bluuebunny/crossref_metadata_2025 huggingface dataset:
Model skuteczności reakcji w organizacji czułej na zdarzenia kryzysowe oraz wizerunkowe elementy składowe systemu odpornościowego organizacji. Na podstawie badań przeprowadzonych wśród polskich przedsiębiorców
Authors: Tworzydło Dariusz , Gawroński Sławomir
Published: October 2022

Cel: w artykule przedstawiono najważniejsze wnioski z badań przeprowadzonych pod kierownictwem jednego z autorów publikacji. Metodologia: artykuł oparty został na wynikach szeregu badań ilościowych przeprowadzonych przez autorów publikacji. Wyniki i wnioski: publikacja zawiera prezentację nowej definicji kryzysu wizerunkowego, opierającej się na danych empirycznych. Dokonano opisu czynników determinujących bezpieczeństwo wizerunkowe organizacji, takich jak przygotowanie, wsparcie eksperckie, świadomość istnienia zagrożeń czy działania analityczne. Ten ostatni aspekt ujęto w schemat pokazujący elementy mające wpływ na to, w jaki sposób organizacja zostanie przygotowana na kryzys. W dalszej części artykułu zaprezentowany został cykl decyzji analitycznych warunkujących bezpieczeństwo wizerunkowe organizacji oraz model skuteczności reakcji w organizacji czułej na zdarzenia kryzysowe.
Plandemia, czyli medialne narracje covidowych sceptyków
Authors: Polkowska Laura
Published: October 2022

Celem artykułu jest próba rekonstrukcji medialnych narracji koronasceptyków. W tekście odtworzono podstawowe wątki fabularne opowieści o „plandemii”, a także czynniki stanowiące o jej wymiarze dramatycznym. Metoda badań, którą zastosowano, obejmuje analizę narracji, pojmowanej jako jedna z form dyskursu. Na materiał badawczy złożyło się 116 tekstów, przede wszystkim o charakterze publicystycznym, opublikowanych w Internecie. Ich analiza pozwoliła sformułować następujące wnioski: 1. Sytuacja pandemiczna w Polsce i na świecie postrzegana jest przez koronasceptyków w kategoriach konfliktu. 2. Role głównych bohaterów opowieści o plandemii są przydzielone na stałe i nie podlegają ewolucji. 3. Wszelkie wątki związane z epidemią – w wyniku procesów poznawczych opartych na racjonalności ograniczonej – włączane są w obręb z góry przyjętego skryptu, opierającego się na analogiach historycznych. 4. Narrator sytuuje samego siebie po stronie bojowników o wolność, dostrzegając w swych antagonistach niebezpiecznych ciemiężycieli. Wartość poznawcza: artykuł został poświęcony jednej z odsłon współczesnego dyskursu publicznego, często postrzeganej jako marginalna, jednak – co pokazują badania opinii publicznej – niepozostającej bez wpływu na dużą część społeczeństwa, a nawet niektóre decyzje rządzących. Przeprowadzona analiza wydaje się istotna również z punktu widzenia postępującej w Polsce polaryzacji postaw społecznych.
Epidemiology and surveillance implications of community-acquired pneumonia in children
Authors: Roh Eui Jeong , Shim Jung Yeon , Chung Eun Hee
Published: October 2022

Community-acquired pneumonia (CAP) is the single largest infectious cause of hospitalization and death in children worldwide. With improved immunizations, the incidence of bacterial pneumonia and the number of colonized bacteria have decreased. However, respiratory viruses are still an important cause of CAP, especially as new infectious agents such severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge. The SARS-CoV-2 virus emerged in 2019 and caused the current coronavirus disease 2019 pandemic. Therefore, it is necessary to elucidate the epidemiology and causative pathogens of CAP. Recently, the Pneumonia and Respiratory Disease Study Group, affiliated with the Korean Academy of Pediatric Allergy and Respiratory Disease, investigated the causative pathogens of respiratory infections in children hospitalized with CAP, the serotype of Streptococcus pneumoniae, and the prevalence of Mycoplasma pneumoniae with gene mutations. Antibiotic resistance and serotype test results can determine the use of empirical antibiotics. Moreover, it is possible to help develop future vaccines by comparing bacterial culture results with vaccine serotype and identifying the changes and prevalence of each serotype. Therefore, we will perform continuous national surveillance and monitor the epidemiology of respiratory pathogens in Korea and worldwide. The surveillance of these respiratory infections can play a role in monitoring the emergence of new infectious diseases such as SARS-CoV-2.
Assessing the effectiveness of DNA barcoding for exploring hidden genetic diversity in deep-sea fishes
Authors: Teramura A , Koeda K , Matsuo A , Sato MP , Senou H , Ho HC , Suyama Y , Kikuchi K , Hirase S
Published: October 2022

The numbers of deep-sea fish species and their genetic diversities are poorly understood because of taxonomic confusion and the lack of robust diagnostic features. However, DNA barcoding using mitochondrial DNA sequences may offer an effective approach to identifying cryptic species and characterizing their genetic diversities. To validate the genetic differentiation identified by DNA mitochondrial barcoding, it is necessary to show that these reflect variations present in nuclear genomic markers. Here, we performed DNA barcoding using cytochrome c oxidase subunit I (COI) sequences and also carried out multiplexed intersimple sequence repeat genotyping by sequencing (MIG-seq) for mesopelagic and demersal fish species from the continental shelf and upper slope of the northwestern Pacific Ocean. We obtained the COI sequences of 115 species from 48 families; the species were identified using the Barcode of Life Data System. Phylogenetic analyses using COI sequences showed high levels of intraspecific genetic differentiation (Kimura 2-parameter distances >2%) in 20 of 115 species, suggesting many cryptic species or intraspecific genetic differentiation previously unknown in these species. We performed phylogenetic and population genetic analyses using multiple single-nucleotide polymorphism loci obtained by MIG-seq of 3 species that showed high levels of intraspecific genetic differentiation in COI sequences. The nuclear markers confirmed the genetic differentiation in all 3 species identified by the COI sequences. The high concordance between these different genetic markers indicates the effectiveness of DNA barcoding for identifying cryptic deep-sea species and characterizing genetic differentiation in these species.
Interactions between anchovy fisheries and Peruvian boobies revealed by bird-borne cameras and movement loggers
Authors: Clark BL , Irigoin-Lovera C , Gonzales-DelCarpio DD , Diaz-Santibañez I , Votier SC , Zavalaga CB
Published: October 2022

Fisheries threaten marine predator populations through bycatch and competition for the same resources, but may also provide feeding opportunities. Understanding benefits and mitigating impacts, therefore, requires a detailed understanding of fishery interactions. The Humboldt Current system supports the world’s largest single-species fishery (Peruvian anchoveta Engraulis ringens), along with abundant marine predators dependent on these forage fish, including seabirds. We combined bird-borne video cameras and GPS-acceleration-dive loggers to quantify the foraging behaviour of chick-rearing Peruvian boobies Sula variegata around Isla Macabi, Peru, in December 2020 and May 2021. Videos revealed that 18% of 77 Peruvian booby foraging trips included feeding at actively fishing purse seine vessels, diving in and around the nets. Most vessel interactions were close to the colony, and we found no difference in foraging effort (e.g. trip duration) between trips with and without vessel interactions. We recorded fishing effort in the foraging range of the colony using remotely sensed data from the vessel monitoring system accessed via Global Fishing Watch, finding more frequent interactions and catch depredation when fishing effort was high near the colony. We found no evidence that birds expended additional energy (e.g. dynamic body acceleration) or travelled to different locations to reach vessels. We emphasise the value of combining high-resolution movement and video loggers with remotely sensed fisheries data to monitor seabird-fishery interactions in detail, rather than just spatio-temporal overlap, and assess the potential for competition and bycatch. Threatened seabird populations may benefit from no-take zones or reduced fishing effort in core foraging areas of colonies.
Adaptation features of freshers to the learning environment at the Belarusian State University
Authors: Korneevets Maksim A. , Filinskaya Larisa V. , Scholkova Tatiana V.
Published: October 2022

The paper considers the problem of first-year students’ adaptation to new social environment and to the conditions of coping with the university educational curriculum. It analyses the features of the first-year students’ adjustment to learning and extracurricular activities (academic and sociocommunicative adaptation). The objective and subjective criteria of freshmen’ adaptation process are highlighted. The article presents the results of the online-survey of the first-year students from 15 faculties of the Belarusian State University, and the findings of the in-depth interviews with the students-orphans and the students expelled from the university after the first semester. The results obtained prove the relevance of the problem under study and make it possible to conclude that the process of adaptation of the first-year students is incomplete. The outcomes also prove the need for psychological and pedagogical support of orphan students, development of the institute of tutoring, conducting sociological research to study the dynamic aspect of adaptation.
Methodological problems of religious diversity research
Authors: Martinovich Vladimir A.
Published: October 2022

This article is devoted to the analysis of the phenomenon of religious diversity as a subject of sociological research. It is shown that numerous theoretical and empirical studies of religious diversity in different countries have not been able to reach the level of analysis of the unique configuration of the general population of religious organisations operating on their territory. The significance of such an analysis for the sociology of religion is substantiated. The dependence of some areas of sociological analysis of religion on the successful study of the totality of different religious organisations that form the basis of religious diversity in the country is emphasised. A number of methodological problems arising from the empirical analysis of religious diversity and caused by the specifics of new religious movements are identified. Particular attention is paid to the analysis of problems in the area of conceptual apparatus, the organisation of the collection of relevant information on different information platforms and the identification of different types of new religious movements documents. Special attention is focused on the introduction into scientific circulation of information about previously unexplored new religious movements. It is shown that there is no provably effective methodology for studying religious diversity in the sociology of religion, but its development inevitably implies the resolution of most of the methodological problems described in the article. It is argued that the study of religious diversity belongs in the sociology of religion to the group of the most complex longitudinal studies with significant heuristic potential.
Group Belongingness and Redistribution Preference: A Survey Experiment in Japan
Authors: Seki Katsunori
Published: October 2022

The political economy of redistribution preference sheds new light on the role of social identification in the process of preference formation and change. Group identity is an undeniable factor that shapes redistribution preference. Echoing the recent advance of the literature, I argue that individuals identify with an income group whose household income is similar to theirs. In-group favoritism arises within that income group. This mechanism makes the poor more supportive of income redistribution while the rich provide less support for redistribution. I also contend that the nation/foreigner cleavage plays a significant role. Native citizens find little to no reason to perceive proximity with foreign-born residents, which renders them less supportive of income redistribution in general. I test these arguments experimentally with a nationally representative sample of Japanese people.
Examining the Correlation Between Academic Achievement and Basic Psychological Needs: A Study on University Students
Authors: Duran Songul , Aydin Cagla
Published: October 2022

Aim: The purpose of this study was to examine the correlation between basic psychological needs and academic achievement in Healthcare Services Vocational High School students. Methods: The researchers conducted the descriptive correlational study with Healthcare Services Vocational High School students in a university. The target population of the study included the Healthcare Services Vocational High School students (n=174) and the sample included 139 students. The researchers collected the data via the Personal Information Form and the Basic Psychological Needs Scale. The researchers calculated the grade-point averages of the students via the end-of-term grade-point averages. Results: Mean age of the students was 19.91±2.20 years. Of the students, 65.5% were female, 51.1% were freshman students and 75.5% received education in the Elderly Care Program. The mean Basic Psychological Needs Scale Autonomy subscale score was 26.06±4.33, the mean Competence subscale score was 19.06±3.59 and the mean Relatedness subscale score was 28.51±4.90. The researchers found statistically significant correlations between the relatedness subscale scores and grade-point averages of the students in a positive direction. Conclusion: Findings of the present study demonstrated that the basic psychological needs of the students were met. As the relatedness scores of the students increased, their grade-point averages increased. Keywords: students, psychologic tests, academic achievement
pH-dependent structural diversity of profilin allergens determines thermal stability
Authors: Hofer Florian , Fischer Anna-Lena , Kamenik Anna S. , Waibl Franz , Fernández-Quintero Monica L. , Liedl Klaus R.
Published: October 2022

The family of profilin allergens is a common class of proteins found in plants, viruses and various eukaryotes including mammals. Profilins are characterized by an evolutionary conserved structural fold, which is responsible for their cross-reactive nature of Immunoglobulin E (IgE) antibodies. Despite their high overall structural similarity, they exhibit substantial differences in their biophysical properties, such as thermal and pH stability. To understand the origin of these functional differences of Amb a 8, Art v 4 and Bet v 2, we performed constant pH molecular dynamics simulation in combination with Gaussian accelerated MD simulations. Depending on the respective protonation at different pH levels, we find distinct differences in conformational flexibility, which are consistent with experimentally determined melting temperatures. These variations in flexibility are accompanied by ensemble shifts in the conformational landscape and quantified and localized by residue-wise B-factors and dihedral entropies. These findings strengthen the link between flexibility of profilin allergens and their thermal stability. Thus, our results clearly show the importance of considering protonation dependent conformational ensembles in solution to elucidate biophysical differences between these structurally similar allergens.
Genomic comparisons confirm Giardia duodenalis sub-assemblage AII as a unique species
Authors: Seabolt Matthew H. , Roellig Dawn M. , Konstantinidis Konstantinos T.
Published: October 2022

Giardia duodenalis is a parasitic flagellated protozoan which infects a wide range of mammalian hosts, including humans, and is subdivided into at least eight genetic assemblages commonly thought to represent cryptic species. Molecular studies have shown that G. duodenalis assemblage A, which parasitizes humans and animals, contains several phylogenetically distinct groupings known as sub-assemblages. Molecular studies employing poor phylogenetic-resolution markers routinely recover these sub-assemblages, implying that they represent evolutionarily distinct clades and possibly cryptic species, a hypothesis which is supported by epidemiologic trends. Here, we further tested this hypothesis by using available data from 41 whole genomes to characterize sub-assemblages and coalescent techniques for statistical estimation of species boundaries coupled to functional gene content analysis, thereby assessing the stability and distinctiveness of clades. Our analysis revealed two new sub-assemblage clades as well as novel signatures of gene content geared toward differential host adaptation and population structuring via vertical inheritance rather than recombination or panmixia. We formally propose sub-assemblage AII as a new species, Giardia hominis, while preserving the name Giardia duodenalis for sub-assemblage AI. Additionally, our bioinformatic methods broadly address the challenges of identifying cryptic microbial species to advance our understanding of emerging disease epidemiology, which should be broadly applicable to other lower eukaryotic taxa of interest. Giardia hominis n. sp. Zoobank LSID: urn:lsid: zoobank.org:pub:4298F3E1-E3EF-4977-B9DD-5CC59378C80E.
Superior antiviral activity of IFNβ in genital HSV-1 infection
Authors: Schmitz Yasmin , Schwerdtfeger Mara , Westmeier Jaana , Littwitz-Salomon Elisabeth , Alt Mira , Brochhagen Leonie , Krawczyk Adalbert , Sutter Kathrin
Published: October 2022

Type I interferons (IFNs) present the first line of defense against viral infections, providing antiviral, immunomodulatory and antiproliferative effects. The type I IFN family contains 12 IFNα subtypes and IFNβ, and although they share the same receptor, they are classified as non-redundant, capable to induce a variety of different IFN-stimulated genes. However, the biological impact of individual subtypes remains controversial. Recent data propose a subtype-specificity of type I IFNs revealing unique effector functions for different viruses and thus expanding the implications for IFNα-based antiviral immunotherapies. Despite extensive research, drug-resistant infections with herpes simplex virus type 1 (HSV-1), which is the common agent of recurrent orogenital lesions, are still lacking a protective or curing therapeutic. However, due to the risk of generalized infections in immunocompromised hosts as well as the increasing incidence of resistance to conventional antiherpetic agents, HSV infections raise major health concerns. Based on their pleiotropic effector functions, the application of type I IFNs represents a promising approach to inhibit HSV-1 replication, to improve host immunity and to further elucidate their qualitative differences. Here, selective IFNα subtypes and IFNβ were evaluated for their therapeutic potential in genital HSV-1 infections. Respectivein vivostudies in mice revealed subtype-specific differences in the reduction of local viral loads. IFNβ had the strongest antiviral efficacy against genital HSV-1 infection in mice, whereas IFNα1, IFNα4, and IFNα11 had no impact on viral loads. Based on flow cytometric analyses of underlying immune responses at local and peripheral sites, these differences could be further assigned to specific modulations of the antiviral immunity early during HSV-1 infection. IFNβ led to enhanced systemic cytokine secretion and elevated cytotoxic responses, which negatively correlated with viral loads in the vaginal tract. These data provide further insights into the diversity of type I IFN effector functions and their impact on the immunological control of HSV-1 infections.
Unraveling the mechanisms of intrinsic drug resistance in Mycobacterium tuberculosis
Authors: Poulton Nicholas C. , Rock Jeremy M.
Published: October 2022

Tuberculosis (TB) is among the most difficult infections to treat, requiring several months of multidrug therapy to produce a durable cure. The reasons necessitating long treatment times are complex and multifactorial. However, one major difficulty of treating TB is the resistance of the infecting bacterium, Mycobacterium tuberculosis (Mtb), to many distinct classes of antimicrobials. This review will focus on the major gaps in our understanding of intrinsic drug resistance in Mtb and how functional and chemical-genetics can help close those gaps. A better understanding of intrinsic drug resistance will help lay the foundation for strategies to disarm and circumvent these mechanisms to develop more potent antitubercular therapies.
Efficient Control of a Mesoporous Fibrillar PEDOT:PSS Aerogel Structure for Promising Thermoelectric Applications
Authors: Weinbach Quentin , Thakkar Swapneel Vijay , Carvalho Alain , Chaplais Gérald , Combet Jérôme , Constantin Doru , Stein Nicolas , Collin Dominique , Biniek Laure
Published: October 2022

Graphical Abstract
Fracture risk, underlying pathophysiology, and bone quality assessment in patients with Turner syndrome
Authors: Ikegawa Kento , Hasegawa Yukihiro
Published: October 2022

Turner syndrome (TS), the most common type of X chromosomal disorder, has various, clinical manifestations. Among these, primary hypogonadism, which may lead to osteoporosis, is a life-long health issue. A high prevalence of fractures associated with osteoporosis is a major problem in patients with TS, where it may be 1.4-2.2 times higher than in healthy individuals and increases with age.

Among the risk factors associated with fractures in TS, hypogonadism is arguably the most important. Estrogen deficiency due to hypogonadism leads to low bone mineral density (BMD), resulting in a high prevalence of bone fractures. Estrogen replacement therapy (ERT) in patients with TS reportedly improved their BMD. However, other causes of low BMD may exist, given that this condition begins in the prepubertal period in patients with TS.

Most previous studies have reported low BMD in patients with TS using dual-energy X-ray absorptiometry (DXA), but this method has some limitations. Areal BMD values assessed by DXA were influenced by bone size and short stature, resulting in an underestimation of BMD. Currently, volumetric BMD values may be accurately obtained using peripheral quantitative computed tomography (pQCT). pQCT, high-resolution pQCT, and the trabecular bone score can also be used to evaluate bone quality, including bone geometry and microarchitecture, in TS.

The present review discusses the high fracture risk, role of estrogen deficiency in low BMD, advantages and disadvantages of various bone assessment methods, and characteristics of bone quality in TS.
High initial FSH dosage reduces the number of available cleavage-stage embryos in a GnRH-antagonist protocol: Real-world data of 8,772 IVF cycles from China
Authors: Luo Xiu , Pei Li , He Yao , Li Fujie , Han Wei , Xiong Shun , Han Shubiao , Li Jingyu , Zhang Xiaodong , Huang Guoning , Ye Hong
Published: October 2022

To evaluate the relationship between the initial follicle stimulating hormone (FSH) dose and the number of available cleavage-stage embryos in in vitro fertilization (IVF) cycles.We included 8772 fresh IVF cycles using a GnRH antagonist protocol at the Genetic and Reproductive Institution of Chongqing, P. R. China, from January 2016 to June 2021.Univariate linear regression was used to evaluate the associations between the initial FSH dosage (≤ 150, 187.5–200, 225, 250, or 300 IU) with the number of available cleavage-stage embryos on day 3. A two-factor linear regression model was applied to calculate the threshold effect of the initial FSH dosage on the number of available cleavage-stage embryos based on a smoothing plot. The initial FSH dose was negatively correlated with the number of available cleavage-stage embryos, independent of female age, body mass index, infertility factors, duration of infertility, anti-Müllerian hormone and basal FSH levels, antral follicle count and the proportions of patients with poor ovarian response or polycystic ovarian syndrome. Using a two-factor linear regression model, we calculated the inflection point to be 200 IU of FSH. The relationship between the initial FSH dose and the number of available cleavage-stage embryos was nonlinear. The initial FSH dose was negatively associated with the number of available cleavage-stage embryos when the initial FSH dose was > 200 IU. Therefore, clinicians should try to avoid unnecessarily increasing the initial FSH dose.
Comparison of grain sorghum and alfalfa for providing heavy metal remediation of sandy soil with different soil amendments and salt stress
Authors: Mbarki Sonia , Talbi Ons , Skalicky Milan , Vachova Pavla , Hejnak Vaclav , Hnilicka Frantisek , Al-ashkar Ibrahim , Abdelly Chedly , Rahman Md Atikur , El Sabagh Ayman , Tlustos Pavel
Published: October 2022

Soil salinity and heavy metal (HM) pollution of soil is an ongoing threat to the plants’ survival that adversely affect the crop productivity and global food security. Therefore, an eco-friendly solution is highly desirable for mitigating the adverse affect of toxic pollutants in plants and soils. This study was aimed to explore how municipal solid waste compost (CO) or farmyard manure (M) supplementation regulates biomass yield, mineral nutritions under salinity, and distribution profile of toxic pullutants of (Medicago sativa L.) and sorghum [Sorghum bicolor (L.) Moench]. The CO and M were supplemented with saline (NaCl) soils, the total experiments were conducted for the three consecutive harvestings (H1, H2 and H3) of sorghum and alfalfa. In this study, the CO supplementation highly enhanced biomas yield (dry weight basis in sorghum during H2, while it showed higher in alfalfa during H3., Interestingly, the M significantly increased nitrogen (N2) and potassium (K+) but reduced sodium (Na+) in alfalfa, while the higher Na+ and phosphorus (P) were accumulated in sorghum fertilizer. As a consequence of these finding, a positive correlation was observed among the plant biomass yield, N and K+ content in alfalfa. Conversely, the high Na+ present in soil declined plant biomass in surghum, indicating that CO supplemetaton was not fully effective under high saline soil conditions. However, the N-P-K distribution improved due to CO and/or M supplementation in saline soils, while Cd accumulation was higher in sorghum compared to alfalfa. Therefore, sorghum can be used to clean up contaminated environments. The PCA results showed the same clusters of treatments and amedments were grouped in same plot, which indicated positive correlation beteween the treatment groups and plants, repectively. These results suggest that M supplementation is useful to mitigate saline stress compared to CO in alfalfa, while sorghum can be recommended as to clean up heavy metals (HMs) from soils. This study further suggest a correlation of minerals (N-P-K) boosting and salinity stress reduction in plants. Therefore, organic amendment-based ecofriendly approach can be useful to mitigate salinity stress in plants as well as effective for clean environment and smart agriculture.
Evolutionary game analysis of green technology innovation under the carbon emission trading mechanism
Authors: Cui Beiqing , Shui Zhonghao , Yang Sen , Lei Tianyi
Published: October 2022

The carbon emission trading mechanism is an environmental regulation that has both market and government orientations and has a significant impact on the innovation of green technology and low-carbon development. Based on the evolutionary game theory and considering the strategic choices of different enterprise types in the carbon trading market, a three-party game model, involving enterprise A, the government, and enterprise B, is constructed. Based on data on the carbon emission trading market, data simulation is used to analyze the evolutionary game trajectory of government and enterprise behavior strategies. This study finds that 1) carbon prices, additional green technology innovation benefits, and innovation incentives have a significant impact on corporate strategy choices, as with higher carbon prices, additional benefits, and greater innovation incentives, green technology innovation can compensate for corporate innovation investment enterprises tending to choose innovative strategies; 2) enterprises with different innovation inputs and outputs have different strategic choices under identical conditions, such as small enterprise B having higher input and lower output than large enterprise A, and therefore, when the government encourages policies such as innovation subsidies, it must treat different types of enterprises differently; and 3) the cost of supervision and punishment can help avoid behaviors such as “floating green” and “fraudulent compensation”, but enterprises and the supervision strategy of the government are affected by the associated supervision cost. This study not only further verifies the Porter hypothesis in both theory and practice but also has important implications for corporate green innovation strategies and government regulatory behavior while providing a reference for the carbon emission trading market and corporate low-carbon development.
Machine learning-based characterization of cuprotosis-related biomarkers and immune infiltration in Parkinson’s disease
Authors: Zhao Songyun , Zhang Li , Ji Wei , Shi Yachen , Lai Guichuan , Chi Hao , Huang Weiyi , Cheng Chao
Published: October 2022

Background: Parkinson’s disease (PD) is a neurodegenerative disease commonly seen in the elderly. On the other hand, cuprotosis is a new copper-dependent type of cell death that can be observed in various diseases.

Methods: This study aimed to identify potential novel biomarkers of Parkinson’s disease by biomarker analysis and to explore immune cell infiltration during the onset of cuprotosis. Gene expression profiles were retrieved from the GEO database for the GSE8397, GSE7621, GSE20163, and GSE20186 datasets. Three machine learning algorithms: the least absolute shrinkage and selection operator (LASSO), random forest, and support vector machine-recursive feature elimination (SVM-RFE) were used to screen for signature genes for Parkinson’s disease onset and cuprotosis-related genes (CRG). Immune cell infiltration was estimated by ssGSEA, and cuprotosis-related genes associated with immune cells and immune function were examined using spearman correlation analysis. Nomogram was created to validate the accuracy of these cuprotosis-related genes in predicting PD disease progression. Classification of Parkinson’s specimens using consensus clustering methods.

Result: Three PD datasets from the Gene Expression Omnibus (GEO) database were combined after eliminating batch effects. By ssGSEA, we identified three cuprotosis-related genes ATP7A, SLC31A1, and DBT associated with immune cells or immune function in PD and more accurate for the diagnosis of Parkinson’s disease course. Patients could benefit clinically from a characteristic line graph based on these genes. Consistent clustering analysis identified two subtypes, with the C2 subtype exhibiting higher immune cell infiltration and immune function.

Conclusion: In conclusion, our study reveals that several newly identified cuprotosis-related genes intervene in the progression of Parkinson’s disease through immune cell infiltration.
Exploration the global single-cell ecological landscape of adenomyosis-related cell clusters by single-cell RNA sequencing
Authors: Lin Jiajing , Liu Li , Zheng Fengque , Chen Saiqiong , Yang Weiwei , Li Jingjing , Mo Steven , Zeng Ding-Yuan
Published: October 2022

Background: Adenomyosis (AM) is a common benign uterine disease that threatens the normal life of patients. Cells associated with microenvironmental immune ecology are crucial in AM, although they are not as well understood at the cellular level.

Methods: Single-cell sequencing (scRNA-seq) data were used to construct an AM global single-cell map, to further identify relevant cell clusters and infer chromosomal copy number variation (CNV) in AM samples. The biological functions of cell clusters were explored and cellular evolutionary processes were inferred by enrichment analysis and pseudotime analysis. In addition, a gene regulatory network (GRN) analysis was constructed to explore the regulatory role of transcription factors in AM progression.

Results: We obtained the expression profiles of 42260 cells and identified 10 cell clusters. By comparing the differences in cell components between AM patients and controls, we found that significant abundance of endometrial cells (EC), epithelial cells (Ep), endothelial cells (En), and smooth muscle cells (SMC) in AM patients. Cell clusters with high CNV levels possessing tumour-like features existed in the ectopic endometrium samples. Moreover, the Ep clusters were significantly involved in leukocyte transendothelial cell migration and apoptosis, suggesting an association with cell apoptosis and migration. En clusters were mainly involved in pathways in cancer and apoptosis, indicating that En has certain malignant features.

Conclusion: This study identified cell clusters with immune-related features, investigated the changes in the immune ecology of the microenvironment of these cells during AM, and provided a new strategy for the treatment of AM.
CXCR1 and its downstream NF-κB inflammation signaling pathway as a key target of Guanxinning injection for myocardial ischemia/reperfusion injury
Authors: Xiao Guangxu , Liu Jiaxu , Wang Huanyi , He Shuang , Liu Jianwei , Fan Guanwei , Lyu Ming , Zhu Yan
Published: October 2022

Guanxinning Injection (GXNI) is used clinically to treat cardiac injury, but its active components and mode of action remains unclear. Therefore, a myocardial ischemia/reperfusion injury (MIRI) model-based integrated strategy including function evaluation, RNA-seq analysis, molecular docking, and cellular thermal shift assay (CETSA) was employed to elucidate the effect and mechanism of GXNI and its main ingredient on cardiac injury. These results revealed that GXNI significantly improved cardiac dysfunction and myocardial injury in I/R mice. RNA-seq analysis clarified that CXCR1-mediated interleukin-8 pathway played a critical role in MIRI. Molecular docking screening identified danshensu (DSS) as the major active components of GXNI targeting CXCR1 protein, which was confirmed in an oxygen-glucose deprivation/reoxygenation-induced cardiomyocytes damage model showing that GXNI and DSS reduced the protein expression of CXCR1 and its downstream NF-κB, COX-2, ICAM-1 and VCAM-1. CETSA and isothermal dose-response fingerprint curves confirmed that DSS combined with CXCR1 in a dose-dependent manner. Furthermore, GXNI and DSS significantly decreased the expression levels of IL-6, IL-1β and TNF-α and the number of neutrophils in post I/R myocardial tissue. In conclusion, this study revealed that GXNI and its active components DSS exert inhibitory effects on inflammatory factor release and leukocyte infiltration to improve I/R-induced myocardial injury by down-regulating CXCR1-NF-κB-COX-2/ICAM-1/VCAM-1 pathway.
Arginase-1 targeting peptide vaccine in patients with metastatic solid tumors – A phase I trial
Authors: Lorentzen Cathrine Lund , Martinenaite Evelina , Kjeldsen Julie Westerlin , Holmstroem Rikke Boedker , Mørk Sofie Kirial , Pedersen Ayako Wakatsuki , Ehrnrooth Eva , Andersen Mads Hald , Svane Inge Marie
Published: October 2022

Background

Arginase-1-producing cells inhibit T cell-mediated anti-tumor responses by reducing L-arginine levels in the tumor microenvironment. T cell-facilitated elimination of arginase-1-expressing cells could potentially restore L-arginine levels and improve anti-tumor responses. The activation of arginase-1-specific T cells may convert the immunosuppressive tumor microenvironment and induce or strengthen local Th1 inflammation. In the current clinical study, we examined the safety and immunogenicity of arginase-1-based peptide vaccination.

Methods

In this clinical phase I trial, ten patients with treatment-refractory progressive solid tumors were treated. The patients received an arginase-1 peptide vaccine comprising three 20-mer peptides from the ARG1 immunological “hot spot” region in combination with the adjuvant Montanide ISA-51. The vaccines were administered subcutaneously every third week (maximum 16 vaccines). The primary endpoint was to evaluate safety assessed by Common Terminology Criteria for Adverse Events 4.0 and laboratory monitoring. Vaccine-specific immune responses were evaluated using enzyme-linked immune absorbent spot assays and intracellular cytokine staining on peripheral blood mononuclear cells. Clinical responses were evaluated using Response Evaluation Criteria in Solid Tumors 1.1.

Results

The vaccination was feasible, and no vaccine-related grade 3–4 adverse events were registered. Nine (90%) of ten patients exhibited peptide-specific immune responses in peripheral blood mononuclear cells. Six (86%) of the seven evaluable patients developed a reactive T cell response against at least one of the ARG1 peptides during treatment. A phenotypic classification revealed that arginase-1 vaccine-specific T cells were both CD4+ T cells and CD8+ T cells. Two (20%) of ten patients obtained stable disease for respectively four- and seven months on vaccination treatment.

Conclusion

The peptide vaccine against arginase-1 was safe. Nine (90%) of ten patients had measurable peptide-specific responses in the periphery blood, and two (20%) of ten patients attained stable disease on protocol treatment.

Clinical trial registration

https://clinicaltrials.gov/ct2/show/NCT03689192, identifier NCT03689192.
Intratumoral neutrophil extracellular traps are associated with unfavorable clinical outcomes and immunogenic context in pancreatic ductal adenocarcinoma
Authors: Chen Xianlong , Ma Heng , Mo Shengwei , Yu Shuangni , Lu Zhaohui , Chen Jie
Published: October 2022

Extracellular traps (ETs) and tumor-infiltrating immune cells play crucial roles in tumor progression. However, little is known about the clinical significance of tumor-infiltrating neutrophils and macrophages and the related ETs in pancreatic ductal adenocarcinoma (PDAC). This study investigates the associations between neutrophil or macrophage infiltration or ET formation and the clinicopathological features, molecular characteristics, immune checkpoint molecules, clinical outcomes, and response to adjuvant chemotherapy (ACT) in PDAC. We performed multiplex immunofluorescence staining to detect ET formation by neutrophils or macrophages using tissue microarrays obtained from 205 patients, and analyzed the immunohistochemistry data for PD-L1, PD-L2, B7-H3, and B7-H4. The ET expression rates in macrophages and neutrophils were 23.9% and 45.4%, respectively. Patients with a high density of neutrophils or positive expression of neutrophil ETs exhibited poorer progression-free survival (PFS) and disease-specific survival (DSS), whereas macrophage ETs were not related to PFS and DSS. Neutrophil infiltration and ET formation were identified as independent prognostic predictors of DSS using univariate and multivariate Cox analyses. Patients with PDAC with lower neutrophil infiltration or negative staining for neutrophil ETs are more likely to benefit from ACT. Patients with PDAC were more accurately stratified based on the infiltration of neutrophils and presence of neutrophil ETs, and patients with low neutrophil infiltration and negative staining for neutrophil ETs showed the best survival. Patients with positive neutrophil ETs demonstrated inferior DSS compared to those with negative neutrophil ETs in the PD-L1 tumor proportion score (TPS) < 1% and PD-L1 IC < 1% subgroups. However, the positive expression of neutrophil ETs was not related to DSS in the PD-L1 TPS ≥ 1% or PD-L1 IC ≥ 1% subgroup. Our findings emphasize the potential of neutrophil infiltration and ETs as prognostic markers that could guide the formulation of more effective personalized treatments for PDAC.
A prognostic signature consisting of metabolism-related genes and SLC17A4 serves as a potential biomarker of immunotherapeutic prediction in prostate cancer
Authors: Li He , Gu Jie , Tian Yuqiu , Li Shuyu , Zhang Hao , Dai Ziyu , Wang Zeyu , Zhang Nan , Peng Renjun
Published: October 2022

Background

Prostate cancer (PCa), a prevalent malignant cancer in males worldwide, screening for patients might benefit more from immuno-/chemo-therapy remained inadequate and challenging due to the heterogeneity of PCa patients. Thus, the study aimed to explore the metabolic (Meta) characteristics and develop a metabolism-based signature to predict the prognosis and immuno-/chemo-therapy response for PCa patients.

Methods

Differentially expressed genes were screened among 2577 metabolism-associated genes. Univariate Cox analysis and random forest algorithms was used for features screening. Multivariate Cox regression analysis was conducted to construct a prognostic Meta-model based on all combinations of metabolism-related features. Then the correlation between MetaScore and tumor was deeply explored from prognostic, genomic variant, functional and immunological perspectives, and chemo-/immuno-therapy response. Multiple algorithms were applied to estimate the immunotherapeutic responses of two MeteScore groups. Further in vitro functional experiments were performed using PCa cells to validate the association between the expression of hub gene SLC17A4 which is one of the model component genes and tumor progression. GDSC database was employed to determine the sensitivity of chemotherapy drugs.

Results

Two metabolism-related clusters presented different features in overall survival (OS). A metabolic model was developed weighted by the estimated regression coefficients in the multivariate Cox regression analysis (0.5154*GAS2 + 0.395*SLC17A4 - 0.1211*NTM + 0.2939*GC). This Meta-scoring system highlights the relationship between the metabolic profiles and genomic alterations, gene pathways, functional annotation, and tumor microenvironment including stromal, immune cells, and immune checkpoint in PCa. Low MetaScore is correlated with increased mutation burden and microsatellite instability, indicating a superior response to immunotherapy. Several medications that might improve patients` prognosis in the MetaScore group were identified. Additionally, our cellular experiments suggested knock-down of SLC17A4 contributes to inhibiting invasion, colony formation, and proliferation in PCa cells in vitro.

Conclusions

Our study supports the metabolism-based four-gene signature as a novel and robust model for predicting prognosis, and chemo-/immuno-therapy response in PCa patients. The potential mechanisms for metabolism-associated genes in PCa oncogenesis and progression were further determined.
Joint together: The etiology and pathogenesis of ankylosing spondylitis
Authors: Xiong Yuehan , Cai Menghua , Xu Yi , Dong Peng , Chen Hui , He Wei , Zhang Jianmin
Published: October 2022

Spondyloarthritis (SpA) refers to a group of diseases with inflammation in joints and spines. In this family, ankylosing spondylitis (AS) is a rare but classic form that mainly involves the spine and sacroiliac joint, leading to the loss of flexibility and fusion of the spine. Compared to other diseases in SpA, AS has a very distinct hereditary disposition and pattern of involvement, and several hypotheses about its etiopathogenesis have been proposed. In spite of significant advances made in Th17 dynamics and AS treatment, the underlying mechanism remains concealed. To this end, we covered several topics, including the nature of the immune response, the microenvironment in the articulation that is behind the disease’s progression, and the split between the hypotheses and the evidence on how the intestine affects arthritis. In this review, we describe the current findings of AS and SpA, with the aim of providing an integrated view of the initiation of inflammation and the development of the disease.
Application of a multi-species bio-economic modelling approach to explore fishing traits within eligible cetacean conservation areas in the Northern Ionian Sea (Central Mediterranean Sea)
Authors: Carlucci Roberto , Cipriano Giulia , Cascione Daniela , Ingrosso Maurizio , Russo Tommaso , Sbrana Alice , Fanizza Carmelo , Ricci Pasquale
Published: October 2022

The assessment of the spatial overlap between eligible cetacean conservation areas (CCAs) and fishing grounds could be a strategic element in the implementation of effective conservation measures in the pelagic offshore areas. A multi-species bio-economic modelling approach has been applied to estimate the fishing traits in eligible CCAs in the Northern Ionian Sea (NIS, Central Mediterranean Sea) between 10-800 m of depth, adopting the Spatial MAnagement of demersal Resources for Trawl fisheries model (SMART). Four possible CCAs were defined according to the distribution of cetacean species, their bio-ecological needs, as well as socio-economic needs of human activities, identifying a Blue, Red, Orange and Green CCAs in the NIS. SMART spatial domain was a grid with 500 square cells (15×15 NM). The analysis was conducted for the period 2016-2019, considering the Otter Trawl Bottom (OTB) fleet activities in the study areas through the Vessel Monitoring System. The spatial extension of fishing activities, hourly fishing effort (h), landings (tons) and economic value (euros) for each CCA and the NIS were estimated as yearly median values. Fishing activities were absent in the Blue CCA, where the presence of the submarine canyon head does not offer accessible fishing grounds. The hourly fishing effort in the Green area accounted for about 22% (3443 h) of the total hourly effort of the NIS, while the Orange and Red areas were about 8% (1226 h) and 2% (295 h), respectively. The Green CCA corresponded to about 14% (36 tons) of the total landings in the NIS, whereas the Orange and Red areas represented about 9% (22 tons) and 6% (16 tons), respectively. The Green CCA accounted for about 13% (156 thousand euros) of the total economic value of the NIS, while the Orange and Red areas represented about 6% (69 thousand euros) and 4% (44thousand euros), respectively. Results showed no or negligible negative effects on trawl activities by potential spatial restrictions due to the establishment of CCAs highlighting the importance to consider spatially integrated information during the establishment process of conservation areas for cetacean biodiversity according to the principles of Ecosystem Based Management.