bluuebunny/crossref_metadata_2025 huggingface dataset:
A Provable and Secure Patient Electronic Health Record Fair Exchange Scheme for Health Information Systems
Authors: Chen Ming-Te , Lin Tsung-Hung
Published: March 2021

In recent years, several hospitals have begun using health information systems to maintain electronic health records (EHRs) for each patient. Traditionally, when a patient visits a new hospital for the first time, the hospital’s help desk asks them to fill in relevant personal information on a piece of paper and verifies their identity on the spot. This patient will find that many of her personal electronic records are in many hospital’s health information systems that she visited in the past, and each EHR in these hospital’s information systems cannot be accessed or shared between these hospitals. This is inconvenient because this patient will again have to provide their personal information. This is time-consuming and not practical. Therefore, in this paper, we propose a practical and provable patient EHR fair exchange scheme for each patient. In this scheme, each patient can securely delegate the information system of a current hospital to a hospital certification authority (HCA) to apply migration evidence that can be used to transfer their EHR to another hospital. The delegated system can also establish a session key with other hospital systems for later data transmission, and each patient can protect their anonymity with the help of the HCA. Additionally, we also provide formal security proofs for forward secrecy and functional comparisons with other schemes.
Intracellular Toxic AGEs (TAGE) Triggers Numerous Types of Cell Damage
Authors: Takeuchi Masayoshi , Sakasai-Sakai Akiko , Takata Takanobu , Takino Jun-ichi , Koriyama Yoshiki , Kikuchi Chigusa , Furukawa Ayako , Nagamine Kentaro , Hori Takamitsu , Matsunaga Tamihide
Published: March 2021

The habitual intake of large amounts of sugar, which has been implicated in the onset/progression of lifestyle-related diseases (LSRD), induces the excessive production of glyceraldehyde (GA), an intermediate of sugar metabolism, in neuronal cells, hepatocytes, and cardiomyocytes. Reactions between GA and intracellular proteins produce toxic advanced glycation end-products (toxic AGEs, TAGE), the accumulation of which contributes to various diseases, such as Alzheimer’s disease, non-alcoholic steatohepatitis, and cardiovascular disease. The cellular leakage of TAGE affects the surrounding cells via the receptor for AGEs (RAGE), thereby promoting the onset/progression of LSRD. We demonstrated that the intracellular accumulation of TAGE triggered numerous cellular disorders, and also that TAGE leaked into the extracellular space, thereby increasing extracellular TAGE levels in circulating fluids. Intracellular signaling and the production of reactive oxygen species are affected by extracellular TAGE and RAGE interactions, which, in turn, facilitate the intracellular generation of TAGE, all of which may contribute to the pathological changes observed in LSRD. In this review, we discuss the relationships between intracellular TAGE levels and numerous types of cell damage. The novel concept of the “TAGE theory” is expected to open new perspectives for research into LSRD.
Effects of Hypoxic Preconditioning and Vascular Endothelial Growth Factor on the Survival of Isolated Primary Retinal Ganglion Cells
Authors: Bae Hyoung Won , Choi Wungrak , Hwang Ah Reum , Lee Sang Yeop , Seong Gong Je , Kim Chan Yun
Published: March 2021

This study aimed to investigate the effect of hypoxic preconditioning (HPC) on primary retinal ganglion cell (RGC) survival and the associated mechanism, including the role of vascular endothelial growth factor (VEGF). Retinas were separated from the enucleated eyeballs of Sprague–Dawley rats on postnatal days 1–4. RGCs were harvested using an immunopanning-magnetic separation system and maintained for 24 h in a defined medium. Hypoxic damage (0.3% O2) was inflicted on the cells using a CO₂ chamber. Anti-VEGF antibody (bevacizumab) was administered to RGCs exposed to hypoxic conditions, and RGC survival rate was compared to that of non-anti-VEGF antibody-treated RGCs. HPC lasting 4 h significantly increased RGC survival rate. In the RGCs exposed to hypoxic conditions for 4 h, VEGF mRNA and protein levels were significantly increased. Treatment with high dose bevacizumab (>1 mg/mL) countered HPC-mediated RGC survival. Protein kinase B and focal adhesion kinase levels were significantly increased in 4-h hypoxia-treated RGCs. HPC showed beneficial effects on primary RGC survival. However, only specifically controlled exposure to hypoxic conditions rendered neuroprotective effects. Strong inhibition of VEGF inhibited HPC-mediated RGC survival. These results indicate that VEGF may play an essential role in promoting cell survival under hypoxic conditions.
Potential Role of Curcumin and Its Nanoformulations to Treat Various Types of Cancers
Authors: Kabir Md. Tanvir , Rahman Md. Habibur , Akter Rokeya , Behl Tapan , Kaushik Deepak , Mittal Vineet , Pandey Parijat , Akhtar Muhammad Furqan , Saleem Ammara , Albadrani Ghadeer M. , Kamel Mohamed , Khalifa Shaden A.M. , El-Seedi Hesham R. , Abdel-Daim Mohamed M.
Published: March 2021

Cancer is a major burden of disease globally. Each year, tens of millions of people are diagnosed with cancer worldwide, and more than half of the patients eventually die from it. Significant advances have been noticed in cancer treatment, but the mortality and incidence rates of cancers are still high. Thus, there is a growing research interest in developing more effective and less toxic cancer treatment approaches. Curcumin (CUR), the major active component of turmeric (Curcuma longa L.), has gained great research interest as an antioxidant, anticancer, and anti-inflammatory agent. This natural compound shows its anticancer effect through several pathways including interfering with multiple cellular mechanisms and inhibiting/inducing the generation of multiple cytokines, enzymes, or growth factors including IκB kinase β (IκKβ), tumor necrosis factor-alpha (TNF-α), signal transducer, and activator of transcription 3 (STAT3), cyclooxygenase II (COX-2), protein kinase D1 (PKD1), nuclear factor-kappa B (NF-κB), epidermal growth factor, and mitogen-activated protein kinase (MAPK). Interestingly, the anticancer activity of CUR has been limited primarily due to its poor water solubility, which can lead to low chemical stability, low oral bioavailability, and low cellular uptake. Delivering drugs at a controlled rate, slow delivery, and targeted delivery are other very attractive methods and have been pursued vigorously. Multiple CUR nanoformulations have also been developed so far to ameliorate solubility and bioavailability of CUR and to provide protection to CUR against hydrolysis inactivation. In this review, we have summarized the anticancer activity of CUR against several cancers, for example, gastrointestinal, head and neck, brain, pancreatic, colorectal, breast, and prostate cancers. In addition, we have also focused on the findings obtained from multiple experimental and clinical studies regarding the anticancer effect of CUR in animal models, human subjects, and cancer cell lines.
Advanced Killing Potential of Thymol against a Time and Temperature Optimized Attached Listeria monocytogenes Population in Lettuce Broth
Authors: Kostoglou Dimitra , Tsaklidou Parthena , Iliadis Ioannis , Garoufallidou Nikoletta , Skarmoutsou Georgia , Koulouris Ioannis , Giaouris Efstathios
Published: March 2021

Fresh vegetables and salads are increasingly implicated in outbreaks of foodborne infections, such as those caused by Listeria monocytogenes, a dangerous pathogen that can attach to the surfaces of the equipment creating robust biofilms withstanding the killing action of disinfectants. In this study, the antimicrobial efficiency of a natural plant terpenoid (thymol) was evaluated against a sessile population of a multi-strain L. monocytogenes cocktail developed on stainless steel surfaces incubated in lettuce broth, under optimized time and temperature conditions (54 h at 30.6 °C) as those were determined following response surface modeling, and in comparison, to that of an industrial disinfectant (benzalkonium chloride). Prior to disinfection, the minimum bactericidal concentrations (MBCs) of each compound were determined against the planktonic cells of each strain. The results revealed the advanced killing potential of thymol, with a concentration of 625 ppm (= 4 × MBC) leading to almost undetectable viable bacteria (more than 4 logs reduction following a 15-min exposure). For the same degree of killing, benzalkonium chloride needed to be used at a concentration of at least 20 times more than its MBC (70 ppm). Discriminative repetitive sequence-based polymerase chain reaction (rep-PCR) also highlighted the strain variability in both biofilm formation and resistance. In sum, thymol was found to present an effective anti-listeria action under environmental conditions mimicking those encountered in the salad industry and deserves to be further explored to improve the safety of fresh produce.
Hypoxia/HIF Modulates Immune Responses
Authors: Chen Yuling , Gaber Timo
Published: March 2021

Oxygen availability varies throughout the human body in health and disease. Under physiological conditions, oxygen availability drops from the lungs over the blood stream towards the different tissues into the cells and the mitochondrial cavities leading to physiological low oxygen conditions or physiological hypoxia in all organs including primary lymphoid organs. Moreover, immune cells travel throughout the body searching for damaged cells and foreign antigens facing a variety of oxygen levels. Consequently, physiological hypoxia impacts immune cell function finally controlling innate and adaptive immune response mainly by transcriptional regulation via hypoxia-inducible factors (HIFs). Under pathophysiological conditions such as found in inflammation, injury, infection, ischemia and cancer, severe hypoxia can alter immune cells leading to dysfunctional immune response finally leading to tissue damage, cancer progression and autoimmunity. Here we summarize the effects of physiological and pathophysiological hypoxia on innate and adaptive immune activity, we provide an overview on the control of immune response by cellular hypoxia-induced pathways with focus on the role of HIFs and discuss the opportunity to target hypoxia-sensitive pathways for the treatment of cancer and autoimmunity.
Dysbiosis and Enhanced Beta-Defensin Production in Hair Follicles of Patients with Lichen Planopilaris and Frontal Fibrosing Alopecia
Authors: Constantinou Andria , Polak-Witka Katarzyna , Tomazou Marios , Oulas Anastasis , Kanti Varvara , Schwarzer Rolf , Helmuth Johannes , Edelmann Anke , Blume-Peytavi Ulrike , Spyrou George , Vogt Annika
Published: March 2021

Despite their distinct clinical manifestation, frontal fibrosing alopecia (FFA) and lichen planopilaris (LPP) display similar histopathologic features. Aberrant innate immune responses to endogenous or exogenous triggers have been discussed as factors that could drive inflammatory cascades and the collapse of the stem cell niche. In this exploratory study, we investigate the bacterial composition of scalp skin and plucked hair follicles (HF) of patients with FFA, LPP and alopecia areata circumscripta (AAc), as well as healthy individuals, in relation to cellular infiltrates and the expression of defense mediators. The most abundant genus in lesional and non-lesional HFs of LPP and FFA patients was Staphylococcus, while Lawsonella dominated in healthy individuals and in AAc patients. We observed statistically significant differences in the ratio of Firmicutes to Actinobacteria between healthy scalp, lesional, and non-lesional sites of FFA and LPP patients. This marked dysbiosis in FFA and LPP in compartments close to the bulge was associated with increased HβD1 and HβD2 expression along the HFs from lesional sites, while IL-17A was increased in lesional HF from AAc patients. The data encourage further studies on how exogenous factors and molecular interactions across the HF epithelium could contribute to disease onset and propagation.
Cannabinoid Signalling in Immune–Reproductive Crosstalk during Human Pregnancy
Authors: Gurm Harmeet , Hirota Jeremy A. , Raha Sandeep
Published: March 2021

Despite the intricate involvement of the endocannabinoid system in various physiological processes, it remains one of the most under-studied biological systems of the human body. The scope of endocannabinoid signalling is widespread, ranging from modulation of immune responses in innate and adaptive immunity to gestational processes in female physiology. Cannabinoid receptors are ubiquitously distributed in reproductive tissues and are thought to play a role in regulating the immune–reproductive interactions required for successful pregnancy, specifically among uterine natural killer cells and placental extravillous trophoblasts. The use of cannabis during pregnancy, however, can perturb endocannabinoid homeostasis through effects mediated by its major constituents, Δ-9-tetrahydrocannabinol and cannabidiol. Decidualization of the endometrium, invasion, and angiogenesis may be impaired as a consequence, leading to clinical complications such as miscarriage and preeclampsia. In this review, the crosstalk between endocannabinoid signalling in uterine natural killer cells and placental extravillous trophoblasts will be examined in healthy and complicated pregnancies. This lays a foundation for discussing the potential of targeting the endocannabinoid system for therapeutic benefit, particularly with regard to the emerging field of synthetic cannabinoids.
A Reassessment of the Therapeutic Potential of a Dopamine Receptor 2 Agonist (D2-AG) in Endometriosis by Comparison against a Standardized Antiangiogenic Treatment
Authors: Tejada Miguel Á. , Santos-Llamas Ana I. , Fernández-Ramírez María José , Tarín Juan J. , Cano Antonio , Gómez Raúl
Published: March 2021

Dopamine receptor 2 agonists (D2-ags) have been shown to reduce the size of tumors by targeting aberrant angiogenesis in pathological tissue. Because of this, the use of a D2-ag was inferred for endometriosis treatment. When assayed in mouse models however, D2-ags have been shown to cause a shift of the immature vessels towards a more mature phenotype but not a significant reduction in the amount of vascularization and size of lesions. These has raised concerns on whether the antiangiogenic effects of these compounds confer a therapeutic value for endometriosis. In the belief that antiangiogenic effects of D2-ags in endometriosis were masked due to non-optimal timing of pharmacological interventions, herein we aimed to reassess the antiangiogenic therapeutic potential of D2-ags in vivo by administering compounds at a timeframe in which vessels in the lesions are expected to be more sensitive to antiangiogenic stimuli. To prove our point, immunodeficient (NU/NU) mice were given a D2-ag (cabergoline), anti-VEGF (CBO-P11) or vehicle (saline) compounds (n = 8 per group) starting 5 days after implantation of a fluorescently labeled human lesion. The effects on the size of the implants was estimated by monitoring the extent of fluorescence emitted by the lesion during the three-week treatment period. Subsequently mice were sacrificed and lesions excised and fixed for quantitative immunohistochemical/immunofluorescent analysis of angiogenic parameters. Lesion size, vascular density and innervation were comparable in D2-ag and anti-VEGF groups and significantly decreased when compared to control. These data suggest that D2-ags are as powerful as standard antiangiogenic compounds in interfering with angiogenesis and lesion size. Our preliminary study opens the way to further exploration of the mechanisms beneath the antiangiogenic effects of D2-ags for endometriosis treatment in humans.
Mechanism of Resveratrol Dimers Isolated from Grape Inhibiting 1O2 Induced DNA Damage by UHPLC-QTOF-MS2 and UHPLC-QQQ-MS2 Analyses
Authors: Kong Qingjun , Zeng Qingzhi , Yu Jia , Xiao Hongxi , Lu Jun , Ren Xueyan
Published: March 2021

Resveratrol dimers have been extensively reported on due to their antioxidative activity. Previous studies revealed that resveratrol dimer has been shown to selectively quench singlet oxygen (1O2), and could protect DNA from oxidative damage. The mechanism of resveratrol dimers protecting DNA against oxidative damage is still not clear. Therefore, in this project, the reactants and products of resveratrol dimers protecting guanine from oxidative damage were qualitatively monitored and quantitatively analyzed by UHPLC-QTOF-MS2 and UHPLC-QQQ-MS2. Results showed that when guanine and resveratrol dimers were attacked by 1O2, mostly resveratrol dimers were oxidized, which protected guanine from oxidation. Resveratrol dimers’ oxidation products were identified and quantified at m/z 467.1134 [M-H]− and 467.1118 [M-H]−, respectively. The resorcinol of resveratrol dimers reacted with singlet oxygen to produce p-benzoquinone, protecting guanine from 1O2 damage. Therefore, it is hereby reported for the first time that the resorcinol ring is the characteristic structure in stilbenes inhibiting 1O2 induced-DNA damage, which provides a theoretical basis for preventing and treating DNA damage-mediated diseases.
Keeping Cool in the Desert: Using Wind Catchers for Improved Thermal Comfort and Indoor Air Quality at Half the Energy
Authors: Saif Jamal , Wright Andrew , Khattak Sanober , Elfadli Kasem
Published: March 2021

In hot arid climates, air conditioning in the summer dominates energy use in buildings. In Kuwait, energy demand in buildings is dominated by cooling, which also determines the national peak electricity demand. Schools contribute significantly to cooling demand, but also suffer from poor ventilation. This paper presents analysis of a ventilation and cooling system for school classrooms using a wind catcher for natural ventilation and evaporative cooling. A school classroom in Kuwait with single-sided ventilation was modelled using the DesignBuilder V5.4/EnergyPlus V9.1 software and calibrated using field data. The model was used to analyse the performance of a wind catcher, with and without evaporative cooling, in terms of energy use, thermal comfort and indoor air quality. Compared to the baseline of using air-conditioning only, a wind catcher with evaporative cooling was found to reduce energy use by 52% during the summer months while increasing the comfortable hours from 76% to 100% without any supplementary air conditioning. While the time below the ASHRAE CO2 limit also improved from 11% to 24% with the wind catcher, the indoor air quality was still poor. These improvements came at the cost of a 14% increase in relative humidity. As the wind catcher solution appears to have potential with further development; several avenues for further research are proposed.
A New Epigenetic Model to Stratify Glioma Patients According to Their Immunosuppressive State
Authors: Polano Maurizio , Fabbiani Emanuele , Andreuzzi Eva , Cintio Federica , Bedon Luca , Gentilini Davide , Mongiat Maurizio , Ius Tamara , Arcicasa Mauro , Skrap Miran , Dal Bo Michele , Toffoli Giuseppe
Published: March 2021

Gliomas are the most common primary neoplasm of the central nervous system. A promising frontier in the definition of glioma prognosis and treatment is represented by epigenetics. Furthermore, in this study, we developed a machine learning classification model based on epigenetic data (CpG probes) to separate patients according to their state of immunosuppression. We considered 573 cases of low-grade glioma (LGG) and glioblastoma (GBM) from The Cancer Genome Atlas (TCGA). First, from gene expression data, we derived a novel binary indicator to flag patients with a favorable immune state. Then, based on previous studies, we selected the genes related to the immune state of tumor microenvironment. After, we improved the selection with a data-driven procedure, based on Boruta. Finally, we tuned, trained, and evaluated both random forest and neural network classifiers on the resulting dataset. We found that a multi-layer perceptron network fed by the 338 probes selected by applying both expert choice and Boruta results in the best performance, achieving an out-of-sample accuracy of 82.8%, a Matthews correlation coefficient of 0.657, and an area under the ROC curve of 0.9. Based on the proposed model, we provided a method to stratify glioma patients according to their epigenomic state.
Elevated Serum Amyloid a Levels Are not Specific for Sarcoidosis but Associate with a Fibrotic Pulmonary Phenotype
Authors: Beijer Els , Roodenburg-Benschop Claudia , Schimmelpennink Milou C. , Grutters Jan C. , Meek Bob , Veltkamp Marcel
Published: March 2021

Elevated Serum Amyloid A (SAA) levels have been found in several inflammatory diseases, including sarcoidosis. SAA is suggested to be involved in sarcoidosis pathogenesis by involvement in granuloma formation and maintenance. We hypothesized that SAA serum levels would be higher in sarcoidosis compared to other non-infectious granulomatous and non-granulomatous diseases. SAA levels were measured in serum from sarcoidosis, Hypersensitivity pneumonitis (HP), and (eosinophilic) granulomatosis with polyangiitis ((E)GPA) patients. Idiopathic pulmonary fibrosis (IPF) patients were included as non-granulomatous disease group. SAA levels of patients with sarcoidosis (31.0 µg/mL), HP (23.4 µg/mL), (E)GPA (36.9 µg/mL), and IPF (22.1 µg/mL) were all higher than SAA levels of healthy controls (10.1 µg/mL). SAA levels did not differ between the diagnostic groups. When SAA serum levels were analyzed in sarcoidosis subgroups, fibrotic sarcoidosis patients showed higher SAA levels than sarcoidosis patients without fibrosis (47.8 µg/mL vs. 29.4 µg/mL, p = 0.005). To conclude, the observation that fibrotic sarcoidosis patients have higher SAA levels, together with our finding that SAA levels were also increased in IPF patients, suggests that SAA may next to granulomatous processes also reflect the process of fibrogenesis. Further studies should clarify the exact role of SAA in fibrosis and the underlying mechanisms involved.
Mesenchymal Stem Cell-Based Therapy for Retinal Degenerative Diseases: Experimental Models and Clinical Trials
Authors: Holan Vladimir , Palacka Katerina , Hermankova Barbora
Published: March 2021

Retinal degenerative diseases, such as age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy or glaucoma, represent the main causes of a decreased quality of vision or even blindness worldwide. However, despite considerable efforts, the treatment possibilities for these disorders remain very limited. A perspective is offered by cell therapy using mesenchymal stem cells (MSCs). These cells can be obtained from the bone marrow or adipose tissue of a particular patient, expanded in vitro and used as the autologous cells. MSCs possess potent immunoregulatory properties and can inhibit a harmful inflammatory reaction in the diseased retina. By the production of numerous growth and neurotrophic factors, they support the survival and growth of retinal cells. In addition, MSCs can protect retinal cells by antiapoptotic properties and could contribute to the regeneration of the diseased retina by their ability to differentiate into various cell types, including the cells of the retina. All of these properties indicate the potential of MSCs for the therapy of diseased retinas. This view is supported by the recent results of numerous experimental studies in different preclinical models. Here we provide an overview of the therapeutic properties of MSCs, and their use in experimental models of retinal diseases and in clinical trials.
3D-Printed Collagen Scaffolds Promote Maintenance of Cryopreserved Patients-Derived Melanoma Explants
Authors: Jeong Yun-Mi , Bang ChulHwan , Park MinJi , Shin Sun , Yun Seokhwan , Kim Chul , Jeong GaHee , Chung Yeun-Jun , Yun Won-Soo , Lee Ji , Jin Songwan
Published: March 2021

The development of an in vitro three-dimensional (3D) culture system with cryopreserved biospecimens could accelerate experimental research screening anticancer drugs, potentially reducing costs and time bench-to-beside. However, minimal research has explored the application of 3D bioprinting-based in vitro cancer models to cryopreserved biospecimens derived from patients with advanced melanoma. We investigated whether 3D-printed collagen scaffolds enable the propagation and maintenance of patient-derived melanoma explants (PDMEs). 3D-printed collagen scaffolds were fabricated with a 3DX bioprinter. After thawing, fragments from cryopreserved PDMEs (approximately 1–2 mm) were seeded onto the 3D-printed collagen scaffolds, and incubated for 7 to 21 days. The survival rate was determined with MTT and live and dead assays. Western blot analysis and immunohistochemistry staining was used to express the function of cryopreserved PDMEs. The results show that 3D-printed collagen scaffolds could improve the maintenance and survival rate of cryopreserved PDME more than 2D culture. MITF, Mel A, and S100 are well-known melanoma biomarkers. In agreement with these observations, 3D-printed collagen scaffolds retained the expression of melanoma biomarkers in cryopreserved PDME for 21 days. Our findings provide insight into the application of 3D-printed collagen scaffolds for closely mimicking the 3D architecture of melanoma and its microenvironment using cryopreserved biospecimens.
Ambiguity about Splicing Factor 3b Subunit 3 (SF3B3) and Sin3A Associated Protein 130 (SAP130)
Authors: Metselaar Paula I. , Hos Celine , Welting Olaf , Bosch Jos A. , Kraneveld Aletta D. , de Jonge Wouter J. , Te Velde Anje A.
Published: March 2021

In 2020, three articles were published on a protein that can activate the immune system by binding to macrophage-inducible C-type lectin receptor (Mincle). In the articles, the protein was referred to as ‘SAP130, a subunit of the histone deacetylase complex.’ However, the Mincle ligand the authors aimed to investigate is splicing factor 3b subunit 3 (SF3B3). This splicing factor is unrelated to SAP130 (Sin3A associated protein 130, a subunit of the histone deacetylase-dependent Sin3A corepressor complex). The conclusions in the three articles were formulated for SF3B3, while the researchers used qPCR primers and antibodies against SAP130. We retraced the origins of the ambiguity about the two proteins and found that Online Mendelian Inheritance in Man (OMIM) added a Nature publication on SF3B3 as a reference for Sin3A associated protein 130 in 2016. Subsequently, companies such as Abcam referred to OMIM and the Nature article in their products for both SF3B3 and SAP130. In turn, the mistake by OMIM followed in the persistent and confusing use of ‘SAP130′ (spliceosome-associated protein 130) as an alternative symbol for SF3B3. With this report, we aim to eliminate the persistent confusion and separate the literature regarding the two proteins.
Facial Rejuvenation with Concentrated Lipograft—A 12 Month Follow-Up Study
Authors: Prantl Lukas , Brix Eva , Kempa Sally , Felthaus Oliver , Eigenberger Andreas , Brébant Vanessa , Anker Alexandra , Strauss Catharina
Published: March 2021

Lipofilling is a popular technique to treat volume loss in aging patients. The isolated adipose tissue is composed of adipocytes and stromal vascular fraction cells, which include adipose-derived stem cells (ASC). We hypothesize that the patient’s wrinkle severity scale (WSS) and patient’s satisfaction on the global aesthetic improvement scale (GAIS) can be improved after using concentrated lipoaspirate. Fourteen patients (54 years ± 11.09 years) with volume loss in the midface area underwent waterjet-assisted liposuction (Human Med AG, Schwerin, Germany). Fat was centrifuged in an ACP Double Syringe (Arthrex GmbH, Munich, Germany) using Rotofix 32A centrifuge (Andreas Hettich, GmbH & Co.KG, Tuttlingen, Germany). Homogenization was performed using the double syringe and a 1.4 mm female–female luerlock connector. After a second centrifugation, patients received periorbital (PO) and nasolabial (NL) lipografting. ASC count was performed after enzymatical digestion. Vitality of cells was assessed using a resazurin assay. During long-term follow up (12 months, n = 10), we found a high patient’s satisfaction (GAIS 1+/−0.52) and a good improvement of the WSS during short- and long-term follow-up. The ASC count of processed lipoaspirate was 2.1-fold higher than of unprocessed lipoaspirate (p < 0.001). The difference of ASC in sedimented and simply centrifuged lipoaspirate was also significant (p < 0.05). Facial rejuvenation with concentrated fat graft offers good results concerning objective aesthetic outcome and patient’s satisfaction.
Apolipoprotein Mimetic Peptides: Potential New Therapies for Cardiovascular Diseases
Authors: Wolska Anna , Reimund Mart , Sviridov Denis O. , Amar Marcelo J. , Remaley Alan T.
Published: March 2021

Since the seminal breakthrough of treating diabetic patients with insulin in the 1920s, there has been great interest in developing other proteins and their peptide mimetics as therapies for a wide variety of other medical disorders. Currently, there are at least 60 different peptides that have been approved for human use and over 150 peptides that are in various stages of clinical development. Peptides mimetic of the major proteins on lipoproteins, namely apolipoproteins, have also been developed first as tools for understanding apolipoprotein structure and more recently as potential therapeutics. In this review, we discuss the biochemistry, peptide mimetics design and clinical trials for peptides based on apoA-I, apoE and apoC-II. We primarily focus on applications of peptide mimetics related to cardiovascular diseases. We conclude with a discussion on the limitations of peptides as therapeutic agents and the challenges that need to be overcome before apolipoprotein mimetic peptides can be developed into new drugs.
Interplay of Hydrophobic Thiol and Polar Epoxy Silicate Groups on Microstructural Development in Low-Alcohol, Crosslinked Sol–Gel Coatings for Corrosion Prevention
Authors: Shetranjiwalla Shegufa , Vreugdenhil Andrew , Strong Oliver
Published: March 2021

We have demonstrated that our patented, crosslinked, sol–gel, epoxy–thiol silicates made from the combination of (a) tetraethoxysilane (TEOS, T), 3-glycidoxypropyltrimethoxysilane (GPTMS, G), and the (b) sulfur-containing 3-mercaptopropyltrimethoxysilane (MPTMS, S) with TEOS in a 1:1 stoichiometric ratio form the 1:1 TGST (crosslinked epoxy and thiol silicates) coating, which can be successfully utilized for the corrosion protection of low-carbon steel. Alcohols that are a by-product of sol–gel reactions influence the network formation, crosslinking density, and formulation stability, are volatile organic contents, and are regulated in the coatings industry. To improve environmental sustainability, a series of low-alcohol (LA) formulations with TG:ST ratios of 3:1 to 1:3 was prepared to investigate the microstructural development and crosslinking reactions emerging from the interplay of the hydrophobic thiol and polar epoxy silicates induced by the low-alcohol environment. The impact on crosslinking density was characterized by Fourier Transform Infrared (FTIR), Raman, XPS, viscosity, and pot-life measurements. Low-alcohol TGST (LA(TGST)) formulations were compared, using the example of 1:1 TGST, to corresponding TGST formulations where alcohols were retained. The reduced impact of LA(TGST) formulations on global warming was quantified. The glossy and scratch-resistant LA(TGST) coatings showed 71% enhanced corrosion protection compared to the non-crosslinked hybrids.
A Stable and Efficient Pt/n-Type Ge Schottky Contact That Uses Low-Cost Carbon Paste Interlayers
Authors: Lin Pei-Te , Chang Jia-Wei , Chang Syuan-Ruei , Li Zhong-Kai , Chen Wei-Zhi , Huang Jui-Hsuan , Ji Yu-Zhen , Hsueh Wen-Jeng , Huang Chun-Ying
Published: March 2021

Ge-based Schottky diodes find applications in high-speed devices. However, Fermi-level pinning is a major issue for the development of Ge-based diodes. This study fabricates a Pt/carbon paste (CP)/Ge Schottky diode using low-cost CP as an interlayer. The Schottky barrier height (ΦB) is 0.65 eV for Pt/CP/n-Ge, which is a higher value than the value of 0.57 eV for conventional Pt/n-Ge. This demonstrates that the CP interlayer has a significant effect. The relevant junction mechanisms are illustrated using feasible energy level band diagrams. This strategy results in greater stability and enables a device to operate for more than 500 h under ambient conditions. This method realizes a highly stable Schottky contact for n-type Ge, which is an essential element of Ge-based high-speed electronics.
High-Drain Field Impacting Channel-Length Modulation Effect for Nano-Node N-Channel FinFETs
Authors: Wang Mu-Chun , Hsieh Wen-Ching , Lin Chii-Ruey , Chu Wei-Lun , Liao Wen-Shiang , Lan Wen-How
Published: March 2021

Three dimensional (3-D) FinFET devices with an ultra-high Si-fin aspect ratio have been developed after integrating a 14Å nitrided gate oxide upon the silicon on insulator (SOI) wafers through an advanced CMOS logic platform. Under the lower gate voltage (VGS-VT) and the higher drain/source voltage VDS, the channel-length modulation (CLM) effect coming from the interaction impact of vertical gate field and horizontal drain field was increased and had to be revised well as the channel length L was decreased. Compared to the 28-nm MOSFETs, the interaction effect from the previous at the tested FinFETs on SOI substrate with the short-channel length L is lower than that at the 28-nm device, which means the interaction severity of both fields for nFinFETs is mitigated, but still necessary to be concerned.
Three-Dimensional Electron Diffraction for Structural Analysis of Beam-Sensitive Metal-Organic Frameworks
Authors: Ge Meng , Zou Xiaodong , Huang Zhehao
Published: March 2021

Electrons interact strongly with matter, which makes it possible to obtain high-resolution electron diffraction data from nano- and submicron-sized crystals. Using electron beam as a radiation source in a transmission electron microscope (TEM), ab initio structure determination can be conducted from crystals that are 6–7 orders of magnitude smaller than using X-rays. The rapid development of three-dimensional electron diffraction (3DED) techniques has attracted increasing interests in the field of metal-organic frameworks (MOFs), where it is often difficult to obtain large and high-quality crystals for single-crystal X-ray diffraction. Nowadays, a 3DED dataset can be acquired in 15–250 s by applying continuous crystal rotation, and the required electron dose rate can be very low (<0.1 e s−1 Å−2). In this review, we describe the evolution of 3DED data collection techniques and how the recent development of continuous rotation electron diffraction techniques improves data quality. We further describe the structure elucidation of MOFs using 3DED techniques, showing examples of using both low- and high-resolution 3DED data. With an improved data quality, 3DED can achieve a high accuracy, and reveal more structural details of MOFs. Because the physical and chemical properties of MOFs are closely associated with their crystal structures, we believe 3DED will only increase its importance in developing MOF materials.
Diagnostic Value of Fluorescence Methods, Visual Inspection and Photographic Visual Examination in Initial Caries Lesion: A Systematic Review and Meta-Analysis
Authors: Thanh Mai Thi Giang , Van Toan Ngo , Toan Do Thi Thanh , Thang Nguyen Phu , Dong Ngoc Quang , Dung Nguyen Tien , Hang Phung Thi Thu , Anh Le Quynh , Tra Nguyen Thu , Ngoc Vo Truong Nhu
Published: March 2021

This systematic review and meta-analysis aimed to investigate the efficacy of fluorescence-based methods, visual inspections, and photographic visual examinations in initial caries detection. A literature search was undertaken in the PubMed and Cochrane databases. Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines were followed, and eligible articles published from 1 January 2009 to 30 October 2019 were included if they met the following criteria: they (1) assessed the accuracy of methods of detecting initial tooth caries lesions on occlusal, proximal, or smooth surfaces in both primary and permanent teeth (in clinical); (2) used a reference standard; (3) reported data regarding the sample size, prevalence of initial tooth caries, and accuracy of the methods. Data collection and extraction, quality assessment, and data analysis were conducted according to Cochrane standards Quality Assessment of Diagnostic Accuracy Studies-2. Statistical analyses were performed using Review Manager 5.3 and STATA 14.0. A total of 12 eligible articles were included in the meta-analysis. The results showed that the sensitivity and specificity of fluorescence-based methods were 80% and 80%, respectively; visual inspection was measured at 80% and 75%, respectively; photographic visual examination was measured at 67% and 79%, respectively. We found that the visual method and the fluorescence method were reliable for laboratory use to detect early-stage caries with equivalent accuracy.
Digital Leadership in the Economies of the G20 Countries: A Secondary Research
Authors: Cahyadi Afriyadi , Magda Róbert
Published: March 2021

Digitalization in leadership practice requires broader research. Today’s economic leaders must be in line with the global mindset in supporting a culture of innovation. The purpose of this study is to investigate the digital leadership capabilities of the G20 countries in terms of digital readiness, innovation, and competitiveness 4.0 and to determine the relationship between these variables. The global digital readiness index 2019 (Cisco 2020) was utilized to obtain data on digital readiness (X), the global innovation index (Cornell University et al. 2019) was applied for the data collection on innovation (Y1), and the global competitiveness 4.0 index (WEF 2019) was used to obtain data on competitiveness 4.0 (Y2). All data were cross-sectional for the year 2019. Digital readiness consists of basic needs, human resources, ease of doing business, business and government investment, start-up environment, technology infrastructure, and technology adoption. The components of innovation are institutions, human capital and research, infrastructure, market sophistication, business sophistication, knowledge and technology outputs, and creative outputs. Competitiveness 4.0 is about institutions, infrastructure, ICT adoption, macroeconomic stability, health, skills, product market, labor market, financial system, market size, business dynamism, and innovation capability. We found that G20 countries had the digital leadership capability in digital readiness, innovation, and competitiveness 4.0. The G20 countries were leaders in global digitalization. Some of them were consistent in digital readiness and innovation. Some were consistent in digital readiness and competitiveness 4.0, and some others were consistent in their 4.0 innovation and competitiveness 4.0. Digital readiness, innovation, and competitiveness 4.0 positively related to each other.
Improved RTT Fairness of BBR Congestion Control Algorithm Based on Adaptive Congestion Window
Authors: Pan Wansu , Tan Haibo , Li Xiru , Li Xiaofeng
Published: March 2021

To alleviate the lower performance of Transmission Control Protocol (TCP) congestion control over complex network, especially the high latency and packet loss scenario, Google proposed the Bottleneck Bandwidth and Round-trip propagation time (BBR) congestion control algorithm. In contrast with other TCP congestion control algorithms, BBR adjusted transfer data by maximizing delivery rate and minimizing delay. However, some evaluation experiments have shown that the persistent queues formation and retransmissions in the bottleneck can lead to serious fairness issues between BBR flows with different round-trip times (RTTs). They pointed out that small RTT differences cause unfairness in the throughput of BBR flows and flows with longer RTT can obtain higher bandwidth when competing with the shorter RTT flows. In order to solve this fairness problem, an adaptive congestion window of BBR is proposed, which adjusts the congestion window gain of each BBR flow in network load. The proposed algorithms alleviate the RTT fairness issue by controlling the upper limit of congestion window according to the delivery rate and queue status. In the Network Simulator 3 (NS3) simulation experiment, it shows that the adaptive congestion window of BBR (BBR-ACW) congestion control algorithm improves the fairness by more than 50% and reduces the queuing delay by 54%, compared with that of the original BBR in different buffer sizes.
Design of a Memristor-Based Digital to Analog Converter (DAC)
Authors: Fahmy Ghazal A. , Zorkany Mohamed
Published: March 2021

A memristor element has been highlighted in recent years and has been applied to several applications. In this work, a memristor-based digital to analog converter (DAC) was proposed due to the fact that a memristor has low area, low power, and a low threshold voltage. The proposed memristor DAC depends on the basic DAC cell, consisting of two memristors connected in opposite directions. This basic DAC cell was used to build and simulate both a 4 bit and an 8 bit DAC. Moreover, a sneak path issue was illustrated and its solution was provided. The proposed design reduced the area by 40%. The 8 bit memristor DAC has been designed and used in a successive approximation register analog to digital converter (SAR-ADC) instead of in a capacitor DAC (which would require a large area and consume more switching power). The SAR-ADC with a memristor-based DAC achieves a signal to noise and distortion ratio (SNDR) of 49.3 dB and a spurious free dynamic range (SFDR) of 61 dB with a power supply of 1.2 V and a consumption of 21 µW. The figure of merit (FoM) of the proposed SAR-ADC is 87.9 fj/Conv.-step. The proposed designs were simulated with optimized parameters using a voltage threshold adaptive memristor (VTEAM) model.
Implementation of an FPGA-Based Current Control and SVPWM ASIC with Asymmetric Five-Segment Switching Scheme for AC Motor Drives
Authors: Tsai Ming-Fa , Tseng Chung-Shi , Cheng Po-Jen
Published: March 2021

This paper presents the design and implementation of an application-specific integrated circuit (ASIC) for a discrete-time current control and space-vector pulse-width modulation (SVPWM) with asymmetric five-segment switching scheme for AC motor drives. As compared to a conventional three-phase symmetric seven-segment switching SVPWM scheme, the proposed method involves five-segment two-phase switching in each switching period, so the inverter switching times and power loss can be reduced by 33%. In addition, the produced PWM signal is asymmetric with respect to the center-symmetric triangular carrier wave, and the voltage command signal from the discrete-time current control output can be given in each half period of the PWM switching time interval, hence increasing the system bandwidth and allowing the motor drive system with better dynamic response. For the verification of the proposed SVPWM modulation scheme, the current control function in the stationary reference frame is also included in the design of the ASIC. The design is firstly verified by using PSIM simulation tool. Then, a DE0-nano field programmable gate array (FPGA) control board is employed to drive a 300W permanent-magnet synchronous motor (PMSM) for the experimental verification of the ASIC.
Synthesis and Transformation of Hollow Rutile Titania Wires by Single Spinneret Electrospinning with Sol-Gel Chemistry
Authors: Kang Chin-Shuo , Evans Edward
Published: March 2021

The work described below was carried out to understand how to control the morphology of nanostructured titania calcined from electrospun nanofibers. This is the first report of hollow rutile nanofibers synthesized from electrospun nanofibers with short calcination time. Titanium isopropoxide was incorporated into the nanofibers as the titania precursor. The electrospinning technique was used to fabricate ceramic/polymer hybrid nanofibers. The electrospun nanofibers were then calcined to produce rutile titania nanofibers with different morphologies (hollow or solid nanofibers), which were characterized by SEM and TEM. The initial concentration of ceramic precursor and the calcination time were shown to control the morphology of the nanofiber. The hollow morphology was only obtained with a concentration of the precursor within a certain level and with short calcination times. The heat treatment profile contributed to particle growth. At longer times, the particle growth led to the closure of the hollow core and all the nanofibers resembled strings of solid particles. A formation mechanism for the hollow nanofibers is also proposed.
A Novel Machine Learning Strategy for the Prediction of Antihypertensive Peptides Derived from Food with High Efficiency
Authors: Wang Liyang , Niu Dantong , Wang Xiaoya , Khan Jabir , Shen Qun , Xue Yong
Published: March 2021

Strategies to screen antihypertensive peptides with high throughput and rapid speed will doubtlessly contribute to the treatment of hypertension. Food-derived antihypertensive peptides can reduce blood pressure without side effects. In the present study, a novel model based on the eXtreme Gradient Boosting (XGBoost) algorithm was developed and compared with the dominating machine learning models. To further reflect on the reliability of the method in a real situation, the optimized XGBoost model was utilized to predict the antihypertensive degree of the k-mer peptides cutting from six key proteins in bovine milk, and the peptide–protein docking technology was introduced to verify the findings. The results showed that the XGBoost model achieved outstanding performance, with an accuracy of 86.50% and area under the receiver operating characteristic curve of 94.11%, which were better than the other models. Using the XGBoost model, the prediction of antihypertensive peptides derived from milk protein was consistent with the peptide–protein docking results, and was more efficient. Our results indicate that using the XGBoost algorithm as a novel auxiliary tool is feasible to screen for antihypertensive peptides derived from food, with high throughput and high efficiency.
Alternative Methods for Measuring the Susceptibility of White Wines to Pinking Alteration: Derivative Spectroscopy and CIEL*a*b* Colour Analysis
Authors: Minute Fabrizio , Giotto Federico , Filipe-Ribeiro Luís , Cosme Fernanda , Nunes Fernando M.
Published: March 2021

Pinking is the term used for describing the pink colouration that appears in white wines produced under reducing conditions when oxidised. The ability to predict the susceptibility of white wines for pinking is of utmost importance for wine producers. In this work, we critically compare the two most currently used methods for measuring pinking susceptibility and the use of the first derivative spectra and the CIEL*a*b* colour space method. The amplitude of the first derivative spectra in the 450–550 nm range has a good correlation with the values obtained by subtracting the extrapolate background at 500 nm (R2 = 0.927); therefore, first derivative spectroscopy seems to be a more straightforward approach for eliminating the background problem that occurs in this method. The CIEL*a*b* method using the a* value after oxidation seems to be the most appropriate method to measure the pinking susceptibility of white wines, showing a very good correlation with the amplitude of the first derivative spectra. The pink colouration visualisation is linearly related to the b* value of the white wine, showing that no universal cut-off value for predicting the pink visualisation should be used. Second derivative spectra allow the observation of the formation of different chromophores in wines after induced oxidation.