bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual Reality Aided Therapy towards Health 4.0: A Two-Decade Bibliometric Analysis
Authors: Liu Zhen , Ren Lingfeng , Xiao Chang , Zhang Ke , Demian Peter
Published: January 2022

Health 4.0 aligns with Industry 4.0 and encourages the application of the latest technologies to healthcare. Virtual reality (VR) is a potentially significant component of the Health 4.0 vision. Though VR in health care is a popular topic, there is little knowledge of VR-aided therapy from a macro perspective. Therefore, this paper was aimed to explore the research of VR in aiding therapy, thus providing a potential guideline for futures application of therapeutic VR in healthcare towards Health 4.0. A mixed research method was adopted for this research, which comprised the use of a bibliometric analysis (a quantitative method) to conduct a macro overview of VR-aided therapy, the identification of significant research structures and topics, and a qualitative review of the literature to reveal deeper insights. Four major research areas of VR-aided therapy were identified and investigated, i.e., post-traumatic stress disorder (PTSD), anxiety and fear related disorder (A&F), diseases of the nervous system (DNS), and pain management, including related medical conditions, therapies, methods, and outcomes. This study is the first to use VOSviewer, a commonly used software tool for constructing and visualizing bibliometric networks and developed by Center for Science and Technology Studies, Leiden University, the Netherlands, to conduct bibliometric analyses on VR-aided therapy from the perspective of Web of Science core collection (WoSc), which objectively and visually shows research structures and topics, therefore offering instructive insights for health care stakeholders (particularly researchers and service providers) such as including integrating more innovative therapies, emphasizing psychological benefits, using game elements, and introducing design research. The results of this paper facilitate with achieving the vision of Health 4.0 and illustrating a two-decade (2000 to year 2020) map of pre-life of the Health Metaverse.
Extended Warranty Strategy and Its Environment Impact of Remanufactured Supply Chain
Authors: Zhang Xuemei , Hu Jiawei , Sun Suqin , Qi Guohu
Published: January 2022

To reduce environmental pollution, the government has issued relevant laws and regulations, and more and more enterprises engage in remanufacturing and recycling used products. Trade old for new and trade old for remanufactured have become marketing means to promote product recycling. The extended warranty service is used to promote the recycling of waste products. To design an optimal extended warranty service strategy and analyze its environment impact in a remanufactured supply chain, game theory is used to model the competitive relationship between a manufacturer and an E-commerce platform. Considering whether the E-commerce platform provides extended warranty service, four models are constructed, and the extended warranty service strategy and its environment impact can be analyzed. The results show that, when the level of substitutability between remanufactured and new products meets a certain rage, new or remanufactured products with extended warranty service strategy can increase the demand for new or remanufactured products, respectively. In the four models, the changing trends of manufacturer’s profit, E-commerce platform’s profit and supply chain’s profit, consumer surplus, environmental impact and social welfare are the same, but only the thresholds are different. From the perspectives of supply chain member, supply chain system, consumer, environment and society, the new and remanufactured products with extended warranty service strategy is the best choice.
Reasons behind Low Cervical Screening Uptake among South Asian Immigrant Women: A Qualitative Exploration
Authors: Alam Zufishan , Deol Hanoor , Dean Judith Ann , Janda Monika
Published: January 2022

Despite advancements in prevention strategies, cervical cancer remains a leading cause of death among underprivileged women. Although Australia has low age-standardized cervical cancer incidence rates compared with other countries, disparities exist in cervical screening uptake among certain population subgroups, especially those from culturally and linguistically diverse (CALD) backgrounds. South Asian immigrant women have been reported to have lower cervical screening uptake than Australian-born women and those from other immigrant backgrounds. The objective of this study was to gain insight into the reasons and barriers for low cervical screening participation among South Asian immigrant women, through qualitative exploration. Semi-structured, in-depth interviews were conducted with 20 women, aged 26–50 years, living in Queensland, Australia, who were recruited via purposive sampling. After translation and transcription of recorded interviews, data was analysed via inductive thematic approach. Resulting themes, illustrating barriers towards screening, included: lack of cervical cancer and screening knowledge, especially of the changes in the revised screening program; effect of preventive, health-seeking behaviours; health care system factors; role of practical constraints and influence of sociocultural beliefs. Results suggest that culturally informed interventions, that involve relevant information provision and behavioural change strategies, to clarify women’s misconceptions, are required.
Social Determinants of Remaining Life Expectancy at Age 60: A District-Level Analysis in Germany
Authors: Siegel Achim , Schug Jonas F. , Rieger Monika A.
Published: January 2022

Remaining life expectancy at age 60 (in short: RLE) is an important indicator of the health status of a population’s elders. Until now, RLE has not been thoroughly investigated at the district level in Germany. In this study we analyzed, based on recent publicly available data (2015–2017), and for men and women separately, how large the RLE differences were in Germany across the 401 districts. Furthermore, we examined a wide range of potential social determinants in terms of their bivariate and multivariate (i.e., partial) impact on men’s and women’s RLE. Men’s district-level RLE ranged between 19.89 and 24.32 years, women’s district-level RLE between 23.67 and 27.16 years. The best single predictor both for men’s and women’s RLE at district level was ‘proportion of employees with academic degree’ with standardized partial regression coefficients of 0.42 (men) and 0.51 (women). Second and third in rank were classic economic predictors, such as ‘household income’ (men), ‘proportion of elder with financial elder support’ (women), and ‘unemployment’ (men and women). Indicators expressing the availability of medical services and staffing levels of nursing homes and services had at best a marginal partial impact. This study contributes to the growing body of evidence that a population’s educational level is a decisive determinant of population health resp. life expectancy in contemporary industrialized societies.
A System for Aligning Geographical Entities from Large Heterogeneous Sources
Authors: Melo André , Er-Rahmadi Btissam , Pan Jeff Z.
Published: January 2022

Aligning points of interest (POIs) from heterogeneous geographical data sources is an important task that helps extend map data with information from different datasets. This task poses several challenges, including differences in type hierarchies, labels (different formats, languages, and levels of detail), and deviations in the coordinates. Scalability is another major issue, as global-scale datasets may have tens or hundreds of millions of entities. In this paper, we propose the GeographicaL Entities AligNment (GLEAN) system for efficiently matching large geographical datasets based on spatial partitioning with an adaptable margin. In particular, we introduce a text similarity measure based on the local-context relevance of tokens used in combination with sentence embeddings. We then come up with a scalable type embedding model. Finally, we demonstrate that our proposed system can efficiently handle the alignment of large datasets while improving the quality of alignments using the proposed entity similarity measure.
Molecular Aspects of Resistance to Immunotherapies—Advances in Understanding and Management of Diffuse Large B-Cell Lymphoma
Authors: Kusowska Aleksandra , Kubacz Matylda , Krawczyk Marta , Slusarczyk Aleksander , Winiarska Magdalena , Bobrowicz Malgorzata
Published: January 2022

Despite the unquestionable success achieved by rituximab-based regimens in the management of diffuse large B-cell lymphoma (DLBCL), the high incidence of relapsed/refractory disease still remains a challenge. The widespread clinical use of chemo-immunotherapy demonstrated that it invariably leads to the induction of resistance; however, the molecular mechanisms underlying this phenomenon remain unclear. Rituximab-mediated therapeutic effect primarily relies on complement-dependent cytotoxicity and antibody-dependent cell cytotoxicity, and their outcome is often compromised following the development of resistance. Factors involved include inherent genetic characteristics and rituximab-induced changes in effectors cells, the role of ligand/receptor interactions between target and effector cells, and the tumor microenvironment. This review focuses on summarizing the emerging advances in the understanding of the molecular basis responsible for the resistance induced by various forms of immunotherapy used in DLBCL. We outline available models of resistance and delineate solutions that may improve the efficacy of standard therapeutic protocols, which might be essential for the rational design of novel therapeutic regimens.
Quaternary Selenides EuLnCuSe3: Synthesis, Structures, Properties and In Silico Studies
Authors: Grigoriev Maxim V. , Solovyov Leonid A. , Ruseikina Anna V. , Aleksandrovsky Aleksandr S. , Chernyshev Vladimir A. , Velikanov Dmitriy A. , Garmonov Alexander A. , Molokeev Maxim S. , Oreshonkov Aleksandr S. , Shestakov Nikolay P. , Matigorov Alexey V. , Volkova Svetlana S. , Ostapchuk Evgeniy A. , Kertman Alexander V. , Schleid Thomas , Safin Damir A.
Published: January 2022

In this work, we report on the synthesis, in-depth crystal structure studies as well as optical and magnetic properties of newly synthesized heterometallic quaternary selenides of the Eu+2Ln+3Cu+1Se3 composition. Crystal structures of the obtained compounds were refined by the derivative difference minimization (DDM) method from the powder X-ray diffraction data. The structures are found to belong to orthorhombic space groups Pnma (structure type Ba2MnS3 for EuLaCuSe3 and structure type Eu2CuS3 for EuLnCuSe3, where Ln = Sm, Gd, Tb, Dy, Ho and Y) and Cmcm (structure type KZrCuS3 for EuLnCuSe3, where Ln = Tm, Yb and Lu). Space groups Pnma and Cmcm were delimited based on the tolerance factor t’, and vibrational spectroscopy additionally confirmed the formation of three structural types. With a decrease in the ionic radius of Ln3+ in the reported structures, the distortion of the (LnCuSe3) layers decreases, and a gradual formation of the more symmetric structure occurs in the sequence Ba2MnS3 → Eu2CuS3 → KZrCuS3. According to magnetic studies, compounds EuLnCuSe3 (Ln = Tb, Dy, Ho and Tm) each exhibit ferrimagnetic properties with transition temperatures ranging from 4.7 to 6.3 K. A negative magnetization effect is observed for compound EuHoCuSe3 at temperatures below 4.8 K. The magnetic properties of the discussed selenides and isostructural sulfides were compared. The direct optical band gaps for EuLnCuSe3, subtracted from the corresponding diffuse reflectance spectra, were found to be 1.87–2.09 eV. Deviation between experimental and calculated band gaps is ascribed to lower d states of Eu2+ in the crystal field of EuLnCuSe3, while anomalous narrowing of the band gap of EuYbCuSe3 is explained by the low-lying charge-transfer state. Ab initio calculations of the crystal structures, elastic properties and phonon spectra of the reported compounds were performed.
Kinome-Wide Profiling Identifies Human WNK3 as a Target of Cajanin Stilbene Acid from Cajanus cajan (L.) Millsp.
Authors: Özenver Nadire , Kadioglu Onat , Fu Yujie , Efferth Thomas
Published: January 2022

Pigeon Pea (Cajanus cajan (L.) Millsp.) is a common food crop used in many parts of the world for nutritional purposes. One of its chemical constituents is cajanin stilbene acid (CSA), which exerts anticancer activity in vitro and in vivo. In an effort to identify molecular targets of CSA, we performed a kinome-wide approach based on the measurement of the enzymatic activities of 252 human kinases. The serine-threonine kinase WNK3 (also known as protein kinase lysine-deficient 3) was identified as the most promising target of CSA with the strongest enzymatic activity inhibition in vitro and the highest binding affinity in molecular docking in silico. The lowest binding affinity and the predicted binding constant pKi of CSA (−9.65 kcal/mol and 0.084 µM) were comparable or even better than those of the known WNK3 inhibitor PP-121 (−9.42 kcal/mol and 0.123 µM). The statistically significant association between WNK3 mRNA expression and cellular responsiveness to several clinically established anticancer drugs in a panel of 60 tumor cell lines and the prognostic value of WNK3 mRNA expression in sarcoma biopsies for the survival time of 230 patients can be taken as clues that CSA-based inhibition of WNK3 may improve treatment outcomes of cancer patients and that CSA may serve as a valuable supplement to the currently used combination therapy protocols in oncology.
Identification and Expression Analysis of the Populus trichocarpa GASA-Gene Family
Authors: Wu Kai , Qu Yanshu , Rong Hao , Han Xin , Tian Yating , Xu Li’an
Published: January 2022

The gibberellic acid-stimulated Arabidopsis (GASA) gene family plays an important regulatory role in the growth and development of plants. In this study, we identified 19 GASA genes using bioinformatics-based methods in Populus trichocarpa, and these PtGASA genes could be divided into three categories based on their phylogenetic relationships. Based on an analysis of the structure and motifs of these genes, it was concluded that PtGASA class II members are more conserved than class I and class III members are, and the results of collinearity analysis showed that members of class II are collinearly related in poplar. Expression analysis of Populus trichocarpa roots, stems, and leaves showed that most of the PtGASA genes are expressed at higher levels in the stems or roots than in the leaves; a similar expression pattern was found in Vitis vinifera, indicating that the GASA-family members mainly play a role in the morphogenesis of poplar. Considering the phenomenon of gene amplification, we found that the higher the similarity of homologous genes was, the more similar the expression patterns. This study represents the first whole-genome identification and expression-profile analysis of the GASA-gene family in poplar, a model species, laying a foundation for functional studies of poplar GASA genes and serving as a reference for related research on other woody plant species.
Nonsteroidal Anti-Inflammatory Drugs as PPARγ Agonists Can Induce PRODH/POX-Dependent Apoptosis in Breast Cancer Cells: New Alternative Pathway in NSAID-Induced Apoptosis
Authors: Kazberuk Adam , Chalecka Magda , Palka Jerzy , Surazynski Arkadiusz
Published: January 2022

Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered to be therapeutics in cancer prevention because of their inhibitory effect on cyclooxygenases (COX), which are frequently overexpressed in many types of cancer. However, it was also demonstrated that NSAIDs provoked a proapoptotic effect in COX knocked-out cancer cells. Here, we suggest that this group of drugs may provoke antineoplastic activity through the activation of PPARγ, which induces proline dehydrogenase/proline oxidase (PRODH/POX)-dependent apoptosis. PRODH/POX is a mitochondrial enzyme that catalyzes proline degradation, during which ATP or reactive oxygen species (ROS) are generated. We have found that NSAIDs induced PRODH/POX and PPARγ expressions (as demonstrated by Western Blot or immunofluorescence analysis) and cytotoxicity (as demonstrated by MTT, cytometric assay, and DNA biosynthesis assay) in breast cancer MCF7 cells. Simultaneously, the NSAIDs inhibited collagen biosynthesis, supporting proline for PRODH/POX-induced ROS-dependent apoptosis (as demonstrated by an increase in the expression of apoptosis markers). The data suggest that targeting proline metabolism and the PRODH/POX–PPARγ axis can be considered a novel approach for breast cancer treatment.
Insulin-like Growth Factor 1 Promotes Cell Proliferation by Downregulation of G-Protein-Coupled Receptor 17 Expression via PI3K/Akt/FoxO1 Signaling in SK-N-SH Cells
Authors: Lin Ka-Na , Zhang Kan , Zhao Wei , Huang Shi-Ying , Li Hao
Published: January 2022

Insulin-like growth factor 1 (IGF-1) not only regulates neuronal function and development but also is neuroprotective in the setting of acute ischemic stroke. G-protein-coupled receptor 17 (GPR17) expression in brain tissue serves as an indicator of brain damage. As whether IGF-1 regulates GPR17 expression remains unknown, the aim of this study is to investigate how IGF-1 regulates GPR17 expression in vitro. Human neuroblastoma SK-N-SH cells were used. Lentivirus-mediated short hairpin RNA (shRNA) was constructed to mediate the silencing of FoxO1, while adenoviral vectors were used for its overexpression. Verification of the relevant signaling cascade was performed using a FoxO1 inhibitor (AS1842856), a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), and a GPR17 antagonist (cangrelor). Cell proliferation was analyzed using EdU staining; immunofluorescence staining was used to detect the expression and subcellular localization of FoxO1. Chromatin immunoprecipitation was used to analyze the binding of FoxO1 to the GPR17 promoter in SK-N-SH cells. The expression of FoxO1, GPR17, and protein kinase B (also known as Akt) mRNA and protein as well as the levels of FoxO1 and Akt phosphorylation were investigated in this study. IGF-1 was found to downregulate FoxO1 and GPR17 expression in SK-N-SH cells while promoting cell viability and proliferation. Inhibition of FoxO1 and antagonism of GPR17 were found to play a role similar to that of IGF-1. Silencing of FoxO1 by lentivirus-mediated shRNA resulted in the downregulation of FoxO1 and GPR17 expression. The overexpression of FoxO1 via adenoviral vectors resulted in the upregulation of FoxO1 and GPR17 expression. Blocking of PI3K signaling by LY294002 inhibited the effect of IGF-1 on GPR17 suppression. Results from chromatin immunoprecipitation revealed that IGF-1 promotes FoxO1 nuclear export and reduces FoxO1 binding to the GPR17 promoter in SK-N-SH cells. Here, we conclude that IGF-1 enhances cell viability and proliferation in SK-N-SH cells via the promotion of FoxO1 nuclear export and reduction of FoxO1 binding to the GPR17 promoter via PI3K/Akt signaling. Our findings suggest that the enhancement of IGF-1 signaling to antagonize GPR17 serves as a potential therapeutic strategy in the management of acute ischemic stroke.
The Aryl Hydrocarbon Receptor (AHR): A Novel Therapeutic Target for Pulmonary Diseases?
Authors: Shivanna Binoy , Chu Chun , Moorthy Bhagavatula
Published: January 2022

The aryl hydrocarbon receptor (AHR) is a cytoplasmic transcription factor that is well-known for regulating xenobiotic metabolism. Studies in knockout and transgenic mice indicate that the AHR plays a vital role in the development of liver and regulation of reproductive, cardiovascular, hematopoietic, and immune homeostasis. In this focused review on lung diseases associated with acute injury and alveolar development, we reviewed and summarized the current literature on the mechanistic role(s) and therapeutic potential of the AHR in acute lung injury, chronic obstructive pulmonary disease, and bronchopulmonary dysplasia (BPD). Pre-clinical studies indicate that endogenous AHR activation is necessary to protect neonatal and adult lungs against hyperoxia- and cigarette smoke-induced injury. Our goal is to provide insight into the high translational potential of the AHR in the meaningful management of infants and adults with these lung disorders that lack curative therapies.
Transcription Factor Movement and Exercise-Induced Mitochondrial Biogenesis in Human Skeletal Muscle: Current Knowledge and Future Perspectives
Authors: Taylor Dale F. , Bishop David J.
Published: January 2022

In response to exercise, the oxidative capacity of mitochondria within skeletal muscle increases through the coordinated expression of mitochondrial proteins in a process termed mitochondrial biogenesis. Controlling the expression of mitochondrial proteins are transcription factors—a group of proteins that regulate messenger RNA transcription from DNA in the nucleus and mitochondria. To fulfil other functions or to limit gene expression, transcription factors are often localised away from DNA to different subcellular compartments and undergo rapid movement or accumulation only when required. Although many transcription factors involved in exercise-induced mitochondrial biogenesis have been identified, numerous conflicting findings and gaps exist within our knowledge of their subcellular movement. This review aims to summarise and provide a critical analysis of the published literature regarding the exercise-induced movement of transcription factors involved in mitochondria biogenesis in skeletal muscle.
Endometriosis: An Inflammatory Disease That Requires New Therapeutic Options
Authors: Donnez Jacques , Cacciottola Luciana
Published: January 2022

Endometriosis, defined as the presence of endometrium-like tissue outside the uterus, is estimated to affect 10% of women of reproductive age [...]
Epigenetics in the Diagnosis and Therapy of Malignant Melanoma
Authors: Santourlidis Simeon , Schulz Wolfgang A. , Araúzo-Bravo Marcos J. , Gerovska Daniela , Ott Pauline , Bendhack Marcelo L. , Hassan Mohamed , Erichsen Lars
Published: January 2022

Epigenetic mechanisms are fundamentally important for cancer initiation and development. However, a survey of the literature reveals that, to date, they appear less comprehensively investigated in melanoma than in many other cancers, e.g., prostate, breast, and colon carcinoma. The aim of this review is to provide a short summary of epigenetic aspects of functional relevance for melanoma pathogenesis. In addition, some new perspectives from epigenetic research in other cancers with potential for melanoma diagnosis and therapy are introduced. For example, the PrimeEpiHit hypothesis in urothelial carcinoma, which, similarly to malignant melanoma, can also be triggered by a single exogenous noxa, states that one of the first steps for cancer initiation could be epigenetic changes in key genes of one-carbon metabolism. The application of such insights may contribute to further progress in the diagnosis and therapy of melanoma, a deadly type of cancer.
Nanoapatites Doped and Co-Doped with Noble Metal Ions as Modern Antibiofilm Materials for Biomedical Applications against Drug-Resistant Clinical Strains of Enterococcus faecalis VRE and Staphylococcus aureus MRSA
Authors: Paluch Emil , Sobierajska Paulina , Okińczyc Piotr , Widelski Jarosław , Duda-Madej Anna , Krzyżanowska Barbara , Krzyżek Paweł , Ogórek Rafał , Szperlik Jakub , Chmielowiec Jacek , Gościniak Grażyna , Wiglusz Rafal J.
Published: January 2022

The main aim of our research was to investigate antiadhesive and antibiofilm properties of nanocrystalline apatites doped and co-doped with noble metal ions (Ag+, Au+, and Pd2+) against selected drug-resistant strains of Enterococcus faecalis and Staphylococcus aureus. The materials with the structure of apatite (hydroxyapatite, nHAp; hydroxy-chlor-apatites, OH-Cl-Ap) containing 1 mol% and 2 mol% of dopants and co-dopants were successfully obtained by the wet chemistry method. The majority of them contained an additional phase of metallic nanoparticles, in particular, AuNPs and PdNPs, which was confirmed by the XRPD, FTIR, UV–Vis, and SEM–EDS techniques. Extensive microbiological tests of the nanoapatites were carried out determining their MIC, MBC value, and FICI. The antiadhesive and antibiofilm properties of the tested nanoapatites were determined in detail with the use of fluorescence microscopy and computer image analysis. The results showed that almost all tested nanoapatites strongly inhibit adhesion and biofilm production of the tested bacterial strains. Biomaterials have not shown any significant cytotoxic effect on fibroblasts and even increased their survival when co-incubated with bacterial biofilms. Performed analyses confirmed that the nanoapatites doped and co-doped with noble metal ions are safe and excellent antiadhesive and antibiofilm biomaterials with potential use in the future in medical sectors.
Water-Soluble Products of Photooxidative Destruction of the Bisretinoid A2E Cause Proteins Modification in the Dark
Authors: Dontsov Alexander , Yakovleva Marina , Trofimova Natalia , Sakina Natalia , Gulin Alexander , Aybush Arseny , Gostev Fedor , Vasin Alexander , Feldman Tatiana , Ostrovsky Mikhail
Published: January 2022

Aging of the retina is accompanied by a sharp increase in the content of lipofuscin granules and bisretinoid A2E in the cells of the retinal pigment epithelium (RPE) of the human eye. It is known that A2E can have a toxic effect on RPE cells. However, the specific mechanisms of the toxic effect of A2E are poorly understood. We investigated the effect of the products of photooxidative destruction of A2E on the modification of bovine serum albumin (BSA) and hemoglobin from bovine erythrocytes. A2E was irradiated with a blue light-emitting diode (LED) source (450 nm) or full visible light (400–700 nm) of a halogen lamp, and the resulting water-soluble products of photooxidative destruction were investigated for the content of carbonyl compounds by mass spectrometry and reaction with thiobarbituric acid. It has been shown that water-soluble products formed during A2E photooxidation and containing carbonyl compounds cause modification of serum albumin and hemoglobin, measured by an increase in fluorescence intensity at 440–455 nm. The antiglycation agent aminoguanidine inhibited the process of modification of proteins. It is assumed that water-soluble carbonyl products formed as a result of A2E photodestruction led to the formation of modified proteins, activation of the inflammation process, and, as a consequence, to the progression of various senile eye pathologies.
A Transcriptome Analysis of mRNAs and Long Non-Coding RNAs in Patients with Parkinson’s Disease
Authors: Salemi Michele , Lanza Giuseppe , Mogavero Maria Paola , Cosentino Filomena I. I. , Borgione Eugenia , Iorio Roberta , Ventola Giovanna Maria , Marchese Giovanna , Salluzzo Maria Grazia , Ravo Maria , Ferri Raffaele
Published: January 2022

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. The number of cases of PD is expected to double by 2030, representing a heavy burden on the healthcare system. Clinical symptoms include the progressive loss of dopaminergic neurons in the substantia nigra of the midbrain, which leads to striatal dopamine deficiency and, subsequently, causes motor dysfunction. Certainly, the study of the transcriptome of the various RNAs plays a crucial role in the study of this neurodegenerative disease. In fact, the aim of this study was to evaluate the transcriptome in a cohort of subjects with PD compared with a control cohort. In particular we focused on mRNAs and long non-coding RNAs (lncRNA), using the Illumina NextSeq 550 DX System. Differential expression analysis revealed 716 transcripts with padj ≤ 0.05; among these, 630 were mRNA (coding protein), lncRNA, and MT_tRNA. Ingenuity pathway analysis (IPA, Qiagen) was used to perform the functional and pathway analysis. The highest statistically significant pathways were: IL-15 signaling, B cell receptor signaling, systemic lupus erythematosus in B cell signaling pathway, communication between innate and adaptive immune cells, and melatonin degradation II. Our findings further reinforce the important roles of mitochondria and lncRNA in PD and, in parallel, further support the concept of inverse comorbidity between PD and some cancers.
Advanced Glycation End-Products (AGEs) of Lysine and Effects of Anti-TCR/Anti-TNF-α Antibody-Based Therapy in the LEW.1AR1-iddm Rat, an Animal Model of Human Type 1 Diabetes
Authors: Baskal Svetlana , Tsikas Stefanos A. , Begou Olga , Bollenbach Alexander , Lenzen Sigurd , Jörns Anne , Tsikas Dimitrios
Published: January 2022

The LEW.1AR1-iddm rat is an animal model of human type 1 diabetes (T1D). Previously, we have shown that combination with anti-TCR/anti-TNF-α antibody-based therapy re-established normoglycemia and increased proteinic arginine-dimethylation in the spleen, yet not in the pancreas. High blood glucose is often associated with elevated formation of advanced glycation end-products (AGEs) which act via their receptor (RAGE). Both anti-TCR and anti-TNF-α are inhibitors of RAGE. The aim of the present work was to investigate potential biochemical changes of anti-TCR/anti-TNF-α therapy in the LEW.1AR1-iddm rat. We determined by stable-isotope dilution gas chromatography-mass spectrometry (GC-MS) the content of free and proteinic AGEs and the Nε-monomethylation of lysine (Lys) residues in proteins of pancreas, kidney, liver, spleen and lymph nodes of normoglycemic control (ngCo, n = 6), acute diabetic (acT1D, n = 6), chronic diabetic (chT1D, n = 4), and cured (cuT1D, n = 4) rats after anti-TCR/anti-TNF-α therapy. Analyzed biomarkers included Lys and its metabolites Nε-carboxymethyl lysine (CML), furosine and Nε-monomethyl lysine (MML). Other amino acids were also determined. Statistical methods including ANOVA, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to evaluate the effects. Most statistical differences between the study groups were observed for spleen, pancreas and kidney, with liver and lymph nodes showing no such differences. In the pancreas, the groups differed with respect to proteinic furosine (p = 0.0289) and free CML (p = 0.0023). In the kidneys, the groups differed with respect to proteinic furosine (p = 0.0076) and CML (p = 0.0270). In the spleen, group differences were found for proteinic furosine (p = 0.0114) and free furosine (p = 0.0368), as well as for proteinic CML (p = 0.0502) and proteinic MML (p = 0.0191). The acT1D rats had lower furosine, CML and MML levels in the spleen than the rats in all other groups. This observation corresponds to the lower citrullination levels previously measured in these rats. PCA revealed diametric associations between PC1 and PC2 for spleen (r = −0.8271, p < 0.0001) compared to pancreas (r = 0.5805, p = 0.0073) and kidney (r = 0.8692, p < 0.0001). These findings underscore the importance of the spleen in this animal model of human T1D. OPLS-DA showed that in total sixteen amino acids differed in the experimental groups.
Molecular Mechanisms of Kidney Injury and Repair
Authors: Rayego-Mateos Sandra , Marquez-Expósito Laura , Rodrigues-Diez Raquel , Sanz Ana B. , Guiteras Roser , Doladé Nuria , Rubio-Soto Irene , Manonelles Anna , Codina Sergi , Ortiz Alberto , Cruzado Josep M. , Ruiz-Ortega Marta , Sola Anna
Published: January 2022

Chronic kidney disease (CKD) will become the fifth global cause of death by 2040, thus emphasizing the need to better understand the molecular mechanisms of damage and regeneration in the kidney. CKD predisposes to acute kidney injury (AKI) which, in turn, promotes CKD progression. This implies that CKD or the AKI-to-CKD transition are associated with dysfunctional kidney repair mechanisms. Current therapeutic options slow CKD progression but fail to treat or accelerate recovery from AKI and are unable to promote kidney regeneration. Unraveling the cellular and molecular mechanisms involved in kidney injury and repair, including the failure of this process, may provide novel biomarkers and therapeutic tools. We now review the contribution of different molecular and cellular events to the AKI-to-CKD transition, focusing on the role of macrophages in kidney injury, the different forms of regulated cell death and necroinflammation, cellular senescence and the senescence-associated secretory phenotype (SAPS), polyploidization, and podocyte injury and activation of parietal epithelial cells. Next, we discuss key contributors to repair of kidney injury and opportunities for their therapeutic manipulation, with a focus on resident renal progenitor cells, stem cells and their reparative secretome, certain macrophage subphenotypes within the M2 phenotype and senescent cell clearance.
ICE-CBF-COR Signaling Cascade and Its Regulation in Plants Responding to Cold Stress
Authors: Hwarari Delight , Guan Yuanlin , Ahmad Baseer , Movahedi Ali , Min Tian , Hao Zhaodong , Lu Ye , Chen Jinhui , Yang Liming
Published: January 2022

Cold stress limits plant geographical distribution and influences plant growth, development, and yields. Plants as sessile organisms have evolved complex biochemical and physiological mechanisms to adapt to cold stress. These mechanisms are regulated by a series of transcription factors and proteins for efficient cold stress acclimation. It has been established that the ICE-CBF-COR signaling pathway in plants regulates how plants acclimatize to cold stress. Cold stress is perceived by receptor proteins, triggering signal transduction, and Inducer of CBF Expression (ICE) genes are activated and regulated, consequently upregulating the transcription and expression of the C-repeat Binding Factor (CBF) genes. The CBF protein binds to the C-repeat/Dehydration Responsive Element (CRT/DRE), a homeopathic element of the Cold Regulated genes (COR gene) promoter, activating their transcription. Transcriptional regulations and post-translational modifications regulate and modify these entities at different response levels by altering their expression or activities in the signaling cascade. These activities then lead to efficient cold stress tolerance. This paper contains a concise summary of the ICE-CBF-COR pathway elucidating on the cross interconnections with other repressors, inhibitors, and activators to induce cold stress acclimation in plants.
Performance Study on Extractive Text Summarization Using BERT Models
Authors: Abdel-Salam Shehab , Rafea Ahmed
Published: January 2022

The task of summarization can be categorized into two methods, extractive and abstractive. Extractive summarization selects the salient sentences from the original document to form a summary while abstractive summarization interprets the original document and generates the summary in its own words. The task of generating a summary, whether extractive or abstractive, has been studied with different approaches in the literature, including statistical-, graph-, and deep learning-based approaches. Deep learning has achieved promising performances in comparison to the classical approaches, and with the advancement of different neural architectures such as the attention network (commonly known as the transformer), there are potential areas of improvement for the summarization task. The introduction of transformer architecture and its encoder model “BERT” produced an improved performance in downstream tasks in NLP. BERT is a bidirectional encoder representation from a transformer modeled as a stack of encoders. There are different sizes for BERT, such as BERT-base with 12 encoders and BERT-larger with 24 encoders, but we focus on the BERT-base for the purpose of this study. The objective of this paper is to produce a study on the performance of variants of BERT-based models on text summarization through a series of experiments, and propose “SqueezeBERTSum”, a trained summarization model fine-tuned with the SqueezeBERT encoder variant, which achieved competitive ROUGE scores retaining the BERTSum baseline model performance by 98%, with 49% fewer trainable parameters.
Factors and Strategies for Improving Construction Management on Sites in Mega-Projects in South Africa: An Explorative Survey
Authors: Aiyetan Ayodeji Olatunji , Das Dillip Kumar
Published: January 2022

Mega-projects, particularly for the development of infrastructure, are being undertaken increasingly in many developing countries. Mega-projects are highly complex and involve significant construction activities. However, mega-projects in Africa face critical challenges of delay and cost overruns because of their nature and the complexities involved. Therefore, using the context of mega-projects in South Africa and stakeholders’ perceptions, the factors that influence construction, and strategies that would alleviate the challenges and improve construction management at sites were examined in this study. Factor analysis and ordinal regression modelling were used to analyse data obtained from a survey conducted among stakeholders. Findings suggested that five principal components and associated factors, including stakeholders, plant and machinery, productivity, workforce and materials, significantly affect construction during mega-projects. Further, eight strategies that are aligned to stakeholder engagement, plants and machinery, productivity, human resources and materials are likely to improve construction management at sites of mega-projects in South Africa. The four most important strategies include making the availability of competent personnel for plant and machinery operation and maintenance, effective supervision and monitoring, the adoption of appropriate stakeholder engagement methods and ensuring transparent and effective engagement, and the implementation of an advanced and effective communication system. Further strategies, such as the identification of stakeholders and common goals and procurement and use of advanced and quality plant and machinery, including the use of robotics and automation, could improve construction at sites. Similarly, strategies such as ensuring availability of adequate and quality material, and management of the site for effective accessibility and operation, although likely to have lesser influence, could also improve construction at sites of mega-projects.
Temperature-Specific and Sex-Specific Fitness Effects of Sympatric Mitochondrial and Mito-Nuclear Variation in Drosophila obscura
Authors: Erić Pavle , Patenković Aleksandra , Erić Katarina , Tanasković Marija , Davidović Slobodan , Rakić Mina , Savić Veselinović Marija , Stamenković-Radak Marina , Jelić Mihailo
Published: January 2022

The adaptive significance of sympatric mitochondrial (mtDNA) variation and the role of selective mechanisms that maintain it are debated to this day. Isofemale lines of Drosophila obscura collected from four populations were backcrossed within populations to construct experimental lines, with all combinations of mtDNA Cyt b haplotypes and nuclear genetic backgrounds (nuDNA). Individuals of both sexes from these lines were then subjected to four fitness assays (desiccation resistance, developmental time, egg-to-adult viability and sex ratio) on two experimental temperatures to examine the role of temperature fluctuations and sex-specific selection, as well as the part that interactions between the two genomes play in shaping mtDNA variation. The results varied across populations and fitness components. In the majority of comparisons, they show that sympatric mitochondrial variants affect fitness. However, their effect should be examined in light of interactions with nuDNA, as mito-nuclear genotype was even more influential on fitness across all components. We found both sex-specific and temperature-specific differences in mitochondrial and mito-nuclear genotype ranks in all fitness components. The effect of temperature-specific selection was found to be more prominent, especially in desiccation resistance. From the results of different components tested, we can also infer that temperature-specific mito-nuclear interactions rather than sex-specific selection on mito-nuclear genotypes have a more substantial role in preserving mtDNA variation in this model species.
Phenology and Potential Fecundity of Neoleucopis kartliana in Greece
Authors: Eleftheriadou Nikoleta , Lubanga Umar , Lefoe Greg , Seehausen M. Lukas , Kenis Marc , Kavallieratos Nickolas G. , Avtzis Dimitrios N.
Published: January 2022

Neoleucopis kartliana Tanasijtshuk (Diptera, Chamaemyiidae) is the most abundant predator of the giant pine scale (GPS), Marchalina hellenica (Hemiptera, Margarodidae) in Greece. GPS is native to Greece and Turkey, where it is not considered a pest of Pinus spp., but a valuable resource for pine honey production. However, its introduction to new areas leads to high population densities of the scale, linked to declines in tree health and insect biodiversity. To assess the potential use of N. kartliana for a classical biological control program in Australia, we studied selected life-history traits of the silver fly, namely its phenology in northern Greece, feeding preferences of adult flies on artificial food sources, and potential fecundity of female flies. The silver fly was present in every site in northern Greece studied and was found to have at least three generations per year in this area. The fly’s overall sex ratio was 1:1, and adult females emerged with no or few mature eggs in their ovaries, but egg production was exponential until at least the eighth day after emergence. These findings increase our knowledge about the biology of N. kartliana and aided in the evaluation of the silver fly as a classical biological control agent against invasive GPS in Australia.
Transepithelial Iontophoresis-Assisted Cross Linking for Progressive Keratoconus: Up to 7 Years of Follow Up
Authors: Vinciguerra Riccardo , Legrottaglie Emanuela , Tredici Costanza , Mazzotta Cosimo , Rosetta Pietro , Vinciguerra Paolo
Published: January 2022

Purpose: To report long-term clinical results of transepithelial cross-linking with iontophoresis (I-CXL) for progressive keratoconus (KC). Methods: Nineteen eyes of 19 patients treated with I-CXL for progressive keratoconus were included in this prospective clinical study. Preoperatively and in all available follow ups (6, 12, 24, 36, 48, 60, 72 and 84 months), the following parameters were measured. Corrected distance visual acuity (CDVA), spherical equivalent and cylinder refraction, corneal topography and aberrometry (Costruzione Strumenti Oftalmici (C.S.O.), Florence, Italy), Scheimpflug tomography (OCULUS Optikgeräte GmbH; Wetzlar, Germany). Definition of progression after I-CXL was 2/3 of the following criteria: increase of “A” value, increase of “B” value, decrease of minimal thickness evaluated with the ABCD progression display above 95% confidence interval for post-CXL population when compared to the scan 12 months post-op. Results: The mean follow-up time of included patients was 63 months (range 12 to 84 months, 5 patients reached 84 months). The general linear model showed no significant change over time in CDVA, Maximum Keratometry, Thinnest point, and A, B, C values of the Belin Progression Display (p > 0.05). Conversely, comatic and high order aberrations decreased significantly over time (both p =< 0.001). Five cases (26.31%) showed significant progression after a mean of 55 months (range 36–72) of follow up. Conclusion: Our study shows the ability of I-CXL to slow down KC progression in the majority of included patients, improving high order and comatic aberrations. A 26% progression rate was reported.
Prenatal and Neonatal Characteristics of Children with Prader-Willi Syndrome
Authors: Grootjen Lionne N. , Uyl Nathalie E. M. , van Beijsterveldt Inge A. L. P. , Damen Layla , Kerkhof Gerthe F. , Hokken-Koelega Anita C. S.
Published: January 2022

Objective: Prader-Willi syndrome (PWS) is a rare genetic syndrome with a wide spectrum of clinical features in early life. Late diagnoses are still present. We characterized the perinatal and neonatal features of PWS, compared them with those of healthy newborns and assessed the prenatal and neonatal differences between the genetic subtypes. Design: A cohort study in children with PWS. The prevalence of variables was compared with healthy infants (PLUTO cohort) and to population statistics from literature. Patients: 244 infants with PWS and 365 healthy infants. Measurements: Data on prenatal and neonatal variables in both cohorts. Population statistics were collected through an extensive literature search. Results: A higher prevalence of maternal age >35 years was found in PWS compared to healthy infants and population statistics, and the highest maternal age was found in the mUPD group. Higher prevalence of polyhydramnios, caesarean section, labour induction and breech presentation, and lower birth weight SDS was found in PWS compared to healthy infants. High prevalences of decreased fetal movements (78.5%), hypotonia (100%), cryptorchism (95.9%) and poor sucking/tube feeding (93.9%) were found in PWS. Conclusions: This study presents an overview of prenatal and neonatal variables in infants with PWS compared to healthy infants. Our findings may increase clinical awareness of the early perinatal signs of PWS by obstetricians, neonatologists and all those involved in infant care, enabling early diagnosis and start of multidisciplinary treatment.
Evaluation of Inhibitory Antibodies against the Muscarinic Acetylcholine Receptor Type 3 in Patients with Primary Biliary Cholangitis and Primary Sclerosing Cholangitis
Authors: Wilde Anne-Christin Beatrice , Greverath Lena Maria , Steinhagen Lara Marleen , de Chamorro Nina Wald , Leicht Elise , Fischer Janett , Herta Toni , Berg Thomas , Preuss Beate , Klein Reinhild , Tacke Frank , Müller Tobias
Published: January 2022

Background: Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) constitute rare chronic inflammatory biliary diseases which likely comprise genetic, environmental and autoimmune factors. Specific inhibitory (auto-) antibodies against the muscarinic acetylcholine receptor type 3 (mAChR3 auto-ab) may contribute to the pathogenesis of chronic biliary inflammation by modulating mAChR3− mediated signaling. Aims: The aim of this study was to analyze the prevalence and relevance of inhibitory mAChR3 auto-ab (mAChR3inh+ auto-ab) in a large cohort of PBC patients from two independent tertiary centers in Berlin and Leipzig in comparison to a large PSC cohort. Baseline parameters and response rates to standard treatment with ursodeoxycholic acid (UDCA) were characterized with respect to the individual mAChR3 auto-ab status. Methods: In total, the study population comprised 437 PBC patients, 187 PSC patients and 80 healthy controls. Clinical and laboratory baseline characteristics were retrieved from medical records. The response to ursodeoxycholic acid (UDCA) therapy after 12 months of treatment was available in 176 PBC and 45 PSC patients. Results: The prevalence of mAChR3inh+ auto-ab was significantly higher among PBC patients (11.2%, 49/437; p = 0.008 vs. healthy controls) and PSC patients (33.6%, 63/187; p < 0.0001 vs. healthy controls) compared to healthy controls (2.5%, 2/80), respectively. PBC patients with mAChR3inh+ auto-ab exhibited significantly higher levels of alkaline phosphatase (ALP) and bilirubin, which constitute established parameters for PBC risk stratification. Moreover, mAChR3inh+ PBC patients tended to show decreased response rates to UDCA therapy compared to PBC patients without mAChR3inh+ auto-ab (mAChR3− PBC). In contrast, PSC patients with mAChR3inh+ auto-ab showed no significant differences in laboratory findings compared to mAChR3 auto-ab negative (mAChR3−) PSC patients. Conclusion: MAChR3inh+ auto-ab might be involved in the pathogenesis and treatment response of chronic biliary inflammation in patients with PBC but not in patients with PSC.
Special Issue on Refractive Surgery
Authors: Moshirfar Majid , Ronquillo Yasmyne C.
Published: January 2022

Laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK), for the treatment of refractive errors, continues to evolve [...]