bluuebunny/crossref_metadata_2025 huggingface dataset:
The Activation of Phosphatidylserine/CD36/TGF-β1 Pathway prior to Surgical Brain Injury Attenuates Neuroinflammation in Rats
Authors: Huang Lei , Tang Hailiang , Sherchan Prativa , Lenahan Cameron , Boling Warren , Tang Jiping , Zhang John H.
Published: August 2020

Neuroinflammation plays an important pathological role in experimental surgical brain injury (SBI). Apoptotic associated with phosphatidylserine (PS) externalization promotes anti-inflammatory mediator TGF-β1 release. In the present study, we investigated the anti-neuroinflammation effect of PS liposome or isoflurane pretreatment via PS/CD36/TGF-β1 signaling in a rat model of SBI. A total of 120 male Sprague-Dawley rats (weighing 280-330 gms) were used. SBI was induced by partial right frontal lobe corticotomy. Intranasal PS liposome or isoflurane inhalation was administered prior to SBI induction. CD36 small interfering RNA (siRNA) was administered intracerebroventricularly. Recombinant Annexin V protein (rAnnexin V) was delivered intranasally. Post-SBI assessments included neurological tests, brain water content, Western blot, and immunohistochemistry. Endogenous CD36 protein levels but not TGF-β1 was significantly increased within peri-resection brain tissues over 72 h after SBI. SBI rats were associated with increased brain water content surrounding corticotomy and neurological deficits. PS liposome pretreatment significantly reduced brain water content and improved some neurological deficits at 24 hours and 72 hours after SBI. PS liposome increased CD36 and TGF-β1 protein levels, but decreased IL-1βand TNFαprotein levels in peri-resection brain tissues at 24 hours after SBI. CD36 siRNA or rAnnexin V partially countered the protective effect of PS liposome. Isoflurane pretreatment produced similar antineuroinflammation and neurological benefits in SBI rats partially by upregulating CD36/Lyn/TGF-β1 signaling. Collectively, our findings suggest that the activation of PS/CD36/TGF-β1 pathway by PS liposome or isoflurane prior to SBI could attenuate neuroinflammation and improve neurological outcomes in rats. PS liposome or isoflurane pretreatment may serve as an effective preventive strategy to minimize the brain injury caused by neurosurgical procedures in patients.
Glutamate Attenuates the Survival Property of IGFR through NR2B Containing N-Methyl-D-aspartate Receptors in Cortical Neurons
Authors: Zhao Xia , Han Chao , Zeng Zhiwen , Liu Linlin , Wang Haitao , Xu Jiangping , Feng Zhong-Ping , Little Peter J. , Quirion Remi , Zheng Wenhua
Published: August 2020

Glutamate-induced neurotoxicity is involved in various neuronal diseases, such as Alzheimer’s disease. We have previously reported that glutamate attenuated the survival signaling of insulin-like growth factor-1 (IGF-1) by N-methyl-D-aspartate receptors (NMDARs) in cultured cortical neurons, which is viewed as a novel mechanism of glutamate-induced neurotoxicity. However, the phosphorylation sites of IGF-1 receptor (IGF-1R) affected by glutamate remain to be elucidated, and importantly, which subtype of NMDARs plays a major role in attenuating the prosurvival effect of IGF-1 is still unknown. In the present study, glutamate was found to attenuate the tyrosine phosphorylation of the IGF-1R and the prosurvival effect of IGF-1 in primary cultured cortical neurons. NMDAR inhibitors, MK801 and AP-5, blocked the inhibitory effect of glutamate on the phosphorylation of IGF-1R and increased cell survival, while DNQX, LY341495, and CPCCOEt had no effect. Interestingly, we found that glutamate decreased the phosphorylation of tyrosine residues 1131, 1135/1136, 1250/1251, and 1316, while it had no effect on tyrosine 950 in cortical neurons. Moreover, using specific antagonists and siRNA to downregulate individual NMDAR subunits, we found that the activation of NR2B-containing NMDARs was essential for glutamate to inhibit IGF-1 signaling. These findings indicate that the glutamate-induced attenuation of IGF-1 signaling is mediated by NR2B-containing NMDARs. Our study also proposes a novel mechanism of altering neurotrophic factor signaling by the activation of NMDARs.
Improving Fairness for Distributed Interactive Applications in Software-Defined Networks
Authors: Xu Ran , Zhang Weiqiang
Published: August 2020

With the popularization of distributed interactive applications (DIAs), for getting good interactive experience among participants, efficient and fair allocation of network resource should be considered. In software-defined networks, the presence of central controllers provides novel solution to deploy customizable routing for interactive applications, which allows fine-grained resource allocation for DIAs to achieve fairness among participants. But opportunities always come with challenges, the wide spread user locations often require distribution of controllers to meet the requirements of applications. Hence, the latency involved among participants is directly affected by the processing time of controllers. In this context, we address the DIAs’ fair resource provisioning problems on computing and links load with the objective of balancing the achievable request rate and fairness among multiple flows in SDN networks. We firstly formulate the problems as a combination of controller loading and routing optimization. Then, we propose proactive assignment controller algorithm based on deep learning and fairness path allocation algorithm to share the bottleneck links. Compared with the state-of-the-art greedy assignment algorithm and priority order allocating algorithm, the final result is proven to get better fairness on controller and link load among DIAs’ participants by trace driven simulation.
Immunologic Response of HIV-Infected Children to Different Regimens of Antiretroviral Therapy: A Retrospective Observational Study
Authors: Mega Teshale Ayele , Usamo Firehiwot Belayneh , Negera Getandale Zeleke
Published: August 2020

Background. Both abacavir- (ABC-) based and zidovudine- (AZT-) based regimens are widely utilized for managing HIV infection in children. Unfortunately, there is a lack of data regarding their immunological response and associated risk factors in Ethiopia. Methods. A retrospective hospital-based cohort study was conducted on HIV-infected children in Jimma Medical Center (JMC). A total of 179 records were reviewed by including data from November 2015 to April 2017. Data were collected on sociodemographic, clinical characteristics of patients and drug-related variables. Data analysis was done using STATA 13.1. Mixed-effect linear regression was performed to assess the difference in CD4+ changes between groups adjusting for baseline characteristics. The change in predicted CD4 count attributed to each regimen was also assessed by marginal analysis. P<0.05 for slope of the random-effect linear regression was used as an indicator for the presence of association. Result. Of 179 patients, 98 (54.7%) were females. The mean (±SD) duration of follow-up was 939.8 ± 478.3 and 984.92 ± 453.1 days for ABC and AZT groups, respectively. AZT group had a significant CD4+ count gain per visit compared with their ABC counterparts ((β = 20.51, 95% CI [6.37–34.65]), P=0.004) over time. The regimen AZT + 3TC + LPV/r tended to have an excellent predicted CD4+ lymphocyte count change relative to all other regimens, while ABC + 3TC + LPV/r had the least immunologic recovery (margins 338.0 cells/mm3 versus 249.13 cells/mm3 (P<0.001)). Baseline CD4+ lymphocyte count, ART group, WHO clinical stages, and viral load were independent predictors for CD4+ change overtime. Conclusion. AZT-based regimens seem to have better immunological response compared to ABC-based regimens. Immunologic response was described worse in patients with a viral load of >1000copies/ml, low baseline CD4+ count, advanced WHO clinical stages, and ABC-containing regimens. Further study is needed to clarify these aspects.
Extracorporeal Shockwave Therapy for Patients with Chronic Achilles Tendinopathy in Long or Short Course
Authors: Yan BaiLi , Wan Yuan , Zhang Hong , Pan MengTing , Zhou Cheng
Published: August 2020

Object. In this study, our aim is to evaluate the efficiency of extracorporeal shockwave therapy (ESWT) on chronic Achilles tendinopathy (CAT) with different courses of disease. Methods. The data of 66 patients with CAT received ESWT was reviewed. According to the disease courses, those cases were allocated to short‐term group (ST group, symptom duration 3‐6 months) and long‐term group (LT group, symptom duration >6 months). Propensity scores match (PSM) method was conducted to eliminate the confound factors in baseline features including gender, sport history, sides, type of CAT, BMI (body mass index), age, and scores evaluated by AOFAS (American Orthopedic Foot and Ankle Society) and VAS (Visual Analogue Scale) before ESWT. After balancing the features between ST and LT group, postinterventional VAS, AOFAS, and rate of Likert satisfaction scale at the 3rd month after first ESWT was statistically analyzed. Results. Among the baseline features in ST and LT group, gender (female ratio, 44.4% vs 71.4%, p = 0.041) and BMI (23.26 ± 2.15 vs 24.63 ± 2.41, p = 0.024) were identified as confound factors. After elimination of biased features with PSM, 3 months after first ESWT, AOFAS and VAS in both groups are significantly improved, when compared with their scores at baseline (p < 0.01). Moreover, at postintervention month 3 (PIM3), AOFAS in ST group is significantly higher than LT group (85.08 ± 9.83 vs 76.76 ± 9.85, t = 76.76 ± 9.85, p = 0.019), and the rate of Likert satisfaction in ST group is better than LT group; although, it did not reach but close to significant level (70.6% vs 47.1%, χ2 = 1.943, p = 0.163). However, there is no statistical difference of VAS scores between two groups after ESWT (1.96 ± 0.98 vs 2.24 ± 1.29, t = 0.703, p = 0.487). Conclusions. ESWT could effectively relieve pain and improve function of hind foot in patients with chronic Achilles tendinopathy, and especially, it could offer better benefit on functional improvement in patients with short duration of CAT symptom.
Pharmacists’ Knowledge and Practice of Issues Related to Using Psychotropic Medication in Elderly People in Ethiopia: A Prospective Cross‐Sectional Study
Authors: Mekonnen Gashaw Binega , Beyna Alemante Tafese
Published: August 2020

Purpose. This study is aimed at assessing pharmacists’ knowledge and practice of issue related to usage of psychotropic medications in elderly people, in Gondar town Northwest, Ethiopia. Methods. A cross‐sectional study was conducted among pharmacists working in community, health center, and hospital pharmacies in Gondar town from March 1 to May 30, 2020. A total of 73 medication retail outlets (40 pharmacies and 33 drug stores) were included in this study. Pharmacy personnel’s knowledge and practice were assessed using self‐administered validated questionnaires. Binary and multivariable logistic regression analyses were used to assess the association between different variables. P < 0.05 was used to declare the association. Result. A total of 144 pharmacists were included in the study; the mean age was 30.13 (SD ±5.87), ranging from 20 to 55years. The mean knowledge score was 7.789 (SD ±2.98), and 75 (52.1%) of them had poor knowledge. The mean practice score was 2.32 ± 0.912 (mean ± SD), and 77 (53.5%) of the respondents had poor practice. All participants had not taken on‐the‐job training about psychotropic medication. Work experience (P < 0.029) and personal monthly income (P < 0.046) were significantly associated with pharmacists’ knowledge. There was a significant association between work experience and practice level (P < 0.043). Conclusion. The knowledge and practice of pharmacy personnel were low for issues related to the use of psychotropic medication in the elderly. This result indicates the need for training for pharmacists on pharmacotherapy of psychotropic medication.
Interleukin-6 Promotes Epithelial-Mesenchymal Transition and Cell Invasion through Integrin β6 Upregulation in Colorectal Cancer
Authors: Sun Qi , Shang Yukui , Sun Fengkai , Dong Xiwen , Niu Jun , Li Fanni
Published: August 2020

The metastatic potential of colorectal cancer (CRC) is intensively promoted by the tumor microenvironment (TME) in a paracrine manner. As a pleiotropic inflammatory cytokine, Interleukin-6 (IL-6) is produced and involved in CRC, the same scenario where integrin αvβ6 also becomes upregulated. However, the relationship between IL-6 and integrin αvβ6 as well as their involvement in the crosstalk between CRC and TME remains largely unclear. In the present study, we demonstrated a positive correlation between the expression of IL-6 and integrin β6 in CRC samples. The mutually promotive interaction between CRC and TME was further determined by an indirect coculture system. CRC cells could augment the secretion of IL-6 from fibroblasts, which in return induced invasion and integrin β6 expression of CRC cells. Through the classic IL-6 receptor/STAT-3 signaling pathway, IL-6 mediated the upregulation of integrin β6, which was involved in the invasion and epithelial-mesenchymal transition of CRC cells induced by IL-6. Taken together, our results reveal a paracrine crosstalk between IL-6 signals originating from the TME and increased the integrin β6 level of CRC. IL-6 induces CRC invasion via upregulation of integrin β6 through the IL-6 receptor/STAT-3 signaling pathway. Combined inhibition of IL-6 along with integrin β6-targeted strategy may indicate new directions for antitumor strategies for CRC.
Magnitude of the Quality Assurance, Quality Control, and Testing in the Shiraz Cohort Heart Study
Authors: Parsa Nader , Zibaeenezhad Mohammad Javad , Trevisan Maurizio , Karimi Akhormeh Ali , Sayadi Mehrab
Published: August 2020

To determine the conclusive integrity in the Shiraz Cohort Heart Study (SCHS) project, management began quality assurance (QA) and quality control (QC) of the collected data throughout the study end‐points. The QA is a focused process that prevents and detects data collection errors and verification of intended requirements in the SCHS. The QC is a subset of QA intended to capture errors in processing data through testing and preventive processes to identify problems, defects, or intended requirements. SCHS involved 10,000 males and females aged 40‐70 over a 10‐year follow‐up period with cardiovascular diseases (CVDs) in the city of Shiraz, Iran. The study measured events and access to preventive care in Shiraz city. The SCHS identified unique barriers to select national study models in developing standardized measures related to variations in ethnicity, religion, cross‐cultural considerations, and others. A suggested response to this problem was to develop a mechanism to standardize elements of the questionnaire, study design, and method of administration. This action was based on the geographically normal distribution of the Family Physician Health and Medical Services in Shiraz. Important QA and QC decisions were developed and adopted in the construction of the SCHS and follow‐up to ensure conclusive integrity.
Evaluation of Hemodynamic Change by Indocyanine Green-FLOW 800 Videoangiography Mapping: Prediction of Hyperperfusion Syndrome in Patients with Moyamoya Disease
Authors: Zhang Xin , Ni Wei , Feng Rui , Li Yanjiang , Lei Yu , Xia Ding , Gao Peng , Yang Shaoxuan , Gu Yuxiang
Published: August 2020

Objective. Hyperperfusion syndrome (HPS) after bypass surgery for moyamoya disease (MMD) mainly results from redistribution of blood flow, which leads to poor outcomes, while effective methods to predict HPS are still lacking. Indocyanine green (ICG) videoangiography can assess regional cerebral blood flow changes semiquantitatively with the application of FLOW 800 software. The purpose of this study was to investigate whether the intraoperative evaluation of local hemodynamic changes around anastomotic sites using FLOW 800 videoangiography mapping can predict the incidence of HPS and clinical outcomes. Methods. Of the patients who were diagnosed with MMD in our hospital between August 2018 and December 2019, who underwent superficial temporal artery-middle cerebral artery bypass surgeries, we investigated 65 hemispheres (in 62 patients) in which intraoperative ICG analysis was performed using FLOW 800 (Zeiss Meditec, Oberkochen, Germany) to evaluate the local cerebral hemodynamics before and after anastomosis. Regions of interest were set at more than 2 points on the brain surface according to the location and situation of recipient arteries in the surgical area. Peak cerebral blood volume (CBV), regional cerebral blood flow (CBF), and time to peak (TTP) were calculated from the selected points. As the data were available intraoperatively, anastomoses were performed in a suitable area. According to the occurrence of HPS, patients were divided into the asymptomatic and symptomatic groups, from which hemodynamic parameters were compared. Furthermore, ROC analysis was performed to determine the diagnostic accuracy of change rates in CBV, CBF, and TTP (i.e., ΔCBV, ΔCBF, and ΔTTP) for predicting HPS. Results. Data from the 62 patients were analyzed, and all patients were closely assessed during hospitalization after the procedures. The values of ΔCBV and ΔCBF were significantly higher in the symptomatic group (p<0.01), while ΔTTP is slightly lower in the symptomatic group with no statistical differences (p=0.72). Hemodynamic parameters including ΔCBV and ΔCBF, calculated by FLOW 800, had high sensitivity and specificity according to the ROC curve (ΔCBV: AUC=0.743, 95% CI, 0.605–0.881, p=0.002; ΔCBF: AUC=0.852, 95% CI, 0.750–0.954, p<0.01), which could be used as predictors for HPS. Conclusions. Intraoperative ICG-FLOW 800 videoangiography mapping is a safe method which can reflect hemodynamic characteristics in the surgical area for MMD, the findings of which correlate with the occurrence of HPS. Parameters including ΔCBV and ΔCBF are proven to be efficient in the prediction of HPS.
Optimal Supply Diversification Strategy under Supply Disruption
Authors: Luo Xiaomeng , Ren Jia
Published: August 2020

When a disruption caused by human or environmental accident occurs in production systems, it may cause a shortage of the supply, and thus the buyers’ procurement behaviors will be influenced. This paper studies a supply chain comprised of a buyer and two types of suppliers: one is cheap but unreliable and the other is reliable but expensive. If there is a major disruption, the unreliable supplier may not be able to fully satisfy the buyer’s order, despite the fact that it exerts additional effort to rebuild capacity; at the same time, the reliable supplier cannot fulfill extra orders from the buyer due to capacity constraints. In this way, the buyer should strategically allocate its order between the two types of suppliers by offering different contracts at the very beginning, and then the unreliable supplier chooses its optimal restoration effort according to the contract if a disruption occurs. The model is built based on the real-life cases such as Walmart and Apple such that it is the buyer who determines the wholesale price of the unreliable supplier’s products. The results show the optimal contracts provided by the buyer under different circumstances, which aims to help managers design their contracts under disruption risks to maximize the company’s profit.
Constrained Unscented Kalman Filter for Structural Identification of Bouc–Wen Hysteretic System
Authors: Kim Sung-Yong , Kim Jaemin
Published: August 2020

The Bouc–Wen hysteresis model has been extensively used to identify earthquake damage on civil structures where hysteretic behavior is expected. One of the challenging problems in the identification of Bouc–Wen parameters is overfitting, which is caused by too many nonphysical model parameters. Limit on the search domain of parameters helps to solve the problem. The unscented Kalman filter (UKF) is widely developed to find Bouc–Wen parameters. In order to improve the accuracy and convergence speed of conventional UKF, this study developed a constrained UKF (CUKF) which can be used for the simultaneous identification of the Bouc–Wen hysteretic model. The proposed CUKF is very helpful when certain parameters can be constrained in a physical sense. We compare the proposed CUKF with conventional UKF to validate its robustness and efficacy in identifying Bouc–Wen parameters.
A Quick Assessment and Optimization Method for a Flutter Aerodynamic Measure of a Typical Flat Box Girder
Authors: Wang Feng , Xiong Chuan , Wang Zijian , Guo Congmin , Bai Hua , Li Jiawu
Published: August 2020

Flutter is one of the most serious wind-induced vibration phenomena for long-span bridges and may cause the collapse of a bridge (e.g., the Old Tacoma Bridge, 1940). The selection and optimization of flutter aerodynamic measures are difficult in wind tunnel tests. It usually takes a long time and consumes more experimental materials. This paper presents a quick assessment and design optimization method for the flutter stability of a typical flat box girder of the long-span bridges. Numerical analysis could provide a reference for wind tunnel tests and improve the efficiency of the test process. Based on the modal energy exchange in the flutter microvibration process, the global energy input and local energy input are analyzed to investigate the vibration suppression mechanism of a flat steel box girder with an upper central stabilizer. Based on the comparison between the experimental and numerical data, a quick assessment method for the optimization work is proposed. It is practical to predict the effects of flutter suppression measures by numerical analysis. Thus, a wind tunnel test procedure for flutter aerodynamic measures is proposed which could save time and experimental materials.
Experimental Study on the Gas Flow Characteristics and Pressure Relief Gas Drainage Effect under Different Unloading Stress Paths
Authors: Zhang Chaolin , Xu Jiang , Wang Enyuan , Peng Shoujian
Published: August 2020

Coal seam gas is a critical substance because it can be a source of a large quantity of clean energy as well as a dangerous source of risk. A pressure relief gas drainage is an effective and widely used method for coal seam gas recovery and gas disaster control in coal mines. A series of pressure relief gas drainage experiments were conducted using large-scale coal samples under different unloading stress paths in this study to explore the unloading stress paths. From the experimental results, the dynamic evolutions of gas pressure, coal temperature, and gas production were analyzed. The trends of gas pressure and coal temperature during pressure relief gas drainage were similar: dropping rapidly first and then slowly with time. Correspondingly, gas production was fast in the early stage of pressure relief gas drainage and became stable thereafter. Meanwhile, gas flow characteristics were significantly affected by the unloading stress paths. Gas pressure and coal temperature had the maximum descent by unloading stress in three directions simultaneously, and the unloading stress of the Z direction had the minimal impact when only unloading in one direction of stress. However, the influence of unloading stress paths on gas production was complex and time dependent. The difference coefficient parameter was proposed to characterize the influence degree of unloading stress paths on the pressure relief gas drainage effect. Eventually, the selection of unloading stress path under different situations was discussed based on time, which is expected to provide the basis for pressure relief gas drainage.
Management of the Vertical Dimension in the Camouflage Treatment of an Adult Skeletal Class III Malocclusion
Authors: Sevillano Manuel Gustavo Chávez , Diaz Gina Judith Flores , de Menezes Luciane Macedo , Nunes Livia Kelly Ferraz , Miguel José Augusto Mendes , Quintão Cátia Cardoso Abdo
Published: August 2020

Treating skeletal class III malocclusions is one of the biggest challenges in Orthodontics. Given the complexity of these cases, orthognathic surgery is often the best treatment option. However, many patients refuse this treatment due to its risks, morbidity, and costs involved. Alternatively, dental compensation can be planned for some of these skeletal problems. This case report presents a dentoalveolar compensation in the orthodontic treatment of a 20-year-old female patient with class III malocclusion, concave profile, anterior crossbite, mandibular prognathism, maxillary retrusion, and a vertical deficiency in the posterior region. Treatment planning involved a multiloop edgewise archwire (MEAW) associated with intermaxillary elastics with counterclockwise rotation of the occlusal plane in the posterior region of the maxilla aiming at obtaining an increased posterior vertical dimension. After 24 months of treatment, the severe anterior crossbite was corrected, and the skeletal class III relationship was camouflaged. At the end of the orthodontic treatment, it was possible to observe an improved facial profile, a nice smile, and a functional occlusion. The results remained stable at a three-year follow-up. The MEAW, associated with the use of elastics, seems to be an effective treatment option for class III camouflage with reduced posterior vertical dimension with no need for additional anchoring devices but requiring adequate bending of wires and patient compliance.
Learn-ing-Based On-AP TCP Performance Enhancement
Authors: Lin Shirong , Jiang Shouxu
Published: August 2020

Data transmissions suffer from TCP’s poor performance since the introduction of the first commercial wireless services in the 1990s. Recent years have witnessed a surge of academia and industry activities in the field of TCP performance optimization. For a TCP flow whose last hop is a wireless link, congestions in the last hop dominate its performance. We implement an integral data sampling, network monitoring, and rate control software-defined wireless networking (SDWN) system. By analysing our sampled data, we find that there exist strong relationships between congestion packet loss behaviors and the instant cross-layer network metric measurements (states). We utilize these qualitative relationships to predict future congestions in wireless links and enhance TCP performance by launch necessary rate control locally on the access points (AP) before the congestions. We also implement modeling and rate control modules on this platform. Our platform senses the instant wireless dynamic and takes actions promptly to avoid future congestions. We conduct real-world experiments to evaluate its performance. The experiment results show that our methods outperform the bottleneck bandwidth and RTT (BBR) protocol and a recently proposed protocol Vivace on throughput, delay, and jitter performance at least 16.5%, 25%, and 12.6%, respectively.
Effect of Lb. plantarum BFE 5092 Fermentation on Antinutrient and Oligosaccharide Composition of Whole Red Haricot Bean (Phaseolus vulgaris L)
Authors: Kitum Vivian C. , Kinyanjui Peter K. , Mathara Julius M. , Sila Daniel N.
Published: August 2020

Common beans are a leguminous plant of the genus Phaseolus. They are rich in protein, energy, and minerals. They confer a wide range of health benefits when consumed. Utilization of common bean has however been poor due to high antinutrient content that results in reduced nutrient digestibility and mineral bioavailability. Flatulence after consumption is also a huge deterrent to common bean consumption. Lactic acid fermentation is the most common form of food fermentation with the Lactobacilli spp dominating most spontaneous fermentations. The objective of this study was to determine the effect of lactic acid bacteria (LAB) on the antinutrient and flatulence causing oligosaccharide composition of red haricot bean. A factorial research design was used in the study. Red haricot beans were sorted and soaked for 15 h. The soaked beans were fermented in 2% salt-sugar solutions for 120 h. Experimental batch was inoculated with Lb. plantarum BFE 5092 (IF), and the control batch was spontaneously fermented (SF). Microbial growth and pH were monitored every 24 h during fermentation. After fermentation, the beans were dried and milled, and the flours were subjected to biochemical analysis. ANOVA was done using SPSS statistics 23. The pH decreased significantly (P<0.05) from 6.06 to 3.9 in both batches at the end of fermentation. The LAB counts significantly increased (P<0.05) in both batches, whereas coliform counts decreased significantly (P<0.05). Fungi were not detected in both batches. Soaking lowered tannins and phytates and raffinose concentrations significantly but had no significant effect on stachyose concentration. At the end of 120 h of fermentation, the tannin content was 109.50 and 54.04 mg/100 g in IF and SF, respectively. Phytates were at 242.52 and 163.43 mg/100 g in IF and SF, respectively. Raffinose content was 32.85 and 32.58 mg/100 g in IF and SF, respectively, while stachyose content was 593.33 and 467.49 mg/100 g in IF and SF, respectively. This research showed that LAB is able to ferment soaked whole red haricot and lower the tannin, phytate, raffinose, and stachyose content significantly. Spontaneous fermentation lowered these antinutrients and oligosaccharides better than inoculation with Lb. plantarum BFE 5092.
Influence of Real‐Time Heating on Mechanical Behaviours of Rocks
Authors: Gu Bin , Wan Zhijun , Zhang Yuan , Ma Yangsheng , Xu Xiaodong Bernard
Published: August 2020

The rock mechanical properties under the effect of high temperature present a great significance on underground rock engineering. In this paper, the mechanical properties of sandstones, marbles, and granites under real‐time heating were investigated with a servo‐controlled compression apparatus. The results show that mechanical behaviours of all the three types of rocks are influenced by real‐time heating to different degrees. Due to thermal cracking, the uniaxial compressive strengths decrease as the heating temperature rises from room temperature to 400°C. Above 400°C, the sandstone exhibits a significant increase in UCS because of the sintering reaction. The sintering enlarges the contact area and friction between crystal grains in the sandstone, which strengthens the bearing capacity. For marbles, the UCS continues to decrease from 400°C to 600°C due to thermal cracking. However, the carbonate in the marble begins to decompose after 600°C. The generated particles would fill the cracks in the marble and increase the strength. For granites, their UCS presents a sharp decline after 400°C because of thermal cracking. For all rock elastic modulus, they present a decreasing trend, and this indicates that the rock’s ability to resist deformation gradually weakens under the effect of temperature. In general, rock mechanical behaviours under real‐time heating differ from those in normal situations, and use of the parameters presented here is important for underground rock engineering related to high temperature and can improve the precision in theoretical and numerical analysis.
The Unique Bipolar Clavicle Dislocation: A Novel Reconstruction Technique and Case Report
Authors: Dev Ameesh , Prabhakar Gautham , Dutta Anil , Dang Khang
Published: August 2020

A bipolar clavicle separation is defined as a simultaneous dislocation of the ipsilateral sternoclavicular joint (SCJ) and acromioclavicular joint (ACJ). This rare injury pattern is usually the result of a high-energy mechanism, such as a motor vehicle collision or fall from height. While there are several treatment options such as screw fixation, sutures, or plate fixations, there is no single standard approach for this infrequent injury. We describe a unique case of bipolar clavicle dislocation, specifically an anteriorly displaced SCJ and posteriorly displaced ACJ, treated with a novel surgical technique—a TightRope technique (Arthex®) and semitendinosus allograft.
Does the Frequency of Watching Television Matters on Overweight and Obesity among Reproductive Age Women in Ethiopia?
Authors: Ahmed Mohammed , Seid Abdu , Kemal Adnan
Published: August 2020

Background. Studies in developed countries have revealed an association of different magnitudes between watching television and the risk of being overweight and obese among reproductive age women. Even so, there is no evidence of such an association in the context of the Ethiopian population. Hence, the study aimed to assess the association between watching television with overweight and obesity in a nationally representative sample of Ethiopian women.Methods. A cross-sectional study was conducted by using secondary data analysis from 2016 Ethiopia demographic and health survey among women aged from 15 to 49 years. The samples were selected using a two-stage stratified cluster sampling technique. A total of 10,074 women were included in the analysis. The outcome variables were both overweight and obesity, whereas the main exposure variable was the frequency of watching television. Multivariate logistic regression analysis was performed for adjusting potential confounders. Adjusted odds ratio (AOR) with 95% confidence intervals was used to declare a statistically significant association.Results. The study found that watching television at least once a week was significantly associated with both overweight (AOR: 1.79; 95% CI: 1.20–2.73) and obesity (AOR: 3.76; 95% CI: 2.04–6.95). The study also divulged that the odds of overweight were higher among women aged 25–39 years (AOR: 2.17; 95% CI: 1.25–3.77) and 40–49 years (AOR: 2.69; 95% CI: 1.45–5.00), urban residents (AOR: 1.76; 95% CI:1.17–2.65), attended higher education (AOR:2.11; 95% CI: 1.22–3.65), and richest in the wealth index (AOR: 2.83; 95% CI:1.71–4.68). Similarly, the odds of obesity were higher among women aged 25–39 years and 40–49 years, attended higher education, and the richest in wealth index.Conclusions. The results from this study demonstrated that watching television at least once a week is associated with obesity among reproductive age women in Ethiopia. Therefore, a social behavioral change communication campaign needs to be taken to improve awareness regarding the harmful consequences of watching television for long hours. Further research studies should be conducted among men and adolescents to determine whether this positive association exists among that target population as well.
The Role of CTHRC1 in Regulation of Multiple Signaling and Tumor Progression and Metastasis
Authors: Mei Dan , Zhu Yue , Zhang Lingling , Wei Wei
Published: August 2020

Collagen triple helix repeat containing-1 (CTHRC1) has been identified as cancer-related protein. CTHRC1 expresses mainly in adventitial fibroblasts and neointimal smooth muscle cells of balloon-injured vessels and promotes cell migration and tissue repair in response to injury. CTHRC1 plays a pivotal role in some pathophysiological processes, including increasing bone mass, preventing myelination, and reversing collagen synthesis in many tumor cells. The ascended expression of CTHRC1 is related to tumorigenesis, proliferation, invasion, and metastasis in various human malignancies, including gastric cancer, pancreatic cancer, hepatocellular carcinoma, keloid, breast cancer, colorectal cancer, epithelial ovarian cancer, esophageal squamous cell carcinoma, cervical cancer, non-small-cell lung carcinoma, and melanoma. And molecules that regulate the expression of CTHRC1 include miRNAs, lncRNAs, WAIF1, and DPAGT1. Many reports have pointed that CTHRC1 could exert different effects through several signaling pathways such as TGF-β, Wnt, integrin β/FAK, Src/FAK, MEK/ERK, PI3K/AKT/ERK, HIF-1α, and PKC-δ/ERK signaling pathways. As a participant in tissue remodeling or immune response, CTHRC1 may promote early-stage cancer. Several recent studies have identified CTHRC1 as an effectual prognostic biomarker for predicting tumor recurrence or metastasis. It is worth noting that CTHRC1 has different cellular localization and mechanisms of action in different cells and different microenvironments. In this article, we focus on the advances in the signaling pathways mediated by CTHRC1 in tumors.
A Dynamic Duopoly Cournot Model with R&D Efforts and Its Dynamic Behavior Analysis
Authors: Zhou Wei , Zhou Jie , Chu Tong , Li Hui
Published: August 2020

In this paper, a dynamic two-stage Cournot duopoly game with R&D efforts is built. Then, the local stability of the equilibrium points are discussed, and the stability condition of the Nash equilibrium point is also deduced through Jury criterion. The complex dynamical behaviors of the built model are investigated by numerical simulations. We found that the unique route to chaos is flip bifurcation, and the increase of adjusting speed will cause the system to lose stability and produce more complex dynamic behavior. In addition, we also found the phenomenon of multistability in the given model. Several kinds of coexistence of attractors are shown. In particular, we found that boundary attractors can coexist with internal attractors, which also aggravates the complexity of the system. At last, the chaotic state in the built system has been successfully controlled.
Abstract A28: Deregulation of KMT2D promotes squamous differentiation in a mouse model of muscle-invasive bladder cancer
Authors: Rong Lijie , Abate-Shen Cory
Published: August 2020

Cell differentiation and plasticity is precisely controlled by specific gene expression programs coordinate with chromatin remodeling, which are often deregulated during tumorigenesis. While divergent histopathologic differentiation in bladder cancer is prevalent and may affect clinical outcome, the underlying mechanisms are not well understood. Here, we aim to elucidate mechanisms for alteration of the histopathologic and molecular features of muscle-invasive bladder cancer (MIBC) by interrogating the functional role of chromatin-remodeling genes using relevant genetically engineered mouse models (GEMMs). High frequency of mutations in chromatin-remodeling genes encoding COMPASS-like chromatin-remodeling complex members has been identified in human MIBC. These genes include “writers” that create histone post-translational modification, such as the lysine methyltransferase KMT2D (MLL2/4), and “erasers” that remove these modifications, such as the lysine demethylase KDM6A (UTX). We have generated GEMMs that enable bladder-specific conditional inactivation of individual chromatin-remodeling genes in combination with loss of function of Trp53 and Pten, which leads to MIBC. Interestingly, bladder tumors from GEMMs having inactivation of Kmt2d along with Trp53 and Pten (e.g., Kmt2d;Trp53;Pten mice) develop a variant histologic phenotype that is not observed in tumors from either the Trp53;Pten or Kdm6a;Trp53;Pten mice. Specifically, these Kmt2d-inactivated tumors share histopathologic features in common with human urothelial carcinoma that display squamous differentiation. Furthermore, expression profiling of these Kmt2d;Trp53;Pten bladder tumors identified a unique set of differentially expressed genes that are enriched for genes representing squamous differentiation in other nonbladder cancers. Our findings suggest that deregulated Kmt2d expression promotes squamous differentiation in MIBC, at least in context of Trp53;pten coinactivation.

Citation Format: Lijie Rong, Cory Abate-Shen. Deregulation of KMT2D promotes squamous differentiation in a mouse model of muscle-invasive bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr A28.
Abstract B02: TP63 isoform expression landscape associations with bladder cancer patient outcomes
Authors: Bankhead Armand , McMaster Thomas , Palmbos Phillip L.
Published: August 2020

Bladder cancer will cause an estimated 17,000 deaths this year in the United States. Transformation-related protein 63 (TP63) is a p53 family transcription factor that has been shown to be important for development and is commonly expressed in bladder cancer. However, the relationship of TP63 to bladder cancer patient outcome remains unclear. Some studies have associated TP63 expression with a positive patient outcome, while others have shown TP63 expression is associated with reduced survival. One potential explanation for this discrepancy is that TP63 is expressed as one of at least 15 unique isoforms, of which there are two main types (TAp63 and DNp63) exhibiting unique functional domains. In this work we define the landscape of TP63 isoform expression and quantify its association with bladder cancer patient outcome using RNA sequencing data from the TCGA bladder cancer cohort and other human bladder cancer samples. To examine the TP63 isoform landscape in bladder cancer, we utilized annotations from Refgene and Ensembl databases and used Cufflinks to identify two potentially novel TP63 isoforms not represented in current TP63 gene annotations. To quantitate isoform expression, we used multiple RNA-Seq expression quantification algorithms (Cufflinks, Kallisto, and Salmon) to infer isoform expression estimates of 15 TP63 isoforms for 408 bladder cancer patients from TCGA. We experimentally validated our findings using a collection of 14 bladder cancer cell lines and show that results translated to an additional collection of 19 primary bladder cancer tumor samples. We find that DNp63 is significantly higher in patients with luminal papillary and basal squamous subtypes, while TAp63 was selectively expressed in patients with basal squamous bladder cancer. Analysis of TP63 isoform expression with clinical data demonstrated that DNp63 trends with improved patient survival (HR=0.94, CI=0.88,1.006, P=0.082), whereas TAp63 is associated with worse patient survival (HR = 1.8, CI=1.38,2.4, P=0.00022) in human bladder cancer. Taken together, this work represents a comprehensive assessment of TP63 isoform expression in the TCGA bladder cancer cohort using contemporary, extended gene isoform annotations and quantifications—underscoring the need for profiling additional bladder cancer cohorts with RNA-Seq for further insight to isoform-specific expression. It also implicates TP63 isoform expression as a potential biomarker of clinical patient outcomes.

Citation Format: Armand Bankhead III, Thomas McMaster, Phillip L. Palmbos. TP63 isoform expression landscape associations with bladder cancer patient outcomes [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr B02.
Abstract IA11: Chemotherapy remodels the bladder cancer immune microenvironment
Authors: Kim William Y.
Published: August 2020

In the United States urothelial carcinoma (UC) of the bladder is the 4th and 9th most frequent malignancy in men and women, respectively, with around 74,000 new cases and 16,000 deaths in 2017. High-grade (HG), muscle-invasive bladder tumors account for the majority of those deaths as patients with metastatic disease have a 5-year survival rate of only 15%. The current standard-of-care first-line therapy for metastatic disease is cisplatin-based combination chemotherapy or immune checkpoint inhibition in patients who are platinum ineligible. Novel immune checkpoint (IC) inhibitors, including anti-PD1 and anti-PD-L1, represent a paradigm shift in cancer therapy and have demonstrated substantial clinical benefits in patients with advanced UC. Despite the enthusiasm engendered by PD-1/PD-L1 axis blockade in metastatic UC, only 15-25% of patients treated in published trials had objective responses. Preliminary studies from our laboratory show that chemotherapy remodels the immune microenvironment of muscle-invasive bladder cancers. We have begun to investigate the mechanisms by which chemotherapy drives a heightened immune response using our recently described genetically engineered murine (GEM) models of bladder cancer.

Citation Format: William Y. Kim. Chemotherapy remodels the bladder cancer immune microenvironment [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA11.
An In Vivo Kras Allelic Series Reveals Distinct Phenotypes of Common Oncogenic Variants
Authors: Zafra Maria Paz , Parsons Marie J. , Kim Jangkyung , Alonso-Curbelo Direna , Goswami Sukanya , Schatoff Emma M. , Han Teng , Katti Alyna , Fernandez Maria Teresa Calvo , Wilkinson John E. , Piskounova Elena , Dow Lukas E.
Published: August 2020

KRAS is the most frequently mutated oncogene in cancer, yet there is little understanding of how specific KRAS amino acid changes affect tumor initiation, progression, or therapy response. Using high-fidelity CRISPR-based engineering, we created an allelic series of new LSL-Kras mutant mice, reflecting codon 12 and 13 mutations that are highly prevalent in lung (KRASG12C), pancreas (KRASG12R), and colon (KRASG13D) cancers. Induction of each allele in either the murine colon or pancreas revealed striking quantitative and qualitative differences between KRAS mutants in driving the early stages of transformation. Furthermore, using pancreatic organoid models, we show that KRASG13D mutants are sensitive to EGFR inhibition, whereas KRASG12C-mutant organoids are selectively responsive to covalent G12C inhibitors only when EGFR is suppressed. Together, these new mouse strains provide an ideal platform for investigating KRAS biology in vivo and for developing preclinical precision oncology models of KRAS-mutant pancreas, colon, and lung cancers.

Significance:

KRAS is the most frequently mutated oncogene. Here, we describe new preclinical models that mimic tissue-selective KRAS mutations and show that each mutation has distinct cellular consequences in vivo and carries differential sensitivity to targeted therapeutic agents.

See related commentary by Kostyrko and Sweet-Cordero, p. 1626.

This article is highlighted in the In This Issue feature, p. 1611
Protective Effects of Allicin on ISO-Induced Rat Model of Myocardial Infarction via JNK Signaling Pathway
Authors: Xu Wen , Li Xiang-peng , Li En-ze , Liu Yue-fen , Zhao Jun , Wei Li-na , Ma Lin
Published: August 2020

Objective: This research was aimed to explore protective effects of allicin on rat model of myocardial infarction via JNK signaling pathway. Methods: Rat myocardial ischemia model was established with subcutaneous injection of isoproterenol (ISO). Seventy-five rats were randomly divided into 5 groups (n = 15): sham group, ISO group, low-dose group (1.2 mg/kg/days for 7 days), medium-dose group (1.8 mg/kg/days for 7 days), and high-dose group (3.6 mg/kg/days for 7 days). Routine HE staining and Masson staining were performed to observe myocardial histopathology. The expression of oxidative stress-related indicators, heart tissue apoptosis-related proteins, and JNK and p-JNK proteins were measured for different groups. Results: Compared with the sham group, the T wave value of the ISO group was significantly increased (p < 0.01). When allicin was administered, the T wave values at different time points in all groups were all decreased. Compared with the sham group, the ratio of eNOS, Bcl-2/Bax was significantly decreased, and p-eNOS, iNOS, caspase-3, caspase-9, and Cyt-c were significantly elevated in the ISO group (p < 0.05). After allicin was administered, significant changes in these proteins were observed in the medium- and high-dose groups. There was no significant change in the expression of JNK protein in the ISO group compared with the sham group; however, the expression of eNOS and p-JNK protein were significantly upregulated (p < 0.01) and the expression of p-eNOS and iNOS were significantly downregulated (p < 0.01). When allicin was administered, expression of p-JNK protein was significantly downregulated. Conclusion: Allicin can reduce oxidative stress damage and cardiomyocyte apoptosis in rat model of myocardial infarction and can significantly regulate JNK signaling pathway.