bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical Activity and Anxiety of Chinese University Students: Mediation of Self-System
Authors: Kayani Sumaira , Kiyani Tayyaba , Kayani Saima , Morris Tony , Biasutti Michele , Wang Jin
Published: April 2021

The present study examined the role of self-enhancement and self-criticism in the relationship between physical activity and anxiety. A total of 305 students from Chinese universities, ranging in age from 18 to 36, completed a questionnaire package comprising a physical activity questionnaire, a self-enhancement strategies scale, a level of self-criticism scale, and a short form of state and trait anxiety scale. Findings highlighted that physical activity had a significant negative correlation with anxiety (r = −0.31, p < 0.01), a significant positive association with self-enhancement (r = 0.43, p < 0.01), and a significant negative relationship with self-criticism (r = −0.14, p < 0.05). It was also found that anxiety was significantly predicted by self-enhancement (−0.21, p < 0.01) and self-criticism (0.44, p < 0.01). Moreover, the mediation model supports the mediation of self-enhancement and self-criticism between physical activity and anxiety in university students. The findings suggest that interventions aimed at promoting physical activity and enhancing the self-system should be worthy strategies for reducing students’ anxiety.
Exploring the Role of IL-36 Cytokines as a New Target in Psoriatic Disease
Authors: Iznardo Helena , Puig Lluís
Published: April 2021

Unmet needs in the treatment of psoriasis call for novel therapeutic strategies. Pustular psoriasis and psoriatic arthritis often represent a therapeutic challenge. Focus on IL-36 cytokines offers an interesting approach, as the IL-36 axis has been appointed a critical driver of the autoinflammatory responses involved in pustular psoriasis. Two IL-36R blocking antibodies, imsidolimab and spesolimab, are currently undergoing phase II and III clinical trials, with promising results.
Mitochondrial Bioenergetic, Photobiomodulation and Trigeminal Branches Nerve Damage, What’s the Connection? A Review
Authors: Ravera Silvia , Colombo Esteban , Pasquale Claudio , Benedicenti Stefano , Solimei Luca , Signore Antonio , Amaroli Andrea
Published: April 2021

Background: Injury of the trigeminal nerve in oral and maxillofacial surgery can occur. Schwann cell mitochondria are regulators in the development, maintenance and regeneration of peripheral nerve axons. Evidence shows that after the nerve injury, mitochondrial bioenergetic dysfunction occurs and is associated with pain, neuropathy and nerve regeneration deficit. A challenge for research is to individuate new therapies able to normalise mitochondrial and energetic metabolism to aid nerve recovery after damage. Photobiomodulation therapy can be an interesting candidate, because it is a technique involving cell manipulation through the photonic energy of a non-ionising light source (visible and NIR light), which produces a nonthermal therapeutic effect on the stressed tissue. Methods: The review was based on the following questions: (1) Can photo-biomodulation by red and NIR light affect mitochondrial bioenergetics? (2) Can photobiomodulation support damage to the trigeminal nerve branches? (preclinical and clinical studies), and, if yes, (3) What is the best photobiomodulatory therapy for the recovery of the trigeminal nerve branches? The papers were searched using the PubMed, Scopus and Cochrane databases. This review followed the ARRIVE-2.0, PRISMA and Cochrane RoB-2 guidelines. Results and conclusions: The reliability of photobiomodulatory event strongly bases on biological and physical-chemical evidence. Its principal player is the mitochondrion, whether its cytochromes are directly involved as a photoacceptor or indirectly through a vibrational and energetic variation of bound water: water as the photoacceptor. The 808-nm and 100 J/cm2 (0.07 W; 2.5 W/cm2; pulsed 50 Hz; 27 J per point; 80 s) on rats and 800-nm and 0.2 W/cm2 (0.2 W; 12 J/cm2; 12 J per point; 60 s, CW) on humans resulted as trustworthy therapies, which could be supported by extensive studies.
Chrysin Inhibits TNFα-Induced TSLP Expression through Downregulation of EGR1 Expression in Keratinocytes
Authors: Yeo Hyunjin , Lee Young Han , Ahn Sung Shin , Jung Euitaek , Lim Yoongho , Shin Soon Young
Published: April 2021

Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that acts as a critical mediator in the pathogenesis of atopic dermatitis (AD). Various therapeutic agents that prevent TSLP function can efficiently relieve the clinical symptoms of AD. However, the downregulation of TSLP expression by therapeutic agents remains poorly understood. In this study, we investigated the mode of action of chrysin in TSLP suppression in an AD-like inflammatory environment. We observed that the transcription factor early growth response (EGR1) contributed to the tumor necrosis factor alpha (TNFα)-induced transcription of TSLP. Chrysin attenuated TNFα-induced TSLP expression by downregulating EGR1 expression in HaCaT keratinocytes. We also showed that the oral administration of chrysin improved AD-like skin lesions in the ear and neck of BALB/c mice challenged with 2,4-dinitrochlorobenzene. We also showed that chrysin suppressed the expression of EGR1 and TSLP by inhibiting the extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2 mitogen-activated protein kinase pathways. Collectively, the findings of this study suggest that chrysin improves AD-like skin lesions, at least in part, through the downregulation of the ERK1/2 or JNK1/2-EGR1-TSLP signaling axis in keratinocytes.
A Cell-Based Approach to Dental Pulp Regeneration Using Mesenchymal Stem Cells: A Scoping Review
Authors: Kim Sahng G.
Published: April 2021

Despite the recent explosion of investigations on dental pulp regeneration using various tissue engineering strategies, the translation of the findings from such studies into therapeutic applications has not been properly achieved. The purpose of this scoping review was to systematically review the efficacy of mesenchymal stem cell transplantation for dental pulp regeneration. A literature search was conducted using five electronic databases from their inception to January 2021 and supplemented by hand searches. A total of 17 studies, including two clinical trials and 15 animal studies using orthotopic pulp regeneration models, were included for the review. The risk of bias for the individual studies was assessed. This scoping review demonstrated that the regeneration of vascularized pulp-like tissue was achieved using the stem cell transplantation strategy in animal models. Autologous cell transplantation in two clinical studies also successfully regenerated vascularized vital tissue. Dental pulp stem cell subpopulations, such as mobilized dental pulp stem cells, injectable scaffolds such as atelocollagen, and a granulocyte-colony forming factor, were the most commonly used for pulp regeneration. The overall risk of bias was unclear for animal studies and was moderate or judged to raise some concerns for clinical studies. More high-quality clinical studies are needed to further determine the safety and efficacy of the stem cell transplantation strategy for dental pulp regeneration.
Fibrinolytic System and Cancer: Diagnostic and Therapeutic Applications
Authors: Mahmood Niaz , Rabbani Shafaat A.
Published: April 2021

Fibrinolysis is a crucial physiological process that helps to maintain a hemostatic balance by counteracting excessive thrombosis. The components of the fibrinolytic system are well established and are associated with a wide array of physiological and pathophysiological processes. The aberrant expression of several components, especially urokinase-type plasminogen activator (uPA), its cognate receptor uPAR, and plasminogen activator inhibitor-1 (PAI-1), has shown a direct correlation with increased tumor growth, invasiveness, and metastasis. As a result, targeting the fibrinolytic system has been of great interest in the field of cancer biology. Even though there is a plethora of encouraging preclinical evidence on the potential therapeutic benefits of targeting the key oncogenic components of the fibrinolytic system, none of them made it from “bench to bedside” due to a limited number of clinical trials on them. This review summarizes our existing understanding of the various diagnostic and therapeutic strategies targeting the fibrinolytic system during cancer.
Micro-Current Stimulation Has Potential Effects of Hair Growth-Promotion on Human Hair Follicle-Derived Papilla Cells and Animal Model
Authors: Hwang Donghyun , Lee Hana , Lee Jinho , Lee Minjoo , Cho Seungkwan , Kim Tackjoong , Kim Hansung
Published: April 2021

Recently, a variety of safe and effective non-pharmacological methods have been introduced as new treatments of alopecia. Micro-current electrical stimulation (MCS) is one of them. It is generally known to facilitate cell proliferation and differentiation and promote cell migration and ATP synthesis. This study aimed to investigate the hair growth-promoting effect of MCS on human hair follicle-derived papilla cells (HFDPC) and a telogenic mice model. We examined changes in cell proliferation, migration, and cell cycle progression with MCS-applied HFDPC. The changes of expression of the cell cycle regulatory proteins, molecules related to the PI3K/AKT/mTOR/Fox01 pathway and Wnt/β-catenin pathway were also examined by immunoblotting. Subsequently, we evaluated the various growth factors in developing hair follicles by RT-PCR in MCS-applied (MCS) mice model. From the results, the MCS-applied groups with specific levels showed effects on HFDPC proliferation and migration and promoted cell cycle progression and the expression of cell cycle-related proteins. Moreover, these levels significantly activated the Wnt/β-catenin pathway and PI3K/AKT/mTOR/Fox01 pathway. Various growth factors in developing hair follicles, including Wnts, FGFs, IGF-1, and VEGF-B except for VEGF-A, significantly increased in MCS-applied mice. Our results may confirm that MCS has hair growth-promoting effect on HFDPC as well as telogenic mice model, suggesting a potential treatment strategy for alopecia.
Common Principles and Specific Mechanisms of Mitophagy from Yeast to Humans
Authors: Kumar Rajesh , Reichert Andreas S.
Published: April 2021

Mitochondria are double membrane-bound organelles in eukaryotic cells essential to a variety of cellular functions including energy conversion and ATP production, iron-sulfur biogenesis, lipid and amino acid metabolism, and regulating apoptosis and stress responses. Mitochondrial dysfunction is mechanistically linked to several neurodegenerative diseases, cancer, and ageing. Excessive and dysfunctional/damaged mitochondria are degraded by selective autophagic pathways known as mitophagy. Both budding yeast and mammals use the well-conserved machinery of core autophagy-related genes (ATGs) to execute and regulate mitophagy. In mammalian cells, the PINK1-PARKIN mitophagy pathway is a well-studied pathway that senses dysfunctional mitochondria and marks them for degradation in the lysosome. PINK1-PARKIN mediated mitophagy relies on ubiquitin-binding mitophagy adaptors that are non-ATG proteins. Loss-of-function mutations in PINK1 and PARKIN are linked to Parkinson´s disease (PD) in humans, and defective mitophagy is proposed to be a main pathomechanism. Despite the common view that yeast cells lack PINK1- and PARKIN-homologs and that mitophagy in yeast is solely regulated by receptor-mediated mitophagy, some studies suggest that a ubiquitination-dependent mitophagy pathway also exists. Here, we will discuss shared mechanisms between mammals and yeast, how mitophagy in the latter is regulated in a ubiquitin-dependent and -independent manner, and why these pathways are essential for yeast cell survival and fitness under various physiological stress conditions.
Seminal Plasma: Relevant for Fertility?
Authors: Rodriguez-Martinez Heriberto , Martinez Emilio A. , Calvete Juan J. , Peña Vega Fernando J. , Roca Jordi
Published: April 2021

Seminal plasma (SP), the non-cellular component of semen, is a heterogeneous composite fluid built by secretions of the testis, the epididymis and the accessory sexual glands. Its composition, despite species-specific anatomical peculiarities, consistently contains inorganic ions, specific hormones, proteins and peptides, including cytokines and enzymes, cholesterol, DNA and RNA—the latter often protected within epididymis- or prostate-derived extracellular vesicles. It is beyond question that the SP participates in diverse aspects of sperm function pre-fertilization events. The SP also interacts with the various compartments of the tubular genital tract, triggering changes in gene function that prepares for an eventual successful pregnancy; thus, it ultimately modulates fertility. Despite these concepts, it is imperative to remember that SP-free spermatozoa (epididymal or washed ejaculated) are still fertile, so this review shall focus on the differences between the in vivo roles of the SP following semen deposition in the female and those regarding additions of SP on spermatozoa handled for artificial reproduction, including cryopreservation, from artificial insemination to in vitro fertilization. This review attempts, including our own results on model animal species, to critically summarize the current knowledge of the reproductive roles played by SP components, particularly in our own species, which is increasingly affected by infertility. The ultimate goal is to reconcile the delicate balance between the SP molecular concentration and their concerted effects after temporal exposure in vivo. We aim to appraise the functions of the SP components, their relevance as diagnostic biomarkers and their value as eventual additives to refine reproductive strategies, including biotechnologies, in livestock models and humans.
Tezepelumab: A Potential New Biological Therapy for Severe Refractory Asthma
Authors: Pelaia Corrado , Pelaia Giulia , Crimi Claudia , Maglio Angelantonio , Gallelli Luca , Terracciano Rosa , Vatrella Alessandro
Published: April 2021

Thymic stromal lymphopoietin (TSLP) is an innate cytokine, belonging to the group of alarmins, which plays a key pathogenic role in asthma by acting as an upstream activator of cellular and molecular pathways leading to type 2 (T2-high) airway inflammation. Released from airway epithelial cells upon tissue damage induced by several noxious agents including allergens, viruses, bacteria, and airborne pollutants, TSLP activates dendritic cells and group 2 innate lymphoid cells involved in the pathobiology of T2-high asthma. Tezepelumab is a fully human monoclonal antibody that binds to TSLP, thereby preventing its interaction with the TSLP receptor complex. Preliminary results of randomized clinical trials suggest that tezepelumab is characterized by a good safety and efficacy profile in patients with severe, uncontrolled asthma.
Connectivity Map Analysis of a Single-Cell RNA-Sequencing -Derived Transcriptional Signature of mTOR Signaling
Authors: Al Mahi Naim , Zhang Erik Y. , Sherman Susan , Yu Jane J. , Medvedovic Mario
Published: April 2021

In the connectivity map (CMap) approach to drug repositioning and development, transcriptional signature of disease is constructed by differential gene expression analysis between the diseased tissue or cells and the control. The negative correlation between the transcriptional disease signature and the transcriptional signature of the drug, or a bioactive compound, is assumed to indicate its ability to “reverse” the disease process. A major limitation of traditional CMaP analysis is the use of signatures derived from bulk disease tissues. Since the key driver pathways are most likely dysregulated in only a subset of cells, the “averaged” transcriptional signatures resulting from bulk analysis lack the resolution to effectively identify effective therapeutic agents. The use of single-cell RNA-seq (scRNA-seq) transcriptomic assay facilitates construction of disease signatures that are specific to individual cell types, but methods for using scRNA-seq data in the context of CMaP analysis are lacking. Lymphangioleiomyomatosis (LAM) mutations in TSC1 or TSC2 genes result in the activation of the mTOR complex 1 (mTORC1). The mTORC1 inhibitor Sirolimus is the only FDA-approved drug to treat LAM. Novel therapies for LAM are urgently needed as the disease recurs with discontinuation of the treatment and some patients are insensitive to the drug. We developed methods for constructing disease transcriptional signatures and CMaP analysis using scRNA-seq profiling and applied them in the analysis of scRNA-seq data of lung tissue from naïve and sirolimus-treated LAM patients. New methods successfully implicated mTORC1 inhibitors, including Sirolimus, as capable of reverting the LAM transcriptional signatures. The CMaP analysis mimicking standard bulk-tissue approach failed to detect any connection between the LAM signature and mTORC1 signaling. This indicates that the precise signature derived from scRNA-seq data using our methods is the crucial difference between the success and the failure to identify effective therapeutic treatments in CMaP analysis.
Single Cell Gene Expression Analysis in a 3D Microtissue Liver Model Reveals Cell Type-Specific Responses to Pro-Fibrotic TGF-β1 Stimulation
Authors: Messner Catherine Jane , Babrak Lmar , Titolo Gaia , Caj Michaela , Miho Enkelejda , Suter-Dick Laura
Published: April 2021

3D cell culture systems are widely used to study disease mechanisms and therapeutic interventions. Multicellular liver microtissues (MTs) comprising HepaRG, hTERT-HSC and THP-1 maintain multicellular interactions and physiological properties required to mimic liver fibrosis. However, the inherent complexity of multicellular 3D-systems often hinders the discrimination of cell type specific responses. Here, we aimed at applying single cell sequencing (scRNA-seq) to discern the molecular responses of cells involved in the development of fibrosis elicited by TGF-β1. To obtain single cell suspensions from the MTs, an enzymatic dissociation method was optimized. Isolated cells showed good viability, could be re-plated and cultured in 2D, and expressed specific markers determined by scRNA-seq, qRT-PCR, ELISA and immunostaining. The three cell populations were successfully clustered using supervised and unsupervised methods based on scRNA-seq data. TGF-β1 led to a fibrotic phenotype in the MTs, detected as decreased albumin and increased αSMA expression. Cell-type specific responses to the treatment were identified for each of the three cell types. They included HepaRG damage characterized by a decrease in cellular metabolism, prototypical inflammatory responses in THP-1s and extracellular matrix remodeling in hTERT-HSCs. Furthermore, we identified novel cell-specific putative fibrosis markers in hTERT-HSC (COL15A1), and THP-1 (ALOX5AP and LAPTM5).
A Breach in Plant Defences: Pseudomonas syringae pv. actinidiae Targets Ethylene Signalling to Overcome Actinidia chinensis Pathogen Responses
Authors: Cellini Antonio , Donati Irene , Farneti Brian , Khomenko Iuliia , Buriani Giampaolo , Biasioli Franco , Cristescu Simona M. , Spinelli Francesco
Published: April 2021

Ethylene interacts with other plant hormones to modulate many aspects of plant metabolism, including defence and stomata regulation. Therefore, its manipulation may allow plant pathogens to overcome the host’s immune responses. This work investigates the role of ethylene as a virulence factor for Pseudomonas syringae pv. actinidiae (Psa), the aetiological agent of the bacterial canker of kiwifruit. The pandemic, highly virulent biovar of this pathogen produces ethylene, whereas the biovars isolated in Japan and Korea do not. Ethylene production is modulated in planta by light/dark cycle. Exogenous ethylene application stimulates bacterial virulence, and restricts or increases host colonisation if performed before or after inoculation, respectively. The deletion of a gene, unrelated to known bacterial biosynthetic pathways and putatively encoding for an oxidoreductase, abolishes ethylene production and reduces the pathogen growth rate in planta. Ethylene production by Psa may be a recently and independently evolved virulence trait in the arms race against the host. Plant- and pathogen-derived ethylene may concur in the activation/suppression of immune responses, in the chemotaxis toward a suitable entry point, or in the endophytic colonisation.
Celecoxib as a Valuable Adjuvant in Cutaneous Melanoma Treated with Trametinib
Authors: Tudor Diana Valentina , Bâldea Ioana , Olteanu Diana Elena , Fischer-Fodor Eva , Piroska Virag , Lupu Mihai , Călinici Tudor , Decea Roxana Maria , Filip Gabriela Adriana
Published: April 2021

Background: Melanoma patients stop responding to targeted therapies mainly due to mitogen activated protein kinase (MAPK) pathway re-activation, phosphoinositide 3 kinase/the mechanistic target of rapamycin (PI3K/mTOR) pathway activation or stromal cell influence. The future of melanoma treatment lies in combinational approaches. To address this, our in vitro study evaluated if lower concentrations of Celecoxib (IC50 in nM range) could still preserve the chemopreventive effect on melanoma cells treated with trametinib. Materials and Methods: All experiments were conducted on SK-MEL-28 human melanoma cells and BJ human fibroblasts, used as co-culture. Co-culture cells were subjected to a celecoxib and trametinib drug combination for 72 h. We focused on the evaluation of cell death mechanisms, melanogenesis, angiogenesis, inflammation and resistance pathways. Results: Low-dose celecoxib significantly enhanced the melanoma response to trametinib. The therapeutic combination reduced nuclear transcription factor (NF)–kB (p < 0.0001) and caspase-8/caspase-3 activation (p < 0.0001), inhibited microphthalmia transcription factor (MITF) and tyrosinase (p < 0.05) expression and strongly down-regulated the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway more significantly than the control or trametinib group (p < 0.0001). Conclusion: Low concentrations of celecoxib (IC50 in nM range) sufficed to exert antineoplastic capabilities and enhanced the therapeutic response of metastatic melanoma treated with trametinib.
Links between Immune Cells from the Periphery and the Brain in the Pathogenesis of Epilepsy: A Narrative Review
Authors: Yamanaka Gaku , Morichi Shinichiro , Takamatsu Tomoko , Watanabe Yusuke , Suzuki Shinji , Ishida Yu , Oana Shingo , Yamazaki Takashi , Takata Fuyuko , Kawashima Hisashi
Published: April 2021

Accumulating evidence has demonstrated that the pathogenesis of epilepsy is linked to neuroinflammation and cerebrovascular dysfunction. Peripheral immune cell invasion into the brain, along with these responses, is implicitly involved in epilepsy. This review explored the current literature on the association between the peripheral and central nervous systems in the pathogenesis of epilepsy, and highlights novel research directions for therapeutic interventions targeting these reactions. Previous experimental and human studies have demonstrated the activation of the innate and adaptive immune responses in the brain. The time required for monocytes (responsible for innate immunity) and T cells (involved in acquired immunity) to invade the central nervous system after a seizure varies. Moreover, the time between the leakage associated with blood–brain barrier (BBB) failure and the infiltration of these cells varies. This suggests that cell infiltration is not merely a secondary disruptive event associated with BBB failure, but also a non-disruptive event facilitated by various mediators produced by the neurovascular unit consisting of neurons, perivascular astrocytes, microglia, pericytes, and endothelial cells. Moreover, genetic manipulation has enabled the differentiation between peripheral monocytes and resident microglia, which was previously considered difficult. Thus, the evidence suggests that peripheral monocytes may contribute to the pathogenesis of seizures.
Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells
Authors: Racki Valentino , Marcelic Marina , Stimac Igor , Petric Daniela , Kucic Natalia
Published: April 2021

Microglial cells are resident macrophages in the brain that have been implicated in the pathophysiology of schizophrenia. There is a lack of studies covering the effects of antipsychotics on microglial cells. The current literature points to a possible anti-inflammatory action without clear mechanisms of action. The aim of this study is to characterize the effects of haloperidol, risperidone and aripiprazole on BV-2 microglial cells in in vitro conditions. We have used immunofluorescence and flow cytometry to analyze the classical pro and anti-inflammatory markers, while a real-time metabolic assay (Seahorse) was used to assess metabolic function. We analyzed the expression of p70S6K to evaluate the mTOR pathway activity with Western blot. In this study, we demonstrate the varying effects of haloperidol, risperidone and aripiprazole administration in BV-2 microglial cells. All three tested antipsychotics were successful in reducing the pro-inflammatory action of microglial cells, although only aripiprazole increased the expression of anti-inflammatory markers. Most significant differences in the possible mechanisms of action were seen in the real-time metabolic assays and in the mTORC1 signaling pathway activity, with aripiprazole being the only antipsychotic to reduce the mTORC1 activity. Our results shed some new light on the effects of haloperidol, risperidone and aripiprazole action in microglial cells, and reveal a novel possible mechanism of action for aripiprazole.
Differential Throttling and Fluidic Thrust Vectoring in a Linear Aerospike
Authors: Ferlauto Michele , Ferrero Andrea , Marsicovetere Matteo , Marsilio Roberto
Published: April 2021

Aerospike nozzles represent an interesting solution for Single-Stage-To-Orbit or clustered launchers owing to their self-adapting capability, which can lead to better performance compared to classical nozzles. Furthermore, they can provide thrust vectoring in several ways. A simple solution consists of applying differential throttling when multiple combustion chambers are used. An alternative solution is represented by fluidic thrust vectoring, which requires the injection of a secondary flow from a slot. In this work, the flow field in a linear aerospike nozzle was investigated numerically and both differential throttling and fluidic thrust vectoring were studied. The flow field was predicted by solving the Reynolds-averaged Navier–Stokes equations. The thrust vectoring performance was evaluated in terms of side force generation and axial force reduction. The effectiveness of fluidic thrust vectoring was investigated by changing the mass flow rate of secondary flow and injection location. The results show that the response of the system can be non-monotone with respect to the mass flow rate of the secondary injection. In contrast, differential throttling provides a linear behaviour but it can only be applied to configurations with multiple combustion chambers. Finally, the effects of different plug truncation levels are discussed.
Machine-Learning-Based User Position Prediction and Behavior Analysis for Location Services
Authors: Jiang Haiyang , He Mingshu , Xi Yuanyuan , Zeng Jianqiu
Published: April 2021

Machine learning (ML)-based methods are increasingly used in different fields of business to improve the quality and efficiency of services. The increasing amount of data and the development of artificial intelligence algorithms have improved the services provided to customers in shopping malls. Most new services are based on customers’ precise positioning in shopping malls, especially customer positioning within shops. We propose a novel method to accurately predict the specific shops in which customers are located in shopping malls. We use global positioning system (GPS) information provided by customers’ mobile terminals and WiFi information that completely covers the shopping mall. According to the prediction results, we learn some of the behavior preferences of users. We use these predicted customer locations to provide customers with more accurate services. Our training dataset is built using feature extraction and screening from some real customers’ transaction records in shopping malls. In order to prove the validity of the model, we also cross-check our algorithm with a variety of machine learning algorithms. Our method achieves the best speed–accuracy trade-off and can accurately locate the shops in which customers are located in shopping malls in real time. Compared to other algorithms, the proposed model is more accurate. User preference behaviors can be used in applications to efficiently provide more tailored services.
Assessing the Intrinsic Strengths of Ion–Solvent and Solvent–Solvent Interactions for Hydrated Mg2+ Clusters
Authors: Delgado Alexis Antoinette Ann , Sethio Daniel , Kraka Elfi
Published: April 2021

Information resulting from a comprehensive investigation into the intrinsic strengths of hydrated divalent magnesium clusters is useful for elucidating the role of aqueous solvents on the Mg2+ ion, which can be related to those in bulk aqueous solution. However, the intrinsic Mg–O and intermolecular hydrogen bond interactions of hydrated magnesium ion clusters have yet to be quantitatively measured. In this work, we investigated a set of 17 hydrated divalent magnesium clusters by means of local vibrational mode force constants calculated at the ωB97X-D/6-311++G(d,p) level of theory, where the nature of the ion–solvent and solvent–solvent interactions were interpreted from topological electron density analysis and natural population analysis. We found the intrinsic strength of inner shell Mg–O interactions for [Mg(H2O)n]2+ (n = 1–6) clusters to relate to the electron density at the bond critical point in Mg–O bonds. From the application of a secondary hydration shell to [Mg(H2O)n]2+ (n = 5–6) clusters, stronger Mg–O interactions were observed to correspond to larger instances of charge transfer between the lp(O) orbitals of the inner hydration shell and the unfilled valence shell of Mg. As the charge transfer between water molecules of the first and second solvent shell increased, so did the strength of their intermolecular hydrogen bonds (HBs). Cumulative local vibrational mode force constants of explicitly solvated Mg2+, having an outer hydration shell, reveal a CN of 5, rather than a CN of 6, to yield slightly more stable configurations in some instances. However, the cumulative local mode stretching force constants of implicitly solvated Mg2+ show the six-coordinated cluster to be the most stable. These results show that such intrinsic bond strength measures for Mg–O and HBs offer an effective way for determining the coordination number of hydrated magnesium ion clusters.
Insect Cultural Services: How Insects Have Changed Our Lives and How Can We Do Better for Them
Authors: Duffus Natalie E. , Christie Craig R. , Morimoto Juliano
Published: April 2021

Societies have benefited directly and indirectly from ecosystem services provided by insects for centuries (e.g., pollination by bees and waste recycling by beetles). The relationship between people and insect ecosystem services has evolved and influenced how societies perceive and relate to nature and with each other, for example, by shaping cultural values (‘cultural ecosystem services’). Thus, better understanding the significance of insect cultural services can change societies’ motivations underpinning conservation efforts. To date, however, we still overlook the significance of many insect cultural services in shaping our societies, which in turn likely contributes to the generalised misconceptions and misrepresentations of insects in the media such as television and the internet. To address this gap, we have reviewed an identified list of insect cultural services that influence our societies on a daily basis, including cultural services related to art, recreation, and the development of traditional belief systems. This list allowed us to formulate a multi-level framework which aims to serve as a compass to guide societies to better appreciate and potentially change the perception of insect cultural services from individual to global levels. This framework can become an important tool for gaining public support for conservation interventions targeting insects and the services that they provide. More broadly, this framework highlights the importance of considering cultural ecosystems services—for which values can be difficult to quantify in traditional terms—in shaping the relationship between people and nature.
A Central Role for Ischemia and OCTA Metrics to Follow DR Progression
Authors: Cunha-Vaz José
Published: April 2021

Diabetic retinopathy (DR) is a frequent complication of diabetes and through its vision-threatening complications, i [...]
Using Out-of-Hospital Cardiac Arrest (OHCA) and Cardiac Arrest Hospital Prognosis (CAHP) Scores with Modified Objective Data to Improve Neurological Prognostic Performance for Out-of-Hospital Cardiac Arrest Survivors
Authors: Song Hogul , Park Jungsoo , You Yeonho , Ahn Hongjoon , Yoo Insool , Kim Seungwhan , Lee Jinwoong , Ryu Seung , Jeong Wonjoon , Cho Yongchul , Kang Changshin
Published: April 2021

This study aimed to determine whether accuracy and sensitivity concerning neurological prognostic performance increased for survivors of out-of-hospital cardiac arrest (OHCA) treated with targeted temperature management (TTM), using OHCA and cardiac arrest hospital prognosis (CAHP) scores and modified objective variables. We retrospectively analyzed non-traumatic OHCA survivors treated with TTM. The primary outcome was poor neurological outcome at 3 months after return of spontaneous circulation (cerebral performance category, 3–5). We compared neurological prognostic performance using existing models after adding objective data obtained before TTM from computed tomography (CT), magnetic resonance imaging (MRI), and biomarkers to replace the no-flow time component of the OHCA and CAHP models. Among 106 patients, 61 (57.5%) had poor neurologic outcomes. The area under the receiver operating characteristic (AUROC) curve for the OHCA and CAHP models was 0.89 (95% confidence interval (CI) 0.81–0.94) and 0.90 (95% CI 0.82–0.95), respectively. The prediction of poor neurological outcome improved after replacing no-flow time with a grey/white matter ratio measured using CT, high-signal intensity (HSI) on diffusion-weighted MRI (DWI), percentage of voxel using apparent diffusion coefficient value, and serum neuron-specific enolase levels. When replaced with HSI on DWI, the AUROC and sensitivity of the OHCA and CAHP models were 0.96 and 74.5% and 0.97 and 83.8%, respectively (100% specificity). Prognoses concerning neurologic outcomes improved compared with existing OHCA and CAHP models by adding new objective variables to replace no-flow time. External validation is required to generalize these results in various contexts.
Quality Assessment of Untargeted Analytical Data in a Large-Scale Metabolomic Study
Authors: Saito Rintaro , Sugimoto Masahiro , Hirayama Akiyoshi , Soga Tomoyoshi , Tomita Masaru , Takebayashi Toru
Published: April 2021

Large-scale metabolomic studies have become common, and the reliability of the peak data produced by the various instruments is an important issue. However, less attention has been paid to the large number of uncharacterized peaks in untargeted metabolomics data. In this study, we tested various criteria to assess the reliability of 276 and 202 uncharacterized peaks that were detected in a gathered set of 30 plasma and urine quality control samples, respectively, using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS). The linear relationship between the amounts of pooled samples and the corresponding peak areas was one of the criteria used to select reliable peaks. We used samples from approximately 3000 participants in the Tsuruoka Metabolome Cohort Study to investigate patterns of the areas of these uncharacterized peaks among the samples and clustered the peaks by combining the patterns and differences in the migration times. Our assessment pipeline removed substantial numbers of unreliable or redundant peaks and detected 35 and 74 reliable uncharacterized peaks in plasma and urine, respectively, some of which may correspond to metabolites involved in important physiological processes such as disease progression. We propose that our assessment pipeline can be used to help establish large-scale untargeted clinical metabolomic studies.
“Small Thyroid Gland” in Reproductive Women without Autoimmune Thyroid Disease—Ultrasonographic Evaluation as a Useful Screening Tool for Hypothyroidism
Authors: Milczarek-Banach Justyna , Miśkiewicz Piotr
Published: April 2021

Proper thyroid function is important for women of childbearing age, as hypothyroidism affects fertility, pregnancy and offspring. The upper reference limit for thyrotropin (TSH) in pregnancy was defined as <2.5 mU/L in the first trimester. Recommendations include either universal screening of TSH before pregnancy, or identifying individuals at “high risk” for thyroid illness. “Small thyroid gland” not associated with autoimmune thyroid disease (AITD) seems to be a reason for hypothyroidism and probably should be included in target case finding procedure before pregnancy. The purpose of this cross-sectional study was to analyze relationships between the thyroid volume and its function, and to determine the thyroid volume as a predictive factor for TSH levels above 2.5 µIU/mL in reproductive women without AITD. We included 151 women without AITD, and aged 18–40. Blood and urine samples were analyzed for parameters of thyroid function. Ultrasound examination of the thyroid was performed. The thyroid volume was negatively correlated with TSH. Women with a thyroid volume in the 1st quartile for the study population presented higher TSH levels versus women in the 4th quartile (p = 0.0132). A thyroid volume cut-off point of 9 mL was the predictive factor for TSH levels above 2.5 µIU/mL (p = 0.0037).
Modified Rio Score with Platform Therapy Predicts Treatment Success with Fingolimod and Natalizumab in Relapsing-Remitting Multiple Sclerosis Patients
Authors: Jamroz-Wiśniewska Anna , Zajdel Radosław , Słowik Agnieszka , Marona Monika , Wnuk Marcin , Adamczyk-Sowa Monika , Adamczyk Bożena , Lasek-Bal Anetta , Puz Przemysław , Stęposz Arkadiusz , Krzystanek Ewa , Patalong-Ogiewa Maja , Pokryszko-Dragan Anna , Budrewicz Sławomir , Koziarska Dorota , Karbicka Anna , Wawrzyniak Sławomir , Fryze Waldemar , Furtak-Niczyporuk Marzena , Rejdak Konrad
Published: April 2021

Background: Reliable markers of disease outcomes in multiple sclerosis (MS) would help to predict the response to treatment in patients treated with high efficacy drugs. No evidence of disease activity (NEDA) has become a treatment goal whereas the modified Rio score (MRS) predicts future suboptimal responders to treatment. The aim of our study was to identify factors that would predict poor response to treatment with natalizumab and fingolimod. Methods: In the multicenter prospective trial, 336 subjects were enrolled, initiating therapy with natalizumab (n = 135) or fingolimod (n = 201). Data on relapse rate, the expanded disability status scale, and MRI results were collected, and MRS was estimated. Results: NEDA-3 after the first year of therapy was 73.9% for natalizumab and 54.8% for fingolimod (p < 0.0001). Patients with MRS = 0 in the last year on platform therapy had the best NEDA-3 (71%) and patients with MRS = 3 had the worst NEDA-3 (41%) in the first year of treatment with the second-line therapy. Conclusion: We conclude that switching to the second-line therapy should occur earlier to enable better results for patients treated with natalizumab or fingolimod. The outcome on both drugs is better with better neurological conditions and lower MRS of the patient on the platform therapy.
Macro- and Micronutrient Cycling and Crucial Linkages to Geochemical Processes in Mangrove Ecosystems
Authors: Alongi Daniel M.
Published: April 2021

High mangrove productivity is sustained by rapid utilization, high retention efficiency and maximum storage of nutrients in leaves, roots, and soils. Rapid microbial transformations and high mineralization efficiencies in tandem with physiological mechanisms conserve scarce nutrients. Macronutrient cycling is interlinked with micronutrient cycling; all nutrient cycles are linked closely to geochemical transformation processes. Mangroves can be N-, P-, Fe-, and Cu-limited; additions of Zn and Mo stimulate early growth until levels above pristine porewater concentrations induce toxicity. Limited nutrient availability is caused by sorption and retention onto iron oxides, clays, and sulfide minerals. Little N is exported as immobilization is the largest transformation process. Mn and S affect N metabolism and photosynthesis via early diagenesis and P availability is coupled to Fe-S redox oscillations. Fe is involved in nitrification, denitrification and anammox, and Mo is involved in NO3− reduction and N2-fixation. Soil Mg, K, Mn, Zn and Ni pool sizes decrease as mangrove primary productivity increases, suggesting increasing uptake and more rapid turnover than in less productive forests. Mangroves may be major contributors to oceanic Mn and Mo cycles, delivering 7.4–12.1 Gmol Mn a−1 to the ocean, which is greater than global riverine input. The global Mo import rate by mangroves corresponds to 15–120% of Mo supply to the oceanic Mo budget.
Risk of Typical Diabetes-Associated Complications in Different Clusters of Diabetic Patients: Analysis of Nine Risk Factors
Authors: Leutner Michael , Haug Nils , Bellach Luise , Dervic Elma , Kautzky Alexander , Klimek Peter , Kautzky-Willer Alexandra
Published: April 2021

Objectives: Diabetic patients are often diagnosed with several comorbidities. The aim of the present study was to investigate the relationship between different combinations of risk factors and complications in diabetic patients. Research design and methods: We used a longitudinal, population-wide dataset of patients with hospital diagnoses and identified all patients (n = 195,575) receiving a diagnosis of diabetes in the observation period from 2003–2014. We defined nine ICD-10-codes as risk factors and 16 ICD-10 codes as complications. Using a computational algorithm, cohort patients were assigned to clusters based on the risk factors they were diagnosed with. The clusters were defined so that the patients assigned to them developed similar complications. Complication risk was quantified in terms of relative risk (RR) compared with healthy control patients. Results: We identified five clusters associated with an increased risk of complications. A combined diagnosis of arterial hypertension (aHTN) and dyslipidemia was shared by all clusters and expressed a baseline of increased risk. Additional diagnosis of (1) smoking, (2) depression, (3) liver disease, or (4) obesity made up the other four clusters and further increased the risk of complications. Cluster 9 (aHTN, dyslipidemia and depression) represented diabetic patients at high risk of angina pectoris “AP” (RR: 7.35, CI: 6.74–8.01), kidney disease (RR: 3.18, CI: 3.04–3.32), polyneuropathy (RR: 4.80, CI: 4.23–5.45), and stroke (RR: 4.32, CI: 3.95–4.71), whereas cluster 10 (aHTN, dyslipidemia and smoking) identified patients with the highest risk of AP (RR: 10.10, CI: 9.28–10.98), atherosclerosis (RR: 4.07, CI: 3.84–4.31), and loss of extremities (RR: 4.21, CI: 1.5–11.84) compared to the controls. Conclusions: A comorbidity of aHTN and dyslipidemia was shown to be associated with diabetic complications across all risk-clusters. This effect was amplified by a combination with either depression, smoking, obesity, or non-specific liver disease.
The Quandary of DNA-Based Treatment Assessment in De Novo Metastatic Prostate Cancer in the Era of Precision Oncology
Authors: Nakken Sigve , Lilleby Wolfgang , Switlyk Marta D. , Knudsen Karen E. , Lilleby Oscar , Zhao Sen , Kaveh Fatemeh , Ekstrøm Per O. , Urbanucci Alfonso , Hovig Eivind
Published: April 2021

Guidelines for genetic testing have been established for multiple tumor types, frequently indicating the most confident molecularly targeted treatment options. However, considering the often-complex presentation of individual cancer patients, in addition to the combinatorial complexity and inherent uncertainties of molecular findings, deriving optimal treatment strategies frequently becomes very challenging. Here, we report a comprehensive analysis of a 68-year-old male with metastatic prostate cancer, encompassing pathology and MRI findings, transcriptomic results, and key genomics findings from whole-exome sequencing, both somatic aberrations and germline variants. We identify multiple somatic aberrations that are known to be enriched in prostate cancer, including a deletion of PTEN and a fusion transcript involving BRCA2. The gene expression patterns in the tumor biopsy were also strikingly similar to prostate tumor samples from TCGA. Furthermore, we detected multiple lines of evidence for homologous recombination repair deficiency (HRD), including a dominant contribution by mutational signature SBS3, which is specifically attributed to HRD. On the basis of the genomic and transcriptomic findings, and in light of the clinical case presentation, we discussed the personalized treatment options that exist for this patient and the various challenges that one faces in the process of translating high-throughput sequencing data towards treatment regimens.
MINDS: Mobile Agent Itinerary Planning Using Named Data Networking in Wireless Sensor Networks
Authors: Pourroostaei Ardakani Saeid
Published: April 2021

Mobile agents have the potential to offer benefits, as they are able to either independently or cooperatively move throughout networks and collect/aggregate sensory data samples. They are programmed to autonomously move and visit sensory data stations through optimal paths, which are established according to the application requirements. However, mobile agent routing protocols still suffer heavy computation/communication overheads, lack of route planning accuracy and long-delay mobile agent migrations. For this, mobile agent route planning protocols aim to find the best-fitted paths for completing missions (e.g., data collection) with minimised delay, maximised performance and minimised transmitted traffic. This article proposes a mobile agent route planning protocol for sensory data collection called MINDS. The key goal of this MINDS is to reduce network traffic, maximise data robustness and minimise delay at the same time. This protocol utilises the Hamming distance technique to partition a sensor network into a number of data-centric clusters. In turn, a named data networking approach is used to form the cluster-heads as a data-centric, tree-based communication infrastructure. The mobile agents utilise a modified version of the Depth-First Search algorithm to move through the tree infrastructure according to a hop-count-aware fashion. As the simulation results show, MINDS reduces path length, reduces network traffic and increases data robustness as compared with two conventional benchmarks (ZMA and TBID) in dense and large wireless sensor networks.