bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping of Rill Erosion of the Middle Volga (Russia) Region Using Deep Neural Network
Authors: Gafurov Artur
Published: March 2022

Soil erosion worldwide is an intense, poorly controlled process. In many respects, this is a consequence of the lack of up-to-date high-resolution erosion maps. All over the world, the problem of insufficient information is solved in different ways, mainly on a point-by-point basis, within local areas. Extrapolation of the results obtained locally to a more extensive territory produces inevitable uncertainties and errors. For the anthropogenic-developed part of Russia, this problem is especially urgent because the assessment of the intensity of erosion processes, even with the use of erosion models, does not reach the necessary scale due to the lack of all the required global large-scale remote sensing data and the complexity of considering regional features of erosion processes over such vast areas. This study aims to propose a new methodology for large-scale automated mapping of rill erosion networks based on Sentinel-2 data. A LinkNet deep neural network with a DenseNet encoder was used to solve the problem of automated rill erosion mapping. The recognition results for the study area of more than 345,000 sq. km were summarized to a grid of 3037 basins and analyzed to assess the relationship with the main natural-anthropogenic factors. Generalized additive models (GAM) were used to model the dependency of rill erosion density to explore complex relationships. A complex nonlinear relationship between erosion processes and topographic, meteorological, geomorphological, and anthropogenic factors was shown.
Assessing the Spectral Information of Sentinel-1 and Sentinel-2 Satellites for Above-Ground Biomass Retrieval of a Tropical Forest
Authors: Stratoulias Dimitris , Nuthammachot Narissara , Suepa Tanita , Phoungthong Khamphe
Published: March 2022

Earth Observation (EO) spectral indices have been an important tool for quantifying and monitoring forest biomass. Nevertheless, the selection of the bands and their combination is often realized based on preceding studies or generic assumptions. The current study investigates the relationship between satellite spectral information and the Above Ground Biomass (AGB) of a major private forest on the island of Java, Indonesia. Biomass-related traits from a total of 1517 trees were sampled in situ and their AGB were estimated from species-specific allometric models. In parallel, the exhaustive band combinations of the Ratio Spectral Index (RSI) were derived from near-concurrently acquired Sentinel-1 and Sentinel-2 images. By applying scenarios based on the entire dataset, the prevalence and monodominance of acacia, mahogany, and teak tree species were investigated. The best-performing index for the entire dataset yielded R2 = 0.70 (R2 = 0.78 when considering only monodominant plots). An application of eight traditional vegetation indices provided, at best, R2 = 0.65 for EVI, which is considerably lower compared to the RSI best combination. We suggest that an investigation of the complete band combinations as a proxy of retrieving biophysical parameters may provide more accurate results than the blind application of popular spectral indices and that this would take advantage of the amplified information obtained from modern satellite systems.
Contact-Fraud Victimization among Urban Seniors: An Analysis of Multilevel Influencing Factors
Authors: Zhang Chunxia , Liu Lin , Zhou Suhong , Feng Jiaxin , Chen Jianguo , Xiao Luzi
Published: March 2022

Fraud crime against seniors has become a serious social problem both at home and abroad. While most of the relevant research focuses on non-contact fraud against seniors, a few studies attend to contact fraud targeted at seniors. By constructing a theoretical framework of “environment–activity–fraud victimization” based on the integration of multiple theories, this study conducts a multilevel logit analysis of contact-fraud victimization among urban seniors in the downtown area of Guangzhou at the individual and neighborhood levels. The results show that contact-fraud victimization among urban seniors is influenced by individual-level factors and neighborhood-level factors, and that individual-level factors play a more significant role. More specifically, seniors with higher education levels and lower levels of self-control are more likely to experience contact-fraud victimization, while seniors who are older and healthier, and have higher household income are significantly less likely to experience contact-fraud victimization. Further, higher levels of collective efficacy and better living environments in the neighborhood significantly reduce the probability of contact-fraud victimization among urban seniors, while the percentage of the migrant population, the percentage of the aging population, and developed traffic environments significantly increase the probability of seniors experiencing contact fraud. This study confirms the feasibility of examining contact-fraud victimization among urban seniors based on the integration of theories, and enriches the research results of crime geography in terms of contact-fraud victimization among urban seniors.
Consistency Analysis and Accuracy Assessment of Three Global Ten-Meter Land Cover Products in Rocky Desertification Region—A Case Study of Southwest China
Authors: Wang Jun , Yang Xiaomei , Wang Zhihua , Cheng Hongbin , Kang Junmei , Tang Hongtao , Li Yan , Bian Zongpan , Bai Zhuoli
Published: March 2022

Rocky desertification is one of the most critical ecological and environmental problems in areas underlain by carbonate rocks globally. Land cover and land use in the region affects large-scale ecosystem processes on a global scale, and many Earth system models rely on accurate land cover information. Therefore, it is important to evaluate current global land cover products and to understand the differences between them, and the findings of these studies can provide guidance to different researchers when using or making land cover products. Whereas there are many studies on the assessment of coarser resolution land cover products, there are few studies on the assessment of higher resolution land cover products (10 m). In order to provide guidance for users of 10 m data, this paper uses the rock deserted southwest region of China as the experimental area. We analyzed the consistency and accuracy of the FROM-GLC, ESA WorldCover 10 and ESRI products using spatial pattern consistency, absolute accuracy assessment of three validation samples, and analyzed their intrinsic relationships among classification systems, classification methods, and validation samples. The results show that (1) the overall accuracy of the FROM-GLC product is the highest, ranging from 49.47 to 62.42%; followed by the overall accuracy of the ESA product, ranging from 45.13 to 64.50%; and the overall accuracy of the ESRI product is the lowest, between 39.03 and 61.94%. (2) The consistency between FROM-GLC and ESA is higher than the consistency between other products, with an area correlation coefficient of 0.94. Analysis of the spatial consistency of the three products shows that the proportion of perfectly consistent areas is low at 44.89%, mainly in areas with low surface heterogeneity and more homogeneous cover types. (3) Across the study area, the main land cover types such as forest and water bodies were the most consistent across the three product species, while the grassland, shrubland, and bareland were lower. All products showed high accuracy in homogeneous areas, with local accuracy varied in other areas, especially at high altitudes in the central and western regions. Therefore, land cover users cannot use these products directly when conducting relevant studies in rocky desertification areas, as their use may introduce serious errors.
Multicellular Modelling of Difficult-to-Treat Gastrointestinal Cancers: Current Possibilities and Challenges
Authors: Hakuno Sarah , Michiels Ellis , Kuhlemaijer Eleonore , Rooman Ilse , Hawinkels Lukas , Slingerland Marije
Published: March 2022

Cancers affecting the gastrointestinal system are highly prevalent and their incidence is still increasing. Among them, gastric and pancreatic cancers have a dismal prognosis (survival of 5–20%) and are defined as difficult-to-treat cancers. This reflects the urge for novel therapeutic targets and aims for personalised therapies. As a prerequisite for identifying targets and test therapeutic interventions, the development of well-established, translational and reliable preclinical research models is instrumental. This review discusses the development, advantages and limitations of both patient-derived organoids (PDO) and patient-derived xenografts (PDX) for gastric and pancreatic ductal adenocarcinoma (PDAC). First and next generation multicellular PDO/PDX models are believed to faithfully generate a patient-specific avatar in a preclinical setting, opening novel therapeutic directions for these difficult-to-treat cancers. Excitingly, future opportunities such as PDO co-cultures with immune or stromal cells, organoid-on-a-chip models and humanised PDXs are the basis of a completely new area, offering close-to-human models. These tools can be exploited to understand cancer heterogeneity, which is indispensable to pave the way towards more tumour-specific therapies and, with that, better survival for patients.
Analysis of Multiple Drug Resistance Mechanism in Different Types of Soft Tissue Sarcomas: Assessment of the Expression of ABC-Transporters, MVP, YB-1, and Analysis of Their Correlation with Chemosensitivity of Cancer Cells
Authors: Moiseeva Natalia I. , Laletina Lidia A. , Fetisov Timur I. , Makhmudova Leyla F. , Manikaylo Angelika E. , Fomina Liliya Y. , Burov Denis A. , Lesovaya Ekaterina A. , Bokhyan Beniamin Y. , Zinovieva Victoria Y. , Vilkova Alice S. , Mekheda Larisa V. , Kozlov Nikolay A. , Scherbakov Alexander M. , Kirilin Evgeny M. , Belitsky Gennady A. , Yakubovskaya Marianna G. , Kirsanov Kirill I.
Published: March 2022

Chemotherapy of soft tissue sarcomas (STS) is restricted by low chemosensitivity and multiple drug resistance (MDR). The purpose of our study was the analysis of MDR mechanism in different types of STS. We assessed the expression of ABC-transporters, MVP, YB-1, and analyzed their correlation with chemosensitivity of cancer cells. STS specimens were obtained from 70 patients without metastatic disease (2018–2020). Expression level of MDR-associated genes was estimated by qRT-PCR and cytofluorimetry. Mutations in ABC-transporter genes were captured by exome sequencing. Chemosensitivity (SI) of STS to doxorubicin (Dox), ifosfamide (Ifo), gemcitabine (Gem), and docetaxel (Doc) was analyzed in vitro. We found strong correlation in ABCB1, ABCC1, and ABCG2 expression. We demonstrated strong negative correlations in ABCB1 and ABCG2 expression with SI (Doc) and SI (Doc + Gem), and positive correlation of MVP expression with SI (Doc) and SI (Doc + Gem) in undifferentiated pleomorphic sarcoma. Pgp expression was shown in 5 out of 44 STS samples with prevalence of synovial sarcoma relapses and it is strongly correlated with SI (Gem). Mutations in MDR-associated genes were rarely found. Overall, STS demonstrated high heterogeneity in chemosensitivity that makes reasonable in vitro chemosensitivity testing to improve personalized STS therapy, and classic ABC-transporters are not obviously involved in MDR appearance.
BRET-Based Biosensors to Measure Agonist Efficacies in Histamine H1 Receptor-Mediated G Protein Activation, Signaling and Interactions with GRKs and β-Arrestins
Authors: Verweij Eléonore W. E. , Bosma Reggie , Gao Meichun , van den Bor Jelle , Al Araaj Betty , de Munnik Sabrina M. , Ma Xiaoyuan , Leurs Rob , Vischer Henry F.
Published: March 2022

The histamine H1 receptor (H1R) is a G protein-coupled receptor (GPCR) and plays a key role in allergic reactions upon activation by histamine which is locally released from mast cells and basophils. Consequently, H1R is a well-established therapeutic target for antihistamines that relieve allergy symptoms. H1R signals via heterotrimeric Gq proteins and is phosphorylated by GPCR kinase (GRK) subtypes 2, 5, and 6, consequently facilitating the subsequent recruitment of β-arrestin1 and/or 2. Stimulation of a GPCR with structurally different agonists can result in preferential engagement of one or more of these intracellular signaling molecules. To evaluate this so-called biased agonism for H1R, bioluminescence resonance energy transfer (BRET)-based biosensors were applied to measure H1R signaling through heterotrimeric Gq proteins, second messengers (inositol 1,4,5-triphosphate and Ca2+), and receptor-protein interactions (GRKs and β-arrestins) in response to histamine, 2-phenylhistamines, and histaprodifens in a similar cellular background. Although differences in efficacy were observed for these agonists between some functional readouts as compared to reference agonist histamine, subsequent data analysis using an operational model of agonism revealed only signaling bias of the agonist Br-phHA-HA in recruiting β-arrestin2 to H1R over Gq biosensor activation.
Reduced Expression of PD-1 in Circulating CD4+ and CD8+ Tregs Is an Early Feature of RRMS
Authors: Machcińska Maja , Kierasińska Magdalena , Michniowska Martyna , Maruszewska-Cheruiyot Marta , Szewczak Ludmiła , Rola Rafał , Karlińska Anna , Stear Michael , Donskow-Łysoniewska Katarzyna
Published: March 2022

Altered regulatory T cell (Treg) function could contribute to MS. The expression of activating and inhibitory receptors influences the activity of Tregs. Our aim was to investigate T cell phenotypes in relapsing–remitting MS (RRMS) patients at an early phase of the disease. We examined the influence of demographic parameters on the distribution of CD4+ and CD8+ T cell subclasses by generalized linear modeling. We also studied the expression of the following markers—CTLA-4, GITR, PD-1, FoxP3, Helios, CD28, CD62L, CD103—on T cell subsets from peripheral blood with a 14-color flow cytometry panel. We used an antibody array to define the profiles of 34 Th1/Th2/Th17 cytokines in the serum. Expression of PD-1 and GITR on CD4+ and CD8+ Tregs was decreased in RRMS patients. The proinflammatory factors IFN-γ, IL-17, IL-17F, TGFβ-1, TGFβ-3, IL-1SRII, IL-12 p40, sgp130, IL-6sR were significantly increased in RRMS patients. Therefore, a deficiency of PD-1 and GITR immune checkpoints on CD4+ and CD8+ Tregs is a feature of RRMS and might underlie impaired T cell control.
Uric Acid and Oxidative Stress—Relationship with Cardiovascular, Metabolic, and Renal Impairment
Authors: Gherghina Mihai-Emil , Peride Ileana , Tiglis Mirela , Neagu Tiberiu Paul , Niculae Andrei , Checherita Ionel Alexandru
Published: March 2022

Background: The connection between uric acid (UA) and renal impairment is well known due to the urate capacity to precipitate within the tubules or extra-renal system. Emerging studies allege a new hypothesis concerning UA and renal impairment involving a pro-inflammatory status, endothelial dysfunction, and excessive activation of renin–angiotensin–aldosterone system (RAAS). Additionally, hyperuricemia associated with oxidative stress is incriminated in DNA damage, oxidations, inflammatory cytokine production, and even cell apoptosis. There is also increasing evidence regarding the association of hyperuricemia with chronic kidney disease (CKD), cardiovascular disease, and metabolic syndrome or diabetes mellitus. Conclusions: Important aspects need to be clarified regarding hyperuricemia predisposition to oxidative stress and its effects in order to initiate the proper treatment to determine the optimal maintenance of UA level, improving patients’ long-term prognosis and their quality of life.
Molecular Characterisation of Flavanone O-methylation in Eucalyptus
Authors: Somaletha Chandran Krishna , Humphries John , Goodger Jason Q.D. , Woodrow Ian E.
Published: March 2022

Flavonoids are ubiquitous polyphenolic compounds in plants, long recognised for their health-promoting properties in humans. Methylated flavonoids have received increasing attention due to the potential of methylation to enhance medicinal efficacy. Recently, Eucalyptus species with high levels of the O-methylated flavanone pinostrobin have been identified. Pinostrobin has potential commercial value due to its numerous pharmacological and functional food benefits. Little is known about the identity or mode of action of the enzymes involved in methylating flavanones. This study aimed to identify and characterise the methyltransferase(s) involved in the regiospecific methylation of pinostrobin in Eucalyptus and thereby add to our limited understanding of flavanone biosynthesis in plants. RNA-seq analysis of leaf tips enabled the isolation of a gene encoding a flavanone 7-O-methyltransferase (EnOMT1) in Eucalyptus. Biochemical characterisation of its in vitro activity revealed a range of substrates upon which EnOMT1 acts in a regiospecific manner. Comparison to a homologous sequence from a Eucalyptus species lacking O-methylated flavonoids identified critical catalytic amino acid residues within EnOMT1 responsible for its activity. This detailed molecular characterisation identified a methyltransferase responsible for chemical ornamentation of the core flavanone structure of pinocembrin and helps shed light on the mechanism of flavanone biosynthesis in Eucalyptus.
Inducible Systemic Gcn1 Deletion in Mice Leads to Transient Body Weight Loss upon Tamoxifen Treatment Associated with Decrease of Fat and Liver Glycogen Storage
Authors: Liu Jun , Kasai Shuya , Tatara Yota , Yamazaki Hiromi , Mimura Junsei , Mizuno Seiya , Sugiyama Fumihiro , Takahashi Satoru , Sato Tsubasa , Ozaki Taku , Tanji Kunikazu , Wakabayashi Koichi , Maeda Hayato , Mizukami Hiroki , Shinkai Yasuhiro , Kumagai Yoshito , Tomita Hirofumi , Itoh Ken
Published: March 2022

GCN1 is an evolutionarily-conserved ribosome-binding protein that mediates the amino acid starvation response as well as the ribotoxic stress response. We previously demonstrated that Gcn1 mutant mice lacking the GCN2-binding domain suffer from growth retardation and postnatal lethality via GCN2-independent mechanisms, while Gcn1-null mice die early in embryonic development. In this study, we explored the role of GCN1 in adult mice by generating tamoxifen-inducible conditional knockout (CKO) mice. Unexpectedly, the Gcn1 CKO mice showed body weight loss during tamoxifen treatment, which gradually recovered following its cessation. They also showed decreases in liver weight, hepatic glycogen and lipid contents, blood glucose and non-esterified fatty acids, and visceral white adipose tissue weight with no changes in food intake and viability. A decrease of serum VLDL suggested that hepatic lipid supply to the peripheral tissues was primarily impaired. Liver proteomic analysis revealed the downregulation of mitochondrial β-oxidation that accompanied increases of peroxisomal β-oxidation and aerobic glucose catabolism that maintain ATP levels. These findings show the involvement of GCN1 in hepatic lipid metabolism during tamoxifen treatment in adult mice.
Receptive Field Sizes of Nyxnob Mouse Retinal Ganglion Cells
Authors: Hölzel Maj-Britt , Howlett Marcus H. C. , Kamermans Maarten
Published: March 2022

Patients with congenital nystagmus, involuntary eye movements, often have a reduced visual acuity. Some of these patients have a retinal-specific mutation in the protein nyctalopin, which is also present in the Nyxnob mouse. In these mice, retinal ganglion cells (RGCs) have oscillatory activity, which leads to expanded axonal projections towards the dLGN and consequently to a desegregation of retinal projections to the brain. In this study, we investigate whether the receptive fields of Nyxnob RGCs have also expanded by measuring the size of their receptive fields using MEA recordings. Contrary to our expectation, relative to wild-type (WT) mice we found receptive field sizes in the Nyxnob retina had not increased but instead had decreased for green-light preferring RGCs. Additionally, we also found the receptive fields of UV-light preferring RGCs are larger than green-light preferring RGCs in both WT and Nyxnob mice.
Identification of Novel Genes Involved in Hyperglycemia in Mice
Authors: Jonas Wenke , Kluth Oliver , Helms Anett , Voß Sarah , Jähnert Markus , Gottmann Pascal , Speckmann Thilo , Knebel Birgit , Chadt Alexandra , Al-Hasani Hadi , Schürmann Annette , Vogel Heike
Published: March 2022

Current attempts to prevent and manage type 2 diabetes have been moderately effective, and a better understanding of the molecular roots of this complex disease is important to develop more successful and precise treatment options. Recently, we initiated the collective diabetes cross, where four mouse inbred strains differing in their diabetes susceptibility were crossed with the obese and diabetes-prone NZO strain and identified the quantitative trait loci (QTL) Nidd13/NZO, a genomic region on chromosome 13 that correlates with hyperglycemia in NZO allele carriers compared to B6 controls. Subsequent analysis of the critical region, harboring 644 genes, included expression studies in pancreatic islets of congenic Nidd13/NZO mice, integration of single-cell data from parental NZO and B6 islets as well as haplotype analysis. Finally, of the five genes (Acot12, S100z, Ankrd55, Rnf180, and Iqgap2) within the polymorphic haplotype block that are differently expressed in islets of B6 compared to NZO mice, we identified the calcium-binding protein S100z gene to affect islet cell proliferation as well as apoptosis when overexpressed in MIN6 cells. In summary, we define S100z as the most striking gene to be causal for the diabetes QTL Nidd13/NZO by affecting β-cell proliferation and apoptosis. Thus, S100z is an entirely novel diabetes gene regulating islet cell function.
Thromboinflammation in Myeloproliferative Neoplasms (MPN)—A Puzzle Still to Be Solved
Authors: Bhuria Vikas , Baldauf Conny K. , Schraven Burkhart , Fischer Thomas
Published: March 2022

Myeloproliferative neoplasms (MPNs), a group of malignant hematological disorders, occur as a consequence of somatic mutations in the hematopoietic stem cell compartment and show excessive accumulation of mature myeloid cells in the blood. A major cause of morbidity and mortality in these patients is the marked prothrombotic state leading to venous and arterial thrombosis, including myocardial infarction (MI), deep vein thrombosis (DVT), and strokes. Additionally, many MPN patients suffer from inflammation-mediated constitutional symptoms, such as fever, night sweats, fatigue, and cachexia. The chronic inflammatory syndrome in MPNs is associated with the up-regulation of various inflammatory cytokines in patients and is involved in the formation of the so-called MPN thromboinflammation. JAK2-V617F, the most prevalent mutation in MPNs, has been shown to activate a number of integrins on mature myeloid cells, including granulocytes and erythrocytes, which increase adhesion and drive venous thrombosis in murine knock-in/out models. This review aims to shed light on the current understanding of thromboinflammation, involvement of neutrophils in the prothrombotic state, plausible molecular mechanisms triggering the process of thrombosis, and potential novel therapeutic targets for developing effective strategies to reduce the MPN disease burden.
Simultaneous Genetic Ablation of PD-1, LAG-3, and TIM-3 in CD8 T Cells Delays Tumor Growth and Improves Survival Outcome
Authors: Ciraolo Elisa , Althoff Stefanie , Ruß Josefine , Rosnev Stanislav , Butze Monique , Pühl Miriam , Frentsch Marco , Bullinger Lars , Na Il-Kang
Published: March 2022

Immune checkpoint inhibitors (ICI) represented a step forward in improving the outcome of patients with various refractory solid tumors and several therapeutic regimens incorporating ICI have already been approved for a variety of tumor entities. However, besides remarkable long-term responses, checkpoint inhibition can trigger severe immune-related adverse events in some patients. In order to improve safety of ICI as well as T cell therapy, we tested the feasibility of combining T cell-based immunotherapy with genetic disruption of checkpoint molecule expression. Therefore, we generated H-Y and ovalbumin antigen-specific CD8+ T cells with abolished PD-1, LAG-3, and TIM-3 expression through CRISPR/Cas9 technology. CD8+ T cells, subjected to PD-1, LAG-3, and TIM-3 genetic editing, showed a strong reduction in immune checkpoint molecule expression after in vitro activation, while no relevant reduction in responsiveness to in vitro stimulation was observed. At the same time, in B16-OVA tumor model, transferred genetically edited OT-1 CD8+ T cells promoted longer survival compared to control T cells and showed enhanced expansion without associated toxicity. Our study supports the notion that antigen-specific adoptive T cell therapy with concomitant genetic disruption of multiple checkpoint inhibitory receptors could represent an effective antitumor immunotherapy approach with improved tolerability profile.
Applications of Antimicrobial Photodynamic Therapy against Bacterial Biofilms
Authors: Songca Sandile Phinda , Adjei Yaw
Published: March 2022

Antimicrobial photodynamic therapy and allied photodynamic antimicrobial chemotherapy have shown remarkable activity against bacterial pathogens in both planktonic and biofilm forms. There has been little or no resistance development against antimicrobial photodynamic therapy. Furthermore, recent developments in therapies that involve antimicrobial photodynamic therapy in combination with photothermal hyperthermia therapy, magnetic hyperthermia therapy, antibiotic chemotherapy and cold atmospheric pressure plasma therapy have shown additive and synergistic enhancement of its efficacy. This paper reviews applications of antimicrobial photodynamic therapy and non-invasive combination therapies often used with it, including sonodynamic therapy and nanozyme enhanced photodynamic therapy. The antimicrobial and antibiofilm mechanisms are discussed. This review proposes that these technologies have a great potential to overcome the bacterial resistance associated with bacterial biofilm formation.
Mitochondrial Sirtuins in Chronic Degenerative Diseases: New Metabolic Targets in Colorectal Cancer
Authors: Colloca Antonino , Balestrieri Anna , Anastasio Camilla , Balestrieri Maria Luisa , D’Onofrio Nunzia
Published: March 2022

Sirtuins (SIRTs) are a family of class III histone deacetylases (HDACs) consisting of seven members, widely expressed in mammals. SIRTs mainly participate in metabolic homeostasis, DNA damage repair, cell survival, and differentiation, as well as other cancer-related biological processes. Growing evidence shows that SIRTs have pivotal roles in chronic degenerative diseases, including colorectal cancer (CRC), the third most frequent malignant disease worldwide. Metabolic alterations are gaining attention in the context of CRC development and progression, with mitochondrion representing a crucial point of complex and intricate molecular mechanisms. Mitochondrial SIRTs, SIRT2, SIRT3, SIRT4 and SIRT5, control mitochondrial homeostasis and dynamics. Here, we provide a comprehensive review on the latest advances on the role of mitochondrial SIRTs in the initiation, promotion and progression of CRC. A deeper understanding of the pathways by which mitochondrial SIRTs control CRC metabolism may provide new molecular targets for future innovative strategies for CRC prevention and therapy.
Collagen Family and Other Matrix Remodeling Proteins Identified by Bioinformatics Analysis as Hub Genes Involved in Gastric Cancer Progression and Prognosis
Authors: Chivu-Economescu Mihaela , Necula Laura G. , Matei Lilia , Dragu Denisa , Bleotu Coralia , Sorop Andrei , Herlea Vlad , Dima Simona , Popescu Irinel , Diaconu Carmen C.
Published: March 2022

Gastric cancer has remained in the top five cancers for over ten years, both in terms of incidence and mortality due to the shortage of biomarkers for disease follow-up and effective therapies. Aiming to fill this gap, we performed a bioinformatics assessment on our data and two additional GEO microarray profiles, followed by a deep analysis of the 40 differentially expressed genes identified. PPI network analysis and MCODE plug-in pointed out nine upregulated hub genes coding for proteins from the collagen family (COL12A1, COL5A2, and COL10A1) or involved in the assembly (BGN) or degradation of collagens (CTHRC1), and also associated with cell adhesion (THBS2 and SPP1) and extracellular matrix degradation (FAP, SULF1). Those genes were highly upregulated at the mRNA and protein level, the increase being correlated with pathological T stages. The high expression of BGN (p = 8 × 10−12), THBS2 (p = 1.2 × 10−6), CTHRC1 (p = 1.1 × 10−4), SULF1 (p = 3.8 × 10−4), COL5A1 (p = 1.3 × 10−4), COL10A1 (p = 5.7 × 10−4), COL12A1 (p = 2 × 10−3) correlated with poor overall survival and an immune infiltrate based especially on immunosuppressive M2 macrophages (p-value range 4.82 × 10−7–1.63 × 10−13). Our results emphasize that these genes could be candidate biomarkers for GC progression and prognosis and new therapeutic targets.
Gene Expression over Time during Cell Transformation Due to Non-Genotoxic Carcinogen Treatment of Bhas 42 Cells
Authors: Ohmori Kiyomi , Kamei Asuka , Watanabe Yuki , Abe Keiko
Published: March 2022

The Bhas 42 cell transformation assay (Bhas 42 CTA) is the first Organization for Economic Cooperation and Development (OECD)-certificated method used as a specific tool for the detection of the cell-transformation potential of tumor-promoting compounds, including non-genotoxic carcinogens (NGTxCs), as separate from genotoxic carcinogens. This assay offers the great advantage of enabling the phenotypic detection of oncotransformation. A key benefit of using the Bhas 42 CTA in the study of the cell-transformation mechanisms of tumor-promoting compounds, including non-genotoxic carcinogens, is that the cell-transformation potential of the chemical can be detected directly without treatment with a tumor-initiating compound since Bhas 42 cell line was established by transfecting the v-Ha-ras gene into a mouse fibroblast cloned cell line. Here, we analyzed the gene expression over time, using DNA microarrays, in Bhas 42 cells treated with the tumor-promoting compound 12-O-tetradecanoylphorbol-13-acetate (TPA), and NGTxC, with a total of three repeat experiments. This is the first paper to report on gene expression over time during the process of cell transformation with only a tumor-promoting compound. Pathways that were activated or inactivated during the process of cell transformation in the Bhas 42 cells treated with TPA were related not only directly to RAS but also to various pathways in the hallmarks of cancer.
INSIDIA 2.0 High-Throughput Analysis of 3D Cancer Models: Multiparametric Quantification of Graphene Quantum Dots Photothermal Therapy for Glioblastoma and Pancreatic Cancer
Authors: Perini Giordano , Rosa Enrico , Friggeri Ginevra , Di Pietro Lorena , Barba Marta , Parolini Ornella , Ciasca Gabriele , Moriconi Chiara , Papi Massimiliano , De Spirito Marco , Palmieri Valentina
Published: March 2022

Cancer spheroids are in vitro 3D models that became crucial in nanomaterials science thanks to the possibility of performing high throughput screening of nanoparticles and combined nanoparticle-drug therapies on in vitro models. However, most of the current spheroid analysis methods involve manual steps. This is a time-consuming process and is extremely liable to the variability of individual operators. For this reason, rapid, user-friendly, ready-to-use, high-throughput image analysis software is necessary. In this work, we report the INSIDIA 2.0 macro, which offers researchers high-throughput and high content quantitative analysis of in vitro 3D cancer cell spheroids and allows advanced parametrization of the expanding and invading cancer cellular mass. INSIDIA has been implemented to provide in-depth morphologic analysis and has been used for the analysis of the effect of graphene quantum dots photothermal therapy on glioblastoma (U87) and pancreatic cancer (PANC-1) spheroids. Thanks to INSIDIA 2.0 analysis, two types of effects have been observed: In U87 spheroids, death is accompanied by a decrease in area of the entire spheroid, with a decrease in entropy due to the generation of a high uniform density spheroid core. On the other hand, PANC-1 spheroids’ death caused by nanoparticle photothermal disruption is accompanied with an overall increase in area and entropy due to the progressive loss of integrity and increase in variability of spheroid texture. We have summarized these effects in a quantitative parameter of spheroid disruption demonstrating that INSIDIA 2.0 multiparametric analysis can be used to quantify cell death in a non-invasive, fast, and high-throughput fashion.
Autoethnography on Researcher Profile Cultivation
Authors: Pańkowska Małgorzata
Published: March 2022

Information Communication Technology (ICT) and social networks have significant impact on everyday life. One the one hand, Internet users enjoy promoting themselves and feel free to disseminate information about themselves through websites and social networks, but on the other hand, people feel forced to reveal information about them on the Internet. Web technologies enable self-promotion for many reasons, i.e., social relations development, acquiring a new job, or research career support. This paper concerns autoethnography application for social science researcher profile cultivation. Autoethnography belongs to qualitative methods and focuses on deep analysis of experiences and competencies in a narrative way. In this study, autoethnography is self-reflection for personal development strategy. This study methodology includes the literature survey and case study. The Literature Survey (LS) on autoethnographic research is included to answer the question for what purposes autoethnography is applied. In the case study, the author proposes to expand autoethnography and presents that beyond stories, statistical data can be used to reveal researcher’s experiences and personality, and data anonymization is a solution for privacy protection in autoethnographic research. The results indicate that perception of individual profile is significantly influenced by ICT, Internet services, and social networks platforms and portals. Contemporary researchers are evaluated by Web statistical measures. The researcher’s profiling is much more complex and statistical measures and metrics provide a general view of the researcher. Application of statistical measures leads to concluding on general competencies of the researcher and precludes a deep focus on local scientific specificity of the researcher. This paper has added value because of presenting the academic community integration with the Internet social networks, e.g., Facebook, LinkedIn, or SciVal. The paper emphasizes transparency and visibility of researchers’ profiles, as well as the necessity to analyze their activities and publications in academic community context and in comparisons with others.
Characterization of Molting Process during the Different Developmental Stages of the Diamondback Moth Plutella xylostella
Authors: Gu Licheng , Wu Zhiwei , Wu Xiaotong , Zhou Yuenan , Yang Pei , Ye Xiqian , Shi Min , Huang Jianhua , Chen Xuexin
Published: March 2022

The molting process of the lepidopteran insects is observed for many species. However, the detailed description of the morphological transformation and behavioral sequence during molting are rarely provided and visualized. Here, we described the molting process of the diamondback moth Plutella xylostella by providing the duration and photographic details of staging criteria of each stage using stereo microscopy and a digital video camera. We divided the morphological transformation of egg development and hatching into five stages, the larval–larval ecdysis and the larval–pupal metamorphosis into five stages, the pupal development and eclosion into three stages, and the post-eclosion behavior into four stages. Several new characters in the molting process that were not previously described in other lepidopteran insects were found, i.e., the larvae contracted anterior-posteriorly then dorsal-ventrally during pre-ecdysis, and the antennae waved backward then forward in the post-eclosion behavior. Our findings will deepen the knowledge of the molting biology of lepidopteran insects and facilitate the study of the underlying mechanisms.
Midgut and Head Transcriptomic Analysis of Silkworms Reveals the Physiological Effects of Artificial Diets
Authors: Li Juan , Chen Chunbing , Zha Xingfu
Published: March 2022

Silkworms, a model lepidopteran insect, have a very simple diet. Artificial diets as an alternative nutrient source for silkworms are gradually being developed. To understand the effects of various nutrients on the growth and development of silkworms, we studied the transcriptomic differences in the midgut and head tissues of male and female silkworms fed either fresh mulberry leaves or artificial diets. In the artificial diet group, compared with the control group (fed mulberry leaves), 923 and 619 differentially expressed genes (DEGs) were identified from the midgut, and 2969 and 3427 DEGs were identified from the head, in female and male silkworms. According to our analysis, the DEGs were mainly involved in the digestion and absorption of nutrients and silkworm innate immunity. These experimental results provide insights into the effects of different foods, such as artificial diets or fresh mulberry leaves, on silkworms.
Editorial “Industrial IoT as IT and OT Convergence: Challenges and Opportunities”
Authors: Giannelli Carlo , Picone Marco
Published: March 2022

During the last decade, the advent of the Internet of Things (IoT) and its quick and pervasive evolution have significantly revolutionized the Information Technology ecosystem [...]
Usefulness of 68-Gallium PET in Type I Gastric Neuroendocrine Neoplasia: A Case Series
Authors: Rinzivillo Maria , Panzuto Francesco , Esposito Gianluca , Lahner Edith , Signore Alberto , Annibale Bruno
Published: March 2022

Background: Type I gastric neuroendocrine neoplasia (gNEN) is a rare and low-grade tumor in which the therapeutic strategy is almost always endoscopic. For this reason, the use of radiology or nuclear medicine imaging is not recommended by guidelines. Conversely, in a small number of cases, locoregional or distant metastases may develop, thus suggesting a role for imaging techniques. This retrospective study was performed to explore the usefulness of [68Ga]Ga-DOTA-SST PET/CT in the management of patients with T1gNENs. Patients and Method: Single-center retrospective analysis, in an ENETS Center of Excellence, of patients with type I gNEN who underwent [68Ga]Ga-DOTA-SST PET/CT. The indication for performing [68Ga]Ga-DOTA-SST PET/CT was generally based on the presence of at least one of the following criteria: (1) polyps > 10 mm; (2) endoscopic positive (R1) margin after previous endoscopic resection; and (3) Ki-67 > 3%. Results: A total of 120 patients with T1gNEN were evaluated. Overall, 15 out of 120 (13%) patients had performed [68Ga]Ga-DOTA-SST PET/CT. The median Ki-67 value was 6% (IQR 1–9): 9 out of 15 (60%) were G1 tumors, and 6 out of 15 (40%) were G2 tumors. Ninety-three percent of patients were treated by tumor endoscopic resection, whereas surgery was performed in two patients (13%) after incomplete endoscopic resection; the remaining patients (6.6%) received somatostatin analogs due to the presence of multiple recurrent tumors. Overall, [68Ga]Ga-DOTA-SST PET/CT was positive in 8 out of 15 patients (53%). Following the [68Ga]Ga-DOTA-SST PET/CT findings, the clinical management was modified in 6 out of 15 (40%) patients. Conclusion: [68Ga]Ga-DOTA-SST PET/CT can be useful in a restricted and selected group of patients with gastric neuroendocrine neoplasia with relevant risk factors to establish the most appropriate therapeutic strategy.
Development and Calibration of the PREMIUM Item Bank for Measuring Respect and Dignity for Patients with Severe Mental Illness
Authors: Fernandes Sara , Fond Guillaume , Zendjidjian Xavier , Michel Pierre , Baumstarck Karine , Lançon Christophe , Samalin Ludovic , Llorca Pierre-Michel , Coldefy Magali , Auquier Pascal , Boyer Laurent ,   Collaborators of the French PREMIUM Group
Published: March 2022

Most patient-reported experience measures (PREMs) are paper-based, leading to a high burden for patients and care providers. The aim of this study was to (1) calibrate an item bank to measure patients’ experience of respect and dignity for adult patients with serious mental illnesses and (2) develop computerized adaptive testing (CAT) to improve the use of this PREM in routine practice. Patients with schizophrenia, bipolar disorder, and major depressive disorder were enrolled in this multicenter and cross-sectional study. Psychometric analyses were based on classical test and item response theories and included evaluations of unidimensionality, local independence, and monotonicity; calibration and evaluation of model fit; analyses of differential item functioning (DIF); testing of external validity; and finally, CAT development. A total of 458 patients participated in the study. Of the 24 items, 2 highly inter-correlated items were deleted. Factor analysis showed that the remaining items met the unidimensional assumption (RMSEA = 0.054, CFI = 0.988, TLI = 0.986). DIF analyses revealed no biases by sex, age, care setting, or diagnosis. External validity testing has generally supported our assumptions. CAT showed satisfactory accuracy and precision. This work provides a more accurate and flexible measure of patients’ experience of respect and dignity than that obtained from standard questionnaires.
Confocal Laser Scanner Evaluation of Bactericidal Effect of Chitosan Nanodroplets Loaded with Benzalkonium Chloride
Authors: Alovisi Mario , Pasqualini Damiano , Mandras Narcisa , Roana Janira , Costamagna Pietro , Comba Allegra , Cavalli Roberta , Luganini Anna , Iandolo Alfredo , Cavallo Lorenza , Scotti Nicola , Berutti Elio
Published: March 2022

The aim was to evaluate the antibacterial efficacy and penetration depth into dentinal tubules of a solution of chitosan nanodroplets (NDs) loaded with Benzalkonium Chloride (BAK). Seventy-two human single-root teeth with fully formed apex were used. Cylindrical root dentin blocks were longitudinally sectioned and enlarged to a size of a Gates Glidden drill #4. After sterilization, root canals were infected with Enterococcus faecalis ATCC 29212 and further incubated for three weeks. Specimens were assigned to three experimental groups (n = 20), plus positive (n = 6) and negative (n = 6) controls. In the first group, irrigation was achieved with 2 mL of NDs solution loaded with BAK (NDs-BAK), in the second with 2 mL of 5% sodium hypochlorite (NaOCl) and in the last with 2 mL of 2% chlorhexidine (CHX). Specimens were rinsed and vertically fractured. Confocal laser scanning microscopy (CLSM) and viability staining were used to analyze the proportions of dead and live bacteria quantitatively. The volume ratio of red fluorescence (dead) was calculated in 3D reconstructions. Data were analyzed by one-way ANOVA and post hoc Bonferroni tests (p < 0.05). The ratio of red fluorescence over the whole green/red fluorescence resulted in a significant comparison of NDs-BAK with NaOCl (p < 0.01) and NaOCl with CHX (p < 0.01). No differences were found between NDs-BAK and CHX (p > 0.05). The mean depth of efficacy was, respectively: NDs-BAK 325.25 μm, NaOCl 273.36 μm and CHX 246.78 μm with no statistical differences between groups. The NaOCl solution showed the highest antimicrobial efficacy, but nanodroplets with BAK seemed to have the same effect as CHX with a high depth of efficacy.
Analysis of the Ability to Tolerate Body Balance Disturbance in Relation to Selected Changes in the Sagittal Plane of the Spine in Early School-Age Children
Authors: Kurzeja Piotr , Gąsienica-Walczak Bartłomiej , Ogrodzka-Ciechanowicz Katarzyna , Prusak Jarosław
Published: March 2022

The study aimed to estimate the ability to tolerate body balance disturbance in relation to selected changes in the sagittal plane of the spine in early school-age children. The study involved 189 children with an average age of 8.3 ± 0.7 years (aged 7–10). The tests included an interview, clinical examination (measurement of body weight and height, assessment of the course of the spinous processes of the thoracic and lumbar vertebrae, assessment of the location of selected anatomical landmarks of the torso), and a physical examination in which the shape of the spine surface was examined with the use of the photogrammetric method and the moiré effect projection. Body balance disturbance tolerance skills (BBDTS) were measured with the rotational test (RT). In the rotational test, the results of body balance disturbance tolerance skills show a slight but statistically significant correlation with the bodyweight of the examined children (Rs = 0.35, p < 0.001). This relationship was also statistically significant in the groups by gender. Among the measured indicators of the curvature of the spine in the sagittal plane, the correlation with the RT test result was mostly related to the α angle and the value was Rs = 0.15 (p = 0.04). In the group of girls, this correlation was stronger and amounted to Rs = 0.26 (p = 0.015). Among other measured correlations, the dependence of variables such as the bodyweight of the subjects and the α angle was shown. In conclusion, increasing lumbar lordosis results in the deterioration of balance disturbance tolerance skills. As body weight increases, body balance disturbance tolerance skills decrease.
Comparative Efficacy and Safety of Tirbanibulin for Actinic Keratosis of the Face and Scalp in Europe: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
Authors: Heppt Markus V. , Dykukha Igor , Graziadio Sara , Salido-Vallejo Rafael , Chapman-Rounds Matt , Edwards Mary
Published: March 2022

Actinic keratosis (AK) is a chronic skin condition that may progress to cutaneous squamous cell carcinoma. We conducted a systematic review of efficacy and safety for key treatments for AK of the face and scalp, including the novel 5-day tirbanibulin 1% ointment. MEDLINE, PubMed, Embase, Cochrane Library, clinical trial registries and regulatory body websites were searched. The review included 46 studies, of which 35 studies included interventions commonly used in Europe and were sufficiently homogenous to inform a Bayesian network meta-analysis of complete clearance against topical placebo or vehicle. The network meta-analysis revealed the following odds ratios and 95% credible intervals: cryosurgery 13.4 (6.2–30.3); diclofenac 3% 2.9 (1.9–4.3); fluorouracil 0.5% + salicylic acid 7.6 (4.6–13.5); fluorouracil 4% 30.3 (9.1–144.7); fluorouracil 5% 35.0 (10.2–164.4); imiquimod 3.75% 8.5 (3.5–22.4); imiquimod 5% 17.9 (9.1–36.6); ingenol mebutate 0.015% 12.5 (8.1–19.9); photodynamic therapy with aminolevulinic acid 24.1 (10.9–52.8); photodynamic therapy with methyl aminolevulinate 11.7 (6.0–21.9); tirbanibulin 1% 11.1 (6.2–20.9). Four sensitivity analyses, from studies assessing efficacy after one treatment cycle only, for ≤25 cm2 treatment area, after 8 weeks post-treatment, and with single placebo/vehicle node confirmed the findings from the base case. Safety outcomes were assessed qualitatively. These results suggest that tirbanibulin 1% offers a novel treatment for AK, with a single short treatment period, favourable safety profile and efficacy, in line with existing topical treatments available in Europe.