bluuebunny/crossref_metadata_2025 huggingface dataset:
A Conversation History-Based Q&A Cache Mechanism for Multi-Layered Chatbot Services
Authors: Makhkamova Ozoda , Kim Doohyun
Published: October 2021

Chatbot technologies have made our lives easier. To create a chatbot with high intelligence, a significant amount of knowledge processing is required. However, this can slow down the reaction time; hence, a mechanism to enable a quick response is needed. This paper proposes a cache mechanism to improve the response time of the chatbot service; while the cache in CPU utilizes the locality of references within binary code executions, our cache mechanism for chatbots uses the frequency and relevance information which potentially exists within the set of Q&A pairs. The proposed idea is to enable the broker in a multi-layered structure to analyze and store the keyword-wise relevance of the set of Q&A pairs from chatbots. In addition, the cache mechanism accumulates the frequency of the input questions by monitoring the conversation history. When a cache miss occurs, the broker selects a chatbot according to the frequency and relevance, and then delivers the query to the selected chatbot to obtain a response for answer. This mechanism showed a significant increase in the cache hit ratio as well as an improvement in the average response time.
Nucleic Acid Vaccines for COVID-19: A Paradigm Shift in the Vaccine Development Arena
Authors: Chavda Vivek , Hossain Md , Beladiya Jayesh , Apostolopoulos Vasso
Published: October 2021

Coronavirus disease, COVID-19, has touched every country globally except five countries (North Korea, Turkmenistan, Tonga, Tuvalu and Nauru). Vaccination is the most effective method to protect against infectious diseases. The objective is to ensure that everyone has access to a COVID-19 vaccine. The conventional vaccine development platforms are complex and time-consuming to obtain desired approved vaccine candidates through rigorous regulatory pathways. These safeguards guarantee that the optimized vaccine product is safe and efficacious for various demographic populations prior to it being approved for general use. Nucleic acid vaccines employ genetic material from a pathogen, such as a virus or bacteria, to induce an immune response against it. Based on the vaccination, the genetic material might be DNA or RNA; as such, it offers instructions for producing a specific pathogen protein that the immune system will perceive as foreign and mount an immune response. Nucleic acid vaccines for multiple antigens might be made in the same facility, lowering costs even more. Most traditional vaccine regimens do not allow for this. Herein, we demonstrate the recent understanding and advances in nucleic acid vaccines (DNA and mRNA based) against COVID-19, specifically those in human clinical trials.
3D Liquid Marble Microbioreactors Support In Vitro Maturation of Prepubertal Ovine Oocytes and Affect Expression of Oocyte-Specific Factors
Authors: Bebbere Daniela , Nieddu Stefano Mario , Ariu Federica , Piras Davide , Ledda Sergio
Published: October 2021

In vitro oocyte maturation (IVM) is a well-established technique. Despite the high IVM rates obtained in most mammalian species, the developmental competence of IVM oocytes is suboptimal. The aim of this work was to evaluate the potential beneficial effects of a liquid marble microbioreactor (LM) as a 3D culture system to mature in vitro prepubertal ovine oocytes, as models of oocytes with intrinsic low competence. Cumulus–oocyte complexes of prepubertal sheep ovaries were in vitro matured in a LM system with hydrophobic fumed-silica-nanoparticles (LM group) or in standard conditions (4W control group). We evaluated: (a) maturation and (b) developmental rates following in vitro fertilization (IVF) and embryo culture; (c) expression of a panel of genes. LM and 4W groups showed similar IVM and IVF rates, while in vitro development to blastocyst stage approached significance (4W: 14.1% vs. LM: 28.3%; p = 0.066). The expression of GDF9, of enzymes involved in DNA methylation reprogramming and of the subcortical maternal complex was affected by the IVM system, while no difference was observed in terms of cell-stress-response. LM microbioreactors provide a suitable microenvironment to induce prepubertal sheep oocyte IVM and should be considered to enhance the developmental competence of oocytes with reduced potential also in other species, including humans.
DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease
Authors: Flook Marisa , Escalera-Balsera Alba , Gallego-Martinez Alvaro , Espinosa-Sanchez Juan Manuel , Aran Ismael , Soto-Varela Andres , Lopez-Escamez Jose Antonio
Published: October 2021

Meniere Disease (MD) is a multifactorial disorder of the inner ear characterized by vertigo attacks associated with sensorineural hearing loss and tinnitus with a significant heritability. Although MD has been associated with several genes, no epigenetic studies have been performed on MD. Here we performed whole-genome bisulfite sequencing in 14 MD patients and six healthy controls, with the aim of identifying an MD methylation signature and potential disease mechanisms. We observed a high number of differentially methylated CpGs (DMC) when comparing MD patients to controls (n= 9545), several of them in hearing loss genes, such as PCDH15, ADGRV1 and CDH23. Bioinformatic analyses of DMCs and cis-regulatory regions predicted phenotypes related to abnormal excitatory postsynaptic currents, abnormal NMDA-mediated receptor currents and abnormal glutamate-mediated receptor currents when comparing MD to controls. Moreover, we identified various DMCs in genes previously associated with cochleovestibular phenotypes in mice. We have also found 12 undermethylated regions (UMR) that were exclusive to MD, including two UMR in an inter CpG island in the PHB gene. We suggest that the DNA methylation signature allows distinguishing between MD patients and controls. The enrichment analysis confirms previous findings of a chronic inflammatory process underlying MD.
Oral Mucositis in Cancer and Potential Use of Omega-3 Free Fatty Acids in Its Management: A Review
Authors: Lessa Roberta Cardim , Alves Fabio de Abreu , Fortunati Erika , Lu Jun
Published: October 2021

Oral mucositis (OM) is a painful condition caused by chemotherapeutic or radiotherapeutic cancer treatments, occurring in patients with different tumour characteristics and locations. OM greatly impacts a patient’s quality of life and cancer recovery. Current OM management strategies are not providing sufficient prevention and treatment; new approaches to injury management are needed. Studies on the benefit of omega-3 free fatty acids (FFA) in human health have increased significantly in recent years. FFA properties have been studied extensively, including their potential therapeutic use in inflammatory conditions. However, omega-3 FFA’s use as a supplementary treatment for OM has not been clinically tested. Preliminary evidence suggests that utilising FFA to manage OM could be a useful strategy for lesion management, assisting with healthy oral mucosa recovery. This review will describe the incidence, risk factors, biology of OM and the current treatment strategies, leading to a discussion of the utility of omega-3 FFA as a novel therapeutic agent for OM.
CCR6 Deficiency Increases Infarct Size after Murine Acute Myocardial Infarction
Authors: Schumacher David , Liehn Elisa A. , Singh Anjana , Curaj Adelina , Wijnands Erwin , Lira Sergio A. , Tacke Frank , Jankowski Joachim , Biessen Erik A.L. , van der Vorst Emiel P.C.
Published: October 2021

Ischemia-reperfusion injury after the reopening of an occluded coronary artery is a major cause of cardiac damage and inflammation after acute myocardial infarction. The chemokine axis CCL20-CCR6 is a key player in various inflammatory processes, including atherosclerosis; however, its role in ischemia-reperfusion injury has remained elusive. Therefore, to gain more insight into the role of the CCR6 in acute myocardial infarction, we have studied cardiac injury after transient ligation of the left anterior descending coronary artery followed by reperfusion in Ccr6−/− mice and their respective C57Bl/6 wild-type controls. Surprisingly, Ccr6−/− mice demonstrated significantly reduced cardiac function and increased infarct sizes after ischemia/reperfusion. This coincided with a significant increase in cardiac inflammation, characterized by an accumulation of neutrophils and inflammatory macrophage accumulation. Chimeras with a bone marrow deficiency of CCR6 mirrored this adverse Ccr6−/− phenotype, while cardiac injury was unchanged in chimeras with stromal CCR6 deficiency. This study demonstrates that CCR6-dependent (bone marrow) cells exert a protective role in myocardial infarction and subsequent ischemia-reperfusion injury, supporting the notion that augmenting CCR6-dependent immune mechanisms represents an interesting therapeutic target.
Probing Individual Particles in Aquatic Suspensions by Simultaneously Measuring Polarized Light Scattering and Fluorescence
Authors: Xiong Zhihang , Wang Hongjian , Li Jiajin , Liao Ran , Mai Haoji , Guan Caizhong , Guo Zhiming , Yang Shangpan , Chen Yan , Liu Biwang , Liu Tong , Li Hongyi , Ding Wenzheng , Zeng Yaguang , Ma Hui
Published: October 2021

Suspended particles play a significant role in aquatic systems. However, existing methods to probe suspended particles have several limitations. In this paper, we present a portable prototype to in situ probe individual particles in aquatic suspensions by simultaneously measuring polarized light scattering and fluorescence, aiming to obtain an effective classification of microplastics and microalgae. Results show that the obtained classification accuracy is significantly higher than that for either of these two methods. The setup also successfully measures submicron particles and discriminates two species of Synechococcus. Our study demonstrates the feasibility of simultaneously measuring polarized light scattering and fluorescence, and the promising capability of our method for further aquatic environmental monitoring.
The Effect of Haematocrit on Measurement of the Mid-Infrared Refractive Index of Plasma in Whole Blood
Authors: Rowe David J. , Owens Daniel R. , Parker Suzanne L. , Faust Saul N. , Wilkinson James S. , Mashanovich Goran Z.
Published: October 2021

Recent advances suggest that miniaturised mid-infrared (MIR) devices could replace more time-consuming, laboratory-based techniques for clinical diagnostics. This work uses Fourier transform infrared spectroscopy to show that the MIR complex refractive index of whole blood varies across a range of haematocrit. This indicates that the use of an evanescent measurement is not sufficient to optically exclude the cellular content of blood in the MIR, as previously assumed. Here, spectral refractive index data is presented in two ways. First, it is given as whole blood with varying haematocrit. Second, it is given as the percentage error that haematocrit introduces to plasma. The maximum error in the effective plasma refractive index due to the haematocrit of healthy adults was 0.25% for the real part n and 11% for the imaginary part k. This implies that calibration measurements of haematocrit can be used to account for errors introduced by the cellular content, enabling plasma spectra and analyte concentrations to be indirectly calculated from a whole blood sample. This methodological advance is of clinical importance as plasma concentration of analytes such as drugs can be determined using MIR without the preprocessing of whole blood.
African Gene Flow Reduces Beta-Ionone Anosmia/Hyposmia Prevalence in Admixed Malagasy Populations
Authors: Razafindrazaka Harilanto , Pereda-Loth Veronica , Ferdenzi Camille , Heiske Margit , Alva Omar , Randriamialisoa Minah , Costedoat Caroline , Signoli Michel , Talou Thierry , Courtade-Saidi Monique , Boland Anne , Deleuze Jean-François , Rouby Catherine , Radimilahy Chantal , Letellier Thierry , Bensafi Moustafa , Pierron Denis
Published: October 2021

While recent advances in genetics make it possible to follow the genetic exchanges between populations and their phenotypic consequences, the impact of the genetic exchanges on the sensory perception of populations has yet to be explored. From this perspective, the present study investigated the consequences of African gene flow on odor perception in a Malagasy population with a predominantly East Asian genetic background. To this end, we combined psychophysical tests with genotype data of 235 individuals who were asked to smell the odorant molecule beta-ionone (βI). Results showed that in this population the ancestry of the OR5A1 gene significantly influences the ability to detect βI. At the individual level, African ancestry significantly protects against specific anosmia/hyposmia due to the higher frequency of the functional gene (OR ratios = 14, CI: 1.8–110, p-value = 0.012). At the population level, African introgression decreased the prevalence of specific anosmia/hyposmia to this odorous compound. Taken together, these findings validate the conjecture that in addition to cultural exchanges, genetic transfer may also influence the sensory perception of the population in contact.
“I Feel Therefore I Decide”: Effect of Negative Emotions on Temporal Discounting and Probability Discounting
Authors: Calluso Cinzia , Devetag Maria Giovanna , Donato Carmela
Published: October 2021

Temporal and probability discounting are considered two fundamental constructs in economic science, as they are associated with phenomena with major societal impact and a variety of sub-optimal behaviors and clinical conditions. Although it is well known that positive and negative affective states bear important cognitive/behavioral consequences, the effect of emotional experiences on decision-making remains unclear due to the existence of many conflicting results. Inspired by the need to understand if and to what extent the current COVID-19 pandemic has determined changes in our decision-making processes by means of the unusual, prolonged experience of negative feelings, in this study we investigate the effect of anger, fear, sadness, physical and moral disgust on intertemporal and risky choices. Results show that all emotions significantly increase subjects’ preferences for immediate rewards over delayed ones, and for risky rewards over certain ones, in comparison to a “neutral emotion” condition, although the magnitude of the effect differs across emotions. In particular, we observed a more pronounced effect in the case of sadness and moral disgust. These findings contribute to the literature on emotions and decision-making by offering an alternative explanation to the traditional motivational appraisal theories. Specifically, we propose that the increased preference for immediate gratification and risky outcomes serves as a mechanism of self-reward aimed at down-regulating negative feelings and restore the individual’s “emotional balance”.
An Automated Lexical Stress Classification Tool for Assessing Dysprosody in Childhood Apraxia of Speech
Authors: McKechnie Jacqueline , Shahin Mostafa , Ahmed Beena , McCabe Patricia , Arciuli Joanne , Ballard Kirrie J.
Published: October 2021

Childhood apraxia of speech (CAS) commonly affects the production of lexical stress contrast in polysyllabic words. Automated classification tools have the potential to increase reliability and efficiency in measuring lexical stress. Here, factors affecting the accuracy of a custom-built deep neural network (DNN)-based classification tool are evaluated. Sixteen children with typical development (TD) and 26 with CAS produced 50 polysyllabic words. Words with strong–weak (SW, e.g., dinosaur) or WS (e.g., banana) stress were fed to the classification tool, and the accuracy measured (a) against expert judgment, (b) for speaker group, and (c) with/without prior knowledge of phonemic errors in the sample. The influence of segmental features and participant factors on tool accuracy was analysed. Linear mixed modelling showed significant interaction between group and stress type, surviving adjustment for age and CAS severity. For TD, agreement for SW and WS words was >80%, but CAS speech was higher for SW (>80%) than WS (~60%). Prior knowledge of segmental errors conferred no clear advantage. Automatic lexical stress classification shows promise for identifying errors in children’s speech at diagnosis or with treatment-related change, but accuracy for WS words in apraxic speech needs improvement. Further training of algorithms using larger sets of labelled data containing impaired speech and WS words may increase accuracy.
Pedagogical Walks through Open and Sheltered Spaces: A Post-Occupancy Evaluation of an Innovative Learning Environment
Authors: Sigurðardóttir Anna Kristín , Hjartarson Torfi , Snorrason Aðalsteinn
Published: October 2021

This paper describes a post-occupancy evaluation of a school building in Iceland that combines open and confined spaces, designed for manifold pedagogical approaches and multiple uses. The school was built for students at the primary and lower secondary school levels and serves a neighborhood still under construction in a coastal town about 40 km from Iceland’s capital area. The building will be an essential part of a larger complex, constituting the heart of its neighborhood, including a compulsory school tied into a preschool, a public library, sports facilities, and a site for local events. Our aim was to map how plans for this innovative learning environment have succeeded, as viewed by practitioners and students. Several research interviews with leaders of the building project and a method called pedagogical walk-throughs were used to collect data. Four focus groups of teachers, teaching assistants, and students were asked to review selected sections of the building. The results serve to show the strengths and weaknesses of the design, as perceived by participants, as well as commend the methodology applied. They provide insights and considerations of value for anyone involved in the design and application of educational spaces.
An Immune-Related Gene Prognostic Index for Triple-Negative Breast Cancer Integrates Multiple Aspects of Tumor-Immune Microenvironment
Authors: Wang Xiaowei , Su Wenjia , Tang Dabei , Jing Jing , Xiong Jing , Deng Yuwei , Liu Huili , Ma Wenjie , Liu Zhaoliang , Zhang Qingyuan
Published: October 2021

Tumor-immune cell compositions and immune checkpoints comprehensively affect TNBC outcomes. With the significantly improved survival rate of TNBC patients treated with ICI therapies, a biomarker integrating multiple aspects of TIME may have prognostic value for improving the efficacy of ICI therapy. Immune-related hub genes were identified with weighted gene co-expression network analysis and differential gene expression assay using The Cancer Genome Atlas TNBC data set (n = 115). IRGPI was constructed with Cox regression analysis. Immune cell compositions and TIL status were analyzed with CIBERSORT and TIDE. The discovery was validated with the Molecular Taxonomy of Breast Cancer International Consortium data set (n = 196) and a patient cohort from our hospital. Tumor expression or serum concentrations of CCL5, CCL25, or PD-L1 were determined with immunohistochemistry or ELISA. The constructed IRGPI was composed of CCL5 and CCL25 genes and was negatively associated with the patient’s survival. IRGPI also predicts the compositions of M0 and M2 macrophages, memory B cells, CD8+ T cells, activated memory CD4 T cells, and the exclusion and dysfunction of TILs, as well as PD-1 and PD-L1 expression of TNBC. IRGPI is a promising biomarker for predicting the prognosis and multiple immune characteristics of TNBC.
Synthesis of a Novel 1D/2D Bi2O2CO3–BiOI Heterostructure and Its Enhanced Photocatalytic Activity
Authors: Peng Yin , Qian Haozhi , Zhao Nannan , Li Yuan
Published: October 2021

A novel 1D/2D Bi2O2CO3–BiOI heterojunction photocatalyst with high-quality interfaces was synthesized through a hydrothermal method by using Bi2O2CO3 nanorods and KI as raw materials. Two-dimensional (2D) BiOI nanosheets uniformly and vertically grow on the 1D porous Bi2O2CO3 rods. Bi2O2CO3–BiOI heterojunctions exhibit better photocatalytic activity than pure Bi2O2CO3 nanorods and BiOI nanosheets. Cr(VI) (30 mg/L), MO (20 mg/L) and BPA (20 mg/L) can be completely degraded in 8–15 min. The superior photocatalytic performance of 1D/2D Bi2O2CO3–BiOI heterojunction is ascribed to the synergistic effects: (a) vertical 2D on 1D multidimensional structure; (b) the formation of the Bi2O2CO3–BiOI p–n heterojunction; (c) high-quality interfaces between Bi2O2CO3 and BiOI.
ER Morphology in the Pathogenesis of Hereditary Spastic Paraplegia
Authors: Sonda Sonia , Pendin Diana , Daga Andrea
Published: October 2021

The endoplasmic reticulum (ER) is the most abundant and widespread organelle in cells. Its peculiar membrane architecture, formed by an intricate network of tubules and cisternae, is critical to its multifaceted function. Regulation of ER morphology is coordinated by a few ER-specific membrane proteins and is thought to be particularly important in neurons, where organized ER membranes are found even in the most distant neurite terminals. Mutation of ER-shaping proteins has been implicated in the neurodegenerative disease hereditary spastic paraplegia (HSP). In this review we discuss the involvement of these proteins in the pathogenesis of HSP, focusing on the experimental evidence linking their molecular function to disease onset. Although the precise biochemical activity of some ER-related HSP proteins has been elucidated, the pathological mechanism underlying ER-linked HSP is still undetermined and needs to be further investigated.
Chemotherapy-Induced Hepatotoxicity in HIV Patients
Authors: Bressan Silvia , Pierantoni Alessandra , Sharifi Saman , Facchini Sergio , Quagliariello Vincenzo , Berretta Massimiliano , Montopoli Monica
Published: October 2021

Human immunodeficiency virus (HIV) affects more than 37 million people globally, and in 2020, more than 680,000 people died from HIV-related causes. Recently, these numbers have decrease substantially and continue to reduce thanks to the use of antiretroviral therapy (ART), thus making HIV a chronic disease state for those dependent on lifelong use of ART. However, patients with HIV have an increased risk of developing some type of cancer compared to patients without HIV. Therefore, treatment of patients who are diagnosed with both HIV and cancer represents a complicated scenario because of the risk associated with drug–drug interaction (DDIs) and related toxicity. Selection of an alternative chemotherapy or ART or temporarily discontinuation of ART constitute a strategy to manage the risk of DDIs. Temporarily withholding ART is the less desirable clinical plan but risks and benefits must be considered in each scenario. In this review we focus on the hepatotoxicity associated with a simultaneous treatment with ART and chemotherapeutic drugs and mechanisms behind. Moreover, we also discuss the effect on the liver caused by the association of immunotherapeutic drugs, which have recently been used in clinical trials and also in HIV patients.
Transcriptomic-Based Identification of the Immuno-Oncogenic Signature of Cholangiocarcinoma for HLC-018 Multi-Target Therapy Exploration
Authors: Lawal Bashir , Kuo Yu-Cheng , Tang Sung-Ling , Liu Feng-Cheng , Wu Alexander T. H. , Lin Hung-Yun , Huang Hsu-Shan
Published: October 2021

Cholangiocarcinomas (CHOLs), hepatobiliary malignancies, are characterized by high genetic heterogeneity, a rich tumor microenvironment, therapeutic resistance, difficulty diagnosing, and poor prognoses. Current knowledge of genetic alterations and known molecular markers for CHOL is insufficient, necessitating the need for further evaluation of the genome and RNA expression data in order to identify potential therapeutic targets, clarify the roles of these targets in the tumor microenvironment, and explore novel therapeutic drugs against the identified targets. Consequently, in our attempt to explore novel genetic markers associated with the carcinogenesis of CHOL, five genes (SNX15, ATP2A1, PDCD10, BET1, and HMGA2), collectively termed CHOL-hub genes, were identified via integration of differentially expressed genes (DEGs) from relatively large numbers of samples from CHOL GEO datasets. We further explored the biological functions of the CHOL-hub genes and found significant enrichment in several biological process and pathways associated with stem cell angiogenesis, cell proliferation, and cancer development, while the interaction network revealed high genetic interactions with a number of onco-functional genes. In addition, we established associations between the CHOL-hub genes and tumor progression, metastasis, tumor immune and immunosuppressive cell infiltration, dysfunctional T-cell phenotypes, poor prognoses, and therapeutic resistance in CHOL. Thus, we proposed that targeting CHOL-hub genes could be an ideal therapeutic approach for treating CHOLs, and we explored the potential of HLC-018, a novel benzamide-linked small molecule, using molecular docking of ligand-receptor interactions. To our delight, HLC-018 was well accommodated with high binding affinities to binding pockets of CHOL-hub genes; more importantly, we found specific interactions of HLC-018 with the conserved sequence of the AT-hook DNA-binding motif of HMGA2. Altogether, our study provides insights into the immune-oncogenic phenotypes of CHOL and provides valuable information for our ongoing experimental validation.
Single-Cell Approaches to Deconvolute the Development of HSCs
Authors: Xiang Yang , Sugimura Ryohichi
Published: October 2021

Hematopoietic stem cells (HSCs) play a core role in blood development. The ability to efficiently produce HSCs from various pluripotent stem cell sources is the Holy Grail in the hematology field. However, in vitro or in vivo HSC production remains low, which may be attributable to the lack of understanding of hematopoiesis. Here, we review the recent progress in this area and introduce advanced technologies, such as single-cell RNA-seq, spatial transcriptomics, and molecular barcoding, which may help to acquire missing information about HSC generation. We finally discuss unresolved questions, the answers to which may be conducive to HSC production, providing a promising path toward HSC-based immunotherapies.
Molecular Mechanisms of Multi-Organ Failure in COVID-19 and Potential of Stem Cell Therapy
Authors: Bhalerao Aditya , Raut Snehal , Noorani Behnam , Mancuso Salvatore , Cucullo Luca
Published: October 2021

As the number of confirmed cases and deaths occurring from Coronavirus disease 2019 (COVID-19) surges worldwide, health experts are striving hard to fully comprehend the extent of damage caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although COVID-19 primarily manifests itself in the form of severe respiratory distress, it is also known to cause systemic damage to almost all major organs and organ systems within the body. In this review, we discuss the molecular mechanisms leading to multi-organ failure seen in COVID-19 patients. We also examine the potential of stem cell therapy in treating COVID-19 multi-organ failure cases.
Recent Advances on Quinazoline Derivatives: A Potential Bioactive Scaffold in Medicinal Chemistry
Authors: Karan Ram , Agarwal Pooja , Sinha Mukty , Mahato Neelima
Published: October 2021

This paper intended to explore and discover recent therapeutic agents in the area of medicinal chemistry for the treatment of various diseases. Heterocyclic compounds represent an important group of biologically active compounds. In the last few years, heterocyclic compounds having quinazoline moiety have drawn immense attention owing to their significant biological activities. A diverse range of molecules having quinazoline moiety are reported to show a broad range of medicinal activities like antifungal, antiviral, antidiabetic, anticancer, anti-inflammatory, antibacterial, antioxidant and other activities. This study accelerates the designing process to generate a greater number of biologically active candidates.
Enantioresolution and Binding Affinity Studies on Human Serum Albumin: Recent Applications and Trends
Authors: Cardoso Tony , Almeida Ana Sofia , Remião Fernando , Fernandes Carla
Published: October 2021

The interaction between proteins and drugs or other bioactive compounds has been widely explored over the past years. Several methods for analysis of this phenomenon have been developed and improved. Nowadays, increasing attention is paid to innovative methods, such as high performance affinity liquid chromatography (HPALC) and affinity capillary electrophoresis (ACE), taking into account various advantages. Moreover, the development of separation methods for the analysis and resolution of chiral drugs has been an area of ongoing interest in analytical and medicinal chemistry research. In addition to bioaffinity binding studies, both HPALC and ACE al-low one to perform other type of analyses, namely, displacement studies and enantioseparation of racemic or enantiomeric mixtures. Actually, proteins used as chiral selectors in chromatographic and electrophoretic methods have unique enantioselective properties demonstrating suitability for the enantioseparation of a large variety of chiral drugs or other bioactive compounds. This review is mainly focused in chromatographic and electrophoretic methods using human serum albumin (HSA), the most abundant plasma protein, as chiral selector for binding affinity analysis and enantioresolution of drugs. For both analytical purposes, updated examples are presented to highlight recent applications and current trends.
Amelioration of Diabetic Nephropathy by Targeting Autophagy via Rapamycin or Fasting: Relation to Cell Apoptosis/Survival
Authors: Gouda Khaled , AbdelHamid Sherihan , Mansour Ahmed , Omar Nesreen , El-Mesallamy Hala
Published: October 2021

Autophagy has been demonstrated to have a beneficial effect on diabetic nephropathy (DN). Rapamycin, an inhibitor of mTOR, was shown to stimulate β-cell autophagy. However, its effects on preventing or ameliorating DN is unclear, and its effects are worth studying. As fasting is now an attractive protective strategy, we aim to compare its effect to rapamycin effects on pancreatic and renal cells. Twenty-eight adult male Wistar Albino rats were randomly divided into four groups, using streptozotocin (STZ) to induce diabetes mellitus (DM). Autophagy was induced by two ways; rapamycin or fasting. The extent of autophagy and apoptosis were investigated by measuring the level of LC3B and p53 proteins, respectively, in pancreatic and kidney tissues using Western blotting (WB) technique and imaging the renal cells under transmission electron microscope. The efflux transporter P-glycoprotein was quantified by WB as well. Rapamycin-induced autophagy occurred concurrently with apoptosis. On the other hand, fasting supported P-glycoprotein recovery and renal cell survival together with disabling β-cells apoptosis. In conclusion, this study provides a potential link between rapamycin or fasting for the cross-regulation of apoptosis and autophagy in the setting of cell stress as DN. Unlike rapamycin, fasting enhanced the active expression of ABCB1 efflux protein, providing insights on the potential ameliorative effects of fasting in DN that require further elucidation.
Modulation of the Physical Properties of 3D Spheroids Derived from Human Scleral Stroma Fibroblasts (HSSFs) with Different Axial Lengths Obtained from Surgical Patients
Authors: Katayama Hiroyasu , Furuhashi Masato , Umetsu Araya , Hikage Fumihito , Watanabe Megumi , Ohguro Hiroshi , Ida Yosuke
Published: October 2021

In the current study, to elucidate the pathological characteristics of myopic scleral stroma, three-dimensional (3D) cultures of human scleral stroma fibroblasts (HSSFs) with several axial lengths (AL, 22.80–30.63 mm) that were obtained from patients (n = 7) were examined. Among the three groups of ALs, <25 mm (n = 2), 25–30 mm (n = 2), and >30 mm (n = 3), the physical properties of the 3D HSSFs spheroids with respect to size and stiffness, the expressions of extracellular matrix (ECM) molecules, including collagen (COL) 1, 4, and 6 and fibronectin (FN) by qPCR and immunohistochemistry (IHC), and the mRNA expression of ECM metabolism modulators including hypoxia-inducible factor 1A (HIF 1A), HIF 2A, lysyl oxidase (LOX), tissue inhibitor of metalloproteinase (TIMP) 1–4, and matrix metalloproteinase (MMP) 2, 9, and 14 as well as several endoplasmic reticulum (ER) stress-related factors were compared. In the largest AL group (>30 mm), the 3D HSSFs spheroids were (1) significantly down-sized and less stiff compared to the other groups, and (2) significant changes were detected in the expression of some ECMs (qPCR; the up-regulation of COL1 and COL4, and the down-regulation of FN, IHC; the up-regulation of COL1 and FN, and down-regulation of COL4). The mRNA expressions of ECM modulators and ER stress-related genes were also altered with increasing AL length (up-regulation of HIF2A, MMP2, XBP1, and MMP14, down-regulation of LOX, TIMP 2 and 3, GRP78, GRP94, IRE1, and ATF6). In addition, a substantial down-regulation of some ER stress-related genes (ATF4, sXPB1 and CHOP) was observed in the 25–30 mm AL group. The findings presented herein suggest that small and stiffer 3D HSSFs spheroids in the largest AL group may accurately replicate the pathological significance of scleral thinning and weakening in myopic eyes. In addition, the modulation of several related factors among the different AL groups may also provide significant insights into our understanding of the molecular mechanisms responsible for causing myopic changes in the sclera.
Synthesis and Photonics Applications of Afzelechin Conjugated Silver Nanoparticles
Authors: Ali Shahid , Rahim Muhammad , Fazil Perveen , Ahmad Malik Shoaib , Ullah Azeem , Shah Muhammad Raza , Rukh Gul , Ateeq Muhammad , Khattak Rozina , Khan Muhammad Sufaid , Abu Ali Ola A. , Saleh Dalia I.
Published: October 2021

The silver nanoparticles were synthesized, functionalized with afzelechin and characterized using UV-Visible spectroscopy. A difference of 20 nm was observed in surface plasmon resonance of bare and functionalized silver nanoparticles which indicates afzelechin conjugation with silver nanoparticles. The atomic force microscopy (AFM) technique was used for the determination of the size and morphology of synthesized silver nanoparticles. The afzelechin conjugated silver nanoparticles were spherical and their sizes ranged from 3 to 10 nm with an average size of 8 nm while the bare silver nanoparticles were also spherical and their sizes ranged from 3 to 10 nm with an average size of 6 nm. The average sizes were also calculated by fitting their UV-Visible absorption spectra. Fitting is based on the Mie and Mie Gans models, which deduced that afzelechin conjugated silver nanoparticles were 96.5% spherical and 3.5% spheroidal with an average size of 5 nm while bare silver nanoparticles were 100% spherical with an average size of 4 nm. Both the fitting model as well as the AFM results showed a difference of 3 nm between the sizes of afzelechin conjugated silver nanoparticles while 2 nm differences was observed for bare silver nanoparticles. The band gap energy of afzelechin conjugated silver nanoparticles and bare silver nanoparticles were calculated via Tauc’s equation and were found to be 5.1 eV and 5.4 eV, respectively. A difference of 0.3 eV was observed in band gap energies of afzelechin conjugated silver nanoparticles and bare silver nanoparticles.
Influences of Curing Period and Sulfate Concentration on the Dynamic Properties and Energy Absorption Characteristics of Cement Soil
Authors: Zhang Jing-Shuang , Xia Xiang-Gang , Ren Bin
Published: October 2021

To study the influences of curing period and sulfate concentration on the dynamic mechanical properties of cement soil, this study used a split Hopkinson pressure bar device. Impact tests were conducted on cement soil specimens with different curing periods and different sulfate concentrations. The relationships between the dynamic stress–strain, dynamic compressive strength, and absorption energy of these cement soil specimens were analyzed. The test results show that with continuous loading, cement soil specimens mainly experience an elastic stage, plastic stage, and failure stage; with increasing curing period and sulfate concentration, the dynamic compressive strength and absorption energy of cement soil specimens follow a trend of first increasing and then decreasing. The dynamic compressive strength and absorption energy of cement soil specimens reached maximum values at a curing period of 14 d and a Na2SO4 solution concentration of 9.0 g/L. Increasing the dynamic compressive strength and absorption energy can effectively improve the ability of cement soil specimens to resist damage. This paper provides a practical reference for the application of cement soil in dynamic environments.
Electronic and Optical Properties of Polythiophene Molecules and Derivatives
Authors: Tsai Huai-Wen , Hsueh Kan-Lin , Chen Mei-Hsin , Hong Che-Wun
Published: October 2021

The electronic and optical properties of polythiophene (PT) for polymer light-emitting diodes (PLEDs) were calculated using density functional theory (DFT) and time-dependent DFT. We calculated the electronic and optical properties of thiophene and PT polymers with degrees of polymerization (DP) from 2 to 30 monomers (T1–T30) and their derivatives. The associated highest occupied molecular orbital (HOMO) energy, lowest unoccupied molecular orbital (LUMO) energy, band gaps, electron orbitals, and molecular structures were determined. As the DP increased, the LUMO energy gradually decreased, and the HOMO energy gradually increased. The band gap of PT approached 2 eV as the DP of the PT polymer increased from 1 to 30. The calculations and exchange–correlation functional were verified against values in the literature and experimental data from cyclic voltammetry (redox potential) and ultraviolet-visible, photoluminescence, and ultraviolet photoelectron spectra. The color of PT PLEDs can be adjusted by controlling the DP of the polymer and the substituents.
Mexican Coastal Dunes: Recipients and Donors of Alien Flora
Authors: Martínez M. Luisa , Castillo-Campos Gonzalo , García-Franco José G. , Pérez-Maqueo Octavio , Mendoza-González Gabriela , Pale-Pale J. Jesús
Published: October 2021

The invasion of natural communities by exotic plants, which may turn into invasive or potentially invasive, is one of the most severe known threats to biodiversity, and coastal dunes are among the most affected habitats. Mexico’s coastal dunes are abundant and contain high plant biodiversity but attempts to determine the occurrence and impact of exotic plants are absent. First, we explored the number of invasive plant species found on Mexican coastal dunes. Second, we analyzed if the coastal dune flora native from Mexico acts as a source of invasive species worldwide. We found the relevant spread of exotic plants towards and from Mexico, reaching high percentages: 5% of the coastal dune flora are considered exotic plants; this increases to 8.7% when only plants typical of the coastal dune environment are considered. The Mexican coastal dunes flora is also a relevant source of invasive plants affecting all continents. Furthermore, almost half of the 35 worst worldwide invasive plants (according to the Global Invasive Species Database GISD) grow on Mexican coastal dunes, most native to Mexico and invasive elsewhere. Indeed, the worldwide exchange of coastal dune flora between Mexico and the world seems massive, relevant and highlights the need for worldwide and countrywide management and control strategies.
The Prognostic Value of Serum Soluble TREM-1 on Outcome in Adult Patients with Sepsis
Authors: Kung Chia-Te , Su Chih-Min , Hsiao Sheng-Yuan , Chen Fu-Cheng , Lai Yun-Ru , Huang Chih-Cheng , Lu Cheng-Hsien
Published: October 2021

Increased soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) levels have been reported in patients with sepsis. We tested the hypotheses that serum sTREM-1 levels increase in the early phase of sepsis and decrease after sepsis under appropriate treatment and that sTREM-1 levels can predict therapeutic outcomes. One hundred and fifty-five patients prospectively underwent blood samples including biochemical data, sTREM-1, and biomarkers on endothelial dysfunction as well as clinical severity index examinations. Blood samples from Days 1, 4, and 7 after admission were checked. For comparison, 50 healthy subjects were selected as healthy control. Those patients who had sepsis had significantly higher sTREM-1 levels than those of healthy control. sTREM-1 levels positively correlated with biomarkers for endothelial dysfunction (ICAM-1, VCAM-1, and E-selectin) and lactate level as well as clinical severity index (maximum 24 h APACHE score and Sequential Organ Failure Assessment (SOFA) score) upon admission. sTREM-1 concentrations were significantly higher from Day 1 to Day 7 in the non-survivors than in the survivors. A stepwise logistic regression analysis showed only sTREM-1 level and maximum 24 h SOFA score upon admission were significantly associated with fatality. Area under the receiver operating characteristic curve analysis for the diagnostic accuracy of sTREM-1 in sepsis-related fatality gave a value of 0.726, with a cutoff value of 384.6 pg/mL (sensitivity = 80.8% and specificity = 61.5%). sTREM-1 level may be valuable in auxiliary diagnosis, and it can serve as a useful biomarker as a screening service and follow-up therapeutic outcomes in sepsis.
Ultra-Low-Power, High-Accuracy 434 MHz Indoor Positioning System for Smart Homes Leveraging Machine Learning Models
Authors: Nawaz Haq , Tahir Ahsen , Ahmed Nauman , Fayyaz Ubaid U. , Mahmood Tayyeb , Jaleel Abdul , Gogate Mandar , Dashtipour Kia , Masud Usman , Abbasi Qammer
Published: October 2021

Global navigation satellite systems have been used for reliable location-based services in outdoor environments. However, satellite-based systems are not suitable for indoor positioning due to low signal power inside buildings and low accuracy of 5 m. Future smart homes demand low-cost, high-accuracy and low-power indoor positioning systems that can provide accuracy of less than 5 m and enable battery operation for mobility and long-term use. We propose and implement an intelligent, highly accurate and low-power indoor positioning system for smart homes leveraging Gaussian Process Regression (GPR) model using information-theoretic gain based on reduction in differential entropy. The system is based on Time Difference of Arrival (TDOA) and uses ultra-low-power radio transceivers working at 434 MHz. The system has been deployed and tested using indoor measurements for two-dimensional (2D) positioning. In addition, the proposed system provides dual functionality with the same wireless links used for receiving telemetry data, with configurable data rates of up to 600 Kbauds. The implemented system integrates the time difference pulses obtained from the differential circuitry to determine the radio frequency (RF) transmitter node positions. The implemented system provides a high positioning accuracy of 0.68 m and 1.08 m for outdoor and indoor localization, respectively, when using GPR machine learning models, and provides telemetry data reception of 250 Kbauds. The system enables low-power battery operation with consumption of <200 mW power with ultra-low-power CC1101 radio transceivers and additional circuits with a differential amplifier. The proposed system provides low-cost, low-power and high-accuracy indoor localization and is an essential element of public well-being in future smart homes.
A Manifold Learning Perspective on Representation Learning: Learning Decoder and Representations without an Encoder
Authors: Schuster Viktoria , Krogh Anders
Published: October 2021

Autoencoders are commonly used in representation learning. They consist of an encoder and a decoder, which provide a straightforward method to map n-dimensional data in input space to a lower m-dimensional representation space and back. The decoder itself defines an m-dimensional manifold in input space. Inspired by manifold learning, we showed that the decoder can be trained on its own by learning the representations of the training samples along with the decoder weights using gradient descent. A sum-of-squares loss then corresponds to optimizing the manifold to have the smallest Euclidean distance to the training samples, and similarly for other loss functions. We derived expressions for the number of samples needed to specify the encoder and decoder and showed that the decoder generally requires much fewer training samples to be well-specified compared to the encoder. We discuss the training of autoencoders in this perspective and relate it to previous work in the field that uses noisy training examples and other types of regularization. On the natural image data sets MNIST and CIFAR10, we demonstrated that the decoder is much better suited to learn a low-dimensional representation, especially when trained on small data sets. Using simulated gene regulatory data, we further showed that the decoder alone leads to better generalization and meaningful representations. Our approach of training the decoder alone facilitates representation learning even on small data sets and can lead to improved training of autoencoders. We hope that the simple analyses presented will also contribute to an improved conceptual understanding of representation learning.
Green System Development in the Medinas of Tunis and Marrakesh—Green Heritage and Urban Livability
Authors: Ben Salem Sarah , Lahmar Chaima , Simon Marianna , Szilágyi Kinga
Published: October 2021

Due to their authentic urban and architectural character, the Medinas of Tunis and Marrakesh became listed among the United Nations educational, scientific, and cultural organization (UNESCO) heritage sites in 1979 and 1985, respectively. Nowadays, the urbanization of the surrounding green areas and the climate change impacts on cities are degrading the Medinas’ livability and their characteristic heritage. On the other hand, scientific knowledge and data about the green system in the dense urban cores of Medinas in the Maghreb region is still not a widely apprehended theme in the scientific domain. This research objective is to initiate nature-based and sustainable solutions in these cities by demonstrating the application of the urban green infrastructure (UGI) approach. As a research methodology, an analysis of the historical green system development in the Medinas is given to highlight their tangible and intangible values. The analysis goes over three periods: first, the medieval Islamic era, then the modern period during the French colony, and the contemporary city as a unique urban landscape. Finally, the study proposes a design guideline to prove the applicability of the UGI in the given historical morphologies by implementing the retained historical values of the historic green heritage in Medinas and the aspects of the site.