bluuebunny/crossref_metadata_2025 huggingface dataset:
Generating High-Granularity COVID-19 Territorial Early Alerts Using Emergency Medical Services and Machine Learning
Authors: Gianquintieri Lorenzo , Brovelli Maria Antonia , Pagliosa Andrea , Dassi Gabriele , Brambilla Piero Maria , Bonora Rodolfo , Sechi Giuseppe Maria , Caiani Enrico Gianluca
Published: July 2022

The pandemic of COVID-19 has posed unprecedented threats to healthcare systems worldwide. Great efforts were spent to fight the emergency, with the widespread use of cutting-edge technologies, especially big data analytics and AI. In this context, the present study proposes a novel combination of geographical filtering and machine learning (ML) for the development and optimization of a COVID-19 early alert system based on Emergency Medical Services (EMS) data, for the anticipated identification of outbreaks with very high granularity, up to single municipalities. The model, implemented for the region of Lombardy, Italy, showed robust performance, with an overall 80% accuracy in identifying the active spread of the disease. The further post-processing of the output was implemented to classify the territory into five risk classes, resulting in effectively anticipating the demand for interventions by EMS. This model shows state-of-art potentiality for future applications in the early detection of the burden of the impact of COVID-19, or other similar epidemics, on the healthcare system.
Exploring the Spatial Heterogeneity and Driving Factors of UAV Logistics Network: Case Study of Hangzhou, China
Authors: He Hongbo , Ye Huping , Xu Chenchen , Liao Xiaohan
Published: July 2022

Urban logistics is an important research topic in human and economic geography; unmanned aerial vehicles (UAVs) are an emerging technology that has huge potential in the field of logistics with the release of control restrictions on low-altitude airspace. The scientific identification of the spatial pattern and impact factors of UAV logistics networks is greatly significant in regards to UAV logistics planning and scheduling. This study considered the urban logistics network of Hangzhou in 2020 as the research topic and used kernel density estimation, a geodetector, and geographic information system (GIS) spatial analysis technology to systematically analyze the spatial patterns and influencing factors at the city and district scales. The study found that a significant spatial pattern was revealed in the UAV logistics network in Hangzhou, and the logistics nodes showed an obvious “core-edge” structure. The urban population, market scale and logistics infrastructure jointly shaped the structure and function of the UAV logistics network, and logistics nodes had a strong coupling relationship with the urban spatial structure. Through interaction detectors, the technical route of urban UAV logistics network construction was analyzed and summarized, and results can provide a scientific basis and case reference for other cities to build and plan UAV logistics networks.
Chemokine CXCL10 Modulates the Tumor Microenvironment of Fibrosis-Associated Hepatocellular Carcinoma
Authors: Brandt Elisa F. , Baues Maike , Wirtz Theresa H. , May Jan-Niklas , Fischer Petra , Beckers Anika , Schüre Björn-Carsten , Sahin Hacer , Trautwein Christian , Lammers Twan , Berres Marie-Luise
Published: July 2022

Hepatocellular carcinoma (HCC) constitutes a devastating health burden. Recently, tumor microenvironment-directed interventions have profoundly changed the landscape of HCC therapy. In the present study, the function of the chemokine CXCL10 during fibrosis-associated hepatocarcinogenesis was analyzed with specific focus on its impact in shaping the tumor microenvironment. C57BL/6J wild type (WT) and Cxcl10 knockout mice (Cxcl10−/−) were treated with diethylnitrosamine (DEN) and tetrachloromethane (CCl4) to induce fibrosis-associated HCCs. Cxcl10 deficiency attenuated hepatocarcinogenesis by decreasing tumor cell proliferation as well as tumor vascularization and modulated tumor-associated extracellular matrix composition. Furthermore, the genetic inactivation of Cxcl10 mediated an alteration of the tumor-associated immune response and modified chemokine/chemokine receptor networks. The DEN/CCl4-treated Cxcl10−/− mice presented with a pro-inflammatory tumor microenvironment and an accumulation of anti-tumoral immune cells in the tissue. The most striking alteration in the Cxcl10−/− tumor immune microenvironment was a vast accumulation of anti-tumoral T cells in the invasive tumor margin. In summary, our results demonstrate that CXCL10 exerts a non-redundant impact on several hallmarks of the tumor microenvironment and especially modulates the infiltration of anti-tumorigenic immune cells in HCC. In the era of microenvironment-targeted HCC therapies, interfering with CXCL10 defines a novel asset for further improvement of therapeutic strategies.
Protecting the Mitochondria in Cardiac Disease
Authors: Lazou Antigone , Ramachandra Chrishan J.
Published: July 2022

Cardiac disease is a broad cluster of several diseases, which include coronary artery disease, valve disease, congenital heart disease, arrhythmia, and cardiomyopathy [...]
scAPAmod: Profiling Alternative Polyadenylation Modalities in Single Cells from Single-Cell RNA-Seq Data
Authors: Qian Lingwu , Fu Hongjuan , Mou Yunwen , Lin Weixu , Ye Lishan , Ji Guoli
Published: July 2022

Alternative polyadenylation (APA) is a key layer of gene expression regulation, and APA choice is finely modulated in cells. Advances in single-cell RNA-seq (scRNA-seq) have provided unprecedented opportunities to study APA in cell populations. However, existing studies that investigated APA in single cells were either confined to a few cells or focused on profiling APA dynamics between cell types or identifying APA sites. The diversity and pattern of APA usages on a genomic scale in single cells remains unappreciated. Here, we proposed an analysis framework based on a Gaussian mixture model, scAPAmod, to identify patterns of APA usage from homogeneous or heterogeneous cell populations at the single-cell level. We systematically evaluated the performance of scAPAmod using simulated data and scRNA-seq data. The results show that scAPAmod can accurately identify different patterns of APA usages at the single-cell level. We analyzed the dynamic changes in the pattern of APA usage using scAPAmod in different cell differentiation and developmental stages during mouse spermatogenesis and found that even the same gene has different patterns of APA usages in different differentiation stages. The preference of patterns of usages of APA sites in different genomic regions was also analyzed. We found that patterns of APA usages of the same gene in 3′ UTRs (3′ untranslated region) and non-3′ UTRs are different. Moreover, we analyzed cell-type-specific APA usage patterns and changes in patterns of APA usages across cell types. Different from the conventional analysis of single-cell heterogeneity based on gene expression profiling, this study profiled the heterogeneous pattern of APA isoforms, which contributes to revealing the heterogeneity of single-cell gene expression with higher resolution.
Effects of Inhaled Corticosteroids on the Innate Immunological Response to Pseudomonas aeruginosa Infection in Patients with COPD
Authors: Cerón-Pisa Noemi , Shafiek Hanaa , Martín-Medina Aina , Verdú Javier , Jordana-Lluch Elena , Escobar-Salom Maria , Barceló Isabel M. , López-Causapé Carla , Oliver Antonio , Juan Carlos , Iglesias Amanda , Cosío Borja G.
Published: July 2022

Inhaled corticosteroids (ICS) use is associated with an increased risk of Pseudomonas aeruginosa (PA) infection in patients with COPD. We aimed to evaluate the effects of ICS on alveolar macrophages in response to PA in COPD patients with and without baseline ICS treatment (COPD and COPD + ICS, respectively) as well as smoker and nonsmoker controls. To do so, cells were infected with PA and cotreated with budesonide (BUD) or fluticasone propionate (FLU). The analysis of NF-κB and c-jun activity revealed a significant increase in both factors in response to PA cotreated with BUD/FLU in smokers but not in COPD or COPD + ICS patients when compared with PA infection alone. The expression of Toll-like receptor 2 (TLR2) and the transcription factor c-jun were induced upon PA infection in nonsmokers only. Moreover, in the smoker and COPD groups, there was a significant increase in TLR2 and a decrease in c-jun expression when treated with BUD/FLU after PA infection, which were not observed in COPD + ICS patients. Therefore, the chronic use of ICS seemingly makes the macrophages tolerant to BUD/FLU stimulation compared with those from patients not treated with ICS, promoting an impaired recognition of PA and activity of alveolar macrophages in terms of altered expression of TLR2 and cytokine production, which could explain the increased risk of PA infection in COPD patients under ICS treatment.
Inflammasomes—New Contributors to Blood Diseases
Authors: Tomasik Jaromir , Basak Grzegorz Władysław
Published: July 2022

Inflammasomes are intracellular multimeric complexes that cleave the precursors of the IL-1 family of cytokines and various proteins, found predominantly in cells of hematopoietic origin. They consist of pattern-recognition receptors, adaptor domains, and the enzymatic caspase-1 domain. Inflammasomes become activated upon stimulation by various exogenous and endogenous agents, subsequently promoting and enhancing inflammatory responses. To date, their function has been associated with numerous pathologies. Most recently, many studies have focused on inflammasomes’ contribution to hematological diseases. Due to aberrant expression levels, NLRP3, NLRP1, and NLRC4 inflammasomes were indicated as predominantly involved. The NLRP3 inflammasome correlated with the pathogenesis of non-Hodgkin lymphomas, multiple myeloma, acute myeloid leukemia, lymphoid leukemias, myelodysplastic neoplasms, graft-versus-host-disease, and sickle cell anemia. The NLRP1 inflammasome was associated with myeloma and chronic myeloid leukemia, whereas NLRC4 was associated with hemophagocytic lymphohistiocytosis. Moreover, specific gene variants of the inflammasomes were linked to disease susceptibility. Despite the incomplete understanding of these correlations and the lack of definite conclusions regarding the therapeutic utility of inflammasome inhibitors, the available results provide a valuable basis for clinical applications and precede upcoming breakthroughs in the field of innovative treatments. This review summarizes the latest knowledge on inflammasomes in hematological diseases, indicates the potential limitations of the current research approaches, and presents future perspectives.
Inhibition of Ubiquitin-Specific Protease-13 Improves Behavioral Performance in Alpha-Synuclein Expressing Mice
Authors: Liu Xiaoguang , Balaraman Kaluvu , Lynch Ciarán C. , Hebron Michaeline , Shah Priya Ketankumar , Hu Shicheng , Stevenson Max , Wolf Christian , Moussa Charbel
Published: July 2022

Ubiquitin-Specific Protease-13 (USP13) promotes protein de-ubiquitination. USP13 levels are upregulated in post-mortem Parkinson’s disease, whereas USP13 knockdown via shRNA reduces alpha-synuclein levels in animal models. We studied the role of USP13 in knockout mice expressing lentiviral human alpha-synuclein and investigated the impact of a small molecule inhibitor of USP13, BK50118-C, on alpha-synuclein pathology and animal behavior. Alpha-synuclein was expressed unilaterally in substantia nigra (SN) of USP13 deficient mice that were treated with a daily intraperitoneal injection of 100 mg/kg BK50118-C or DMSO for four consecutive weeks, and behavioral and functional assays were performed. Wild-type USP13+/+ mice expressing lentiviral human alpha-synuclein showed motor and behavioral defects that were not seen in partially (USP13+/−) or completely (USP13−/−) deficient USP13 mice. BK50118-C displayed a wide and favorable therapeutic dose range in vivo. Treatment with BK50118-C significantly reduced ubiquitinated alpha-synuclein, increased dopamine levels, and improved motor and behavioral symptoms in wild-type (USP13+/+), but not USP13 deficient, mice. These data suggest that USP13 is critical to the neuropathology of alpha-synuclein, whereas a novel small molecule inhibitor of USP13 is a potential therapeutic agent of alpha-synucleinopathies.
The Role of Pyrazolopyridine Derivatives on Different Steps of Herpes Simplex Virus Type-1 In Vitro Replicative Cycle
Authors: Miranda Milene D. , Chaves Otávio Augusto , Rosa Alice S. , Azevedo Alexandre R. , Pinheiro Luiz Carlos da Silva , Soares Vinicius C. , Dias Suelen S. G. , Abrantes Juliana L. , Bernardino Alice Maria R. , Paixão Izabel C. P. , Souza Thiago Moreno L. , Fontes Carlos Frederico L.
Published: July 2022

Herpes simplex virus type-1 (HSV-1) infection causes several disorders, and acyclovir is used as a reference compound. However, resistant strains are commonly observed. Herein, we investigate the effects of N-heterocyclic compounds (pyrazolopyridine derivatives), named ARA-04, ARA-05, and AM-57, on HSV-1 in vitro replication. We show that the 50% effective concentration (EC50) values of the compounds ARA-04, ARA-05, and AM-57 were 1.00 ± 0.10, 1.00 ± 0.05, and 0.70 ± 0.10 µM, respectively. These compounds presented high 50% cytotoxic concentration (CC50) values, which resulted in a selective index (SI) of 1000, 1000, and 857.1 for ARA-04, ARA-05, and AM-57, respectively. To gain insight into which step of the HSV-1 replication cycle these molecules would impair, we performed adsorption and penetration inhibition assays and time-of-addition experiments. Our results indicated that ARA-04 and ARA-05 affected viral adsorption, while AM-57 interfered with the virus replication during its α- and γ-phases and decreased ICP27 content during initial and late events of HSV-1 replication. In addition, we also observed that AM-57 caused a strong decrease in viral gD content, which was reinforced by in silico calculations that suggested AM-57 interacts preferentially with the viral complex between a general transcription factor and virion protein (TFIIBc-VP16). In contrast, ARA-04 and ARA-05 interact preferentially in the proteins responsible for the viral adsorption process (nectin-1 and glycoprotein). Thus, our results suggest that the 1H-pyrazolo[3,4-b]pyridine derivatives inhibit the HSV-1 replicative cycle with a novel mechanism of action, and its scaffold can be used as a template for the synthesis of promising new molecules with antiviral effects, including to reinforce the presented data herein for a limited number of molecules.
Clinical Tear Fluid Proteomics—A Novel Tool in Glaucoma Research
Authors: Nättinen Janika , Aapola Ulla , Nukareddy Praveena , Uusitalo Hannu
Published: July 2022

Tear fluid forms the outermost layer of the ocular surface and its characteristics and composition have been connected to various ocular surface diseases. As tear proteomics enables the non-invasive investigation of protein levels in the tear fluid, it has become an increasingly popular approach in ocular surface and systemic disease studies. Glaucoma, which is a set of multifactorial diseases affecting mainly the optic nerve and retinal ganglion cells, has also been studied using tear proteomics. In this condition, the complete set of pathophysiological changes occurring in the eye is not yet fully understood, and biomarkers for early diagnosis and accurate treatment selection are needed. More in-depth analyses of glaucoma tear proteomics have started to emerge only more recently with the implementation of LC-MS/MS and other modern technologies. The aim of this review was to examine the published data of the tear protein changes occurring during glaucoma, its topical treatment, and surgical interventions.
Four Novel PAX9 Variants and the PAX9-Related Non-Syndromic Tooth Agenesis Patterns
Authors: Liu Haochen , Liu Hangbo , Su Lanxin , Zheng Jinglei , Feng Hailan , Liu Yang , Yu Miao , Han Dong
Published: July 2022

The purpose of this research was to investigate and identify PAX9 gene variants in four Chinese families with non-syndromic tooth agenesis. We identified pathogenic gene variants by whole-exome sequencing (WES) and Sanger sequencing and then studied the effects of these variants on function by bioinformatics analysis and in vitro experiments. Four novel PAX9 heterozygous variants were identified: two missense variants (c.191G > T (p.G64V) and c.350T > G (p.V117G)) and two frameshift variants (c.352delC (p.S119Pfs*2) and c.648_649insC(p.Y217Lfs*100)). The bioinformatics analysis showed that these variants might be pathogenic. The tertiary structure analysis showed that these four variants could cause structural damage to PAX9 proteins. In vitro functional studies demonstrated that (1) the p.Y217Lfs*100 variant greatly affects mRNA stability, thereby affecting endogenous expression; (2) the p. S119Pfs* 2 variant impairs the subcellular localization of the nuclear expression of the wild-type PAX9 protein; and (3) the four variants (p.G64V, p.V117G, p.S119Pfs*2, and p.Y217Lfs*100) all significantly affect the downstream transcriptional activity of the BMP4 gene. In addition, we summarized and analyzed tooth missing positions caused by PAX9 variants and found that the maxillary second molar (84.11%) and mandibular second molar (84.11%) were the most affected tooth positions by summarizing and analyzing the PAX9-related non-syndromic tooth agenesis positions. Our results broaden the variant spectrum of the PAX9 gene related to non-syndromic tooth agenesis and provide useful information for future genetic counseling.
Therapeutic Effect of Erythropoietin on Alzheimer’s Disease by Activating the Serotonin Pathway
Authors: Shim Kyu-Ho , Ha Sungchan , Choung Jin Seung , Choi Jee In , Kim Daniel Youngsuk , Kim Jong Moon , Kim MinYoung
Published: July 2022

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by memory impairment in patients. Erythropoietin (EPO) has been reported to stimulate neurogenesis. This study was conducted to determine the regenerative effects of EPO in an AD model and to assess its underlying mechanism. Recombinant human EPO was intraperitoneally administered to AD mice induced by intracerebroventricular Aβ oligomer injection. Behavioral assessments with novel object recognition test and passive avoidance task showed improvement in memory function of the EPO-treated AD mice compared to that of the saline-treated AD mice (p < 0.0001). An in vivo protein assay for the hippocampus and cortex tissue indicated that EPO treatment modulated neurotransmitters, including dopamine, serotonin, and adrenaline. EPO treatment also restored the activity of serotonin receptors, including 5-HT4R, 5-HT7R, and 5-HT1aR (p < 0.01), at mRNA levels. Furthermore, EPO seemed to exert an anti-inflammatory influence by downregulating TLR4 at mRNA and protein levels (p < 0.05). Finally, an immunohistochemical assay revealed increments of Nestin(+) and NeuN(+) neuronal cells in the CA3 region in the EPO-treated AD mice compared to those in the saline-treated AD mice. The conclusion is that EPO administration might be therapeutic for AD by activating the serotonergic pathway, anti-inflammatory action, and neurogenic characteristics.
A WRKY Protein, MfWRKY40, of Resurrection Plant Myrothamnus flabellifolia Plays a Positive Role in Regulating Tolerance to Drought and Salinity Stresses of Arabidopsis
Authors: Huang Zhuo , Wang Jiatong , Li Yuan , Song Li , Chen Duo’er , Liu Ling , Jiang Cai-Zhong
Published: July 2022

WRKY transcription factors (TFs), one of the largest transcription factor families in plants, play an important role in abiotic stress responses. The resurrection plant, Myrothamnus flabellifolia, has a strong tolerance to dehydration, but only a few WRKY proteins related to abiotic stress response have been identified and functionally characterized in M. flabellifolia. In this study, we identified an early dehydration-induced gene, MfWRKY40, of M. flabellifolia. The deduced MfWRKY40 protein has a conserved WRKY motif but lacks a typical zinc finger motif in the WRKY domain and is localized in the nucleus. To investigate its potential roles in abiotic stresses, we overexpressed MfWRKY40 in Arabidopsis and found that transgenic lines exhibited better tolerance to both drought and salt stresses. Further detailed analysis indicated that MfWRKY40 promoted primary root length elongation and reduced water loss rate and stomata aperture (width/length) under stress, which may provide Arabidopsis the better water uptake and retention abilities. MfWRKY40 also facilitated osmotic adjustment under drought and salt stresses by accumulating more osmolytes, such as proline, soluble sugar, and soluble protein. Additionally, the antioxidation ability of transgenic lines was also significantly enhanced, represented by higher chlorophyll content, less malondialdehyde and reactive oxygen species accumulations, as well as higher antioxidation enzyme activities. All these results indicated that MfWRKY40 might positively regulate tolerance to drought and salinity stresses. Further investigation on the relationship of the missing zinc finger motif of MfWRKY40 and its regulatory role is necessary to obtain a better understanding of the mechanism underlying the excellent drought tolerance of M. flabellifolia.
Low-Dose-Rate Radiation-Induced Secretion of TGF-β3 Together with an Activator in Small Extracellular Vesicles Modifies Low-Dose Hyper-Radiosensitivity through ALK1 Binding
Authors: Hanson Ingunn , Pitman Kathinka E. , Altanerova Ursula , Altaner Čestmír , Malinen Eirik , Edin Nina F. J.
Published: July 2022

Hyper-radiosensitivity (HRS) is the increased sensitivity to low doses of ionizing radiation observed in most cell lines. We previously demonstrated that HRS is permanently abolished in cells irradiated at a low dose rate (LDR), in a mechanism dependent on transforming growth factor β3 (TGF-β3). In this study, we aimed to elucidate the activation and receptor binding of TGF-β3 in this mechanism. T-47D cells were pretreated with inhibitors of potential receptors and activators of TGF-β3, along with addition of small extracellular vesicles (sEVs) from LDR primed cells, before their radiosensitivity was assessed by the clonogenic assay. The protein content of sEVs from LDR primed cells was analyzed with mass spectrometry. Our results show that sEVs contain TGF-β3 regardless of priming status, but only sEVs from LDR primed cells remove HRS in reporter cells. Inhibition of the matrix metalloproteinase (MMP) family prevents removal of HRS, suggesting an MMP-dependent activation of TGF-β3 in the LDR primed cells. We demonstrate a functional interaction between TGF-β3 and activin receptor like kinase 1 (ALK1) by showing that TGF-β3 removes HRS through ALK1 binding, independent of ALK5 and TGF-βRII. These results are an important contribution to a more comprehensive understanding of the mechanism behind TGF-β3 mediated removal of HRS.
Phenotype Characterization of a Mice Genetic Model of Absolute Blindness
Authors: Milla-Navarro Santiago , Pazo-González Mateo , Germain Francisco , de la Villa Pedro
Published: July 2022

Recent technological development requires new approaches to address the problem of blindness. Such approaches need to be able to ensure that no cells with photosensitive capability remain in the retina. The presented model, Opn4−/− × Pde6brd10/rd10 (O×Rd) double mutant murine, is a combination of a mutation in the Pde6b gene (photoreceptor degeneration) together with a deletion of the Opn4 gene (responsible for the expression of melanopsin in the intrinsically photosensitive retinal ganglion cells). This model has been characterized and compared with those of WT mice and murine animal models displaying both mutations separately. A total loss of pupillary reflex was observed. Likewise, behavioral tests demonstrated loss of rejection to illuminated spaces and a complete decrease in visual acuity (optomotor test). Functional recordings showed an absolute disappearance of various wave components of the full-field and pattern electroretinogram (fERG, pERG). Likewise, visual evoked potential (VEP) could not be recorded. Immunohistochemical staining showed marked degeneration of the outer retinal layers and the absence of melanopsin staining. The combination of both mutations has generated an animal model that does not show any photosensitive element in its retina. This model is a potential tool for the study of new ophthalmological approaches such as optosensitive agents.
Mammalian Sulfatases: Biochemistry, Disease Manifestation, and Therapy
Authors: Mashima Ryuichi , Nakanishi Mahito
Published: July 2022

Sulfatases are enzymes that catalyze the removal of sulfate from biological substances, an essential process for the homeostasis of the body. They are commonly activated by the unusual amino acid formylglycine, which is formed from cysteine at the catalytic center, mediated by a formylglycine-generating enzyme as a post-translational modification. Sulfatases are expressed in various cellular compartments such as the lysosome, the endoplasmic reticulum, and the Golgi apparatus. The substrates of mammalian sulfatases are sulfolipids, glycosaminoglycans, and steroid hormones. These enzymes maintain neuronal function in both the central and the peripheral nervous system, chondrogenesis and cartilage in the connective tissue, detoxification from xenobiotics and pharmacological compounds in the liver, steroid hormone inactivation in the placenta, and the proper regulation of skin humidification. Human sulfatases comprise 17 genes, 10 of which are involved in congenital disorders, including lysosomal storage disorders, while the function of the remaining seven is still unclear. As for the genes responsible for pathogenesis, therapeutic strategies have been developed. Enzyme replacement therapy with recombinant enzyme agents and gene therapy with therapeutic transgenes delivered by viral vectors are administered to patients. In this review, the biochemical substrates, disease manifestation, and therapy for sulfatases are summarized.
A Journey to the Core of the Plant Cell Cycle
Authors: Gutierrez Crisanto
Published: July 2022

Production of new cells as a result of progression through the cell division cycle is a fundamental biological process for the perpetuation of both unicellular and multicellular organisms. In the case of plants, their developmental strategies and their largely sessile nature has imposed a series of evolutionary trends. Studies of the plant cell division cycle began with cytological and physiological approaches in the 1950s and 1960s. The decade of 1990 marked a turn point with the increasing development of novel cellular and molecular protocols combined with advances in genetics and, later, genomics, leading to an exponential growth of the field. In this article, I review the current status of plant cell cycle studies but also discuss early studies and the relevance of a multidisciplinary background as a source of innovative questions and answers. In addition to advances in a deeper understanding of the plant cell cycle machinery, current studies focus on the intimate interaction of cell cycle components with almost every aspect of plant biology.
Photoreceptor Cells Constitutively Express IL-35 and Promote Ocular Immune Privilege
Authors: Yu Cheng-Rong , Yadav Manoj Kumar , Kang Minkyung , Jittayasothorn Yingyos , Dong Lijin , Egwuagu Charles E.
Published: July 2022

Interleukin-27 is constitutively secreted by microglia in the retina or brain, and upregulation of IL-27 during neuroinflammation suppresses encephalomyelitis and autoimmune uveitis. However, while IL-35 is structurally and functionally similar to IL-27, the intrinsic roles of IL-35 in CNS tissues are unknown. Thus, we generated IL-35/YFP-knock-in reporter mice (p35-KI) and demonstrated that photoreceptor neurons constitutively secrete IL-35, which might protect the retina from persistent low-grade inflammation that can impair photoreceptor functions. Furthermore, the p35-KI mouse, which is hemizygous at the il12a locus, develops more severe uveitis because of reduced IL-35 expression. Interestingly, onset and exacerbation of uveitis in p35-KI mice caused by extravasation of proinflammatory Th1/Th17 lymphocytes into the retina were preceded by a dramatic decrease of IL-35, attributable to massive death of photoreceptor cells. Thus, while inflammation-induced death of photoreceptors and loss of protective effects of IL-35 exacerbated uveitis, our data also suggest that constitutive production of IL-35 in the retina might have housekeeping functions that promote sterilization immunity in the neuroretina and maintain ocular immune privilege.
The Impact of Cameraria ohridella (Lepidoptera, Gracillariidae) on the State of Aesculus hippocastanum Photosynthetic Apparatus in the Urban Environment
Authors: Holoborodko Kyrylo , Seliutina Oksana , Alexeyeva Anna , Brygadyrenko Viktor , Ivanko Iryna , Shulman Mariya , Pakhomov Olexander , Loza Iryna , Sytnyk Svitlana , Lovynska Viktoriia , Grytsan Yurii , Bandura Liubov
Published: July 2022

The paper presents the results on resistance of Aesculus hippocastanum Linnaeus, 1753 trees to Cameraria ohridella Deschka & Dimić, 1986 (Lepidoptera, Gracillariidae) impact under conditions of a modern urban environment on the example of Dnipro city as the largest industrial city in Ukraine. Field experiments were conducted in all park areas of the city, which allowed covering the full gradient of the existing urban environment and considered the different degrees of the tree settlement by the invasive insect species. The research of the impact of C. ohridella caterpillars’ vital activity on the photosynthetic apparatus state was carried out by applying a chlorophyll fluorescence induction technique. Diagnosis of photosynthetic dysfunction of fresh Ae. hippocastanum leaves was conducted using a portable “Floratest” fluorometer manufactured in Ukraine. Interpretation of the obtained Kautsky curves showed that significant changes in their critical parameters associated with the degree of leaf damage by C. ohridella caterpillars were not detected. The influence of tree growth site conditions on the following 4 main indicators of chlorophyll fluorescence induction was established: the initial value of fluorescence induction after irradiation; the value of “plateau” fluorescence induction; the maximum value of fluorescence induction; the stationary value of fluorescence induction after light adaptation of the plant leaf. It was found that the efficiency coefficients of photochemical processes in Ae. hippocastanum trees growing in low terrain levels differed significantly, which can probably be interpreted as their response to the specific characteristics of the urban environment.
Minimal Surgical Manpower for Living Donor Liver Transplantation
Authors: Kim Seoung Hoon , Park Jang Ho , An Byoung Ho
Published: July 2022

Background: Living donor liver transplantation (LDLT) is widely performed with good outcomes in the current era of improved surgical techniques. However, few studies have addressed how many human resources are required in the surgery itself. This study aimed to introduce how to perform LDLT with minimal manpower and evaluate the outcomes in adult patients. Methods: The main surgical procedures of donor and recipient operations of LDLT were performed by a single specialist surgeon who led a team of minimal manpower that only included one fellow, one resident, one intern, and three nurses. He also provided postsurgical care and followed up all the patients as a primary care physician. The outcomes were analyzed from the standpoints of the feasibility and acceptability. Results: Between November 2018 and February 2020, a total of 47 patients underwent LDLT. Ten patients had ABO-incompatible donors. The median age of the overall recipients was 57 years old (36–71); 37 patients (78.7%) were male. The MELD score was 10 (6–40), and the main etiologies were hepatic malignancy (38 patients or 80.9%) and liver failure (9 patients or 19.1%). The median age of the overall donors was 34 years old (19–62); 22 patients (46.8%) were male. All the graft types were right liver except for one case of extended right liver with middle hepatic vein. All donors had an uneventful recovery with no complications. There was one intraoperative mortality due to cardiac arrest after reperfusion in one recipient. Hepatic artery thrombosis was developed in 5 (10.6%) recipients. An acute rejection episode occurred in one patient. The median follow-up period for all the patients was 32.9 months (range, 24.7–39.8). Biliary complications were developed in 11 (23.4%) recipients. In total, 7 (15%) patients died, including 1 intraoperative mortality, 5 from cancer recurrence, and 1 from intracranial hemorrhage. The 1-, 2-, and 3-year overall survival rates in the recipient group were 91.5%, 87.2%, and 85.1%, respectively. Conclusions: LDLT with minimal surgical manpower is feasible under the supervision of a single expert surgeon who has the capacity for all the main surgical procedures in both donor and recipient operations without compromising the outcomes in the present era of advanced surgical management.
Diffraction Enhanced Imaging Analysis with Pseudo-Voigt Fit Function
Authors: Mani Deepak , Kupsch Andreas , Müller Bernd R. , Bruno Giovanni
Published: July 2022

Diffraction enhanced imaging (DEI) is an advanced digital radiographic imaging technique employing the refraction of X-rays to contrast internal interfaces. This study aims to qualitatively and quantitatively evaluate images acquired using this technique and to assess how different fitting functions to the typical rocking curves (RCs) influence the quality of the images. RCs are obtained for every image pixel. This allows the separate determination of the absorption and the refraction properties of the material in a position-sensitive manner. Comparison of various types of fitting functions reveals that the Pseudo-Voigt (PsdV) function is best suited to fit typical RCs. A robust algorithm was developed in the Python programming language, which reliably extracts the physically meaningful information from each pixel of the image. We demonstrate the potential of the algorithm with two specimens: a silicone gel specimen that has well-defined interfaces, and an additively manufactured polycarbonate specimen.
A Comprehensive Review on Temporal-Action Proposal Generation
Authors: Sooksatra Sorn , Watcharapinchai Sitapa
Published: July 2022

Temporal-action proposal generation (TAPG) is a well-known pre-processing of temporal-action localization and mainly affects localization performance on untrimmed videos. In recent years, there has been growing interest in proposal generation. Researchers have recently focused on anchor- and boundary-based methods for generating action proposals. The main purpose of this paper is to provide a comprehensive review of temporal-action proposal generation with network architectures and empirical results. The pre-processing step for input data is also discussed for network construction. The content of this paper was obtained from the research literature related to temporal-action proposal generation from 2012 to 2022 for performance evaluation and comparison. From several well-known databases, we used specific keywords to select 71 related studies according to their contributions and evaluation criteria. The contributions and methodologies are summarized and analyzed in a tabular form for each category. The result from state-of-the-art research was further analyzed to show its limitations and challenges for action proposal generation. TAPG performance in average recall ranges from 60% up to 78% in two TAPG benchmarks. In addition, several future potential research directions in this field are suggested based on the current limitations of the related studies.
Time Is Money: Considerations for Measuring the Radiological Reading Time
Authors: Sexauer Raphael , Bestler Caroline
Published: July 2022

Timestamps in the Radiology Information System (RIS) are a readily available and valuable source of information with increasing significance, among others, due to the current focus on the clinical impact of artificial intelligence applications. We aimed to evaluate timestamp-based radiological dictation time, introduce timestamp modeling techniques, and compare those with prospective measured reporting. Dictation time was calculated from RIS timestamps between 05/2010 and 01/2021 at our institution (n = 108,310). We minimized contextual outliers by simulating the raw data by iteration (1000, vector size (µ/sd/λ) = 100/loop), assuming normally distributed reporting times. In addition, 329 reporting times were prospectively measured by two radiologists (1 and 4 years of experience). Altogether, 106,127 of 108,310 exams were included after simulation, with a mean dictation time of 16.62 min. Mean dictation time was 16.05 min head CT (44,743/45,596), 15.84 min for chest CT (32,797/33,381), 17.92 min for abdominal CT (n = 22,805/23,483), 10.96 min for CT foot (n = 937/958), 9.14 min for lumbar spine (881/892), 8.83 min for shoulder (409/436), 8.83 min for CT wrist (1201/1322), and 39.20 min for a polytrauma patient (2127/2242), without a significant difference to the prospective reporting times. In conclusion, timestamp analysis is useful to measure current reporting practice, whereas body-region and radiological experience are confounders. This could aid in cost–benefit assessments of workflow changes (e.g., AI implementation).
Influence of Corrosion Damage on Fatigue Limit Capacities of Offshore Wind Turbine Substructure
Authors: Li Ying , Zhang Yu , Wang Wenhua , Li Xin , Wang Bin
Published: July 2022

The decrease in structural capacities under the limit states caused by structural corrosion is a potential hazard for the safety of offshore structures. Considering the influence of corrosion factors, a fatigue analysis of the typical tubular joints of an offshore wind turbine (OWT) substructure under operation and wave loads during the service period was performed. The structural corrosion was equivalent to a two-parameter Weibull distribution in the analysis. According to the Miner linear fatigue accumulation criterion, the accumulated fatigue damage of three different typical tubular joints in the initial stage and at operation periods of 10, 20, and 30 years was calculated. The most critical tubular joint of the studied OWT substructure is located at the connection between the pile foundations and braces. Owing to the increase in structural corrosion during the operation period, a remarkable decrease in the tubular joint fatigue capacities under the operation and wave loads was observed.
Heterologous Expressed NbSWP12 from Microsporidia Nosema bombycis Can Bind with Phosphatidylinositol 3-Phosphate and Affect Vesicle Genesis
Authors: Chen Jie , Li Zhi , Sheng Xiaotian , Huang Jun , Sun Quan , Huang Yukang , Wang Rong , Wu Yujiao , Long Mengxian , Bao Jialing , Zhou Zeyang , Pan Guoqing
Published: July 2022

Microsporidia are a big group of single-celled obligate intracellular organisms infecting most animals and some protozoans. These minimalist eukaryotes lack numerous genes in metabolism and vesicle trafficking. Here, we demonstrated that the spore wall protein NbSWP12 of microsporidium Nosema bombycis belongs to Bin/Amphiphysin/Rvs (BAR) protein family and can specifically bind with phosphatidylinositol 3-phosphate [Ptdlns(3)P]. Since Ptdlns(3)P is involved in endosomal vesicle biogenesis and trafficking, we heterologous expressed NbSWP12 in yeast Saccharomyces cerevisiae and proved that NbSWP12 can target the cell membrane and endocytic vesicles. Nbswp12 transformed into Gvp36 (a BAR protein of S. cerevisiae) deletion mutant rescued the defect phenotype of vesicular traffic. This study identified a BAR protein function in vesicle genesis and sorting and provided clues for further understanding of how microsporidia internalize nutrients and metabolites during proliferation.
The Utility of (1→3)-β-D-Glucan Testing in the Diagnosis of Coccidioidomycosis in Hospitalized Immunocompromised Patients
Authors: Al-Obaidi Mohanad M. , Ayazi Parham , Shi Aishan , Campanella Matthew , Connick Elizabeth , Zangeneh Tirdad T.
Published: July 2022

Coccidioidomycosis is a fungal infection endemic to the Southwestern United States which is associated with high morbidity and mortality in immunocompromised hosts. Serology is the main diagnostic tool, although less sensitive among immunocompromised hosts. (1→3)-β-D-glucan (BDG) is a non-specific fungal diagnostic test that may identify suspected coccidioidomycosis and other invasive fungal infections. We retrospectively investigated the utility of BDG between 2017 and 2021 in immunocompromised hosts with positive Coccidioides spp. cultures at our institutions. During the study period, there were 368 patients with positive cultures for Coccidioides spp.; among those, 28 patients were immunocompromised hosts, had both Coccidioides serology and BDG results available, and met other inclusion and exclusion criteria. Half of the patients had positive Coccidioides serology, and 57% had a positive BDG ≥ 80 pg/mL. Twenty-three (82%) had at least one positive test during their hospitalization. Among immunocompromised hosts with suspicion for coccidioidomycosis, the combination of Coccidioides serology and BDG can be useful in the initial work up and the timely administration of appropriate antifungal therapy. However, both tests failed to diagnose many cases, underscoring the need for better diagnostic techniques for identifying coccidioidomycosis in this population.
Digoxin Derivatives Sensitize a Saccharomyces cerevisiae Mutant Strain to Fluconazole by Inhibiting Pdr5p
Authors: de Moraes Daniel Clemente , Tessis Ana Claudia , Rollin-Pinheiro Rodrigo , Princival Jefferson Luiz , Villar José Augusto Ferreira Perez , Barbosa Leandro Augusto , Barreto-Bergter Eliana , Ferreira-Pereira Antônio
Published: July 2022

The poor outcome of treatments for fungal infections is a consequence of the increasing incidence of resistance to antifungal agents, mainly due to the overexpression of efflux pumps. To surpass this mechanism of resistance, a substance able to inhibit these pumps could be administered in association with antifungals. Saccharomyces cerevisiae possesses an efflux pump (Pdr5p) homologue to those found in pathogenic yeast. Digoxin is a natural product that inhibits Na+, K+-ATPase. The aim of this study was to evaluate whether digoxin and its derivatives (i.e., DGB, digoxin benzylidene) can inhibit Pdr5p, reversing the resistance to fluconazole in yeasts. An S. cerevisiae mutant strain that overexpresses Pdr5p was used in the assays. The effects of the compounds on yeast growth, efflux activity, and Pdr5p ATPase activity were measured. All derivatives enhanced the antifungal activity of fluconazole against S. cerevisiae, in comparison to fluconazole alone, with FICI values ranging from 0.031 to 0.500. DGB 1 and DGB 3 presented combined effects with fluconazole against a Candida albicans strain, with fractional inhibitory concentration index (FICI) values of 0.625 and 0.281, respectively The compounds also inhibited the efflux of rhodamine 6G and Pdr5p ATPase activity, with IC50 values ranging from 0.41 μM to 3.72 μM. The results suggest that digoxin derivatives impair Pdr5p activity. Considering the homology between Pdr5p and efflux pumps from pathogenic fungi, these compounds are potential candidates to be used in association with fluconazole to treat resistant fungal infections.
A Giant Falls: The Impact of Evergrande on Asian Stock Indexes
Authors: Almeida Dora , Dionísio Andreia , Haque Muhammad Enamul , Ferreira Paulo
Published: July 2022

The economic growth of China has been driven by the development of its real estate market, especially after the 2008 crisis. This growth is mostly related to the huge housing bubble and growing amounts of sovereign debt that have been redirected to corporations in the sector. Evergrande is one of those corporations; it is a Chinese company in the construction and real estate sector, a global giant with investments in many parts of the world. Its bond default in September 2021 sounded alerts in financial markets. Several news outlets spoke of the “next Lehman Brothers”, and apprehension was very high, especially in Asian markets. This research work aims to evaluate the impact of Evergrande’s bond default on six Asian stock markets, using an event study approach. The results show a strong reaction from the markets towards the event in study, even anticipating it. Furthermore, it is worth mentioning a quick reversion to “normal” behavior, indicating the rapid absorption of information by the markets.
Supply Chain Risk Management in Young and Mature SMEs
Authors: Foli Samuel , Durst Susanne , Davies Lidia , Temel Serdal
Published: July 2022

In this article, we examine how external factors such as demand, security regulation, cyber risks, and relative performance influence supply chain risk management (SCRM) in young and mature small and medium-sized enterprises (SMEs) in Turkey. For this, we utilised fuzzy set qualitative comparative analysis (fsQCA) using data from 137 Turkish SMEs. Our results suggest a single significant path for explaining SCRM in young SMEs, while we found three significant paths for explaining SCRM in mature SMEs. Furthermore, the results indicate that demand risk is the only external factor for young SMEs to realise SCRM success. For mature SMEs, demand risk and/or relative performance are essential to explain SCRM performance. Based on our findings, we theoretically contribute by unravelling the pathways through which external factors influence SCRM performance. Moreover, practitioners could align their strategies towards these pathways when constructing a strategy for achieving SCRM performance.
Analysis of Land Use Optimization of Metro Station Areas Based on Two-Way Balanced Ridership in Xi’an
Authors: Zhao Meng , Tong Haiyan , Li Bo , Duan Yaqiong , Li Yubai , Wang Jianpo , Lei Kexin
Published: July 2022

With the development of metro systems, the problem of unbalanced ridership into and out of the stations, caused by the singleness of station area development, has become increasingly prominent. Research on land use optimization in metro station areas based on a two-way balance of ridership is proposed. First, the stepwise regression analysis method was used to build a relationship model between ridership and the land use index under the guidance of the two-way balance of ridership. Second, the range was optimized by calculating the land use factors of the metro station area. Finally, the land use of the metro station area was optimized from the perspectives of development intensity and land usage. Taking metro stations in Xi’an as an example, the results show that the land use characteristics of metro station areas are quite different. Under the guidance of the two-way balance of ridership, the current land use values of Daminggongxi Station, Nanshaomen Station, and Tiyuchang Station exceed the optimal value range and can be reduced by more than 2.78%. The current land use values of Chaoyangmen Station, Longshouyuan Station, and Weiyijie Station are within the optimized range. The land use values of Kaiyuanmen Station, Banpo Station, and Fengchengwulu Station are below the optimized range and could be increased by more than 13.7%. In addition, optimizing the development intensity or adjusting the land type is further proposed to ensure that the land use factors of station areas are within the calculated optimal value range. The results provide a reference for the optimization of land use in the Xi’an metro station area.