics.
Functional glutamate transporters are expressed in the carotid chemoreceptor
Authors: Li Chaohong , Huang Lu , Jia Xianglei , Zhao Baosheng , Chen Lingyun , Liu Yuzhen
Published: April 2020

Background: The carotid body (CB) plays a critical role in cyclic intermittent hypoxia (CIH)-induced chemosensitivity; however, the underlying mechanism remains uncertain. We have demonstrated the presence of multiple inotropic glutamate receptors (iGluRs) in CB, and that CIH exposure alters the level of some iGluRs in CB, indicating glutamatergic signaling functioning in the carotid chemoreflex response to hypoxia. The glutamatergic neurotransmission is not only dependent on glutamate and glutamate receptors, but is also dependent on glutamate transporters, including vesicular glutamate transporters (VGluTs) and excitatory amino acid transporters (EAATs). Here, we have further assessed the expression and distribution of VGluTs and EAATs in human and rat CB and the effect of CIH exposure on the expression level of glutamate transporters.Methods: The mRNA and protein expression of VGluTs and EAATs in the CB were detected by RT-PCR and Western blot. The distribution of VGluT3, EAAT2 and EAAT3 were observed by immunohistochemistry staining and immunofluorescence staining. Male Sprague-Dawley (SD) rats were exposed to CIH (FIO2 10%-21%, 3 min/3 min for 8 hours per day) for 2 weeks. The Student’s t test was performed.Results: Here, we report on the presence of mRNAs for VGluT1-3 and EAAT1-3 in human CB, which is consistent with our previous results in rat CB. The proteins of VGluT1 and 3, EAAT2 and 3, but not VGluT2 and EAAT1, were detected with diverse levels in human and rat CB. Immunostaining showed that VGluT3, the major type of VGluTs in CB, was co-localized with tyrosine hydroxylase in type I cells. EAAT2 and EAAT3 were distributed not only in type I cells, but also in glial fibrillary acidic protein positive type II cells. Moreover, we found that exposure of SD rats to CIH enhanced the protein level of EAAT3 as well as TH, but attenuated the level of VGluT3 and EAAT2 in CB. Conclusions: Our study suggests that glutamate transporters are expressed in the CB, and that glutamate transporters may contribute to glutamatergic signaling-dependent carotid chemoreflex to CIH.
Sentinel lymph node identification in early stage ovarian cancer: is it still possible after prior tumor resection?
Authors: Laven Pim , Kruitwagen Roy , Zusterzeel Petra , Slangen Brigitte , Gorp Toon van , Pol Jochem van der , Lambrechts Sandrina
Published: April 2020

Objective: Sentinel lymph node (SLN) detection in ovarian cancer is feasible when tracers are injected before the pathological ovary is resected. This study aims to investigate whether the SLN identification is also feasible in patients whose ovarian tumor has already been resected with injection of the tracer into the ovarian ligaments stumps, i.e. in the event that a frozen section confirms malignancy. Methods: Patients who underwent laparotomy with frozen section confirming an ovarian malignancy, and those who underwent a second staging laparotomy after prior resection of a malignant ovarian mass, were included. Blue dye and a radioactive isotope were injected in the stumps of the ligamentum ovarium proprium and the ligamentum infundibulo-pelvicum. After an interval of at least 15-minutes, the sentinel node(s) were identified using either the gamma-probe and / or blue dye.Results: A total of 11 patients were included in the study, the sentinel node (SLN) procedure was completed in all 11 patients. At least one SLN was identified in 3 patients, resulting in a rather low detection rate of 27,3%. Conclusion: In this study we showed that SLN procedure after (previous) resection of the tumor seems inferior to detect sentinel nodes when compared to injection of the tracer in the ovarian ligaments before tumor resection.Trial registration on clinical trials: NCT02540551 https://clinicaltrials.gov/ct2/show/NCT02540551
Determination Of State Economic Activities - Developing Countries In East Asia & Pacific Using Classical Approaches
Authors: Fuddin Muhammad Khoirul
Published: April 2020

Countries in East Asia and the Pacific region are potential countries with fairly strong economic growth rates amid slowing global economic growth. One contributing factor to economic growth in East Asia and the Pacific can be seen using a classical approach where economic growth is seen from capital, natural resources, incoming foreign investment and the use of technology. This research wants to see how big these factors are in influencing the economic activities of developing countries in East Asia and the Pacific. The methodology used in this study is to use a Vector Error Correction Model by focusing on the impulse response function and variance decomposition to see the response of several variables due to changes in other variables and to see how much the proportion of one variable affects other variables in the short term or long term. In the short term, incoming foreign investment and technology affect productive land while in the long run productive land is influenced by incoming foreign investment and human resources. In the short term, GDP is not affected by any variable, whereas in the long term GDP is affected by human resources, incoming foreign investment, and technology. In the long run, human resources are affected by incoming foreign investment. Foreign investment that enters in the short term is influenced by productive land and human resources, whereas in the long run, only human resources can directly influence foreign investment. Technology in the short term is influenced by productive land and incoming foreign investment while in the long run technology is influenced by incoming foreign investment and human resources. The economic growth reflected in GDP and productive land contained in East Asia and the Pacific was largely influenced by technology in the final period. Incoming foreign investment and technology are largely influenced by productive land. Whereas the human resources found in East Asia and the Pacific are mostly influenced by GDP.
An exploration of perceptions and preferences for healthy eating in Dutch consumers: A qualitative pilot study
Authors: Coumans Juul M.J. , Bolman Catherine A.W. , Lechner Lilian , Oenema Anke
Published: April 2020

Background Unhealthy dietary patterns are highly prevalent in Western countries, and they have been associated with depression, hypertension, heart diseases, cancer, diabetes type 2 and obesity. Many dietary interventions have been developed to promote dietary behaviour, yet most do not achieve the intended dietary change. This study aims to provide a better understanding of what (Dutch) consumers perceive as a healthy diet (and how this relates to the current (Dutch) nutrition guidelines) and their preferences for how to eat (more) healthily. This is an essential consideration for the development of tailored interventions aimed to help people adopt changes in their dietary behaviour.Methods Seventy-eight participants filled in an online questionnaire containing both open-and closed-ended questions. The qualitative data was analysed using content analysis resulting in a classification scheme that two students used to identify to which category each part of a participant’s answer belonged.Results For both the perception of a healthy diet and how to eat healthily four major categories and a residual category were identified but some with different subcategories: dietary patterns, food processing, food products, content/nutrients, and other. The results showed that how people perceived a healthy diet was mostly represented at the level of food product (vegetables and fruit) and the content/nutrient level (carbohydrates); whereas how they would like to eat healthily was mostly represented at the level of food processing (preparation), food product (vegetables) and dietary patterns (amount).Conclusions Our findings are mostly in line with how the Dutch dietary guidelines are communicated (“product level”). However, laypersons primarily mention separate aspects instead of naming the guidelines as a whole. Health policymakers can use this insight in future communications regarding guidelines to the general public. A challenge for future (eHealth) diet interventions is how to implement and tailor dietary information that optimally connects with the perceptions of the target population.
Ischemia considerations for the development of an organ and tissue donor derived bone marrow bank
Authors: Woods Erik John , Sherry Aubrey M. , Woods John R. , Hardin James W. , LaFontaine Michael , Brandacher Gerald , Johnstone Brian H.
Published: April 2020

Background
Deceased organ donors represent an untapped source of therapeutic bone marrow (BM) that can be recovered in 3–5 times the volume of that obtained from living donors, tested for quality, cryopreserved, and banked indefinitely for future on-demand use. However, a challenge for a future BM banking system built to a genetically diverse scale, will be to manage the prolonged ischemia times that inevitably occur, when bones procured at geographically-dispersed locations are shipped to distant facilities for processing. The goals of this study were: (a) to quantify, under realistic and scaled procurement and shipping conditions, the relationship between ischemia time and the quality of hematopoietic stem and progenitor cells (HSPCs) derived from deceased-donor BM; (b) to identify ischemia-time boundaries beyond which HSPC quality is adversely affected; and (c) to investigate whole-body cooling as a strategy for preserving cell viability and function.
Methods
Seventy-five bones from 62 deceased donors were analyzed for CD34 + viability following their exposure to various periods of warm-ischemia time (WIT), cold-ischemia time (CIT), and body-cooling time (BCT). Regression models were developed to quantify the independent associations of WIT, CIT, and BCT, with the viability and function of recovered HSPCs.
Results
Results demonstrate that under “real-world” scenarios: (a) combinations of warm- and cold-ischemia times favorable to the recovery of high-quality HSPCs are achievable (e.g., CD34 + cell viabilities in the range of 80–90% were commonly observed); (b) cooling the body prior to bone recovery is detrimental to cell viability (e.g., CD34 + viability < 73% with, vs. >89% without body cooling); and (c) vertebral bodies (VBs) are a superior source of HSPCs compared to ilia (IL) (e.g., %CD34 + viability > 80% when VBs were the source, vs. <74% when IL were the source).
Conclusions
Our quantitative models can be used to formulate ischemia-time tolerance limits and HSPC quality-acceptance criteria, and to inform an emerging BM banking system seeking to institute data-driven industry standards.
Prediction of post-stroke epilepsy using machine learning method
Authors: Peng Anjiao , Yang Xiaorong , Wen Zhining , Li Wanling , Tang Yusha , Lai Wanlin , Qiu Xiangmiao , Zhang Lin , He Shixu , Chen Lei
Published: April 2020

Background : Stroke is one of the most important causes of epilepsy and we aimed to find if it is possible to predict patients with high risk of developing post-stroke epilepsy (PSE) at the time of discharge using machine learning methods. Methods : Patients with stroke were enrolled and followed at least one year. Machine learning methods including support vector machine (SVM), random forest (RF) and logistic regression (LR) were used to learn the data. Results : A total of 2730 patients with cerebral infarction and 844 patients with cerebral hemorrhage were enrolled and the risk of PSE was 2.8% after cerebral infarction and 7.8% after cerebral hemorrhage in one year. Machine learning methods showed good performance in predicting PSE. The area under the receiver operating characteristic curve (AUC) for SVM and RF in predicting PSE after cerebral infarction was close to 1 and it was 0.92 for LR. When predicting PSE after cerebral hemorrhage, the performance of SVM was best with AUC being close to 1, followed by RF ( AUC = 0.99) and LR (AUC = 0.85) . Conclusion : Machine learning methods could be used to predict patients with high risk of developing PSE, which will help to stratify patients with high risk and start treatment earlier. Nevertheless, more work is needed before the application of thus intelligent predictive model in clinical practice.
Prognostic Value of Three Rapid Scoring Scales and Combined Score for the Assessment of Patients with Coronavirus Disease 2019
Authors: Hu Hai , Kong Weili , Yao Ni , Qiu Yanru , Gu Hailing , Xu Wei
Published: April 2020

Background: Severe coronavirus disease 2019 (COVID-19) is associated with high mortality, whereas mild cases generally have a good prognosis. Therefore, the rapid assessment and timely classification of patients with COVID-19-related pneumonia are very important. However, no scoring system has been designated for the rapid assessment and prognosis of patients with COVID-19. Such a system is urgently needed. Objective: To explore the factors affecting mortality in patients with COVID-19 and to verify if the predictive value of the three rapid scoring scales [the Modified Early Warning Score (MEWS), Rapid Acute Physiology Score (RAPS) and Rapid Emergency Medicine Score (REMS)] that are commonly used in emergency departments can also be used for the prognostication of COVID-19 patients. Methods: The study included adult patients diagnosed with COVID-19 in Wuhan, China from February 7 to March 7, 2020. Kaplan–Meier and Cox survival analyses were performed to identify the risk factors associated with COVID-19-related death. C-index analysis was used to evaluate the abilities of the three scoring scales and their combined score to predict the prognosis of COVID-19 patients. Results: Older age, decreased lymphocyte count, increased respiration frequency, and low blood oxygen saturation level were identified as independent risk factors for mortality among patients with COVID-19. The Cox regression analysis demonstrated that MEWS, RAPS, and REMS had a statistically significant ability to predict mortality in COVID-19 patients (P < 0.05). Stats the C-index of MEWS, RAPS, REMS, and the combined score resulted 0.7,0.66, 0.82, and 0.83 respectively. Conclusion: Patients with an old age, increased respiration frequency, low blood oxygen saturation level, and decreased lymphocyte count are at a high risk of COVID-19-related mortality. Moreover, our analysis revealed that the REMS had a better prognostic ability than the MEWS and RAPS when applied to COVID-19 patients. Our findings suggest that the REMS can be used as a rapid scoring tool for the early assessment of COVID-19 severity.
CDR1as related miRNA-mRNA networks in differentiating goat skeletal muscle satellite cells
Authors: Kyei Bismark , Li Li , Yang Liu , Zhan Siyuan , Li Juntao , Chen Yuan , Zhang Xujia , Zheng Shuailong , Xu Xiaoli , Odame Emmanuel , Cao Jiaxue , Guo Jiazhong , Zhong Tao , Wang Linjie , Zhang Hongping
Published: April 2020

Background: Myogenesis is a complex process controlled by several coding and non-coding RNAs (ncRNAs) such as circular RNAs (circRNAs) that well-known function as endogenous microRNAs (miRNAs) sponges. Over the past few years, numerous circRNAs have been known and their roles in biological processes have begun to be understood. Cerebellar Degeneration-Related protein 1 antisense (CDR1as), the most spotlighted circRNA as miR-7 sponge that has been blooming circRNAs’ research for a decade, and can potentially sponge several miRNAs in disease and muscle physiology. Nevertheless, the linear-RNAs-differed character that the acute interventions for circRNAs do not affect miRNAs levels, and has retarded the transcriptome-wide discovery of miRNAs sponged by. Therefore, the purpose of this study was to provide the transcriptomic effect of CDR1as during muscle differentiation.Methods: siCDR1as and siDICER1 were transfected into goat skeletal muscle satellite cells (SMSCs). RNA-seq technology and bioinformatics tools were used to analyze genes that are deregulated by siCDR1as and siDICER1. quantitative PCR was used to verify the expression levels of the differentially expressed mRNAs and miRNAs. Results: Here, to systematically identify miRNAs targeting CDR1as, we employed the critical enzyme DICER1 that governs the biogenesis of miRNAs. The deficiency of either DICER1 or CDR1as inhibited myogenic differentiation of SMSCs, and knockdown of DICER1 decreased the expression of CDR1as. Moreover, we screened for the targeted messenger RNAs (mRNAs) and miRNAs in SMSCs transfected with siDICER1 or siCDR1as respectively and found out that some well-known muscle-related pathways such as phosphoinositide 3-kinase (PI3K)-AKT signaling pathway, Rap1 signaling pathway, and MAPK signaling pathway were enriched in all groups. Further, regarding the miRNAs identified in siDICER1 and siCDR1as together with the sequence complementary information, we identified 11 miRNAs including miR-1, miR-206, and miR-27a-5p which are more likely to be novel targets for CDR1as. Conclusion: In summary, our study provides a perspective on the potential functions and relationship between CDR1as and DICER1 during muscle development.
Dietary phosphatidylcholine promotes breast cancer in the hyperlipidemic E0771 murine model
Authors: Onono Fredrick O , Chelvarajan Lakshman , Yan Baoxiang , Adindu Ebubechi , Bedingar Esias
Published: April 2020

BackgroundCancer cells are characterized by aberrant phosphatidylcholine (PC) metabolism. PC can be synthesized de novo or absorbed from diet, after digestion, by the intestinal enterocytes. Here, we investigated the association of dietary intake of PC and breast cancer development in mice. MethodsWe used tandem mass spectrometry methods to quantitate PC content of various fat sources used to manufacture rodent diets. Rodent diets were then formulated with either casein or amino acids in place of casein. To test the effects of dietary PC on tumor growth we fed low density lipoprotein receptor-null (LDLR–/–) mice high fat diets formulated with casein (high PC) or amino acids in place of casein (low PC). Endogenous PC biosynthesis and levels of total circulated plasma PC was monitored using stable isotope tracer choline and mass spectrometry analysis. Tumors were induced in mice after 12 weeks of high fat diet feeding. Since PC-derived molecules are important transducers of mitogenic signals, we tested the effects of inhibiting production of lysophosphatidic acid (LPA) using a recently described autotaxin (ATX) inhibitor. Finally, plasma inflammatory cytokine levels were analyzed to determine the effects of diets and ATX inhibition on systemic cytokine milieu. ResultsWe found that casein is the main source of PC when present in rodent diets. Replacing casein with amino acids increased the relative proportion of endogenously biosynthesized PC in mouse plasma. Compared to diets containing casein, amino acid-defined diets decreased primary tumor growth in the hyperlipidemic estrogen-receptor positive E0771 breast cancer mouse model. Inhibition of autotaxin with the potent inhibitor PAT-505 did not attenuate breast cancer development in these hyperlipidemic mice. Further, replacing casein with amino acids or treatment with PAT-505 significantly reduced systemic markers of inflammation. ConclusionOur results show that casein is a significant source of PC when present in rodent diets. Diets formulated with amino acids in place of casein have higher proportion of circulating PC from the endogenous biosynthetic pool. Casein-containing high fat diets promote primary breast tumor development in mice through mechanisms that involve systemic inflammation but is independent of LPA production by autotaxin.
ADCY2, ADCY5, and GRIA1 are the key genes of cAMP signaling pathway to participate in osteoporotic peripheral and spinal fracture after the manipulation of Wnt signaling
Authors: Zuo Xiaohua , Zhou Changdong , Zhu Xuepiao , Liu Dan , Wang Yan , Bao Hongguang , Zhang Kai , Zhang Yong
Published: April 2020

Background
Osteoporotic peripheral and spinal fracture, characterized by high morbidity and mortality, has become a health burden for the aging population. The inactivation of the Wnt signaling has been proved to promote osteoporotic fractures. Our study is to identify the key genes, miRNAs, and pathways that possibly lead to osteoporosis and osteoporotic peripheral and spinal fracture after the aberrant activation or mutation of Wnt signaling pathway.
Methods
Impute R package was used to screen out the differently expressed genes (DEGs) and differently expressed miRNAs in GEO datasets. STRING and Metascape were used to construct protein-protein interactions (PPI) network, gene ontology (GO) enrichment and pathway enrichment.
Results
562 DEGs were screened out using Impute R package, and a PPI network involving the 562 DEGs was constructed using STRING and Metascape. GO enrichment and pathway enrichment showed that the 562 DEGs were associated with membrane protein-related signaling pathways. Then, 75 genes between the target genes of miR-18a-3p and 562 DEGs were overlapped using Venny 2.1.0. Finally, the cAMP signaling pathway was identified as the key pathway, whilst ADCY2, ADCY5, and GRIA1 were identified the key genes that possibly participate in osteoporotic peripheral and spinal fracture after the manipulation of Wnt signaling pathway.
Conclusions
The results demonstrated that ADCY2, ADCY5, and GRIA1 were the key genes to regulate the cAMP signaling pathway in osteoporotic peripheral and spinal fracture after abnormal Wnt signaling.
Evaluation of Youtube Video Content About Developmental Dysplasia of the Hip
Authors: Oztermeli Ahmet , Karahan Nazım
Published: April 2020

Background: The purpose of this study is to investigate the quality and reliability of YouTube videos regarding developmental dysplasia of the hip (DDH).YouTube is one of the most popular websites used as a source of information, but the variety in authorship and lack of a peer-review process are problems.Methods: The search string “developmental dysplasia of the hip” was inputted to the YouTube search engine, and the first 52 videos returned as a response were assessed. The Video Power Index (VPI) (like ratio*view ratio/100) was used to assess the popularity of the videos. Global Quality Score (GQS) and developmental dysplasia of the hip scores (DDHS) were used to evaluate the quality and educational quality of the videos, and The Journal of the American Medical Association Score (JAMAS) was used to evaluate the accuracy of the source of information.Results: According to our research, the mean duration time of the videos was 526 s (SD: 813), and the average view count of the videos was 34,644. The mean time since upload was 1907 days (SD: 1137). On average, the videos received 10.9 comments, 210.3 likes, and 6.8 dislikes. The mean like ratio and VPI were 92.9 (SD: 19.57) and 25.8 (SD: 53.43), respectively. The mean JAMAS, GQS, and DDHS of all videos evaluated were 1.37 (SD: 0.7), 2.46 (SD: 1.09), and 4.63 (SD: 5.00), respectively. The DDHS and GQS were positively correlated (p:0.001 r: 65.8%). The GQS and the DDHS were higher in the academic group than in the commercial group (p:0.01). (p:0.037).Conclusions: The videos regarding DDH on YouTube generally had poor quality. As a result, to maintain an optimal parent–physician or patient–physician relationship, we suggest that international health societies make their own educational videos for parents, patients, and fellow physicians.
Dynamical Analysis of Corona-virus (COVID−19) Epidemic Model by Differential Transform Method
Authors: Christopher A. John , Magesh N. , Preethi G. Tamil
Published: April 2020

The aim of this paper is applying the Differential Transformation Method (DTM) to analyze and find the solution for the mathematical model described by the system of nonlinear ordinary differential equations which describe the epidemiology of the most threatening virus called Corona-virus later labelled as COVID-19. The behaviour of the outcomes is presented in terms of plots. Finally, the present study may help you to examine the wild class of real world models and also aid to predict their behaviour with respect to parameters considered in the model. The purpose of this study is to estimate the effectiveness of preventive measures, predicting future outbreaks and potential control strategies using the mathematical model.
Historical, Current, and Future Perspectives for Controlled Environment Hydroponic Food Crop Production in the United States
Authors: Walters Kellie J. , Behe Bridget K. , Currey Christopher J. , Lopez Roberto G.
Published: April 2020

Controlled environment (CE) food crop production has existed in the United States for many years, but recent improvements in technology and increasing production warranted a closer examination of the industry. Therefore, our objectives were to characterize historical trends in CE production, understand the current state of the U.S. hydroponics industry, and use historical and current trends to inform future perspectives. In the 1800s, CE food production emerged and increased in popularity until 1929. After 1929, when adjusted for inflation (AFI), CE food production stagnated and decreased until 1988. From 1988 to 2014, the wholesale value of CE food production increased from $64.2 million to $796.7 million AFI. With the recent increase in demand for locally grown food spurring an increase in CE production, both growers and researchers have been interested in using hydroponic CE technologies to improve production and quality. Therefore, we surveyed U.S. hydroponic food crop producers to identify current hydroponic production technology adoption and potential areas for research needs. Producers cited a wide range of technology utilization; more than half employed solely hydroponic production techniques, 56% monitored light intensity, and more than 80% monitored air temperature and nutrient solution pH and electrical conductivity. Additionally, the growing environments varied from greenhouses (64%), indoors in multilayer (31%) or single-layer (7%) facilities, to hoop houses or high tunnels (29%). Overall, producers reported managing the growing environment to improve crop flavor and the development of production strategies as the most beneficial research areas, with 90% stating their customers would pay more for crops with increased flavor. Lastly, taking historical data and current practices into account, perspectives on future hydroponic CE production are discussed. These include the importance of research on multiple environmental parameters instead of single parameters in isolation and the emphasis on not only increasing productivity but improving crop quality including flavor, sensory attributes, and postharvest longevity.
Digital Video Project: An Authentic Assessment to Assess Students’ Speaking Skills
Authors: Sumardi Sumardi , ‘Adzima Rohmatul , Wijaya Andik Nur
Published: April 2020

This study was conducted to explore the use of digital video projects and to describe students' perceptions towards digital video project in the speaking assessment. The recorded students' speaking performances were assessed based on a speaking rubric that was adopted and modified to meet the requirements in authentic assessment using digital video projects. The criteria focused on three aspects, they are content, delivery, and creativity. This research involved 25 private university students from non-English departments who joined the English course at Universitas Slamet Riyadi Surakarta. The study utilized a content analysis method with a qualitative approach. The data were collected through the analysis of students' speaking rubric to explore the use of digital video project in speaking assessment and open-ended questionnaire to know the students' perception towards digital video project in the speaking assessment. In completing the project, the students follow four steps: starting the project, developing the project, reporting to the class, and assessing the project. The findings showed that digital video project helps learners to improve their ability to create a right introduction, keep their voice volume and expression, and promote their creativity to make interesting videos. The implication of the research is by employing the digital video project they create, students learn to speak and explore their ideas.
Analisis Kemampuan Koneksi Matematis Mahasiswa dalam Memahami Konsep Dimensi Tiga di STKIP Getsempena
Authors: Putra Juanda Kelana , Fajri Nurul
Published: April 2020

Pada pembelajaran matematika, kemampuan koneksi matematis menjadi salah satu aspek yang harus diperhatikan. Penelitian ini bertujuan untuk mendeskripsikan dan menganalisa Kemampuan Koneksi Mahasiswa Pendidikan Matematika STKIP Bina Bangsa Getsempena Banda Aceh dalam memahami konsep Dimensi Tiga pada mata kuliah Geometri Ruang. Pengumpulan data dilakukan dengan menggunakan soal tes koneksi matematis, studi dokumentasi dan wawancara. Hasil penelitian ini adalah: 1) tingkat kemampuan koneksi matematis mahasiswa pendidikan matematika masih tergolong rendah; 2) kesulitan masalah koneksi matematis yang dihadapi mahasiswa pendidikan matematika umumnya adalah kesulitan dalam menyelesaikan soal koneksi yang berhubungan antar topik matematika, khususnya konsep Phytagoras, konsep perbandingan trigonometri, konsep segitiga, konsep operasi pecahan dan konsep akar.

Kata kunci: kemampuan koneksi matematis, dimensi tiga.
A two-stage multiple-point conceptual model to predict river stage-discharge process using machine learning approaches
Authors: Alizadeh Farhad , Faregh Gharamaleki Alireza , Jalilzadeh Rasoul
Published: April 2020

Due to the complex nature of river stage-discharge process, the present study tried to develop a unique strategy to predict it precisely. The proposed conceptual strategy has some advantages to cover the shortcomings. First, it uses one model instead of several models to predict multiple points instead of one point. On the one hand, the constructed model was inspired by physical-based model (to include time-space attributes of the catchment). On the other hand, ensemble empirical mode decomposition algorithm (EEMD), wavelet transform (WT), and mutual information (MI) were employed as a hybrid pre-processing approach conjugated to support vector machine. For this end, a conceptual strategy (multi-station model) was developed to forecast the Souris River discharge more accurately. The strategy used herein was capable of covering uncertainties and complexities of river discharge modeling. First, a classic model along with WT was performed to predict the 1-day-ahead river discharge for each single station. Therefore DWT-EEMD and feature selection were used for decomposed subseries using MI to be employed in conceptual models. In the proposed feature selection method, some useless subseries were deleted to achieve better performance. The results approved efficiency of the proposed WT-EEMD-MI approach to improve accuracy of different modeling strategies.
Evaluating the impacts of environmental factors on soil moisture temporal dynamics at different time scales
Authors: Chai Qi , Wang Tiejun , Di Chongli
Published: April 2020

Soil moisture displays complex spatiotemporal patterns across scales, making it important to disentangle the impacts of environmental factors on soil moisture temporal dynamics at different time scales. This study evaluated the factors affecting soil moisture dynamics at different time scales using long-term soil moisture data obtained from Nebraska and Utah. The empirical mode decomposition method was employed to decompose soil moisture time series into different temporal components with several intrinsic mode functions (IMFs) and one residual component. Results showed that the percent variance contribution (PVC) of IMFs to the total soil moisture temporal variance tended to increase for the IMFs with longer time periods. It indicated that the long-term soil moisture variations in study regions were mainly determined by low-temporal frequency signals related to seasonal climate and vegetation variations. Besides, the PVCs at short- and medium-temporal ranges were positively correlated with climate dryness, while negatively at longer temporal ranges. Moreover, the results suggested that the impact of climate on soil moisture dynamics at different time scales might vary across different climate zones, while soil effect was comparatively less in both regions. It provides additional insights into understanding soil moisture temporal dynamics in regions with contrasting climatic conditions.
Identification of 2-Fluoropalmitic Acid as a Potential Therapeutic Agent Against Glioblastoma
Authors: Jiapaer Shabierjiang , Furuta Takuya , Dong Yu , Kitabayashi Tomohiro , Sabit Hemragul , Zhang Jiakang , Zhang Guangtao , Tanaka Shingo , Kobayashi Masahiko , Hirao Atsushi , Nakada Mitsutoshi
Published: April 2020

Background:

Glioblastomas (GBMs) are aggressive malignant brain tumors. Although chemotherapy
with temozolomide (TMZ) can extend patient survival, most patients eventually demonstrate resistance. Therefore,
novel therapeutic agents that overcome TMZ chemoresistance are required to improve patient outcomes.

Purpose:

Drug screening is an efficient method to find new therapeutic agents from existing drugs. In this study,
we explored a novel anti-glioma agent by drug screening and analyzed its function with respect to GBM treatment
for future clinical applications.

Methods:

Drug libraries containing 1,301 diverse chemical compounds were screened against two glioma stem
cell (GSC) lines for drug candidate selection. The effect of selected agents on GSCs and glioma was estimated
through viability, proliferation, sphere formation, and invasion assays. Combination therapy was performed to
assess its ability to enhance TMZ cytotoxicity against GBM. To clarify the mechanism of action, we performed
methylation-specific polymerase chain reaction, gelatin zymography, and western blot analysis.

Results:

The acyl-CoA synthetase inhibitor 2-fluoropalmitic acid (2-FPA) was selected as a candidate anti-glioma
agent. 2-FPA suppressed the viability and stem-like phenotype of GSCs. It also inhibited proliferation and invasion
of glioma cell lines. Combination therapy of 2-FPA with TMZ synergistically enhanced the efficacy of TMZ.
2-FPA suppressed the expression of phosphor-ERK, CD133, and SOX-2; reduced MMP-2 activity; and increased
methylation of the MGMT promoter.

Conclusion:

2-FPA was identified as a potential therapeutic agent against GBM. To extend these findings,
physiological studies are required to examine the efficacy of 2-FPA against GBM in vivo.