bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological and anatomical development of glycinergic inhibition in the mouse superior paraolivary nucleus following hearing onset
Authors: Rajaram Ezhilarasan , Pagella Sara , Grothe Benedikt , Kopp-Scheinpflug Conny
Published: July 2020

Neuronal activity regulates development and maturation of neural circuits. This activity can include spontaneous burst firing or firing elicited by sensory input during early development. For example, auditory brainstem circuits involved in sound localization require acoustically evoked activity to form properly. Here we show, that an inhibitory circuit, involved in processing sound offsets, gaps, and rhythmically modulated vocal communication signals, matures before the onset of acoustically evoked activity.
Regulation of vocal precision by noradrenergic modulation of a motor nucleus
Authors: Sheldon Zachary P. , Castelino Christina B. , Glaze Christopher M. , Bibu Steve P. , Yau Elvina , Schmidt Marc F.
Published: July 2020

Norepinephrine (NE) function is often implicated in regulating arousal levels. Recent theory suggests that the noradrenergic system also regulates the optimization of behavior with respect to reward maximization by controlling a switch between exploration and exploitation of the specific actions that yield greatest utility. We show in the songbird that NE can act directly on a cortical motor area and cause a switch between exploratory and exploitative behavior.
The role of the anterior intraparietal sulcus and the lateral occipital cortex in fingertip force scaling and weight perception during object lifting
Authors: van Polanen Vonne , Rens Guy , Davare Marco
Published: July 2020

This article provides new insights into the neural mechanisms underlying object lifting and perception. Using transcranial magnetic stimulation during object lifting, we show that effects of previous experience on force scaling and weight perception are not mediated by the anterior intraparietal sulcus or the lateral occipital cortex (LO). In contrast, we highlight a unique role for LO in load force scaling, suggesting different brain processes for grip and load force scaling in object manipulation.
Secoisolariciresinol Diglucoside Delays the Progression of Aging-Related Diseases and Extends the Lifespan ofCaenorhabditis elegansvia DAF-16 and HSF-1
Authors: Lu Min , Tan Lin , Zhou Xiao-Gang , Yang Zhong-Lin , Zhu Qing , Chen Jian-Ning , Luo Huai-Rong , Wu Gui-Sheng
Published: July 2020

Secoisolariciresinol diglucoside (SDG) is a phytoestrogen and rich in food flaxseed, sunflower seeds, and sesame seeds. Among the beneficial pharmacological activities of SDG on health, many are age related, such as anticancer, antidiabetes, antioxidant, and neuroprotective effects. Thus, we investigated if SDG had an effect on antiaging inCaenorhabditis elegans(C. elegans). Our results showed that SDG could extend the lifespan ofC. elegansby up to 22.0%, delay age-related decline of body movement, reduce the lethality of heat and oxidative stress, alleviate dopamine neurodegeneration induced by 6-hydroxydopamine (6-OHDA), and decrease the toxicity of Aβprotein inC. elegans. SDG could increase the expression of the downstream genes of DAF-16, DAF-12, NHR-80, and HSF-1 at mRNA level. SDG could not extend the lifespan of mutants from genesdaf-16,hsf-1,nhr-80,daf-12,glp-1,eat-2, andaak-2. The above results suggested that SDG might enhance the stress resistance, delay the progression of aging-related diseases, and extend the lifespan ofC. elegansvia DAF-16 and HSF-1.
miR‐1258 Regulates Cell Proliferation and Cell Cycle to Inhibit the Progression of Breast Cancer by Targeting E2F1
Authors: Zhao Xianbao
Published: July 2020

Objective. This study is designed to clarify that miR‐1258 targets E2F1 to regulate the proliferation and cell cycle of breast cancer (BC) cells and consequently suppress the progression of BC. Methods. Bioinformatics analysis was used to analyze the differentially expressed genes in BC. The expression of miR‐1258 and E2F1 mRNA in BC cell lines and immortalized breast epithelial cell lines were detected by qRT‐PCR. The proliferation and growth activity of BC cells were detected by MTT and colony formation assays. The apoptosis and cell cycle of BC cells were detected by flow cytometry and the targeting relationship between miR‐1258 and E2F1 was identified by dual‐luciferase assay. Results. The expression of miR‐1258 was decreased while that of E2F1 was increased in BC cells. Overexpression of miR‐1258 and silencing E2F1 could inhibit the cell proliferation and growth, block cells in the G0/G1 phase, and promote cell apoptosis. Besides, miR‐1258 inhibited cell proliferation and growth, block cells in the G0/G1 phase, and promote cell apoptosis by downregulating E2F1. Conclusion. miR‐1258 regulates the proliferation and cell cycle to inhibit the progression of BC by targeting and downregulating E2F1.
Research on Dynamic and Complexity of Energy-Saving Investment about Multichannel and Multienergy Supply Chain
Authors: Wu Fang
Published: July 2020

Considering the multienergy structure of the electricity market and supply-side competition reform in China, a dual-channel and multiproduct supply chain model is constructed. There are three players in the game model: new energy company and traditional energy company provide energy for the market and the State Grid at the same time. The State Grid is a retailer who buys electricity from two companies and supplies to the market after converting and transmitting the power. Three companies can invest in grid management for saving energy and reducing losses. The energy loss rate is an exponential function of line loss investment. Through the bifurcation graph, Lyapunov exponent, and the basin of parameter, the complex characteristics of the investment market are analyzed. It is interesting to find the Grazing–Hopf bifurcation which usually occurs in nonlinear circuits. The mixed expectation of bounded rationality and the naive expectation is conducive to suppressing the bifurcation and chaos of the market. When external shocks occur, the control model has good robustness.
Automatic Detection of Brain Tumor on Computed Tomography Images for Patients in the Intensive Care Unit
Authors: Fahmi Fahmi , Apriyulida Fitri , Nasution Irina Kemala , Sawaluddin
Published: July 2020

Patients in the intensive care unit require fast and efficient handling, including in-diagnosis service. The objectives of this study are to produce a computer-aided system so that it can help radiologists to classify the types of brain tumors suffered by patients quickly and accurately; to build applications that can determine the location of brain tumors from CT scan images; and to get the results of the analysis of the system design. The combination of the zoning algorithm with Learning Vector Quantization can increase the speed of computing and can classify normal and abnormal brains with an average accuracy of 85%.
Saturdays-in-Motion: Education and Empowerment through an Interdisciplinary Team Approach for Parkinson’s Disease in Cali-Colombia
Authors: Muñoz Beatriz E. , Quintana-Peña Valentina , Gonzalez Maria C. , Valderrama Jaime A. , Castaño-Pino Yor Jaggy , Rincón Domiciano , Navarro Andrés , Orozco Jorge L.
Published: July 2020

Introduction. Parkinson’s disease (PD) is one of the most prevalent age-related neurodegenerative disorders. The progression of PD produces an important disease burden in patients due to functional impairment, which also has repercussions on caregivers. In addition, it has become a challenge for health systems, especially in developing countries, which have limited resources. Multidisciplinary teams with a community approach have proved effective in high-income countries; however, there is no reported literature in low- and middle-income countries about this kind of initiative. Objective. This paper aims to document the experience of patients, caregivers, and experts in a community approach as an innovative model in a middle-income country. Methods. A quantitative descriptive research was conducted. The selection criteria were having a PD diagnosis, attending with a caregiver to Saturdays in Motion (SIM), or being a clinical expert invited to SIM. PD patients and their caregivers answered three surveys on their points of view with respect to SIM: SIM and their quality of life (QoL) and PDQ-39 and Zarit, whereas clinical experts completed two questions related to the SIM program. Descriptive statistics were used to summarize the results of the surveys and clinical tests. Results. Forty-eight, twenty-four, and twenty-one subjects answered surveys one, two, and three, respectively. In total, four clinical experts were interviewed. 87.9% of the patients consider that SIM activities improved their QoL. The most affected areas in PDQ-39 were those related to the social area. Around 66.6% of the caregivers reported a mild burden on Zarit and think that SIM enhances the PD patient’s QoL. Clinical experts highlighted the sense of community and empathy. Conclusion. Our preliminary experience shows a multidisciplinary model with a community approach which redefines the traditional relationship between patients, caregivers, and clinical experts. This aim of this initiative is that education and empowerment patients and caregivers reach a better perception of QoL.
Close2U: An App for Monitoring Cancer Patients with Enriched Information from Interaction Patterns
Authors: Navarro-Alamán Javier , Lacuesta Raquel , García-Magariño Iván , Gallardo Jesús , Ibarz Elena , Lloret Jaime
Published: July 2020

The management of cancer patients’ symptoms in doctor consultations is a cornerstone in clinical care, this process being fundamental for the follow-up of the evolution of these. This article presents an application that allows collecting periodically and systematically the data of cancer patients and their visualization by the medical team. In this article, we made the analysis, design, implementation, and final evaluation by analyzing the correlation of this data collection with interaction patterns to determine how the user information can be enriched with information from the interaction patterns. We have followed an agile methodology based on the iterative and incremental development of successive prototypes with increased fidelity, where the requirements and solutions have evolved over time according to the need and assessments made. The comprehensive analysis of the patient’s condition allowed us to perform a first analysis of the correlation of the states of patients concerning mood, sleeping quality, and pain with the interaction patterns. A future goal of this project is to optimize the process of data collection and the analysis of information. Another future goal is to reduce the time dedicated to reporting the evolution of symptoms in face-to-face consultations and to help professionals in analyzing the patient’s evolution even in the period that has not been attended in person.
High Expression of the Long Noncoding RNA SNHG15 in Cancer Tissue Samples Predicts an Unfavorable Prognosis of Cancer Patients: A Meta-Analysis
Authors: Zhang Cheng , Ke Yang , Liu Xin , Wang Xinghong , Li Yuehua , Zhou Jian , Zhang Heng , Wang Lin
Published: July 2020

Background. Although the prognostic value of lncRNA small nucleolar RNA host gene 15 (SNHG15) expression in cancers has been evaluated in many studies, the results remain controversial. This meta-analysis aimed to clarify the role of SNHG15 in the prognosis of different cancer patients. Materials and Methods. Eligible studies were selected from PubMed, PMC, EMBASE, Web of Science, and Cochrane Library according to the inclusion and exclusion criteria (up to December 20, 2019). The primary outcome was overall survival (OS) and recurrence-free survival (RFS). The secondary outcome was other clinicopathological parameters (including advanced TNM stage, lymph node metastasis, distant metastases, and gender). The Cancer Genome Atlas (TCGA) dataset was used to verify the analysis results. Results. Eleven eligible studies were eventually included, involving 9 different types of cancer and 1,079 patients. The high expression of SNHG15 was indicative of a significantly poor OS of cancer patients (HR = 1.96, 95% CI = 1.55–2.47, P<0.00001). Subgroup analysis showed that the high expression of SNHG15 was associated with a significantly poor OS of patients with digestive cancer (HR = 1.91, 95% CI = 1.38–2.66, P=0.0001), but not lung cancer (HR = 1.83, 95% CI = 0.89–3.76, P=0.010). The RFS of patients with high expression of SNHG15 was shorter than that of patients with low expression of SNHG15 (HR = 2.03, 95% CI = 1.46–2.83, P<0.00001). In addition, high SNHG15 expression level was significantly correlated with later TNM stage (OR = 3.05, 95% CI = 2.31–4.02, P<0.00001), lymphatic metastasis (OR = 3.20, 95% CI = 2.30–4.45, P<0.00001), and distant metastasis (OR = 5.05, 95% CI = 2.15–11.85, P=0.0002). The TCGA verification results were consistent with those observed in our meta-analysis. Conclusion. High expression of the long noncoding RNA SNHG15 in cancer tissue samples predicts an unfavorable prognosis for cancer patients. LncRNA SNHG15 can be used as an adverse prognostic biomarker for cancer patients.
Development of Polymer and Surfactant Based Naringenin Nanosuspension for Improvement of Stability, Antioxidant, and Antitumour Activity
Authors: Md Shadab , Alhakamy Nabil A. , Akhter Sohail , Awan Zuhier A. Y. , Aldawsari Hibah M. , Alharbi Waleed S. , Haque Anzarul , Choudhury Hira , Sivakumar Ponnurengam Malliappan
Published: July 2020

Nanosuspensions are widely reported to enhance the solubility of poorly soluble drugs. In addition to enhancement in solubility, improvement of stability and therapeutic efficacy would be an added advantage. In the present study, premilling and subsequent high-pressure homogenization were carried out to produce naringenin nanosuspension. Hydroxypropyl methylcellulose and sodium dodecyl sulfate were evaluated for their performance as stabilizers under various homogenization cycles. The prepared nanosuspensions were studied for average particle size and size distribution, zeta potential, solubility, drug release, antioxidant activity, and in vitro antitumor activity. It was observed that both hydroxypropyl methylcellulose-stabilized nanosuspension and sodium dodecyl sulfate-stabilized nanosuspension produced an enhancement in physical stability, antioxidant potential, and in vitro cytotoxicity compared with naringenin. Furthermore, hydroxypropyl methylcellulose-stabilized nanosuspension was found to be better than sodium dodecyl sulfate-stabilized nanosuspension in terms of particle size and size distribution, storage stability, and drug release. This study showed that nanosuspension formulations could be a potential strategy for improving dissolution and antitumor activity of naringenin.
[Retracted] Circular RNA circFAT1(e2) Promotes Osteosarcoma Progression and Metastasis by Sponging miR‐181b and Regulating HK2 Expression
Authors: Gu Huijie , Cheng Xiangyang , Xu Jun , Zhou Kaifeng , Bian Chong , Chen Guangnan , Yin Xiaofan
Published: July 2020

As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. Nevertheless, how circRNAs participate in osteosarcoma (OS) development and progression are not well understood. In the present study, we identified a circRNA circFAT1(e2) with an upregulated expression level in OS tissues. By functional experiments, we found that circFAT1(e2) depletion significantly suppressed the proliferation and reduced migration in OS. In terms of mechanism, we found that circFAT1(e2) inhibited miR‐181b, while miR‐181b targeted HK2. By releasing the inhibition of miR‐181b on HK2 expression, leading to attenuated OS progression. Mechanistic investigations suggested that circFAT1(e2) served as a competing endogenous RNA (ceRNA) of miR‐181b to enhance HK2 expression. On the whole, our study indicated that circFAT1(e2) exerted oncogenic roles in OS and suggested the circFAT1(e2)/miR‐181b/HK2 axis might be a potential therapeutic target.
Research on Horizontal Coefficient of Consolidation of Vietnam’s Soft Soil
Authors: Nguyen Thi Nu , Son Bui Truong , Ngoc Do Minh
Published: July 2020

The horizontal coefficient of consolidation is the most important parameter for designing the improvement of soil soft by prefabricated vertical drains (PVDs) combined with surcharge and vacuum preloading. This paper presents the experimental study on the horizontal coefficient of consolidation (ch) of some soft soils distributed in Vietnam. Thechvalue was determined by the laboratory test and CPTu dissipation test. The laboratory tests included the Rowe consolidation cell test and constant rate of strain consolidation with radial drainage test. Two types of consolidation laboratory tests were performed. The experimental results indicated that thechvalue is always larger than the vertical coefficient of consolidation of soil (cv). The ratio ofch/cvdepends on the consolidated pressure, type of soil, and the anisotropy of soil. The ratio ofch/cvis different in different types of soft soil in Vietnam. In the normally consolidated state, thech/cvratio ranges from 1.35 to 10.59. It was necessary to choose thechvalue at the consolidated stress level for calculating the PVD spacing.
Protective Effect of DPPD on Mercury Chloride-Induced Hepatorenal Toxicity in Rats
Authors: Nabil Ahmed , Elshemy Mohamed M. , Asem Medhat , Gomaa Heba F.
Published: July 2020

Mercury is a global environmental pollutant, accumulating mainly in the kidney and liver inducing hepatorenal toxicity, oxidative stress, and tissue damage. Oxidative stress is caused by an imbalance between free radicals’ production and cellular antioxidant defense systems. In the present study, we investigated the effect of N N′-diphenyl-1, 4-phenylenediamine (DPPD) antioxidant activity against mercury chloride- (HgCl2-) induced renal and hepatic toxicity. Thirty adult female Sprague Dawley rats were divided into three equal groups: the first group was injected with saline only and served as a control, the second group was injected with HgCl2, and the third group received DPPD + HgCl2 rats injected with HgCl2 without treatment showing a significant increase in alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, and uric acids compared to control. Moreover, the second group showed a significant reduction in the activity of the antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH)) in addition to a marked increase in the malondialdehyde (MDA) content, histopathological alterations, collagen deposition, CD8%, CD4%, and TGF-β% in kidney and liver tissues compared with the control group. Treatment with DPPD showed significant recovery (p≤0.001) in all previous parameters and histopathological examination. In conclusion, we suggested that DPPD may have a promising antioxidant capacity, gives it the applicability to be used as a prophylactic agent against mercury-induced hepatorenal cytotoxicity in the future.
Differential Equation Models for Education Charges of Universities in China and the Applications
Authors: Liu Minhang , Su Hua
Published: July 2020

In recent years, with the expansion of university enrollment in China, the cost of running a school is getting higher and higher. Under the circumstance of insufficient state investment in higher education, the education charge paid by students has become an important source of the university income. It has become a hot topic of social concern to formulate a reasonable charging model to enable more students to enter higher education institutions. In this paper, we mainly put forward the basic differential equation models describing the problem of higher education charges in China. Through the qualitative analysis of these two basic models, we draw several conditions for universities to maintain or stabilize their education charges and give some suggestions on macrocontrol of university education charges in China.
A Deep Cycle Limit Learning Machine Method for Urban Expressway Traffic Incident Detection
Authors: Fang YunFeng , Yang Qingfang , Zheng Lili , Zhou Xiangyu , Peng Bo
Published: July 2020

In Beijing, Shanghai, Hangzhou, and other cities in China, traffic congestion caused by traffic incidents also accounts for 50% to 75% of the total traffic congestion on expressways. Therefore, it is of great significance to study an accurate and timely automatic traffic incident detection algorithm for ensuring the operation efficiency of expressways and improving the level of road safety. At present, many effective automatic event detection algorithms have been proposed, but the existing algorithms usually take the original traffic flow parameters as input variables, ignoring the construction of feature variable sets and the screening of important feature variables. This paper presents an automatic event detection algorithm based on deep cycle limit learning machine. The traffic flow, speed, and occupancy of downstream urban expressway are extracted as input values of the deep-loop neural network. The initial connection weights and output thresholds of the deep-loop neural network are optimized by using the improved particle swarm optimization (PSO) algorithm for global search. The higher classification accuracy of the extreme learning machine is trained, and the generalization performance of the extreme learning machine is improved. In addition, the extreme learning machine is used as a learning unit for unsupervised learning layer by layer. Finally, the microwave detector data of Tangqiao viaduct in Hangzhou are used to verify the experiment and compared with LSTM, CNN, gradient-enhanced regression tree, SVM, BPNN, and other methods. The results show that the algorithm can transfer low-level features layer by layer to form a more complete feature representation, retaining more original input information. It can save expensive computing resources and reduce the complexity of the model. Moreover, the detection accuracy of the algorithm is high, the detection rate is higher than 98%, and the false alarm rate is lower than 3%. It is better than LSTM, CNN, gradient-enhanced regression tree, and other algorithms. It is suitable for urban expressway traffic incident detection.
Impact of Global Value Chain Embedding on Total-Factor Energy Productivity of Chinese Industrial Sectors
Authors: Feng Xiwen , Xin Mingshang , Cui Xinghua
Published: July 2020

In the four decades since China’s reform and opening up, China has been playing an active role in global value chain (GVC) due to its abundant resources. China has gained enormous benefits from opening up, but has also suffered huge energy costs in the process. In this study, we incorporated global value chains and energy consumption into a unified analysis framework and calculated the energy total-factor productivity (ETFP) of China’s industry and the degree of participation in GVC. In addition, in order to discover the contradictions and problems between China's participation in global value chains and the improvement of total energy factor productivity, the panel smooth transformation model (PSTR) was used to empirically test the nonlinear relationship between the ETFP and the degree of participation in GVC in China. From the analysis results, GVC participation, as well as the subdivided shallow GVC participation and deep GVC participation, first promoted the effect on ETFP and then suppressed it, showing an inverted U-shaped single threshold characteristic. The results indicated that in the progress of starting to participate in the GVC, the effect of technological progress of the GVC overweighed the scale effect of energy consumption, resulting in the growth of ETFP. However, due to the gradual reduction of technology dividends and the “low-end lock-in” situation, China was placed in the value chain by the developed countries, and the technological effect was gradually smaller than the scale effect of energy consumption. As a result, the increase in the total-factor productivity of energy was inhibited. At the same time, in the further examination of industry heterogeneity, the inverted U-shaped influence trend was more significant in high energy-consuming industries. The conclusions of this study can provide a new perspective and policy focus for China's participation in GVC to achieve the goal of increasing ETFP.
Stock Market Temporal Complex Networks Construction, Robustness Analysis, and Systematic Risk Identification: A Case of CSI 300 Index
Authors: Wan Xiaole , Zhang Zhen , Zhang Chi , Meng Qingchun
Published: July 2020

The Chinese stock 300 index (CSI 300) is widely accepted as an overall reflection of the general movements and trends of the Chinese A-share markets. Among the methodologies used in stock market research, the complex network as the extension of graph theory presents an edged tool for analyzing internal structure and dynamic involutions. So, the stock data of the CSI 300 were chosen and divided into two time series, prepared for analysis via network theory. After stationary test and coefficients calculated for daily amplitudes of stock, two “year-round” complex networks were constructed, respectively. Furthermore, the network indexes, including out degree centrality, in degree centrality, and betweenness centrality, were analyzed by taking negative correlations among stocks into account. The first 20 stocks in the market networks, termed “major players,” “gatekeeper,” and “vulnerable players,” were explored. On this basis, temporal networks were constructed and the algorithm to test robustness was designed. In addition, quantitative indexes of robustness and evaluation standards of network robustness were introduced and the systematic risks of the stock market were analyzed. This paper enriches the theory on temporal network robustness and provides an effective tool to prevent systematic stock market risks.
The Effect of Art Therapy and Music Therapy on Breast Cancer Patients: What We Know and What We Need to Find Out—A Systematic Review
Authors: Kievisiene Justina , Jautakyte Rasa , Rauckiene-Michaelsson Alona , Fatkulina Natalja , Agostinis-Sobrinho Cesar
Published: July 2020

Objective. To systematically review the evidence available on the effects of art therapy and music therapy interventions in patients with breast cancer. Design. Systematic search was conducted in PubMed, EBSCO, and Cochrane Central databases. Articles were scanned using the following keywords: “art therapy” or “music therapy” and “breast cancer” or “breast neoplasms,” “breast carcinoma,” “breast tumor,” and “mammary cancer.” Only RCTs published in English, with a control group and experimental group, and presenting pre‐/post‐therapy results were included. PRISMA guidelines for this systematic review were followed. Results. Twenty randomized controlled trials matched the eligibility criteria. Nine studies evaluated the effect of art therapy, and eleven evaluated the effect of music therapy. Improvements were measured in stress, anxiety, depression reduction, pain, fatigue, or other cancer‐related somatic symptoms’ management. Overall, the results show that art therapy was oriented towards the effects on quality of life and emotional symptoms while music therapy is the most often applied for anxiety reduction purposes during or before surgeries or chemotherapy sessions. Conclusion. Art and music therapies show effective opportunities for breast cancer patients to reduce negative emotional state and improve the quality of life and seem to be promising nonmedicated treatment options in breast oncology. However, more detailed and highly descriptive single therapy and primary mental health outcome measuring RCTs are necessary to draw an evidence‐based advise for the use of art and music therapies.
Development of MicroRNAs as Potential Therapeutics against Cancer
Authors: Abd-Aziz Noraini , Kamaruzman Nur Izyani , Poh Chit Laa
Published: July 2020

MicroRNAs (miRNAs) are small noncoding RNAs that function at the posttranscriptional level in the cellular regulation process. miRNA expression exerts vital effects on cell growth such as cell proliferation and survival. In cancers, miRNAs have been shown to initiate carcinogenesis, where overexpression of oncogenic miRNAs (oncomiRs) or reduced expression of tumor suppressor miRNAs has been reported. In this review, we discuss the involvement of miRNAs in tumorigenesis, the role of synthetic miRNAs as either mimics or antagomirs to overcome cancer growth, miRNA delivery, and approaches to enhance their therapeutic potentials.
Innovative Methodology for Sulfur Release from Copper Tailings by the Oxidation Roasting Process
Authors: Luo Bing , Peng Tongjiang , Sun Hongjuan
Published: July 2020

To effectively prevent the accumulation of copper tailings from producing acid mine drainage (AMD) and maximize the comprehensive utilization of copper tailings, the process of oxidation roasting was adopted to release sulfur in the form of SO2 to achieve the purpose of sulfur recovery later. Based on the AMD risk assessment, thermogravimetric (TG) analysis, and differential scanning calorimeter (DSC) analysis, the influences of roasting temperature, residence time, and air flow in the roasting process were investigated. The thermal stability, reaction equilibrium, mineral transformation, and residual S content were characterized by TG-DSC, HSC chemical software 6.0, X-ray diffraction (XRD), and combustion neutralization, respectively. The optimum conditions for sulfur release in the roasting process were shown with a temperature of 1200°C, a residence time of 60 min, and an air flow of 0.8 L/min. Under these conditions, the sulfur release rate was 99.82%, and the residual S content was 0.05%. Subsequently, the process of sulfur release was proposed as four steps: oxidative decomposition of pyrrhotite, formation of ferric sulfate, decomposition of ferric sulfate, and formation of hematite. All of the findings could propose a theoretical and experimental reference for the recovery of the sulfur component from tailings rich in sulfide minerals.
Nonlinear Dynamic Analysis of Solution Multiplicity of Buoyancy Ventilation in Two Vertically Connected Open Cavities with Unequal Heights
Authors: Wang Yuxing , Wei Chunyu
Published: July 2020

Solution multiplicity of natural ventilation in buildings is of much importance for personnel safety and ventilation design. In this paper, a new mathematical model of buoyancy pressure ventilation for two vertically connected open cavities is presented. Compared with the previous published papers studying two vertically connected open cavities with equal heights and hot source E2 < 0 in the upper room, we study two vertically connected open cavities with unequal heights and hot source E2 < 0 or E2 > 0 in the upper room. By solving and analyzing the equilibrium points and characteristic roots of the differential equations, we analyze the stability of two systems with upward flow pattern and downward pattern and obtain the criteria to determine the stability and existence of solutions for two scenarios. According to these criteria, the multiple steady states of buoyancy ventilation in two vertically connected open cavities with unequal heights and variable strength of hot sources can be obtained. These criteria can be used to design buoyancy ventilation or natural exhaust ventilation systems in two vertically connected open cavities. Compared with two stable states of buoyancy ventilation existing in two vertically connected open cavities with equal heights in the previously published papers, we find that more stable states and unstable states of buoyancy ventilation exist in two vertically connected open cavities with unequal heights in our paper. Finally, bifurcation diagrams and the phase portraits for the two scenarios are given.
Establishing a Porcine Eye Model for Manual Sub-Bowman Layer Photorefractive Keratomileusis
Authors: Tian Mingxia , Ma Ping , Mu Guoying , Chen Lijing , Feng Jie
Published: July 2020

Objective. To establish a porcine eye model for manual sub-Bowman layer photorefractive keratomileusis (SBPRK), which is a reformed surface ablation refractive surgery that results in preserving the corneal Bowman layer (BL).Methods. The SBPRK group consisted of eleven eyes of 8 healthy pigs with BL flaps by mechanical technique followed by laser ablation. Regarding the remaining 5 eyes, 3 random eyes had transepithelium photorefractive keratectomy (TransPRK) (the TransPRK group), while the other 2 eyes were untreated (the blank control group). All the pigs were followed up for 8 weeks. Slit-lamp biomicroscopy and optical coherence tomography (OCT) were examined before the surgeries and at 1 week, 4 weeks, and 8 weeks after the surgeries.Results. In a few days after the surgery, 3 eyes of the SBPRK group were excluded from the study because of poor healing of the corneal flaps. At the 1stpostoperative week, one eye had an irregular defect of about 3 mm in the central corneal epithelium area; the cornea of the other 7 eyes had just light edema with intact epithelium just like the cornea of the TransPRK group. At the 4thweek, in the SBPRK group, the cornea was slightly hazy (haze stage 1). While in the TransPRK group, the cornea was hazier (haze stage 2). At the 8thweek, in the SBPRK group, both corneas were almost transparent, and the edges of the BL flaps could not be clearly seen. Meanwhile, in the TransPRK group, the corneal haze became lighter and thinner. OCT showed that, in the SBPRK group, there was high reflection in the BL layer, and it was obvious at 1 week postoperation, decreased at 4 weeks, and calmed down at 8 weeks. However, in the TransPRK group, the high reflection diffused in the anterior corneal stroma at 1 week postoperation, enhanced at 4 weeks, and weakened at 8 weeks.Conclusions. Preserving the BL while conducting surface refractive surgery may result in less haze than TransPRK. However, further study is still needed, and this technique still requires refining until it becomes a standard clinical procedure.
Human Cancers Express TRAILshort, a Dominant Negative TRAIL Splice Variant, Which Impairs Immune Effector Cell Killing of Tumor Cells
Authors: Aboulnasr Fatma , Krogman Ashton , Graham Rondell P. , Cummins Nathan W. , Misra Anisha , Garcia-Rivera Enrique , Anderson Jeff R. , Natesampillai Sekar , Kogan Nicole , Aravamudan Murali , Nie Zilin , Chung Thomas D.Y. , Buick Richard , Feldman Andrew L. , King Rebecca L. , Novak Anne J. , Ansell Stephen M. , Kenderian Saad , Badley Andrew D.
Published: July 2020

Purpose:

TNF-related apoptosis inducing ligand (TRAIL) expression by immune cells contributes to antitumor immunity. A naturally occurring splice variant of TRAIL, called TRAILshort, antagonizes TRAIL-dependent cell killing. It is unknown whether tumor cells express TRAILshort and if it impacts antitumor immunity.

Experimental Design:

We used an unbiased informatics approach to identify TRAILshort expression in primary human cancers, and validated those results with IHC and ISH. TRAILshort-specific mAbs were used to determine the effect of TRAILshort on tumor cell sensitivity to TRAIL, and to immune effector cell dependent killing of autologous primary tumors.

Results:

As many as 40% of primary human tumors express TRAILshort by both RNA sequencing and IHC analysis. By ISH, TRAILshort expression is present in tumor cells and not bystander cells. TRAILshort inhibition enhances cancer cell lines sensitivity to TRAIL-dependent killing both in vitro and in immunodeficient xenograft mouse models. Immune effector cells isolated from patients with B-cell malignancies killed more autologous tumor cells in the presence compared with the absence of TRAILshort antibody (P < 0.05).

Conclusions:

These results identify TRAILshort in primary human malignancies, and suggest that TRAILshort blockade can augment the effector function of autologous immune effector cells.

See related commentary by de Miguel and Pardo, p. 5546
A Diagnostic Biopsy-Adapted Immunoscore Predicts Response to Neoadjuvant Treatment and Selects Patients with Rectal Cancer Eligible for a Watch-and-Wait Strategy
Authors: El Sissy Carine , Kirilovsky Amos , Van den Eynde Marc , Muşină Ana-Maria , Anitei Maria-Gabriela , Romero Alfredo , Marliot Florence , Junca Audelaure , Doyen Jérôme , Mlecnik Bernhard , Haicheur Nacilla , Fredriksen Tessa , Lagorce Christine , Jouret-Mourin Anne , Leonard Daniel , Bibeau Frédéric , Iseas Soledad , Roca Enrique L. , Cabanne Ana M. , Vaccaro Carlos A. , Santino Juan P. , Huertas Eduardo , Tougeron David , Carvalho Carlos , Figueiredo Nuno , Perez Rodrigo O. , Habr-Gama Angelita , Scripcariu Viorel , Gerard Jean-Pierre , Galon Jérôme , Zeitoun Guy , Pagès Franck
Published: July 2020

Purpose:

No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted immunoscore (ISB) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy (“Watch-and-Wait”).

Experimental Design:

Biopsies from two independent cohorts (n1 = 131, n2 = 118) of patients with LARC treated with nT followed by radical surgery were immunostained for CD3+ and CD8+ T cells and quantified by digital pathology to determine ISB. The expression of immune-related genes post-nT was investigated (n = 64 patients). Results were correlated with response to nT and disease-free survival (DFS). The ISB prognostic performance was further assessed in a multicentric cohort (n = 73 patients) treated by Watch-and-Wait.

Results:

ISB positively correlated with the degree of histologic response (P < 0.001) and gene expression levels for Th1 orientation and cytotoxic immune response, post-nT (P = 0.006). ISB high identified patients at lower risk of relapse or death compared with ISB low [HR, 0.21; 95% confidence interval (CI), 0.06–0.78; P = 0.009]. Prognostic performance of ISB for DFS was confirmed in a validation cohort. ISB was an independent parameter, more informative than pre- (P < 0.001) and post-nT (P < 0.05) imaging to predict DFS. ISB combined with imaging post-nT discriminated very good responders that could benefit from organ preservation strategy. In the “Watch-and-Wait” cohort (n = 73), no relapse was observed in patients with ISB high (23.3%).

Conclusions:

ISB predicts response to nT and survival in patients with LARC treated by surgery. Its usefulness in the selection of patients eligible for a Watch-and-Wait strategy is strongly suggested.
The Role of Specific ATP-Binding Cassette Transporters in the Acquired Resistance to Pyrrolobenzodiazepine Dimer–Containing Antibody–Drug Conjugates
Authors: Corbett Simon , Huang Shiran , Zammarchi Francesca , Howard Philip W. , van Berkel Patrick H. , Hartley John A.
Published: July 2020

Antibody–drug conjugates (ADC) containing pyrrolobenzodiazepine (PBD) dimers are being evaluated clinically in both hematologic and solid tumors. These include ADCT-301 (camidanlumab tesirine) and ADCT-402 (loncastuximab tesirine) in pivotal phase II trials that contain the payload tesirine, which releases the PBD dimer warhead SG3199. An important consideration in future clinical development is acquired resistance. The aim was to generate and characterize PBD acquired resistant cell lines in both hematologic and solid tumor settings. Human Karpas-299 (ALCL) and NCI-N87 (gastric cancer) cells were incubated with increasing IC50 doses of ADC (targeting CD25 and HER2, respectively) or SG3199 in a pulsed manner until stable acquired resistance was established. The level of resistance achieved was approximately 3,000-fold for ADCT-301 and 3-fold for SG3199 in Karpas-299, and 8-fold for ADCT-502 and 4-fold for SG3199 in NCI-N87. Cross-resistance between ADC and SG3199, and with an alternative PBD-containing ADC or PBD dimer was observed. The acquired resistant lines produced fewer DNA interstrand cross-links, indicating an upstream mechanism of resistance. Loss of antibody binding or internalization was not observed. A human drug transporter PCR Array revealed several genes upregulated in all the resistant cell lines, including ABCG2 and ABCC2, but not ABCB1(MDR1). These findings were confirmed by RT-PCR and Western blot, and inhibitors and siRNA knockdown of ABCG2 and ABCC2 recovered drug sensitivity. These data show that acquired resistance to PBD-ADCs and SG3199 can involve specific ATP-binding cassette drug transporters. This has clinical implications as potential biomarkers of resistance and for the rational design of drug combinations.
Fatty Acid Oxidation Is an Adaptive Survival Pathway Induced in Prostate Tumors by HSP90 Inhibition
Authors: Nassar Zeyad D. , Mah Chui Yan , Centenera Margaret M. , Irani Swati , Sadowski Martin C. , Scott Julia S. , Nguyen Elizabeth V. , Nagarajan Shilpa R. , Moldovan Max , Lynn David J. , Daly Roger J. , Hoy Andrew J. , Butler Lisa M.
Published: July 2020

HSP90 is a molecular chaperone required for stabilization and activation of hundreds of client proteins, including many known oncoproteins. AUY922 (luminespib), a new-generation HSP90 inhibitor, exhibits potent preclinical efficacy against several cancer types including prostate cancer. However, clinical use of HSP90 inhibitors for prostate cancer has been limited by toxicity and treatment resistance. Here, we aimed to design an effective combinatorial therapeutic regimen that utilizes subtoxic doses of AUY922, by identifying potential survival pathways induced by AUY922 in clinical prostate tumors. We conducted a proteomic analysis of 30 patient-derived explants (PDE) cultured in the absence and presence of AUY922, using quantitative mass spectrometry. AUY922 significantly increased the abundance of proteins involved in oxidative phosphorylation and fatty acid metabolism in the PDEs. Consistent with these findings, AUY922-treated prostate cancer cell lines exhibited increased mitochondrial mass and activated fatty acid metabolism processes. We hypothesized that activation of fatty acid oxidation is a potential adaptive response to AUY922 treatment and that cotargeting this process will sensitize prostate cancer cells to HSP90 inhibition. Combination treatment of AUY922 with a clinical inhibitor of fatty acid oxidation, perhexiline, synergistically decreased viability of several prostate cancer cell lines, and had significant efficacy in PDEs. The novel drug combination treatment induced cell-cycle arrest and apoptosis, and attenuated the heat shock response, a known mediator of HSP90 treatment resistance. This combination warrants further preclinical and clinical investigation as a novel strategy to overcome resistance to HSP90 inhibition.

Implications:

Metabolic pathways induced in tumor cells by therapeutic agents may be critical, but targetable, mediators of treatment resistance.
Anhedonia in Depressive Disorder: A Narrative Review
Authors: De Fruyt Jürgen , Sabbe Bernard , Demyttenaere Koen
Published: July 2020

Since the introduction of DSM-III anhedonia has become a core depressive criterion and is defined as the loss of interest or pleasure. Although the origin of the word goes back to the end of the 19th century and numerous anhedonic symptoms are described in classic texts on depression, this centrality in the diagnosis of depression is only recent. Anhedonia is best described as a symptom complex with unclear boundaries cutting across the tripartite model of the mind (affect, volition, and cognition). Popular concepts of anhedonia pertain to the pleasure cycle and positive affectivity. These concepts partially overlap and are often mixed up, but clearly stem from different theoretical backgrounds: the affective science of reward processing versus more general, dimensional modelling of affect. The former concept seems more suitable to understand anhedonic emotions, the latter more suitable to understand anhedonic mood or trait. This narrative review covers the history of “anhedonia,” the different anhedonic phenomena, and psychopathological concepts. An attempt is made to go beyond a merely descriptive psychopathology. Neurobiological and psychological insights shed a light on how symptoms are made and interconnected; these insights possibly call for a new psychopathological language.
Surgical Treatment for Traumatic Macular Holes: Reconstructive Changes in Foveal Microstructures and Visual Predictors Analysis
Authors: Wang Meizi , Yu Yanping , Wang Zengyi , Liang Xida , Liu Wu
Published: July 2020

Purpose: To investigate the reconstructive changes in foveal microstructures postoperatively and analyze the visual predictors in eyes with surgically closed traumatic macular holes (TMHs). Methods: Seventy-one eyes with TMHs that underwent vitrectomy, internal limiting membrane (ILM) peeling, and gas tamponade were reviewed. Clinical data, best-corrected visual acuity, and spectral-domain optical coherence tomography (SD-OCT) images were recorded. The length of the ellipsoid zone (EZ) defect and the integrity of postoperative external limiting membrane (ELM) were measured. Preoperative and 1-month postoperative features were analyzed, respectively, as potential predictors of visual acuity at 6 months postoperatively. Results: The primary hole closure rate was 90.14% (64/71). In 43 cases of initially closed TMHs with SD-OCT scans preoperatively and at 1 and 6 months postoperatively, the number of eyes with intact ELM increased from 18 (41.86%) at 1 month to 26 (60.47%) at 6 months (p = 0.08), while the number of eyes with a restored EZ band remained the same in 2 eyes (4.65%). The mean length of the EZ defect progressively decreased postoperatively (p < 0.001). Poorer preoperative visual acuity (p = 0.002), lower mean macular hole (MH) height (p = 0.012), and greater preoperative mean length of EZ defect (p < 0.001) were associated with worse visual acuity 6 months postoperatively, but only the preoperative length of the EZ defect was proved to be a predictor, with the cutoff value of 1,800 μm provided by the receiver-operating characteristics (ROC) curve. Worse visual acuity and greater mean length of the EZ defect at 1 month were also associated with worse final visual acuity. Conclusions: The mean length of the EZ defect both preoperatively and 1 month postoperatively were predictors of visual outcomes at 6 months postoperatively.
Comparison of Internal Limiting Membrane Peeling and Flap Removal to Flap Insertion on Visual Outcomes in Highly Myopic Eyes with Macular-Hole Retinal Detachment
Authors: Iwase Takehito , Baba Takayuki , Kakisu Masato , Yokouchi Hirotaka , Yamamoto Shuichi
Published: July 2020

Introduction: To compare the morphological and visual outcomes after pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling and flap removal to that with flap insertion in eyes with myopic macular-hole retinal detachment (MHRD). Methods: Forty-six eyes of 45 patients with MHRD were studied. Eighteen eyes were treated by PPV with ILM peeling and flap removal and 28 eyes by flap insertion, respectively. The baseline characteristics and postoperative findings were compared between the 2 groups. Results: The average age of the cases was 70.0 ± 8.5 years. The best-corrected visual acuity (BCVA) improved, from 1.51 ± 0.14 to 1.31 ± 0.20 logMAR units in the flap removal group, and from 1.20 ± 0.10 to 0.88 ± 0.10 logMAR units in the flap insertion group (p = 0.049). A significantly larger number of MHs were closed in the flap insertion group (96 vs. 50% in the removed group; p < 0.001). Restoration of the ellipsoid zone (EZ) and external limiting membrane (ELM) was also better in the flap insertion group than in the flap removal group (EZ 14 vs. 6%, p = 0.003; ELM 36 vs. 6%, p < 0.001). Discussion: The technique of ILM peeling with flap insertion is more effective in closing the MH, and results in better BCVA and better restoration of the outer retinal microstructures than flap removal.