bluuebunny/crossref_metadata_2025 huggingface dataset:
The COVID-19 pandemic: a global health crisis
Authors: Pollard Casey A. , Morran Michael P. , Nestor-Kalinoski Andrea L.
Published: September 2020

The novel coronavirus SARS-CoV-2 was identified as the causative agent for a series of atypical respiratory diseases in the Hubei Province of Wuhan, China in December of 2019. The disease SARS-CoV-2, termed COVID-19, was officially declared a pandemic by the World Health Organization on March 11, 2020. SARS-CoV-2 contains a single-stranded, positive-sense RNA genome surrounded by an extracellular membrane containing a series of spike glycoproteins resembling a crown. COVID-19 infection results in diverse symptoms and morbidity depending on individual genetics, ethnicity, age, and geographic location. In severe cases, COVID-19 pathophysiology includes destruction of lung epithelial cells, thrombosis, hypercoagulation, and vascular leak leading to sepsis. These events lead to acute respiratory distress syndrome (ARDS) and subsequent pulmonary fibrosis in patients. COVID-19 risk factors include cardiovascular disease, hypertension, and diabetes, which are highly prevalent in the United States. This population has upregulation of the angiotensin converting enzyme-2 (ACE2) receptor, which is exploited by COVID-19 as the route of entry and infection. Viral envelope proteins bind to and degrade ACE2 receptors, thus preventing normal ACE2 function. COVID-19 infection causes imbalances in ACE2 and induces an inflammatory immune response, known as a cytokine storm, both of which amplify comorbidities within the host. Herein, we discuss the genetics, pathogenesis, and possible therapeutics of COVID-19 infection along with secondary complications associated with disease progression, including ARDS and pulmonary fibrosis. Understanding the mechanisms of COVID-19 infection will allow the development of vaccines or other novel therapeutic approaches to prevent transmission or reduce the severity of infection.
Exploring the Mechanism on the Medullary Visceral Zone Inhibiting the Cholinergic Anti-inflammatory Pathway Induced by Sepsis
Authors: Li H. B. , Zhou Y. , Zhao A. H. , Guo L. L. , Petricevich Vera L.
Published: September 2020

Inflammatory storm is an important pathological mechanism of multiple organ dysfunction, and it is associated with most deaths in septic patients, deserving to be studied. Recent findings have confirmed that the Medullary Visceral Zone (MVZ) regulates inflammation and immunity through the cholinergic anti-inflammatory pathway (CAP), but how sepsis affects the MVZ and leads to uncontrolled inflammation remain unclear. The current study reported that sepsis induced MVZ to inhibit CAP which underlies the inflammation storm. Our studies have shown that the rat models of sepsis prepared by cecal ligation and puncture had a higher inflammatory level, higher mortality, and higher Murine Sepsis Score. In septic rats, some indicators of heart rate variability (HRV) such as SDNN, HF band, RMSSD, SD1, and SD2 significantly reduced. In MVZ of septic rats, many cholinergic and catecholaminergic neurons showed apoptotic, with low expressions of tyrosine hydroxylase and choline acetyltransferase. The α7nAChR agonist GTS-21 can improve these pathologies, while the α7nAChR antagonist MLA is the opposite. Our study demonstrates for the first time that cholinergic and catecholaminergic neurons in MVZ went through significant apoptosis and inactiveness in sepsis, which contributes to the inhibition of CAP and acceleration of the inflammation storm in early sepsis. Intervening with CAP has a significant effect on the activity and apoptosis of MVZ neurons while altering systemic inflammation and immunity; in addition, for the first time, we confirmed that some indicators of HRV such as SDNN, HF band, RMSSD, SD1, and SD2 can reflect the activity of CAP, but the CAP interference had little effect on these indicators.
Clinical Properties and Diagnostic Methods of COVID‐19 Infection in Pregnancies: Meta‐Analysis
Authors: Uygun-Can Banu , Acar-Bolat Bilge
Published: September 2020

We aimed to summarize reliable medical evidence by the meta‐analysis of all published retrospective studies that examined data based on the detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) by clinical symptoms, molecular (RT‐PCR) diagnosis, and characteristic CT imaging features in pregnant women. The MEDLINE, PubMed, Scopus, ISI Web of Science, ClinicalKey, and CINAHL databases were used to select the studies. Then, 384 articles were received, including the studies until 01/May/2020. As a result of the full‐text evaluation, 12 retrospective articles covering all the data related were selected. A total of 181 pregnant cases with SARS‐CoV‐2 infections were included in the meta‐analysis within the scope of these articles. According to the results, the incidence of fever was 38.1% (95% CI: 14.2‐65%) and cough was 22% (95% CI: 10.8‐35.2%) among all clinical features of pregnant cases with SARS‐CoV‐2 infection. So, fever and cough are the most common symptoms in pregnant cases with SARS‐CoV‐2 infection, and 91.8% (95% CI: 76.7‐99.9%) of RT‐PCR results are positive. Moreover, abnormal CT incidence is 97.9% (95% CI: 94.2‐99.9%) positive. No case was death. However, as this virus spreads globally, it should not be overlooked that the incidence will increase in pregnant women and maybe in the risky group. RT‐PCR and CT can be used together in an accurate and safe diagnosis. In conclusion, these findings will provide important guidance for current studies regarding the clinical features and correct detection of SARS‐CoV‐2 infection in pregnant women, as well as whether it will create emergency tables that will require the use of a viral drug.
Advancing Transportation Routing Decisions Using Riemannian Manifold Surfaces
Authors: Tokgöz Emre , Awudu Iddrisu , Kuppusamy Saravanan , Du Yuchuan
Published: September 2020

We consider several real-world driving factors such as the time spent at traffic signs (e.g., yield signs and stop signs), speed limits, and the topology of the surface to develop realistic and accurate routing solutions. Though these factors increase the complexity of modeling, they provide the flexibility to evaluate the routing solutions from different perspectives: cost, distance, and time, to name a few. First, we develop a set of algorithms based on the Riemannian manifold surface (RMS) to factor in the Earth’s curvature to calculate distances. Second, we present a multiobjective, nonlinear, mixed-integer model (MINLP) that minimizes the distance traveled, time traveled, traveling costs, and time spent on traffic signs to design and evaluate the routes where the waiting times associated with traffic lights, stop signs, and yield signs are stochastic. Finally, we apply MINLP and RMS-based algorithms to a set of real-life and short- and long-distance transportation problems and analyze the results from computational experiments and discrete event simulations. We show that our approaches are on par with the state-of-the-art application, Google Maps, and yield realistic routing solutions that generate significant cost savings.
Delta Shocks and Vacuums to the Isentropic Euler Equations with the Flux Perturbation for van der Waals Gas
Authors: Wang Jinhuan , Nie Yongbin , De Bartolo Samuele
Published: September 2020

In this paper, we study the isentropic Euler equations with the flux perturbation for van der Waals gas, in which the density has both lower and upper bounds due to the introduction of the flux approximation and the molecular excluded volume. First, we solve the Riemann problem of this system and construct the Riemann solutions. Second, the formation mechanisms of delta shocks and vacuums are analyzed for the Riemann solutions as the pressure, the flux approximation, and the molecular excluded volume all vanish. Finally, some numerical simulations are demonstrated to verify the theoretical analysis.
Chromodomain Helicase DNA‐Binding Protein 5 Inhibits Renal Cell Carcinoma Tumorigenesis by Activation of the p53 and RB Pathways
Authors: Huang Sheng , Yan Qitao , Xiong Shilin , Peng Yiqi , Zhao Rui , Liu Chunxiao
Published: September 2020

Chromodomain helicase DNA‐binding protein 5 (CHD5) plays a crucial tumor suppressor role in multiple types of tumors. For this study, we investigated its clinical significance and the molecular mechanism(s) underlying tumorigenesis in renal cell carcinoma (RCC). Initially, CHD5 expression was assessed in primary tumor tissue and in tissue array. Correlations among CHD5 expression and clinicopathological characteristics were analyzed. Next, lentivirus‐mediated CHD5 overexpression in the ACHN and 769‐P cells was used to assess effects on proliferation, migration, invasion ability, and the regulation of the p14ARF/p53 and p16INK4a/RB signaling pathways. Finally, a xenograft mouse model was used to verify its impact on tumor growth in vivo. Results demonstrated that CHD5 was downregulated in tumor tissues and that low CHD5 expression was correlated with advanced TNM stage, high Fuhrman grade, lymph node metastasis, and poor survival. Overexpression of CHD5 inhibited proliferation, migration, and invasion in vitro; prompted cell cycle G1 phase arrest; induced apoptosis; and suppressed tumor growth in vivo. Furthermore, we confirmed that CHD5 activates the p53 and RB pathways to inhibit tumorigenesis in RCC. In summary, CHD5 is involved in the initiation and progression of RCC and may serve as a diagnostic biomarker and a potential therapeutic target for RCC.
A Modified Incremental Harmonic Balance Method for 2-DOF Airfoil Aeroelastic Systems with Nonsmooth Structural Nonlinearities
Authors: Ni Ying-Ge , Zhang Wei , Lv Yi , Georgantzinos Stylianos
Published: September 2020

A modified incremental harmonic balance method is presented to analyze the aeroelastic responses of a 2-DOF airfoil aeroelastic system with a nonsmooth structural nonlinearity. The current method, which combines the traditional incremental harmonic balance method and a fast Fourier transform, can be used to obtain the higher-order approximate solution for the aeroelastic responses of a 2-DOF airfoil aeroelastic system with a nonsmooth structural nonlinearity using significantly fewer linearized algebraic equations than the traditional method, and the dominant frequency components of the response can be obtained by a fast Fourier transform of the numerical solution. Thus, periodic solutions can be obtained, and the calculation process can be simplified. Furthermore, the nonsmooth nonlinearity was expanded into a Fourier series. The procedures of the modified incremental harmonic balance method were demonstrated using systems with hysteresis and free play nonlinearities. The modified incremental harmonic balance method was validated by comparing with the numerical solutions. The effect of the number of harmonics on the solution precision as well as the effect of the free-play and stiffness ratio on the response amplitude is discussed.
Reproductive Health Right Practice among Preparatory School Female Students of Assela Town, Arsi Zone, Oromia Regional State, Ethiopia
Authors: Tafa Segni Mesfin , Tafa Tigist , Fekadu Hailu , Adugna Shimelis , Assegid Meselech , Cecatti Jose Guilherme
Published: September 2020

Introduction. Knowledge and practice toward reproductive health right (RHR) is critical to protect young women, especially school girls, from unwanted reproductive outcomes as improving access to reproductive health services. However, the majority of young people including female secondary school students in Ethiopia have very little knowledge on the youth’s reproductive health rights. The aim of this study was to assess knowledge and practice toward reproductive health right among preparatory female students in Assela Town, Arsi Zone, Ethiopia. Methods. A study was conducted among 403 preparatory school female students in Assela Town. Simple random sampling was employed to select the subjects, and a self-administered questionnaire was used to collect data. The collected data were entered using EPI Info version 3.5.4 and exported to SPSS version 21 for analysis. Descriptive and logistic regression analysis was carried out. Result. Sixty percent of girls discussed reproductive issues openly with their peers. About 94% of the respondents knew, at least, one contraceptive method; injectable (91.2%) was the most known type of contraceptives. Marital status, father occupation, discussion on sexual and reproductive issues, and having sexual partners were affecting the practice of reproductive health rights. Conclusions. Knowledge of the students was moderate on reproductive health right which was 70%. Practice of sexual and reproductive health rights was 22.6% among the study participants. It is recommended that promotion on sexual and reproductive health right through media is important.
The Application of Mitochondrial COI Gene‐Based Molecular Identification of Forensically Important Scuttle Flies (Diptera: Phoridae) in Korea
Authors: Kim Hajin , Shin Sang Eon , Ko Kwang Soo , Park Seong Hwan
Published: September 2020

Phoridae are a family of necrophagous flies commonly found in indoor death scene. They account for approximately 19.7% of the entomofauna in human cadavers in Korea. Additionally, this taxon is an indicator of indoor hygiene, and these flies appear in environments where access by other necrophagous insects is difficult, such as enclosed rooms. Thus, they are likely to be used as forensic evidence. Despite their importance in forensic investigations and environmental hygiene, detailed studies on the taxonomy and molecular barcoding for this family are scarce, including in Korea. Because accurate taxonomic information regarding necrophagous insects collected from a death‐related scene is essential during medicolegal investigations, molecular barcoding data could be useful as well as reliable. In this paper, full‐length nucleotide sequences of genes coding for the cytochrome c oxidase subunit I (COI) in 79 Phoridae larvae collected from 20 medicolegal autopsy cases in Korea were phylogenetically analyzed by comparing their sequences to the foreign barcoding data of Phoridae. Six mitochondrial haplogroups were identified, which two of them matched to foreign Phoridae fly species haplotypes, Megaselia scalaris (Loew, 1866) and M. spiracularis Schmitz 1938. Taxonomies of five other haplogroups, with nucleotide distances ranging from 1.68% to 2.26% from the M. scalaris group, could not be confirmed solely based on the molecular barcoding data. Further research should be performed to determine whether these five haplogroups are diverged conspecifics of M. scalaris or a closely related sister cryptic species of M. scalaris.
Numerical Study of Electromagnetic Loss and Heat Transfer in an Oil-Immersed Transformer
Authors: Si Wen-Rong , Fu Chen-Zhao , Wu Xu-Tao , Zhou Xiu , Li Xiu-Guang , Yu Yi-Ting , Jia Xiao-Yu , Yang Jian , Laurent Hervé
Published: September 2020

Transformer is one of the most important pieces of equipment in power system. The insulation aging and lifespan of transformer are significantly affected by hot spot distributions of internal components inside. In the present paper, the electromagnetic losses of different components and heat transfer process in a three-phase forced oil circulation transformer (400 kVA-15 kV/400 V) are numerically studied with finite element method. The leakage magnetic flux and eddy current loss density for metal components and oil tank are carefully analyzed, and the effect of metal components’ electromagnetic loss on hot spot temperature of different components and oil flow in transformer is also studied. It is found that the surface current of metal components is generated by leakage magnetic flux, and surface current density is large when leakage magnetic flux concentrates. The effect caused by relative magnetic permeability of metal components is remarkable on electromagnetic loss of metal components and oil tank, while the effect caused by relative magnetic permeability of transformer tank is relatively small. Due to the mixing of metal components on oil flow, the heat transfer of core is enhanced, its hot spot temperature is lowered, and the hot spot locations of coil and core also change. These results are meaningful for further understanding of heat transfer process in transformer and important for the optimal design of transformer.
Characteristics and Applications of Sewage Sludge Biochar Modified by Ferrous Sulfate for Remediating Cr(VI)‐Contaminated Soils
Authors: Li Yuan-Yuan , Zhang Ting-Ting , Ning Zhi , Chen Jin-Hong
Published: September 2020

Background. Soil contamination by hexavalent chromium is becoming a main environmental concern in China. This study developed a sewage sludge biochar modified by FeSO4 (CHBC) as a new reductant for Cr(VI)‐contaminated soil. The effectiveness of CHBC‐stabilized Cr(VI)‐contaminated soil was investigated. Methods. Typical industrial Cr(VI)‐contaminated soil in China was chosen as the medium. The total and Cr(VI) contents of the contaminated soil were 1014.6 and 973.5 mg/kg, respectively. The effectiveness of the Cr(VI)‐contaminated soil stabilized by CHBC was investigated by the leaching test (US EPA method 1312), the simplified bioaccessibility extraction test (US EPA 2007 protocol and British Geological Survey), alkaline digestion (US EPA method 3060A), sequential extraction (BCR sequential extraction procedure), X‐ray diffraction, and the risk assessment code test. Results. Results show that CHBC substantially reduced the leachability and Cr(VI) content of the contaminated soil. The leachability and content of Cr(VI) were lower than the thresholds of the Environmental Quality Standards of Soil in China for civil reuse and the China Environmental Quality Standards of surface water for civil use when the soil was stabilized with 10% dosage of CHBC. Conclusion. CHBC is highly efficient in stabilizing Cr(VI) and can effectively reduce the leachability and bioavailability of Cr in contaminated soil and thus feasible for stabilizing Cr(VI)‐contaminated soil and shows potential for application in the field.
Rebamipide with Proton Pump Inhibitors (PPIs) versus PPIs Alone for the Treatment of Endoscopic Submucosal Dissection‐Induced Ulcers: A Meta‐analysis
Authors: Liu Junyuan , Xiong Zhencheng , Geng Xuhua , Cui Meihua
Published: September 2020

Objective. To contrast the effect of rebamipide with proton pump inhibitors (PPIs) versus PPIs alone for the treatment of endoscopic submucosal dissection (ESD‐) induced ulcers. Methods. PubMed, Embase, the Cochrane library, the WanFang database, and China National Knowledge Infrastructure (CNKI) were searched to identify studies that met the inclusion criteria. Results. Nine randomized controlled trials (RCTs) were recognized, including 1170 patients. In general, rebamipide plus PPIs acted better than PPIs alone against ESD‐induced ulcers at four weeks (RR = 1.42, 95% CI: 1.13‐1.78, P = 0.003) but showed no significant differences at eight weeks (RR = 1.03, 95% CI: 0.97‐1.10, P = 0.315). The use of rebamipide plus PPIs was superior to PPIs alone for ESD‐induced ulcers greater than 20 mm in size (20‐40 mm: RR = 1.98, 95% CI: 1.22‐3.23, P = 0.006; >40 mm: RR = 5.14, 95% CI: 1.49‐17.74, P = 0.010). In addition, rebamipide plus PPI therapy was discovered to be significantly more effective than PPIs alone for lower ESD‐induced ulcers (RR = 1.82, 95% CI: 1.04‐3.20, P = 0.037). There were no significant differences between the treatment groups with the ulcer reduction rate. Conclusion. Evidences now available show rebamipide plus PPIs is practical for protecting against ESD‐induced ulcers at four weeks but not at eight weeks, especially large ulcers (>20 mm). However, we still need more high‐quality RCTs in the future to supplement our conclusions.
Oleanolic Acid Decreases IL-1β-Induced Activation of Fibroblast-Like Synoviocytes via the SIRT3-NF-κB Axis in Osteoarthritis
Authors: Bao Jiapeng , Yan Weifeng , Xu Kai , Chen Mengyao , Chen Zhonggai , Ran Jisheng , Xiong Yan , Wu Lidong , Seth Ratanesh K.
Published: September 2020

Synovial inflammation is a major pathological feature of osteoarthritis (OA), which is a chronic degenerative joint disease. Fibroblast-like synoviocytes (FLS), localized in the synovial membrane, are specialized secretory cells. During OA synovitis, FLS produce chemokines and cytokines that stimulate chondrocytes to secrete inflammatory cytokines and activate matrix metalloproteinases (MMPs) in FLS. Recent studies have demonstrated that sirtuin 3 (SIRT3) performs as a key regulator in maintaining mitochondrial homeostasis in OA. This study aims at ascertaining whether SIRT3 is involved in OA synovitis. The overexpression (OE) and knockdown (KD) of SIRT3 are established by short hairpin RNA (shRNA) and recombinant plasmid in human FLS. The anti-inflammatory effect of SIRT3 underlying in oleanolic acid- (OLA-) prevented interleukin-1β- (IL-1β-) induced FLS dysfunction is then evaluated in vitro. Additionally, the molecular mechanisms of SIRT3 are assessed, and the interaction between SIRT3 and NF-κB is investigated. The data suggested that SIRT3 can be detected in human synovial tissues during OA, and OLA could elevate SIRT3 expression. OE-SIRT3 and OLA exhibited equal authenticity to repress inflammation and reverse oxidative stress changes in IL-1β-induced human FLS dysfunction. KD-SIRT3 was found to exacerbate inflammation and oxidative stress changes in human FLS. Furthermore, it was found that SIRT3 could directly bind with NF-κB, resulting in the suppression of NF-κB activation induced by IL-1β in human FLS, which then repressed synovial inflammation in OA. In general, the activation of SIRT3 by OLA inhibited synovial inflammation by suppressing the NF-κB signal pathway in FLS, and this suggested that SIRT3 is a potential target for OA synovitis therapy.
A Novel Model-Free Intelligent Proportional-Integral Supertwisting Nonlinear Fractional-Order Sliding Mode Control of PMSM Speed Regulation System
Authors: Gao Peng , Lv Xiaodong , Ouyang Huimin , Mei Lei , Zhang Guangming
Published: September 2020

This study proposes a novel model-free intelligent proportional-integral supertwisting nonlinear fractional-order sliding mode control (MF-iPI-ST-NLFOSMC) strategy for permanent magnet synchronous motor (PMSM) speed regulation system. First of all, a model independent intelligent proportional-integral (iPI) control strategy is adopted for the motor speed regulation system. Next, a novel model-free supertwisting nonlinear fractional-order sliding mode control (ST-NLFOSMC) strategy is constructed based on the ultralocal model of PMSM. Meanwhile, a linear extended state observer (LESO) is used to estimate the unknown terms of the ultralocal model. Then, this study presents the novel hybrid MF-iPI-ST-NLFOSMC strategy which integrates the model-free ST-NLFOSMC strategy, the model-free iPI control strategy, and the LESO. Moreover, the stability of the proposed hybrid MF-iPI-ST-NLFOSMC strategy is proved by the Lyapunov stability theorem and fractional-order theory. Finally, the simulations and comparison results verify that the hybrid MF-iPI-ST-NLFOSMC strategy proposed in this paper has better performance than the other model-free controllers in terms of the static characteristic, dynamic characteristic, and robustness.
Experimental and Theoretical Investigation of Overburden Failure Law of Fully Mechanized Work Face in Steep Coal Seam
Authors: Liao Ze , Feng Tao , Yu Weijian , Wu Genshui , Li Ke
Published: September 2020

In this study, both theoretical analysis and similar simulation experiment are employed to investigate the overburden failure law of fully mechanized face in the steep coal seam. By establishing the mechanical model of inclined rock beam, the deflection equation of overlying strata beam is obtained. Based on the geological conditions of Xiangyong coal mine in Hunan Province of China, the laws of roof deformation and failure in steep coal seam are obtained by similar simulation experiments. The results showed that the roof deformation of the goaf is relatively large after the working face advances along the strike, and the deformation mainly occurs in the upper roof of the goaf. The backward gangue in the immediate roof fills the lower part of the goaf, which plays a supporting role in the lower part of the roof and floor. The roof fracture of goaf is located in the middle and upper parts of the working face, which is consistent with the results derived from the mechanical model. After the roof fracture, a “trapezoid” bending fracture area and the secondary stability system area is formed, which is composed of four areas: the lower falling and filling support area, the upper strata bending fracture area, the fracture extension area, and the roof bending sinking area.
Academic Integrity in Higher Education of Ukraine: Current State and Call for Action
Authors: Luniachek Vadym , Brovdii Alla , Kulakovskyi Oleksandr , Varenko Tetyana , Tirri Kirsi
Published: September 2020

The research aims to define the scope and challenges of intellectual property rights protection in higher schools of Ukraine and offer recommendations to address those for higher education officials and university leaders. The findings of the research rely on the results of an anonymous expert survey conducted among non-law students of two institutions of higher education using a specially designed questionnaire. They reveal a significantly low level of students’ awareness and knowledge of intellectual property rights, academic integrity, and protection thereof, which undermines the internal education quality. At the same time, there exists a high demand for receiving the relevant knowledge within the university programmes the students are enrolled in. It, therefore, seems expedient to design and include “Intellectual Property and Academic Integrity” as a subject in the curricula of higher educational institutions of Ukraine to be taught at the first year of training, and develop a special course in the fundamentals of intellectual property and academic writing to build the students’ relevant competences. Similarly, it is essential that the teaching staff should be trained accordingly and have the relevant powers and tools to impart and enforce academic integrity rights protection.
The Effects of GABAergic System under Cerebral Ischemia: Spotlight on Cognitive Function
Authors: Li Juan , Chen Luting , Guo Feng , Han Xiaohua , Ferreri Florinda
Published: September 2020

In this review, we present evidence about the changes of the GABAergic system on the hippocampus under the ischemic environment, which may be an underlying mechanism to the ischemia-induced cognitive deficit. GABAergic system, in contrast to the glutamatergic system, is considered to play an inhibitory effect on the central nervous system over the past several decades. It has received widespread attention in the area of schizophrenia and epilepsy. The GABAergic system has a significant effect in promoting neural development and formation of local neural circuits of the brain, which is the structural basis of cognitive function. There have been a number of reviews describing changes in the GABAergic system in cerebral ischemia in recent years. However, no study has investigated the changes in the system in the hippocampus during cerebral ischemic injury, which results in cognitive impairment, particularly at the chronic ischemic stage and the late phase of ischemia. We present a review of the changes of the GABAergic system in the hippocampus under ischemia, including GABA interneurons, extracellular GABA neurotransmitter, and GABA receptors. Several studies are also listed correlating amelioration of cognitive impairment by regulating the GABAergic system in the hippocampus damaged under ischemia. Furthermore, exogenous cell transplantation, which improves cognition by modulating the GABAergic system, will also be described in this review to bring new insight and strategy on solving cognitive deficits caused by cerebral ischemia.
Chemical and Physical Properties of Meadowfoam Seed Oil and Extra Virgin Olive Oil: Focus on Vibrational Spectroscopy
Authors: Zielińska Aleksandra , Wójcicki Krzysztof , Klensporf-Pawlik Dorota , Dias-Ferreira João , Lucarini Massimo , Durazzo Alessandra , Lucariello Giuseppe , Capasso Raffaele , Santini Antonello , Souto Eliana B. , Nowak Izabela , Cuisset Arnaud
Published: September 2020

In food industry, vegetable oils are commonly used as functional ingredients. Cold pressed oils containing fatty acids show a variety of chemical properties, which are mainly dependent on the saturation of fatty acids. In this study, we have analyzed meadowfoam seed oil (MSO), obtained from seeds of Limnanthes alba, and extra virgin olive oil (EVO). Firstly, the fatty acids composition, denoted as Cox value, was determined for the oils that are considered as the most stable. The Cox value for MSO reached 0.032, while that for EVO was 1.780. We have also determined the content of fatty acids in both of the oils using gas chromatography, while the use of mid-infrared (MIR) and near-infrared (NIR) spectroscopy allowed us to assign bands corresponding to the vibrations present in the tested functional groups. Significant differences in the shape and intensity of some bands were observed due to different content of unsaturated fatty acids. Vibrational spectroscopy methods confirmed the presence of long chain fatty acids in MSO.
The Topological Entropy of Cyclic Permutation Maps and Some Chaotic Properties on Their MPE sets
Authors: Li Risong , Lu Tianxiu
Published: September 2020

In this paper, we study some chaotic properties ofs-dimensional dynamical system of the formΨa1,a2,…,as=gsas,g1a1,…,gs−1as−1,whereak∈Hkfor anyk∈1,2,…,s, s≥2is an integer, andHkis a compact subinterval of the real lineℝ=−∞,+∞for anyk∈1,2,…,s. Particularly, a necessary and sufficient condition for a cyclic permutation mapΨa1,a2,…,as=gsas,g1a1,…,gs−1as−1to be LY-chaotic or h-chaotic or RT-chaotic or D-chaotic is obtained. Moreover, the LY-chaoticity, h-chaoticity, RT-chaoticity, and D-chaoticity of such a cyclic permutation map is explored. Also, we proved that the topological entropyhΨof such a cyclic permutation map is the same as the topological entropy of each of the following maps:gj∘gj−1∘⋯∘g1l∘gs∘gs−1∘⋯∘gj+1,ifj=1,…,s−1andgs∘gs−1∘⋯∘g1, and thatΨis sensitive if and only if at least one of the coordinates maps ofΨsis sensitive.
Metformin Mitigates DPP-4 Inhibitor-Induced Breast Cancer Metastasis via Suppression of mTOR Signaling
Authors: Kawakita Emi , Yang Fan , Kumagai Asako , Takagaki Yuta , Kitada Munehiro , Yoshitomi Yasuo , Ikeda Takayuki , Nakamura Yuka , Ishigaki Yasuhito , Kanasaki Keizo , Koya Daisuke
Published: September 2020

The biological influence of antidiabetic drugs on cancer cells and diabetic cancer patients has not yet been completely elucidated. We reported that a dipeptidyl peptidase (DPP)-4 inhibitor accelerates mammary cancer metastasis by inducing epithelial–mesenchymal transition (EMT) through the CXCL12/CXCR4/mTOR axis. Metformin has been shown to inhibit the mTOR signaling pathway. In this study, we investigated whether metformin mitigates breast cancer metastasis induced by a DPP-4 inhibitor via suppression of mTOR signaling. In cultured mouse mammary and human breast cancer cells, metformin suppressed DPP-4 inhibitor KR62436 (KR)-induced EMT and cell migration via suppression of the mTOR pathway associated with AMPK activation. For the in vivo study, metformin intervention was performed in an allograft 4T1 breast cancer model mouse with or without KR. We also analyzed mice transplanted with shRNA-mediated DPP-4 knockdown 4T1 cells. Treatment with metformin inhibited the lung metastasis of DPP-4–deficient 4T1 mammary tumor cells generated by either KR administration or DPP-4 knockdown. Immunostaining of primary tumors indicated that DPP-4 suppression promoted the expression of EMT-inducing transcription factor Snail through activation of the CXCR4-mediated mTOR/p70S6K pathway in an allograft breast cancer model; metformin abolished this alteration. Metformin treatment did not alter DPP-4–deficiency-induced expression of CXCL12 in either plasma or primary tumors. Our findings suggest that metformin may serve as an antimetastatic agent by mitigating the undesirable effects of DPP-4 inhibitors in patients with certain cancers.

Implications:

Metformin could combat the detrimental effects of DPP-4 inhibitor on breast cancer metastasis via mTOR suppression, suggesting the potential clinical relevance.

Visual Overview:

http://mcr.aacrjournals.org/content/molcanres/19/1/61/F1.large.jpg.
First-in-Human Trial of the Oral Ataxia Telangiectasia and RAD3-Related (ATR) Inhibitor BAY 1895344 in Patients with Advanced Solid Tumors
Authors: Yap Timothy A. , Tan David S.P. , Terbuch Angelika , Caldwell Reece , Guo Christina , Goh Boon Cher , Heong Valerie , Haris Noor R. Md. , Bashir Saira , Drew Yvette , Hong David S. , Meric-Bernstam Funda , Wilkinson Gary , Hreiki Joseph , Wengner Antje M. , Bladt Friedhelm , Schlicker Andreas , Ludwig Matthias , Zhou Yinghui , Liu Li , Bordia Sonal , Plummer Ruth , Lagkadinou Eleni , de Bono Johann S.
Published: September 2020

Targeting the ataxia telangiectasia and RAD3-related (ATR) enzyme represents a promising anticancer strategy for tumors with DNA damage response (DDR) defects and replication stress, including inactivation of ataxia telangiectasia mutated (ATM) signaling. We report the dose-escalation portion of the phase I first-in-human trial of oral ATR inhibitor BAY 1895344 intermittently dosed 5 to 80 mg twice daily in 21 patients with advanced solid tumors. The MTD was 40 mg twice daily 3 days on/4 days off. Most common adverse events were manageable and reversible hematologic toxicities. Partial responses were achieved in 4 patients and stable disease in 8 patients. Median duration of response was 315.5 days. Responders had ATM protein loss and/or deleterious ATM mutations and received doses ≥40 mg twice daily. Overall, BAY 1895344 is well tolerated, with antitumor activity against cancers with certain DDR defects, including ATM loss. An expansion phase continues in patients with DDR deficiency.

Significance:

Oral BAY 1895344 was tolerable, with antitumor activity in heavily pretreated patients with various advanced solid tumors, particularly those with ATM deleterious mutations and/or loss of ATM protein; pharmacodynamic results supported a mechanism of action of increased DNA damage. Further study is warranted in this patient population.

See related commentary by Italiano, p. 14.

This article is highlighted in the In This Issue feature, p. 1
Comparing Fiducial-Based and Intraoperative Computed Tomography-Based Registration for Frameless Stereotactic Brain Biopsy
Authors: Saß Benjamin , Pojskic Mirza , Bopp Miriam , Nimsky Christopher , Carl Barbara
Published: September 2020

Objective: The aim of this work was to compare fiducial-based and intraoperative computed tomography (iCT)-based registration for frameless stereotactic brain biopsy. Methods: Of 50 frameless stereotactic biopsies with the VarioGuide, 30 cases were registered as iCT based and 20 as fiducial based. Statistical analysis of the target registration error (TRE), dose length product, effective radiation dose (ED), operation time, and diagnostic yield was performed. Results: The mean TRE was significantly lower using iCT-based registration (mean ± SD: 0.70 ± 0.32 vs. 2.43 ± 0.73 mm, p < 0.0001). The ED was significantly lower when using iCT-based registration compared to standard navigational CT (mean ± SD: 0.10 ± 0.13 vs. 2.23 ± 0.34 mSv, p < 0.0001). Post-biopsy iCT was associated with a significant lower (p < 0.0001) ED compared to standard CT (mean ± SD: 1.04 ± 0.18 vs. 1.65 ± 0.26 mSv). The mean surgical time was shorter using iCT-based registration, although the mean total operating room (OR) time did not differ significantly. The diagnostic yield was 96.7% (iCT group) versus 95% (fiducial group). Post-biopsy imaging revealed severe bleeding in 3.3% (iCT group) versus 5% (fiducial group). Conclusion: iCT-based registration for frameless stereotactic biopsies increases the accuracy significantly without negative effects on the surgical time or the overall time in the OR. Appropriate scan protocols in iCT registration contribute to a significant reduction of the radiation exposure. The high accuracy of the iCT makes it the more favorable registration strategy when taking biopsies of small tumors or lesions near eloquent brain areas.
Erhöhtes Risiko für psychiatrische Nebenwirkungen unter Infliximab-Therapie?
Authors: Bengsch Bertram
Published: September 2020

Introduction: Infliximab (IFX) was the first anti-tumor necrosis factor (TNFα) antibody to be used in the treatment of severe chronic inflammatory diseases, such as Crohn’s disease and rheumatoid arthritis. A number of serious adverse drug reactions are known to be associated with IFX use; they include infections, malignancies, and injection site reactions. Although a few case reports have described potential psychiatric adverse events (including suicide attempts and manic episodes), the latter are barely mentioned in IFX’s summary of product characteristics. The objective of the present retrospective study was to detect potential psychiatric adverse events associated with IFX treatment by analyzing a national discharge abstract database. Materials and methods: We performed an historical cohort study by analyzing data from the French national hospital discharge abstract database (PMSI) between 2008 and 2014. All patients admitted with one of the five diseases treated with IFX were included. Results: Of the 325,319 patients included in the study, 7,600 had been treated with IFX. The proportion of hospital admissions for one or more psychiatric events was higher among IFX-exposed patients (750 out of 7,600; 9.87%) than among non-exposed patients (17,456 out of 317,719; 5.49%). After taking account of potential confounders in the cohort as a whole, a semi-parametric Cox regression analysis gave an overall hazard ratio (HR) [95% confidence interval] (CI) of 4.5 [3.95; 5.13] for a hospital admission with a psychiatric adverse event during treatment with IFX. The HR (95%CI) for a depressive disorder was 4.97 (7.35; 6.68). Even higher risks were observed for certain pairs of adverse events and underlying pathologies: psychotic disorders in patients treated for ulcerative colitis (HR = 5.43 [2.01; 14.6]), manic episodes in patients treated for severe psoriasis (HR = 12.6 [4.65; 34.2]), and suicide attempts in patients treated for rheumatoid arthritis (HR = 4.45 [1.11; 17.9]). Discussion: The present retrospective, observational study confirmed that IFX treatment is associated with an elevated risk of psychiatric adverse events. Depending on the disease treated, physicians should be aware of these potential adverse events.
Uveitis on nivolumab: When it rains, it pours...
Authors: Pleyer Uwe
Published: September 2020

Nivolumab is an anti-programmed cell death protein 1 monoclonal antibody that is used to treat metastatic cutaneous malignant melanoma. Although bilateral uveitis has been reported as a side effect of nivolumab administration, there are few reports of Vogt-Koyanagi-Harada disease (VKH)-like uveitis. We report such a case. A 63-year-old woman with metastatic cutaneous malignant melanoma experienced visual loss in both eyes 10 days after her second nivolumab injection. Her decimal best-corrected visual acuity (BCVA) was 0.7 in the right eye and 0.4 in the left eye. Examination revealed bilateral granulomatous keratic precipitates and posterior synechiae in the left eye. Optical coherence tomography showed multiple sites of serous retinal detachment (SRD) in the left eye and wavy retinal pigment epithelium in both eyes. Fluorescein angiography revealed multiple pinpoint-sized areas of leakage in both eyes and active leakage from the disc in her right eye. Indocyanine green angiography (IA) showed choroidal hyperfluorescence due to choroidal vascular leakage, with hypofluorescent dark spots during the late phase. These findings supported a diagnosis of VKH-like uveitis following nivolumab injections. Nivolumab was discontinued because of headache. Anterior chamber inflammation disappeared 3 weeks after starting topical corticosteroid treatment, and the SRD disappeared within 3 months. Her decimal BCVA recovered to 1.0 in the right eye and to 0.9 in the left eye. Also, the fluorescein angiography and IA findings had improved by 4 months. We concluded that careful follow-up is required after nivolumab treatment because VKH-like panuveitis might develop.
Geometria: soluções detalhadas para 20 problemas de Olimpíadas Internacionais de Matemática
Authors:   Universidade de São Paulo. Faculdade de Zootecnia e Engenharia de Alimentos, Linares Juan López
Published: September 2020

Este livro faz parte de um projeto de longo prazo de incentivo à participação em Olimpíadas de Matemáticas, no qual são apresentados 20 problemas de Geometria Plana Euclidiana. O texto conta com 37 figuras que facilitam acompanhar a resolução daqueles. Muitos dos desafios têm como complementos gráficos interativos no site do Geogebra e vídeos no YouTube - Trigonometria, Teorema e Desigualdade de Ptolomeu, Potência de um Ponto e Eixo Radical, Congruência e Semelhança de Triângulos e Cálculo de Área são discutidos. Tipicamente cada questão se vale de conhecimentos ligados a mais de um ramo da Matemática. O objetivo é que o material possa de fato ser lido e estudado por estudantes de língua portuguesa (e talvez espanhola) que se preparam para as fases finais das olimpíadas nacionais ou internacionais. Espera-se também que a presente abordagem sirva de apoio aos professores do Ensino Médio que se aventuram em tópicos mais avançados. Em comparação com outras soluções disponíveis, as apresentadas neste texto usam argumentos menos rebuscados e um número menor de transições a serem preenchidas pelo leitor.
Sex Disparities in the Management and Outcomes of Cardiogenic Shock Complicating Acute Myocardial Infarction in the Young
Authors: Vallabhajosyula Saraschandra , Ya’Qoub Lina , Singh Mandeep , Bell Malcolm R. , Gulati Rajiv , Cheungpasitporn Wisit , Sundaragiri Pranathi R. , Miller Virginia M. , Jaffe Allan S. , Gersh Bernard J. , Holmes David R. , Barsness Gregory W.
Published: September 2020

Background:

There are limited data on how sex influences the outcomes of acute myocardial infarction-cardiogenic shock (AMI-CS) in young adults.

Methods:

A retrospective cohort of AMI-CS admissions aged 18 to 55 years, during 2000 to 2017, was identified using the National Inpatient Sample. Use of coronary angiography, percutaneous coronary intervention, mechanical circulatory support and noncardiac interventions was identified. Outcomes of interest included in-hospital mortality, use of cardiac interventions, hospitalization costs, and length of stay.

Results:

A total 90 648 AMI-CS admissions ≤55 years of age were included, of which 26% were women. Higher rates of CS were noted in men (2.2% in 2000 to 4.8% in 2017) compared with women (2.6% in 2000 to 4.0% in 2017;
P
<0.001). Compared with men, women with AMI-CS were more frequently of Black race, from a lower socioeconomic status, with higher comorbidity, and admitted to rural and small hospitals (all
P
<0.001). Women had lower rates of ST-segment elevation presentation (73.0% versus 78.7%), acute noncardiac organ failure, cardiac arrest (34.3% versus 35.7%), and received less-frequent coronary angiography (78.3% versus 81.4%), early coronary angiography (49.2% versus 54.1%), percutaneous coronary intervention (59.2% versus 64.0%), and mechanical circulatory support (50.3% versus 59.2%; all
P
<0.001). Female sex was an independent predictor of in-hospital mortality (23.0% versus 21.7%; adjusted odds ratio, 1.11 [95% CI, 1.07–1.16];
P
<0.001). Women had lower hospitalization costs ($156 372±$198 452 versus $167 669±$208 577;
P
<0.001) but comparable lengths of stay compared with men.

Conclusions:

In young AMI-CS admissions, women are treated less aggressively and experience higher in-hospital mortality than men.
Associations of Carotid Intima‐Media Thickness and Plaque Heterogeneity With the Risks of Stroke Subtypes and Coronary Artery Disease in the Japanese General Population: The Circulatory Risk in Communities Study
Authors: Shimoda Saeko , Kitamura Akihiko , Imano Hironori , Cui Renzhe , Muraki Isao , Yamagishi Kazumasa , Umesawa Mitsumasa , Sankai Tomoko , Hayama‐Terada Mina , Kubota Yasuhiko , Shimizu Yuji , Okada Takeo , Kiyama Masahiko , Iso Hiroyasu
Published: September 2020

Background

Evidence on the associations of carotid intima‐media thickness and carotid plaque characteristics with stroke subtypes and coronary artery disease risks in Asians is limited. This study investigated these associations in the Japanese general population.

Methods and Results

Maximum intima‐media thicknesses of both the common carotid artery and internal carotid artery and carotid plaque characteristics were evaluated in 2943 Japanese subjects aged 40 to 75 years without history of cardiovascular disease. Subjects were followed up for a median of 15.1 years. Using a multivariate Cox proportional hazard model, we found that hazard ratios (HRs) and 95% CIs for the highest (≥1.07 mm) versus lowest (≤0.77 mm) quartiles of maximum intima‐media thicknesses of the common carotid artery were 1.97 (1.26–3.06) for total stroke, 1.52 (0.67–3.41) for hemorrhagic stroke, 2.45 (1.41–4.27) for ischemic stroke, 3.60 (1.64–7.91) for lacunar infarction, 1.53 (0.69–3.41) for nonlacunar cerebral infarction, 2.68 (1.24–5.76) for coronary artery disease, and 2.11 (1.44–3.12) for cardiovascular disease (similar results were found for maximum intima‐media thicknesses of the internal carotid artery). HRs(95% CIs) for heterogeneous plaque versus no plaque were 1.58 (1.09–2.30) for total stroke, 1.25 (0.58–2.70) for hemorrhagic stroke, 1.74 (1.13–2.67) for ischemic stroke, 1.84 (1.03–3.19) for lacunar infarction, 1.58 (0.80–3.11) for nonlacunar cerebral infarction, 2.11 (1.20–3.70) for coronary artery disease, and 1.71 (1.25–2.35) for cardiovascular disease.

Conclusions

Maximum intima‐media thicknesses of the common carotid artery, maximum intima‐media thicknesses of the internal carotid artery, and heterogeneous plaque were associated with the risks of stroke, lacunar infarction, coronary artery disease, and cardiovascular disease in Asians.