bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue Engineering Strategies for Retina Regeneration
Authors: Rajendran Nair Deepthi S. , Seiler Magdalene J. , Patel Kahini H. , Thomas Vinoy , Martinez Camarillo Juan Carlos , Humayun Mark S. , Thomas Biju B.
Published: March 2021

The retina is a complex and fragile photosensitive part of the central nervous system which is prone to degenerative diseases leading to permanent vision loss. No proven treatment strategies exist to treat or reverse the degenerative conditions. Recent investigations demonstrate that cell transplantation therapies to replace the dysfunctional retinal pigment epithelial (RPE) cells and or the degenerating photoreceptors (PRs) are viable options to restore vision. Pluripotent stem cells, retinal progenitor cells, and somatic stem cells are the main cell sources used for cell transplantation therapies. The success of retinal transplantation based on cell suspension injection is hindered by limited cell survival and lack of cellular integration. Recent advances in material science helped to develop strategies to grow cells as intact monolayers or as sheets on biomaterial scaffolds for transplantation into the eyes. Such implants are found to be more promising than the bolus injection approach. Tissue engineering techniques are specifically designed to construct biodegradable or non-degradable polymer scaffolds to grow cells as a monolayer and construct implantable grafts. The engineered cell construct along with the extracellular matrix formed, can hold the cells in place to enable easy survival, better integration, and improved visual function. This article reviews the advances in the use of scaffolds for transplantation studies in animal models and their application in current clinical trials.
Multi-Stage Dynamic Transmission Network Expansion Planning Using LSHADE-SPACMA
Authors: Refaat Mohamed , Aleem Shady , Atia Yousry , Ali Ziad , Sayed Mahmoud
Published: March 2021

This paper introduces a multi-stage dynamic transmission network expansion planning (MSDTNEP) model considering the N-1 reliability constraint. The integrated planning problem of N-1 security and transmission expansion planning is essential because a single line outage could be a triggering event to rolling blackouts. Two suggested scenarios were developed to obtain the optimal configuration of the Egyptian West Delta Network’s realistic transmission (WDN) to meet the demand of the potential load growth and ensure the system reliability up to the year 2040. The size of a blackout, based on the amount of expected energy not supplied, was calculated to evaluate both scenarios. The load forecasting (up to 2040) was obtained based on an adaptive neuro-fuzzy inference system because it gives excellent results compared to conventional methods. The linear population size reduction—Success-History-based Differential Evolution with semi-parameter adaptation (LSHADE-SPA) hybrid—covariance matrix adaptation evolution strategy (CMA-ES) algorithm (LSHADE-SPACMA)—is applied to solve the problem. The semi-adaptive nature of LSHADE-SPACMA and the hybridization between LSHADE and CMA-ES are able to solve complex optimization problems. The performance of LSHADE-SPACMA in solving the problem is compared to other well-established methods using three testing systems to validate its superiority. Then, the MSDTNEP of the Egyptian West Delta Network is presented, and the numerical results of the two scenarios are compared to obtain an economic plan and avoid a partial or total blackout.
Fake It Till You Make It: Guidelines for Effective Synthetic Data Generation
Authors: Dankar Fida K. , Ibrahim Mahmoud
Published: March 2021

Synthetic data provides a privacy protecting mechanism for the broad usage and sharing of healthcare data for secondary purposes. It is considered a safe approach for the sharing of sensitive data as it generates an artificial dataset that contains no identifiable information. Synthetic data is increasing in popularity with multiple synthetic data generators developed in the past decade, yet its utility is still a subject of research. This paper is concerned with evaluating the effect of various synthetic data generation and usage settings on the utility of the generated synthetic data and its derived models. Specifically, we investigate (i) the effect of data pre-processing on the utility of the synthetic data generated, (ii) whether tuning should be applied to the synthetic datasets when generating supervised machine learning models, and (iii) whether sharing preliminary machine learning results can improve the synthetic data models. Lastly, (iv) we investigate whether one utility measure (Propensity score) can predict the accuracy of the machine learning models generated from the synthetic data when employed in real life. We use two popular measures of synthetic data utility, propensity score and classification accuracy, to compare the different settings. We adopt a recent mechanism for the calculation of propensity, which looks carefully into the choice of model for the propensity score calculation. Accordingly, this paper takes a new direction with investigating the effect of various data generation and usage settings on the quality of the generated data and its ensuing models. The goal is to inform on the best strategies to follow when generating and using synthetic data.
Multi-Objective Optimization of Permanent Magnet Synchronous Motor for Electric Vehicle Considering Demagnetization
Authors: You Yong-min , Yoon Keun-young
Published: March 2021

The irreversible demagnetization of permanent magnets causes the deterioration of the performance in permanent magnet synchronous motors (PMSMs), which are used for electric vehicles. NdFeB, which is the permanent magnet most commonly used in PMSMs for electric vehicles, is easily demagnetized at high temperatures. Because traction motors for electric vehicles reach high temperatures, and a high current can be instantaneously applied, permanent magnets of PMSM can be easily demagnetized. Therefore, it is important to study the demagnetization phenomenon of PMSMs for electric vehicles. However, since the demagnetization analysis procedure is complicated, previous studies have not been able to perform optimization considering demagnetization characteristics. In this study, we optimized the shape of a PMSM for electric vehicles by considering the demagnetization characteristics of permanent magnets using an automated design of experiments procedure. Using this procedure, a finite element analysis for each experimental point determined by a sampling method can be performed quickly and easily. The multi-objective function minimizes the demagnetization rate and maximizes the average torque, and the constraints are the efficiency and torque ripple. Various metamodels were generated for each of the multi-objective functions and constraints, and the metamodels with the best prediction performance were selected. By applying a multi-objective genetic algorithm, 1902 various optimal solutions were obtained. When the weight rate of the demagnetization rate to the torque was set to 0.1:0.9, the demagnetization rate and average torque were improved by 4.45% and 2.7%, respectively, compared to those of the initial model. The proposed multi-objective optimization method can guide the design of PMSMs for electric vehicles with high reliability and strong demagnetization characteristics.
Flow Control of Radial Inlet Chamber and Downstream Effects on a Centrifugal Compressor Stage
Authors: Han Fenghui , Wang Zhe , Mao Yijun , Tan Jiajian , Li Wenhua
Published: March 2021

Radial inlet chambers are widely used in various multistage centrifugal compressors, although they induce extra flow loss and inlet distortions. In this paper, the detailed flow characteristics inside the radial inlet chamber of an industrial centrifugal compressor have been numerically investigated for flow control and performance improvement. First, the numerical results are validated against the experimental data, and flow conditions inside the inlet chambers with different structures are compared. They indicate that, in the non-guide vane scheme, sudden expansions, tangential flows and flow separations in the spiral and annular convergent channels are the major causes of flow loss and distortions, while using guide vanes could introduce additional flow impacts, separations and wakes. Based on the flow analysis, structure improvements have been carried out on the radial inlet chamber, and an average increase of 4.97% has been achieved in the inlet chamber efficiencies over different operating conditions. However, the results further reveal that the increases in the performance and overall flow uniformity just in the radial inlet chamber do not necessarily mean a performance improvement in the downstream components, and the distribution of the positive tangential velocity at the impeller inlet might be a more essential factor for the efficiency of the whole compressor.
First Results on Moss Biomonitoring of Trace Elements in the Central Part of Georgia, Caucasus
Authors: Chaligava Omari , Nikolaev Igor , Khetagurov Khetag , Lavrinenko Yulia , Bazaev Anvar , Frontasyeva Marina , Vergel Konstantin , Grozdov Dmitry
Published: March 2021

The moss biomonitoring technique was used for assessment of air pollution in the central part of Georgia, Caucasus, in the framework of the UNECE ICP Vegetation. A total of 35 major and trace elements were determined by two complementary analytical techniques, epithermal neutron activation analysis (Na, Mg, Al, Cl, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Zn, Se, B, Rb, Sr, Zr, Mo, Sb, I, Cs, Ba, La, Ce, Nd, Sm, Eu, Tb, Yb, Hf, Ta, W, Th, and U) and atomic absorption spectrometry (Cu, Cd, and Pb) in the moss samples collected in 2019. Principal Component Analyses was applied to show the association between the elements in the study area. Four factors were determined, of which two are of geogenic origin (Factor 1 including Na, Al, Sc, Ti, V, Cr, Fe, Co, Ni, Th, and U and Factor 3 with As, Sb, and W), mixed geogenic–anthropogenic (Factor 2 with Cl, K, Zn, Se, Br, I, and Cu) and anthropogenic (Factor 4 comprising Ca, Cd, Pb, and Br). Geographic information system (GIS) technologies were used to construct distributions maps of factor scores over the investigated territory. Comparison of the median values with the analogous data of moss biomonitoring in countries with similar climatic conditions was carried out.
Characteristics and Health Risk Assessment of PM2.5-Bound PAHs during Heavy Air Pollution Episodes in Winter in Urban Area of Beijing, China
Authors: Luo Mei , Ji Yuanyuan , Ren Yanqin , Gao Fuhong , Zhang Hao , Zhang Lihui , Yu Yanqing , Li Hong
Published: March 2021

PM2.5 level has decreased significantly in Beijing in recent years due to the strict air quality control measures taken in Jingjinji Region and the surrounding areas. However, the variation characteristics of the concentrations of PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) in Beijing in recent years are still not so clear. In order to understand the pollution status of PM2.5-bound PAHs in Beijing, fifteen PAHs were measured in a typical urban area of Beijing from 1 March to 20 March 2018. The average mass concentration of the 15 PAHs was 21 ng/m3 and higher in the nighttime than that in the daytime. The proportion of 4-ring PAHs in 15 PAHs was highest (43%), while 6-ring PAHs was lowest (10%). The levels of PAHs were higher during heavy pollution episodes than those in non-heavy pollution episodes, and the proportions of 5- and 6-ring PAHs were increased during a heavy pollution episode. PAHs posed obvious carcinogenic risks to the exposed populations, and the risk was higher during heavy pollution episodes than the average value of the whole monitoring period. The main sources of PAHs were traffic emissions and coal/biomass burning. Air masses from the south-southeast had a great influence on the PM2.5 levels during a heavy pollution episode. It is recommended that not only the PM2.5 levels but also the PAHs levels bounded in PM2.5 should be controlled to protect human health in Beijing.
Single-Institutional Experience of Chronic Intracranial Electroencephalography Based on the Combined Usage of Subdural and Depth Electrodes
Authors: Takayama Yutaro , Ikegaya Naoki , Iijima Keiya , Kimura Yuiko , Yokosako Suguru , Muraoka Norihiro , Kosugi Kenzo , Kaneko Yuu , Yamamoto Tetsuya , Iwasaki Masaki
Published: March 2021

Implantation of subdural electrodes on the brain surface is still widely performed as one of the “gold standard methods” for the presurgical evaluation of epilepsy. Stereotactic insertion of depth electrodes to the brain can be added to detect brain activities in deep-seated lesions to which surface electrodes are insensitive. This study tried to clarify the efficacy and limitations of combined implantation of subdural and depth electrodes in intractable epilepsy patients. Fifty-three patients with drug-resistant epilepsy underwent combined implantation of subdural and depth electrodes for long-term intracranial electroencephalography (iEEG) before epilepsy surgery. The detectability of early ictal iEEG change (EIIC) were compared between the subdural and depth electrodes. We also examined clinical factors including resection of MRI lesion and EIIC with seizure freedom. Detectability of EIIC showed no significant difference between subdural and depth electrodes. However, the additional depth electrode was useful for detecting EIIC from apparently deep locations, such as the insula and mesial temporal structures, but not in detecting EIIC in patients with ulegyria (glial scar). Total removal of MRI lesion was associated with seizure freedom. Depth electrodes should be carefully used after consideration of the suspected etiology to avoid injudicious usage.
Multi-Channel RF Supervision Module for Thermal Magnetic Resonance Based Cancer Therapy
Authors: Han Haopeng , Oberacker Eva , Kuehne Andre , Wang Shuailin , Eigentler Thomas Wilhelm , Grass Eckhard , Niendorf Thoralf
Published: March 2021

Glioblastoma multiforme (GBM) is the most lethal and common brain tumor. Combining hyperthermia with chemotherapy and/or radiotherapy improves the survival of GBM patients. Thermal magnetic resonance (ThermalMR) is a hyperthermia variant that exploits radio frequency (RF)-induced heating to examine the role of temperature in biological systems and disease. The RF signals’ power and phase need to be supervised to manage the formation of the energy focal point, accurate thermal dose control, and safety. Patient position during treatment also needs to be monitored to ensure the efficacy of the treatment and avoid damages to healthy tissue. This work reports on a multi-channel RF signal supervision module that is capable of monitoring and regulating RF signals and detecting patient motion. System characterization was performed for a broad range of frequencies. Monte-Carlo simulations were performed to examine the impact of power and phase errors on hyperthermia performance. The supervision module’s utility was demonstrated in characterizing RF power amplifiers and being a key part of a feedback control loop regulating RF signals in heating experiments. Electromagnetic field simulations were conducted to calculate the impact of patient displacement during treatment. The supervision module was experimentally tested for detecting patient motion to a submillimeter level. To conclude, this work presents a cost-effective RF supervision module that is a key component for a hyperthermia hardware system and forms a technological basis for future ThermalMR applications.
Homologous Recombination Deficiency Testing for BRCA-Like Tumors: The Road to Clinical Validation
Authors: Ladan Marjolijn M. , van Gent Dik C. , Jager Agnes
Published: March 2021

Germline BRCA mutations result in homologous recombination deficiency (HRD) in hereditary breast and ovarian cancer, as well as several types of sporadic tumors. The HRD phenotype makes these tumors sensitive to DNA double strand break-inducing agents, including poly-(ADP-ribose)-polymerase (PARP) inhibitors. Interestingly, a subgroup of cancers without a BRCA mutation also shows an HRD phenotype. Various methods for selecting patients with HRD tumors beyond BRCA-mutations have been explored. These methods are mainly based on DNA sequencing or functional characteristics of the tumor. We here discuss the various tests and the status of their clinical validation.
EPHA2 Interacts with DNA-PKcs in Cell Nucleus and Controls Ionizing Radiation Responses in Non-Small Cell Lung Cancer Cells
Authors: Kaminskyy Vitaliy O. , Hååg Petra , Novak Metka , Végvári Ákos , Arapi Vasiliki , Lewensohn Rolf , Viktorsson Kristina
Published: March 2021

Ephrin (EFN)/Erythropoietin-producing human hepatocellular receptors (Eph) signaling has earlier been reported to regulate non-small cell lung cancer (NSCLC) cell survival and cell death as well as invasion and migration. Here, the role of Ephrin type-A receptor 2 (EphA2) on the DNA damage response (DDR) signaling and ionizing radiation (IR) cellular effect was studied in NSCLC cells. Silencing of EphA2 resulted in IR sensitization, with increased activation of caspase-3, PARP-1 cleavage and reduced clonogenic survival. Profiling of EphA2 expression in a NSCLC cell line panel showed a correlation to an IR refractory phenotype. EphA2 was found to be transiently and rapidly phosphorylated at Ser897 in response to IR, which was paralleled with the activation of ribosomal protein S6 kinase (RSK). Using cell fractionation, a transient increase in both total and pSer897 EphA2 in the nuclear fraction in response to IR was revealed. By immunoprecipitation and LC-MS/MS analysis of EphA2 complexes, nuclear localized EphA2 was found in a complex with DNA-PKcs. Such complex formation rapidly increased after IR but returned back to basal level within an hour. Targeting EphA2 with siRNA or by treatment with EFNA1 ligand partly reduced phosphorylation of DNA-PKcs at S2056 at early time points after IR. Thus, we report that EphA2 interacts with DNA-PKcs in the cell nucleus suggesting a novel mechanism involving the EphA2 receptor in DDR signaling and IR responsiveness.
Granulocyte Colony Stimulating Factor Expression in Breast Cancer and Its Association with Carbonic Anhydrase IX and Immune Checkpoints
Authors: Chafe Shawn C. , Riaz Nazia , Burugu Samantha , Gao Dongxia , Leung Samuel C. Y. , Lee Anna F. , Lee Cheng-Han , Dedhar Shoukat , Nielsen Torsten O.
Published: March 2021

Purpose: Granulocyte colony-stimulating factor (G-CSF) and hypoxia modulate the tumour immune microenvironment. In model systems, hypoxia-induced carbonic anhydrase IX (CAIX) has been associated with G-CSF and immune responses, including M2 polarization of macrophages. We investigated whether these associations exist in human breast cancer specimens, their relation to breast cancer subtypes, and clinical outcome. Methods: Using validated protocols and prespecified scoring methodology, G-CSF expression on carcinoma cells and CD163 expression on tumour-associated macrophages were assayed by immunohistochemistry and applied to a tissue microarray series of 2960 primary excision specimens linked to clinicopathologic, biomarker, and outcome data. Results: G-CSFhigh expression showed a significant positive association with ER negativity, HER2 positivity, presence of CD163+ M2 macrophages, and CAIX expression. In univariate analysis, G-CSFhigh phenotype was associated with improved survival in non-luminal cases, although the CAIX+ subset had a significantly adverse prognosis. A significant positive association was observed between immune checkpoint biomarkers on tumour-infiltrating lymphocytes and both G-CSF- and CAIX-expressing carcinoma cells. Immune checkpoint biomarkers correlated significantly with favourable prognosis in G-CSFhigh/non-luminal cases independent of standard clinicopathological features. Conclusions: The prognostic associations linking G-CSF to immune biomarkers and CAIX strongly support their immunomodulatory roles in the tumour microenvironment.
The Japanese Wild-Derived Inbred Mouse Strain, MSM/Ms in Cancer Research
Authors: Okumura Kazuhiro , Saito Megumi , Isogai Eriko , Wakabayashi Yuichi
Published: March 2021

MSM/Ms is a unique inbred mouse strain derived from the Japanese wild mouse, Mus musculus molossinus, which has been approximately 1 million years genetically distant from standard inbred mouse strains mainly derived from M. m. domesticus. Due to its genetic divergence, MSM/Ms has been broadly used in linkage studies. A bacterial artificial chromosome (BAC) library was constructed for the MSM/Ms genome, and sequence analysis of the MSM/Ms genome showed approximately 1% of nucleotides differed from those in the commonly used inbred mouse strain, C57BL/6J. Therefore, MSM/Ms mice are thought to be useful for functional genome studies. MSM/Ms mice show unique characteristics of phenotypes, including its smaller body size, resistance to high-fat-diet-induced diabetes, high locomotive activity, and resistance to age-onset hearing loss, inflammation, and tumorigenesis, which are distinct from those of common inbred mouse strains. Furthermore, ES (Embryonic Stem) cell lines established from MSM/Ms allow the MSM/Ms genome to be genetically manipulated. Therefore, genomic and phenotypic analyses of MSM/Ms reveal novel insights into gene functions that were previously not obtained from research on common laboratory strains. Tumorigenesis-related MSM/Ms-specific genetic traits have been intensively investigated in Japan. Furthermore, radiation-induced thymic lymphomas and chemically-induced skin tumors have been extensively examined using MSM/Ms.
A Novel Bispecific Antibody Targeting EGFR and VEGFR2 Is Effective against Triple Negative Breast Cancer via Multiple Mechanisms of Action
Authors: Mohan Nishant , Luo Xiao , Shen Yi , Olson Zachary , Agrawal Atul , Endo Yukinori , Rotstein David S. , Pelosof Lorraine C. , Wu Wen Jin
Published: March 2021

Both EGFR and VEGFR2 frequently overexpress in TNBC and cooperate with each other in autocrine and paracrine manner to enhance tumor growth and angiogenesis. Therapeutic mAbs targeting EGFR (cetuximab) and VEGFR2 (ramucirumab) are approved by FDA for numerous cancer indications, but none of them are approved to treat breast cancers. TNBC cells secrete VEGF-A, which mediates angiogenesis on endothelial cells in a paracrine fashion, as well as promotes cancer cell growth in autocrine manner. To disrupt autocrine/paracrine loop in TNBC models in addition to mediating anti-EGFR tumor growth signaling and anti-VEGFR2 angiogenic pathway, we generated a BsAb co-targeting EGFR and VEGFR2 (designated as anti-EGFR/VEGFR2 BsAb), using publicly available sequences in which cetuximab IgG backbone is connected to the single chain variable fragment (scFv) of ramucirumab via a glycine linker. Physiochemical characterization data shows that anti-EGFR/VEGFR2 BsAb binds to both EGFR and VEGFR2 in a similar binding affinity comparable to parental antibodies. Anti-EGFR/VEGFR2 BsAb demonstrates in vitro and in vivo anti-tumor activity in TNBC models. Mechanistically, anti-EGFR/VEGFR2 BsAb not only directly inhibits both EGFR and VEGFR2 in TNBC cells but also disrupts autocrine mechanism in TNBC xenograft mouse model. Furthermore, anti-EGFR/VEGFR2 BsAb inhibits ligand-induced activation of VEGFR2 and blocks paracrine pathway mediated by VEGF secreted from TNBC cells in endothelial cells. Collectively, our novel findings demonstrate that anti-EGFR/VEGFR2 BsAb inhibits tumor growth via multiple mechanisms of action and warrants further investigation as a targeted antibody therapeutic for the treatment of TNBC.
CENPE Inhibition Leads to Mitotic Catastrophe and DNA Damage in Medulloblastoma Cells
Authors: Iegiani Giorgia , Gai Marta , Di Cunto Ferdinando , Pallavicini Gianmarco
Published: March 2021

Medulloblastoma (MB) is the most frequent brain tumor in children. The standard treatment consists in surgery, followed by radiotherapy and chemotherapy. These therapies are only partially effective since many patients still die and those who survive suffer from neurological and endocrine disorders. Therefore, more effective therapies are needed. Primary microcephaly (MCPH) is a rare disorder caused by mutations in 25 different genes. Centromere-associated protein E (CENPE) heterozygous mutations cause the MCPH13 syndrome. As for other MCPH genes, CENPE is required for normal proliferation and survival of neural progenitors. Since there is evidence that MB shares many molecular features with neural progenitors, we hypothesized that CENPE could be an effective target for MB treatment. In ONS-76 and DAOY cells, CENPE knockdown induced mitotic defects and apoptosis. Moreover, CENPE depletion induced endogenous DNA damage accumulation, activating TP53 or TP73 as well as cell death signaling pathways. To consolidate CENPE as a target for MB treatment, we tested GSK923295, an allosteric inhibitor already in clinical trial for other cancer types. GSK923295, induced effects similar to CENPE depletion with higher penetrance, at low nM levels, suggesting that CENPE’s inhibition could be a therapeutic strategy for MB treatment.
Angiogenesis Inhibitors for Colorectal Cancer. A Review of the Clinical Data
Authors: Hansen Torben Frøstrup , Qvortrup Camilla , Pfeiffer Per
Published: March 2021

Since the late 1990s, therapy for metastatic colorectal cancer (mCRC) has changed considerably, and the combination of doublet or triplet chemotherapy and a targeted agent are now routinely used. The targeting of angiogenesis, the development of new blood vessels, represents a key element in the overall treatment strategy. Since the approval in 2004 of the first anti-angiogenetic drug, multiple agents have been approved and others are currently under investigation. We present an overview of the recent literature on approved systemic treatment of mCRC, with a focus on anti-angiogenic drugs, and current treatment approaches, and elaborate on the future role of angiogenesis in colorectal cancer as seen from a clinical perspective. The treatment of mCRC, in general, has changed from “one strategy fits all” to a more personalized approach. This is, however, not entirely the case for anti-angiogenetic treatments, partly due to a lack of validated biomarkers. The anti-angiogenetic standard treatment at the present primarily includes monoclonal antibodies. The therapeutic field of angiogenesis, however, has received increased interest after the introduction of newer combinations. These approaches will likely change the current treatment strategy, once again, to the overall benefit of patients.
TiO2-Graphene Quantum Dots Nanocomposites for Photocatalysis in Energy and Biomedical Applications
Authors: Bokare Anuja , Chinnusamy Sowbaranigha , Erogbogbo Folarin
Published: March 2021

The focus of current research in material science has shifted from “less efficient” single-component nanomaterials to the superior-performance, next-generation, multifunctional nanocomposites. TiO2 is a widely used benchmark photocatalyst with unique physicochemical properties. However, the large bandgap and massive recombination of photogenerated charge carriers limit its overall photocatalytic efficiency. When TiO2 nanoparticles are modified with graphene quantum dots (GQDs), some significant improvements can be achieved in terms of (i) broadening the light absorption wavelengths, (ii) design of active reaction sites, and (iii) control of the electron-hole (e−-h+) recombination. Accordingly, TiO2-GQDs nanocomposites exhibit promising multifunctionalities in a wide range of fields including, but not limited to, energy, biomedical aids, electronics, and flexible wearable sensors. This review presents some important aspects of TiO2-GQDs nanocomposites as photocatalysts in energy and biomedical applications. These include: (1) structural formulations and synthesis methods of TiO2-GQDs nanocomposites; (2) discourse about the mechanism behind the overall higher photoactivities of these nanocomposites; (3) various characterization techniques which can be used to judge the photocatalytic performance of these nanocomposites, and (4) the application of these nanocomposites in biomedical and energy conversion devices. Although some objectives have been achieved, new challenges still exist and hinder the widespread application of these nanocomposites. These challenges are briefly discussed in the Future Scope section of this review.
Role of Tumor-Derived Extracellular Vesicles in Glioblastoma
Authors: Chen Yunping , Jin Yan , Wu Nan
Published: March 2021

Glioblastoma (GBM) is the most common primary central nervous system tumor and one of the most lethal cancers worldwide, with morbidity of 5.26 per 100,000 population per year. These tumors are often associated with poor prognosis and terrible quality of life. Extracellular vesicles (EVs) are membrane-bound nanoparticles secreted by cells and contain lipid, protein, DNA, mRNA, miRNA and other bioactive substances. EVs perform biological functions by binding or horizontal transfer of bioactive substances to target cell receptors. In recent years, EVs have been considered as possible targets for GBM therapy. A great many types of research demonstrated that EVs played a vital role in the GBM microenvironment, development, progression, angiogenesis, invasion, and even the diagnosis of GBM. Nevertheless, the exact molecular mechanisms and roles of EVs in these processes are unclear. It can provide the basis for GBM treatment in the future that clarifying the regulatory mechanism and related signal pathways of EVs derived from GBM and their clinical value in GBM diagnosis and treatment. In this paper, the research progress and clinical application prospects of GBM-derived EVs are reviewed and discussed.
Disulfiram Acts as a Potent Radio-Chemo Sensitizer in Head and Neck Squamous Cell Carcinoma Cell Lines and Transplanted Xenografts
Authors: Yao Wenhao , Qian Xu , Ochsenreither Sebastian , Soldano Ferrone , DeLeo Albert B. , Sudhoff Holger , Oppel Felix , Kuppig Andreas , Klinghammer Konrad , Kaufmann Andreas M. , Albers Andreas E.
Published: March 2021

The poor prognosis of locally advanced and metastatic head and neck squamous cell carcinoma (HNSCC) is primarily mediated by the functional properties of cancer stem cells (CSCs) and resistance to chemoradiotherapy. We investigated whether the aldehyde dehydrogenase (ALDH) inhibitor disulfiram (DSF) can enhance the sensitivity of therapy. Cell viability was assessed by the 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) and apoptosis assays, and the cell cycle and reactive oxygen species (ROS) levels were evaluated by fluorescence-activated cell sorting (FACS). The radio-sensitizing effect was measured by a colony formation assay. The synergistic effects were calculated by combination index (CI) analyses. The DSF and DSF/Cu2+ inhibited the cell proliferation (inhibitory concentration 50 (IC50) of DSF and DSF/Cu2+ were 13.96 μM and 0.24 μM). DSF and cisplatin displayed a synergistic effect (CI values were <1). DSF or DSF/Cu2+ abolished the cisplatin-induced G2/M arrest (from 52.9% to 40.7% and 41.1%), and combining irradiation (IR) with DSF or DSF/Cu2+ reduced the colony formation and attenuated the G2/M arrest (from 53.6% to 40.2% and 41.9%). The combination of cisplatin, DSF or DSF/Cu2+, and IR enhanced the radio-chemo sensitivity by inducing apoptosis (42.04% and 32.21%) and ROS activity (46.3% and 37.4%). DSF and DSF/Cu2+ enhanced the sensitivity of HNSCC to cisplatin and IR. Confirming the initial data from patient-derived tumor xenograft (PDX) supported a strong rationale to repurpose DSF as a radio-chemosensitizer and to assess its therapeutic potential in a clinical setting.
Notch Signaling Regulation in HCC: From Hepatitis Virus to Non-Coding RNAs
Authors: Giovannini Catia , Fornari Francesca , Piscaglia Fabio , Gramantieri Laura
Published: March 2021

The Notch family includes evolutionary conserved genes that encode for single-pass transmembrane receptors involved in stem cell maintenance, development and cell fate determination of many cell lineages. Upon activation by different ligands, and depending on the cell type, Notch signaling plays pleomorphic roles in hepatocellular carcinoma (HCC) affecting neoplastic growth, invasion capability and stem like properties. A specific knowledge of the deregulated expression of each Notch receptor and ligand, coupled with resultant phenotypic changes, is still lacking in HCC. Therefore, while interfering with Notch signaling might represent a promising therapeutic approach, the complexity of Notch/ligands interactions and the variable consequences of their modulations raises concerns when performed in undefined molecular background. The gamma-secretase inhibitors (GSIs), representing the most utilized approach for Notch inhibition in clinical trials, are characterized by important adverse effects due to the non-specific nature of GSIs themselves and to the lack of molecular criteria guiding patient selection. In this review, we briefly summarize the mechanisms involved in Notch pathway activation in HCC supporting the development of alternatives to the γ-secretase pan-inhibitor for HCC therapy.
Molecular Dynamics Simulation on the Interaction between Palygorskite Coating and Linear Chain Alkane Base Lubricant
Authors: Zhang Jin , Yang Lv , Wang Yue , Wu Huaichao , Cai Jiabin , Xu Shusheng
Published: March 2021

Molecular dynamics (MD) simulations were conducted to investigate the interactions between a palygorskite coating and linear chain alkanes (dodecane C12, tetradecane C14, hexadecane C16, and octadecane C18), representing base oils in this study. The simulation models were built by placing the alkane molecules on the surface of the palygorskite coating. These systems were annealed and geometrically optimized to obtain the corresponding stable configurations, followed by the analysis of the structural changes occurring during the MD process. The interfacial interaction energies, mean square displacements, and self-diffusion coefficients of the systems were evaluated to characterize the interactions between base lubricant molecules and palygorskite coating. It was found that the alkanes exhibited self-arrangement ability after equilibrium. The interfacial interaction was attractive, and the electrostatic energy was the main component of the binding energy. The chain length of the linear alkanes had a significant impact on the intensity of the interfacial interactions and the molecular diffusion behavior. Moreover, the C12 molecule exhibited higher self-diffusion coefficient values than C14, C16 and C18. Therefore, it could be the best candidate to form an orderliness and stable lubricant film on the surface of the palygorskite coating. The present work provides new insight into the optimization of the structure and composition of coatings and lubricants, which will guide the experimental development of these systems for practical applications.
Why Is Deep Learning Challenging for Printed Circuit Board (PCB) Component Recognition and How Can We Address It?
Authors: Mallaiyan Sathiaseelan Mukhil Azhagan , Paradis Olivia P. , Taheri Shayan , Asadizanjani Navid
Published: March 2021

In this paper, we present the need for specialized artificial intelligence (AI) for counterfeit and defect detection of PCB components. Popular computer vision object detection techniques are not sufficient for such dense, low inter-class/high intra-class variation, and limited-data hardware assurance scenarios in which accuracy is paramount. Hence, we explored the limitations of existing object detection methodologies, such as region based convolutional neural networks (RCNNs) and single shot detectors (SSDs), and compared them with our proposed method, the electronic component localization and detection network (ECLAD-Net). The results indicate that, of the compared methods, ECLAD-Net demonstrated the highest performance, with a precision of 87.2% and a recall of 98.9%. Though ECLAD-Net demonstrated decent performance, there is still much progress and collaboration needed from the hardware assurance, computer vision, and deep learning communities for automated, accurate, and scalable PCB assurance.
Structural Analysis of Interstratified Illite-Smectite by the Rietveld Method
Authors: Wang Xiaoli , Wang Hejing
Published: March 2021

Rietveld method is a powerful tool in obtaining structural information of clay minerals by using of X-ray diffraction (XRD) patterns. However, the interstratified illite-smectites (I-S) show various stacking defects preventing the direct application of this method. It was shown that the Rietveld method combined with a recursive structure-factor calculation can be used for describing the stacking disorder of I-S. In this study, a series of samples with different stacking sequences and different proportions of layer types were chosen to verify the applicability of Rietveld method in determination of structural parameters of I-S. The Rietveld refinements were carried out on powder samples and oriented specimens in air-dry (AD) and ethylene glycol (EG) state. The structural information obtained by X-ray fluorescence (XRF) and thermal analysis were used as an independent test of the reliability of the refinements. The refined and experimental results were compared systematically and the relationship between structural parameter was discussed. For powder and oriented specimens, the refined results of occupancies of potassium and iron and the proportion of illitic layers showed consistent results. The refined value of cis-vacant layers was in good agreement with the experimental data. The reliability of the refinements increased with increasing proportion of illitic layers.
Tensile Behavior of Self-Compacting Steel Fiber Reinforced Concrete Evaluated by Different Test Methods
Authors: Ding Xinxin , Li Changyong , Zhao Minglei , Li Jie , Geng Haibin , Lian Lei
Published: March 2021

Due to the mechanical properties related closely to the distribution of steel fibers in concrete matrix, the assessment of tensile strength of self-compacting steel fiber reinforced concrete (SFRC) is significant for the engineering application. In this paper, seven groups of self-compacting SFRC were produced with the mix proportion designed by using the steel fiber-aggregates skeleton packing test method. The hooked-end steel fibers with length of 25.1 mm, 29.8 mm and 34.8 mm were used, and the volume fraction varied from 0.4% to 1.4%. The axial tensile test of notched sectional prism specimen and the splitting tensile test of cube specimen were carried out. Results show that the axial tensile strength was higher than the splitting tensile strength for the same self-compacting SFRC, the axial tensile work and toughness was not related to the length of steel fiber. Finally, the equations for the prediction of tensile strength of self-compacting SFRC are proposed considering the fiber distribution and fiber factor, and the adaptability of splitting tensile test for self-compacting SFRC is discussed.
Diversity of Brazilian Troglobitic Fishes: Models of Colonization and Differentiation in Subterranean Habitats
Authors: Trajano Eleonora
Published: March 2021

The Brazilian subterranean ichthyofauna is distinguished worldwide by high taxonomic and phylogenetic diversity, involving at least 30 exclusively subterranean (troglobitic) lineages. This may be explained by high native epigean diversty, allied to opportunities for colonization and genetic isolation in the subterranean biotope, thence originating troglobites. An updated list of Brazilian troglobitic lineages and a review of previous hypotheses on modes of colonization and differentiation in subterranean habitats are presented with fresh data and models. Colonization of and isolation in the subterranean biotope are independent processes, usually separate over time. Access to subterranean habitats varies from the (sub)horizontal through sinkholes and resurgences of base-level streams and vadose tributaries to the vertical by shallow and deep phreatic waters through the hyporheic zone. Phenotypic differentiation of subterranean populations originating troglobites may be achieved by various, non-mutually exclusive modes of genetic isolation, e.g., directly in base-level streams and upper tributaries through the extinction of epigean populations, due to drainage discontinuation in dry paleoclimatic phases (or by other causes), by topographic isolation due to a lowering of the regional base level and karst catchments or by parapatric differentiation. Differentiation may also be a consequence of transition from lotic to lentic waters in flooded caves, and from shallow to deep phreatic habitats.
Molecular Diversity and Evolution of Antimicrobial Peptides in Musca domestica
Authors: Qi Sudong , Gao Bin , Zhu Shunyi
Published: March 2021

As a worldwide sanitary insect pest, the housefly Musca domestica can carry and transmit more than 100 human pathogens without suffering any illness itself, indicative of the high efficiency of its innate immune system. Antimicrobial peptides (AMPs) are the effectors of the innate immune system of multicellular organisms and establish the first line of defense to protect hosts from microbial infection. To explore the molecular diversity of the M. domestica AMPs and related evolutionary basis, we conducted a systematic survey of its full AMP components based on a combination of computational approaches. These components include the cysteine-containing peptides (MdDefensins, MdEppins, MdMuslins, MdSVWCs and MdCrustins), the linear α-helical peptides (MdCecropins) and the specific amino acid-rich peptides (MdDomesticins, MdDiptericins, MdEdins and MdAttacins). On this basis, we identified multiple genetic mechanisms that could have shaped the molecular and structural diversity of the M. domestica AMPs, including: (1) Gene duplication; (2) Exon duplication via shuffling; (3) Protein terminal variations; (4) Evolution of disulfide bridges via compensation. Our results not only enlarge the insect AMP family members, but also offer a basic platform for further studying the roles of such molecular diversity in contributing to the high efficiency of the housefly antimicrobial immune system.
Postmortem Ocular Findings in the Optical Coherence Tomography Era: A Proof of Concept Study Based on Six Forensic Cases
Authors: Nioi Matteo , Napoli Pietro Emanuele , Demontis Roberto , Locci Emanuela , Fossarello Maurizio , d’Aloja Ernesto
Published: March 2021

Postmortem analysis of the ocular globe is an important topic for forensic pathology and transplantology. Although crucial elements may be gathered from examining cadaveric eyes, the latter do not routinely undergo in-depth analysis. The paucity of quantitative and objective data that are obtainable using current, invasive necroscopic techniques is the main reason for the limited interest in this highly specialized procedure. The aim of the current study is to describe and to object for the first time the postmortem ocular changes by mean of portable optical coherence tomography for evaluating ocular tissues postmortem. The design involved the postmortem analysis (in situ, and without enucleation) of 12 eyes by portable spectral-domain Optical Coherence Tomography. The scans were performed, in corneal, retinal and angle modality at different intervals: <6 h, 6th, 12th, and 24th hour and after autopsy (25th–72nd hour). The morphological changes in the cornea, sclera, vitreous humor and aqueous humor were easy to explore and objectify in these tissues in first 72 h postmortem. On the other hand, the “in situ” observation of the retina was difficult due to the opacification of the lenses in the first 24 h after death.
Effect of the Cut-Off Level for Thyroid-Stimulating Hormone on the Prevalence of Subclinical Hypothyroidism among Infertile Mexican Women
Authors: Arce-Sánchez Lidia , Vitale Salvatore Giovanni , Flores-Robles Claudia Montserrat , Godines-Enriquez Myrna Souraye , Noventa Marco , Urquia-Figueroa Carmen Marcela , Martínez-Cruz Nayeli , Estrada-Gutierrez Guadalupe , Espino y Sosa Salvador , Romo-Yañez José , Montoya-Estrada Araceli , Reyes-Muñoz Enrique
Published: March 2021

The primary aim of this study was to compare the prevalence of subclinical hypothyroidism (SCH) using two different cut-off levels for TSH values (≥2.5 mIU/L versus ≥4.1 mIU/L). The secondary objective was to analyze the clinical-biochemical characteristics in women with and without SCH. This was a retrospective cross-sectional study. In total, 1496 Mexican women with infertility were included: Group 1, women with TSH levels ranging between 0.3 and 2.49 mIU/L, n = 886; Group 2, women with TSH between 2.5 and 4.09 mIU/L, n = 390; and Group 3, women with TSH ≥4.1 mIU/L n = 220. SCH prevalence was 40.7% (CI 95%: 38.3–43.3%) with TSH cut-off ≥ 2.5 mIU/L, and 14.7% (CI 95%: 12.7–16.5%) with TSH cut-off ≥ 4.1 mIU/L, (p = 0.0001). The prevalence of overweight was higher in Group 2 than in Groups 1 and 3. Thyroid autoimmunity, obesity and insulin resistance were higher in Group 3 than in Group 1 (p < 0.05). No other differences were observed between groups. Conclusions: The prevalence of SCH in our selected patients increased almost three times using a TSH cut-off ≥ 2.5 mIU/L compared with a TSH cut-off ≥ 4.1 mIU/L. Women with TSH ≥4.1 mIU/L compared with TSH cut-off ≤ 2.5 mIU/L more often presented with obesity, thyroid autoimmunity and insulin resistance.
Effect of Turmeric Concentrations on the Rate of Growth of Oral Bacteria—An In-Vitro Study
Authors: Yang Yun Xuan , Wu Vicky , Malak Hadi , Ahamed Aliya Peer , Lo Aaron , Abraham Yannis , Miller Catherine
Published: March 2021

Background and Aim: The aim of this study was to evaluate the effect of varying concentrations of a turmeric solution on the growth rates of oral bacteria sampled from dental students. Methods: Bacterial cultures were grown overnight in aerobic conditions from plaque samples obtained from five test subjects. With the exception of the control, samples were exposed to different treatments; including chlorhexidine gluconate 2 mg/mL, prepared turmeric solution (TS) mouthwash: TS 0.25 mL (7.375 mg/mL), TS 0.5 mL (14.75 mg/mL), and TS 1 mL (29.50 mg/mL). Growth rate of the bacterial cultures were assessed by monitoring changes in optical density readings at 600 nm at hourly intervals for a six-hour period. The data were plotted and the exponential trend was used to calculate individual rates of growth. Data was analyzed using a one-way ANOVA with the significance confirmed using the Tukey-HSD test. Results: Growth observed in the bacteria exposed to the turmeric solution, was significantly greater (p < 0.05) when compared with the bacteria exposed to the medium alone. There was a significant difference found between the bacterial growth rate of the 1 mL turmeric solution against the growth rate of the bacteria in the 0.25 and 0.5 mL turmeric solutions. Conclusion: Comparison of growth rates of oral bacteria suggested that turmeric solutions of concentrations between 7.357 and 29.5 mg/mL (0.25–1 mL) were unlikely to exhibit bacteriostatic or bactericidal properties, and, conversely, increased bacterial growth. Considering this result, it is unlikely that turmeric mouthwash made from store-bought turmeric would have any antibacterial effects against oral bacteria, and may even promote bacterial growth.