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Low-frequency non-syndromic hearing loss (LFNSHL) is a rare auditory disorder affecting frequencies ≤ 2000 Hz. To elucidate its genetic basis, we conducted whole-exome sequencing on nine Chinese families (31 affected individuals) with LFNSHL. Four heterozygous pathogenic variants, including two novel variants, were identified in common LFNSHL-related genes (WFS1, DIAPH1) and less common genes (TNC, EYA4), achieving a 44% genetic diagnosis rate. All genetically diagnosed patients had early adulthood-onset hearing loss except for one WFS1 variant case, and all exhibited progressive hearing loss. Our findings indicate that LFNSHL is predominantly inherited in an autosomal dominant manner. Further review showed that WFS1 mutations typically cause childhood-onset LFNSHL, while DIAPH1 and EYA4 mutations result in adulthood-onset LFNSHL; interestingly, WFS1 mutations generally progress to moderate hearing loss, milder than DIAPH1, TNC, and EYA4 mutations. Additionally, tinnitus was more prevalent in patients with WFS1, DIAPH1, and EYA4 mutations than those with TNC mutations. Notably, hearing loss deteriorated at all frequencies, becoming markedly severe after age 50 for TNC and WFS1 mutations, and after age 40 for EYA4 mutations. Mutations in WFS1 were predominantly missense, with the p.Ser807 codon and the protein's C-terminal intracytoplasmic domain identified as mutation hotspots. Comparative analysis revealed a higher incidence of bilateral symmetrical progressive LFNSHL in genetically diagnosed patients than those without. This study, the first to investigate LFNSHL genetics in a Chinese cohort, underscores the complex genetic landscape and phenotypic variability of LFNSHL, providing valuable insights for future diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Abstract Background The molecular mechanisms and signaling pathways involved in tooth morphogenesis have been the research focus in the fields of tooth and bone development. However, the cell population in molars at the late bell stage and the mechanisms of hard tissue formation and mineralization remain limited knowledge. Results Here, we used the rat mandibular first and second molars as models to perform single-cell RNA sequencing (scRNA-seq) analysis to investigate cell identity and driver genes related to dental mesenchymal cell differentiation during the late bell hard tissue formation stage. We identified seven main cell types and investigated the heterogeneity of mesenchymal cells. Subsequently, we identified novel cell marker genes, including Pclo in dental follicle cells, Wnt10a in pre-odontoblasts, Fst and Igfbp2 in periodontal ligament cells, and validated the expression of Igfbp3 in the apical pulp. The dynamic model revealed three differentiation trajectories within mesenchymal cells, originating from two types of dental follicle cells and apical pulp cells. Apical pulp cell differentiation is associated with the genes Ptn and Satb2, while dental follicle cell differentiation is associated with the genes Tnc, Vim, Slc26a7, and Fgfr1. Cluster-specific regulons were analyzed by pySCENIC. In addition, the odontogenic function of driver gene TNC was verified in the odontoblastic differentiation of human dental pulp stem cells. The expression of osteoclast differentiation factors was found to be increased in macrophages of the mandibular first molar. Conclusions Our results revealed the cell heterogeneity of molars in the late bell stage and identified driver genes associated with dental mesenchymal cell differentiation. These findings provide potential targets for diagnosing dental hard tissue diseases and tooth regeneration.

Background/Objectives: Tendon structure is predominantly composed of the extracellular matrix (ECM), and genetic variants in non-collagenous ECM components may influence susceptibility to tendinopathy. We investigated the potential influence of single nucleotide polymorphisms (SNPs) in fibrillin-2 (FBN2), tenascin-C (TNC), and matrix metalloproteinase-3 (MMP3) on the tendon regeneration failure phenotype and impact on the susceptibility to tendinopathy in Brazilian high-performance athletes. Methods: This case–control study was conducted with 397 high-performance athletes from different sports modalities (197 tendinopathy cases and 200 controls), and they were analyzed by validated TaqManTM SNP genotyping assays of the SNPs FBN2 (rs331079), TNC (rs2104772), and MMP3 (rs591058). Results: Out of the 197 tendinopathy cases, 63% suffered from chronic tendon pain and 22% experienced more than three episodes of disease manifestation. The TNC-rs2104772-A allele was significantly associated with tendinopathy (OR: 1.4; 95% CI: 1.1–1.8), while athletes carrying the MMP3-rs591058-T allele were linked to an increased risk of more episodes of disease manifestation (OR: 1.7; 95% CI: 1.1–2.8). The TNC-MMP3 tendon regeneration failure phenotype (TNC-A/MMP3-T) was associated with an increased risk of tendinopathy (OR: 1.4; 95% CI: 1.1–2.0) and episodes of disease manifestation (OR: 2.0; 95% CI: 1.2–3.5). Athletes with tendinopathy who had the TNC-A/MMP3-T interaction were more prone to experiencing more than three disease exacerbations (OR: 4.3; 95% CI: 1.8–10.5) compared to TNC-A/TNC-C. Conclusions: This study suggests that rs2104772 and rs591058 SNPs could be involved in the tendon regeneration failure phenotype and may influence the molecular mechanism related to the regulation of the tendon ECM during training workload. [ABSTRACT FROM AUTHOR]

Background: The molecular mechanisms and signaling pathways involved in tooth morphogenesis have been the research focus in the fields of tooth and bone development. However, the cell population in molars at the late bell stage and the mechanisms of hard tissue formation and mineralization remain limited knowledge. Results: Here, we used the rat mandibular first and second molars as models to perform single-cell RNA sequencing (scRNA-seq) analysis to investigate cell identity and driver genes related to dental mesenchymal cell differentiation during the late bell hard tissue formation stage. We identified seven main cell types and investigated the heterogeneity of mesenchymal cells. Subsequently, we identified novel cell marker genes, including Pclo in dental follicle cells, Wnt10a in pre-odontoblasts, Fst and Igfbp2 in periodontal ligament cells, and validated the expression of Igfbp3 in the apical pulp. The dynamic model revealed three differentiation trajectories within mesenchymal cells, originating from two types of dental follicle cells and apical pulp cells. Apical pulp cell differentiation is associated with the genes Ptn and Satb2, while dental follicle cell differentiation is associated with the genes Tnc, Vim, Slc26a7, and Fgfr1. Cluster-specific regulons were analyzed by pySCENIC. In addition, the odontogenic function of driver gene TNC was verified in the odontoblastic differentiation of human dental pulp stem cells. The expression of osteoclast differentiation factors was found to be increased in macrophages of the mandibular first molar. Conclusions: Our results revealed the cell heterogeneity of molars in the late bell stage and identified driver genes associated with dental mesenchymal cell differentiation. These findings provide potential targets for diagnosing dental hard tissue diseases and tooth regeneration. [ABSTRACT FROM AUTHOR]

Consolidation with autologous hematopoietic stem cell transplantation (HSCT) has improved survival for patients with central nervous system tumors (CNSTs). The impact of the autologous graft CD34+ dose on patient outcomes is unknown. We wanted to analyze the relationship between CD34+ dose, total nucleated cell (TNC) dose, and clinical outcomes, including overall survival (OS), progression-free survival (PFS), relapse, non-relapse mortality (NRM), endothelial-injury complications (EIC), and time to neutrophil engraftment in children undergoing autologous HSCT for CNSTs. A retrospective analysis of the CIBMTR database was performed. Children aged 3.6×106/kg CD34+ cells experienced superior PFS (p = .04) and OS (p = .04) compared to children receiving ≤3.6 × 106/kg. Relapse rates were lower in patients receiving >3.6 × 106/kg CD34+ cells (p = .05). Higher CD34+ doses were not associated with increased NRM (p = .59). Stratification of CD34+ dose by quartile did not reveal any statistically significant differences between quartiles for 3-year PFS (p = .66), OS (p = .29), risk of relapse (p = .57), or EIC (p = .87). There were no significant differences in patient outcomes based on TNC, and those receiving a TNC >4.4 × 108/kg did not experience superior PFS (p = .26), superior OS (p = .14), reduced risk of relapse (p = .37), or reduced NRM (p = .25). Children with medulloblastoma had superior PFS (p < .001), OS (p = .01), and relapse rates (p = .001) compared to those with other CNS tumor types. Median time to neutrophil engraftment was 10 days versus 12 days in the highest and lowest infused CD34+ quartiles, respectively. For children undergoing autologous HSCT for CNSTs, increasing CD34+ cell dose was associated with significantly improved OS and PFS, and lower relapse rates, without increased NRM or EICs.

Abstract Background Chronic migraine (CM) is a debilitating neurofunctional disorder primarily affecting females, characterized by central sensitization. Central sensitization refers to the enhanced response to sensory stimulation, which involves changes in neuronal excitability, synaptic plasticity, and neurotransmitter release. Environmental enrichment (EE) can increase the movement, exploration, socialization and other behaviors of mice. EE has shown promising effects in various neurological disorders, but its impact on CM and the underlying mechanism remains poorly understood. Therefore, the purpose of this study was to determine whether EE has the potential to serve as a cost-effective intervention strategy for CM. Methods A mouse CM model was successfully established by repeated administration of nitroglycerin (NTG). We selected adult female mice around 8 weeks old, exposed them to EE for 2 months, and then induced the CM model. Nociceptive threshold tests were measured using Von Frey filaments and a hot plate. The expression of c-Fos, calcitonin gene-related peptide (CGRP) and inflammatory response were measured using WB and immunofluorescence to evaluate central sensitization. RNA sequencing was used to find differentially expressed genes and signaling pathways. Finally, the expression of the target differential gene was investigated. Results Repeated administration of NTG can induce hyperalgesia in female mice and increase the expression of c-Fos and CGRP in the trigeminal nucleus caudalis (TNC). Early exposure of mice to EE reduced NTG-induced hyperalgesia in CM mice. WB and immunofluorescence revealed that EE inhibited the overexpression of c-Fos and CGRP in the TNC of CM mice and alleviated the inflammatory response of microglia activation. RNA sequencing analysis identified that several central sensitization-related signaling pathways were altered by EE. VGluT1, a key gene involved in behavior, internal stimulus response, and ion channel activity, was found to be downregulated in mice exposed to EE. Conclusion EE can significantly ameliorate hyperalgesia in the NTG-induced CM model. The mechanisms may be to modulate central sensitization by reducing the expression of CGRP, attenuating the inflammatory response, and downregulating the expression of VGluT1, etc., suggesting that EE can serve as an effective preventive strategy for CM.

China’s hop market and its development have a significant impact on China’s beer market. As a world leader in beer production, China pays considerable attention to the production of hops of the appropriate quality and quantity, taking into account international requirements to increase exports in the future. The formation of the hop production infrastructure was carried out in several stages. The current stage is characterized by the presence of both Chinese companies, joint ventures and representative offices of major multinational companies that import hops into the territory of the People’s Republic of China. The number of farms and areas of hop production have been changing over the past 10 years, and the main hop growing areas are Gansu and Xinjiang Autonomous Region. The economic entities grow Chinese varieties of hops, and the main variety in terms of planting area is Tsingtao Flower. Hop cultivation is carried out under the influence of administrative decisions of local authorities of the People’s Republic of China as well as national and global trends in the hop and beer markets. Despite the functioning of world leaders in hop production on the territory of the People’s Republic of China, problematic issues do not allow to improve the quality of grown hops to ensure the domestic market, which requires the import of hops from Germany, the Czech Republic, and the USA.

Background: Chronic migraine (CM) is a debilitating neurofunctional disorder primarily affecting females, characterized by central sensitization. Central sensitization refers to the enhanced response to sensory stimulation, which involves changes in neuronal excitability, synaptic plasticity, and neurotransmitter release. Environmental enrichment (EE) can increase the movement, exploration, socialization and other behaviors of mice. EE has shown promising effects in various neurological disorders, but its impact on CM and the underlying mechanism remains poorly understood. Therefore, the purpose of this study was to determine whether EE has the potential to serve as a cost-effective intervention strategy for CM. Methods: A mouse CM model was successfully established by repeated administration of nitroglycerin (NTG). We selected adult female mice around 8 weeks old, exposed them to EE for 2 months, and then induced the CM model. Nociceptive threshold tests were measured using Von Frey filaments and a hot plate. The expression of c-Fos, calcitonin gene-related peptide (CGRP) and inflammatory response were measured using WB and immunofluorescence to evaluate central sensitization. RNA sequencing was used to find differentially expressed genes and signaling pathways. Finally, the expression of the target differential gene was investigated. Results: Repeated administration of NTG can induce hyperalgesia in female mice and increase the expression of c-Fos and CGRP in the trigeminal nucleus caudalis (TNC). Early exposure of mice to EE reduced NTG-induced hyperalgesia in CM mice. WB and immunofluorescence revealed that EE inhibited the overexpression of c-Fos and CGRP in the TNC of CM mice and alleviated the inflammatory response of microglia activation. RNA sequencing analysis identified that several central sensitization-related signaling pathways were altered by EE. VGluT1, a key gene involved in behavior, internal stimulus response, and ion channel activity, was found to be downregulated in mice exposed to EE. Conclusion: EE can significantly ameliorate hyperalgesia in the NTG-induced CM model. The mechanisms may be to modulate central sensitization by reducing the expression of CGRP, attenuating the inflammatory response, and downregulating the expression of VGluT1, etc., suggesting that EE can serve as an effective preventive strategy for CM. [ABSTRACT FROM AUTHOR]

Nitrogen is one of the critical factors in water pollution and eutrophication, so applying the deep learning method in remote sensing inversion of nitrogen can provide basic information for environmental management. This paper proposes a two-step feature extraction method to solve the problem that the number of bands in water quality inversion is insufficient and the deep learning method cannot be fully exploited. Firstly, manual feature extraction is completed through the fusion between bands to obtain a set of high-latitude shallow factors, which make the features rich and diverse. Then, a one-dimensional convolutional residual network (ResNet-1D) is constructed, and the deep features are automatically extracted through convolution operations of the model, where the residual learning is used to reduce the training difficulty. The full connection is established through depth features. The comparison of models shows that the Mean Relative Error (MRE) is decreased by at least 10% in both test and validation datasets. Finally, the spatiotemporal distribution of total nitrogen concentration (TNC) in the coastal waters of Shandong is explored. In general, the spatial distribution is that the concentration near the coast is higher than the far. The temporal variation is that the monthly mean of the TNC is low in March, moderate in May and August, and high in October; the annual average value of TNC is 0.3mg/L, which has decreased slightly year by year since 2014. [ABSTRACT FROM AUTHOR]

The effects of meat pH on muscle fiber characteristics, cortisol level, and Tenascin C (TNC) gene expression were examined. The muscle samples (n=100) were randomly collected from the Longissimus thoracis et lumborum (LTL) to determine meat pH at 24 hours (meat pH24h) postmortem. Muscle samples (five samples per group) with divergent meat pH levels (low versus high) were selected to study muscle fiber characteristics and mRNA expression based on quantitative real-time polymerase chain reaction (qRT-PCR). Blood samples (five samples per group) of the two meat pH levels were taken for serum cortisol analysis. The results showed that there was no significant differences between the groups for the muscle fiber characteristics of total number of fibers, muscle fiber diameter, cross-section area, perimysium thickness, and endomysium thickness. Different meat pH24h values did not affect the cortisol level. The mRNA expression of the TNC gene was significantly (p<0.05) downregulated in the low meat pH24h group compared to the high meat pH24h group. In conclusion, meat pH24h was unrelated to the cortisol level and muscle fiber characteristics. However, the TNC gene might play a role in meat pH24h in pigs. [ABSTRACT FROM AUTHOR]

Engrailed 2 (EN2) is a homeodomain‐containing protein that is dysregulated in many types of cancer. However, the role of EN2 in non‐small cell lung cancer (NSCLC) and the mechanism underlying its biological function are largely unclear. Here, we showed that EN2 played an oncogenic function in NSCLC and greatly enhanced the malignant phenotype of NSCLC cells. Meanwhile, EN2 was able to boost the expression of a well‐studied oncogenic Tenascin‐C (TNC) gene, which in turn activated the AKT signaling pathway. Interestingly, we found that EN2 directly bound to the super‐enhancer (SE) region in the TNC locus. The histone marker H3K27ac was also enriched in the region, indicating the activation of the SE. Treatment of the cells with JQ1, an inhibitor of SE activity, abrogated the effect of EN2 on the expression of TNC and phosphorylation of AKT‐Ser473. Collectively, our work unveils a novel mode of EN2 function, in which EN2 governs the SE in the TNC locus, consequently activating the oncogenic TNC–AKT axis in NSCLC. [ABSTRACT FROM AUTHOR]

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The study is devoted to the assessment of the dynamics of digitalization and innovative development of modern TNCs in the context of a globalized economy, where digital transformation determines new development trajectories for countries and international companies. The conducted research focuses on the analysis of international and domestic indices that measure the level of digitization of economies, in particular the Digital Economy and Society Index (DESI), which combines indicators of communication, human capital, integration of digital technologies, and digital public services. The analysis covers the period of the last ten years, highlighting the dynamics of the development of the countries of the European Union in the context of digital competitiveness, the formation of digital business platforms, and corporate processes. The study points to the importance of understanding not only the benefits of digitalization but also the potential challenges, such as the growing energy consumption of data centers and the «throwaway» culture, which contributes to the systematic obsolescence of techniques and the transition to the digital tools of conducting international business. The central element of the analysis is the concept of the «data value chain», which allows you to assess the value of data from its collection to monetization. Highlighting this concept highlights the complexity of measuring the value of data and the need to develop new approaches to its evaluation. The study also draws attention to the diversity of digital TNCs, including digital-only companies and those using hybrid models. Particular attention is paid to the analysis of the evolution of assets, sales, and net income of these companies, highlighting the significant impact of the Covid-19 pandemic on the digital economy. A significant part of the study is devoted to the ranking of digital TNCs, which includes a detailed analysis of changes in the composition of the top 100 companies over the past five years. This allows us to conclude about the rapid development of Internet platforms, e-commerce, and digital content, partly caused by the pandemic. The research findings emphasize the importance of digital transformation for the global economy and the need to adapt the development strategies of digital TNCs to changing conditions, ensuring their sustainable development in the future [ABSTRACT FROM AUTHOR]

The article notes that in the context of globalization, multinational corporations exert an increasing influence on the economies of their home countries, host countries, and the overall state of international economic relations. The authors underline that tax planning is one of the TNC activities that grabs attention of the global public in terms of both its favorable and unfavorable effects. The article offers its own definition of the term «tax landscape», in which, unlike the existing ones, vertical, horizontal and temporal aspects are distinguished. The vertical aspect is presented as a synthesis of the supranational level of taxation and the national one; horizontal, as a system of tax rules and laws within a separate state; temporal, as a change in the main elements of taxation over time. It has been proven that at the current stage of formation of tax landscapes to characterize the supranational level, it is necessary to take into account the elements of taxation defined as part of the implementation of the international BEPS project: the global minimum tax, tax rates for surplus profits, and surplus profits as an object of taxation. The authors have been able to divide the studied countries into three groups depending on the level of direct taxation: high (United States, Canada and Australia), moderate (Great Britain, France, Italy, India, Germany and Switzerland), and low (China and Saudi Arabia). The first group (the United States) and the second group (the United Kingdom, Germany, France, Switzerland, and Italy) have been found to have the greatest tax losses as a result of «tax havens.» The level of direct taxation (profit and capital) in the countries of registration and countries of digital presence, the volatility of tax legislation, and compliance with the conditions of tax justice have been proposed as factors of the tax landscape to be taken into account by transnational corporations when developing tax planning strategies.

The article notes that in the context of globalization, multinational corporations exert an increasing influence on the economies of their home countries, host countries, and the overall state of international economic relations. The authors underline that tax planning is one of the TNC activities that grabs attention of the global public in terms of both its favorable and unfavorable effects. The article offers its own definition of the term «tax landscape», in which, unlike the existing ones, vertical, horizontal and temporal aspects are distinguished. The vertical aspect is presented as a synthesis of the supranational level of taxation and the national one; horizontal, as a system of tax rules and laws within a separate state; temporal, as a change in the main elements of taxation over time. It has been proven that at the current stage of formation of tax landscapes to characterize the supranational level, it is necessary to take into account the elements of taxation defined as part of the implementation of the international BEPS project: the global minimum tax, tax rates for surplus profits, and surplus profits as an object of taxation. The authors have been able to divide the studied countries into three groups depending on the level of direct taxation: high (United States, Canada and Australia), moderate (Great Britain, France, Italy, India, Germany and Switzerland), and low (China and Saudi Arabia). The first group (the United States) and the second group (the United Kingdom, Germany, France, Switzerland, and Italy) have been found to have the greatest tax losses as a result of «tax havens.» The level of direct taxation (profit and capital) in the countries of registration and countries of digital presence, the volatility of tax legislation, and compliance with the conditions of tax justice have been proposed as factors of the tax landscape to be taken into account by transnational corporations when developing tax planning strategies. [ABSTRACT FROM AUTHOR]

BACKGROUND: From the pathological mechanism of Western medicine, ligamentum flavum hypertrophy is the key pathogenic factor of lumbar spinal stenosis, and there is a lack of biological information on lumbar spinal stenosis of the Qi deficiency and blood stasis type. OBJECTIVE: To analyze and compare differential protein expression between hypertrophic and normal ligamentum flavum in patients with lumbar spinal stenosis of the Qi deficiency and blood stasis type. METHODS: Ligamentum flavum tissue samples were collected from six lumbar spinal stenosis patients with Qi deficiency and blood stasis, including three cases of ligamentum flavum hypertrophy (experimental group) and three cases of normal ligamentum flavum (control group). 4D Label free quantitative proteomic detection was performed to screen differentially expressed proteins. Gene oncology and Kyoto Encyclopedia of Genes and Genomes were used for enrichment analysis. RESULTS AND CONCLUSION: There were 183 differentially expressed proteins between the two groups, including 87 up-regulated and 96 down-regulated. Gene oncology enrichment analysis showed that biological processes mainly focused on cell processes, biological regulation and response to stimuli. Cell composition was concentrated in cell, intracellular, and protein-complex species. The main molecular functions included linkage, catalytic activity and molecular function regulator. The up-regulated proteins were mainly enriched to lysosomal signaling pathway, rheumatoid arthritis signaling pathway, and Staphylococcus aureus infection signaling pathway, while the down-regulated proteins were enriched to eight signaling pathways, namely p53 signaling pathway, renal cell carcinoma signaling pathway, transforming growth factor β signaling pathway, ubiquitin-mediated protein hydrolysis signaling pathway, Ca signaling pathway, cGMP-PKG signaling pathway, hypoxia-inducible factor 1 signaling pathway, and proteoglycan signaling pathway in cancer. INHBA, MMP14, TNC, HTRA1, FGF2 were the important differentially expressed proteins in the experimental group. To conclude, there are differential protein expressions between hypertrophic and normal ligamentum flavum in patients with Qi-stagnation and blood-stasis type lumbar spinal stenosis. INHBA may be the determinant of this disease, and its mechanism may be the activation of transforming growth factor β/Smad related signaling pathway, causing ligamentum flavum hypertrophy and subsequently leading to lumbar spinal stenosis. [ABSTRACT FROM AUTHOR]

Background: Adequate stem cell collection is essential for successful stem cell transplantation. Heparin enhances stem cell mobilization by competing with heparin sulfate proteoglycans. Heparin is also used as an anticoagulant before leukapheresis. Here, we evaluated the effects of heparin on stem cell mobilization in patients who underwent autologous stem cell transplantation (ASCT). Methods: We evaluated patients who underwent ASCT. Patients were divided into two groups: those who received heparin plus citrate (heparinized patients) and those who received citrate only (nonheparinized patients) for anticoagulation. Univariate and multivariate analyses were also performed. The collection efficiency 2 (CE2) for CD34+ cells was calculated and compared between heparinized and nonheparinized patients. Results: This study included 1017 patients. There were 478 (47%) heparinized and 539 (53%) nonheparinized patients. The number of collected CD34+ cells was significantly higher in heparinized patients (P <.00001). The multivariate analyses showed that using heparin was an independent positive factor for collected CD34+ cells (adj‐R2 = 0.744; F = 369.331, P <.00001). CE2 was significantly higher in heparinized patients than in nonheparinized patients (66.8% vs 52.1%; P <.00001). The rate of collecting at least 2 × 106/kg CD34+ cells was 3.3 times higher for heparinized patients in poor mobilizers (P <.00001). Heparinized patients had significantly higher total nucleated and mononuclear cell counts (P <.00001 and <.00001, respectively). Conclusion: Heparin enhances stem cell collection and increases CE2. The use of heparin may reduce the need for other strategies to increase stem cell mobilization. [ABSTRACT FROM AUTHOR]

In individuals with chronic neuropathic pain, the posterior insular cortex (PIC) has been found to exhibit increased glutamatergic activity, and the dysgranular portion of PIC (DPIC) has been investigated as a novel cortical target for pain modulation. However, the role of DPIC glutamatergic neurons (DPICg) in trigeminal neuropathic pain (TNP) remains unclear. Here, we examined the outcomes of DPICg inhibition in a rat model of chronic constriction injury of the infraorbital nerve (CCI-ION). Animals were randomly divided into TNP, sham, and control groups. TNP animals underwent CCI-ION surgery. Either optogenetic or null viruses were delivered to the contralateral DPICg of TNP and sham animals. In vivo single-unit extracellular recordings from the ipsilateral spinal trigeminal nucleus caudalis (TNC) and contralateral ventral posteromedial (VPM) thalamus were obtained under both "ON" and "OFF" stimulation states. Behavioral responses during the stimulation-OFF and stimulation-ON phases were examined. Expression of c-Fos, pERK, and CREB immunopositive neurons were also observed. Optogenetic inhibition of contralateral DPICg decreased the neural firing rate in both TNC and VPM thalamus, the expression of sensory-responsive cell bodies, and transcriptional factors in the DPIC of TNP group. Improvements in hyperalgesia, allodynia, and anxiety-like responses in TNP animals were also observed during stimulation-ON condition. In fine, descending pain processing is influenced by neuroanatomical projections from the DPIC to the pain matrix areas, and DPICg could play a necessary role in this neural circuitry. Therefore, the antinociceptive effect of DPICg inhibition in this study may provide evidence for the therapeutic potential of DPICg in TNP. [ABSTRACT FROM AUTHOR]

The Mobility on Demand (MOD) Sandbox Demonstration Program provides a venue through which integrated MOD concepts and strategies, supported through local partnerships, are demonstrated in real-world settings. For the 11 MOD Sandbox Demonstration projects, an independent evaluation was conducted that includes an analysis of project impacts from performance measures provided by the project partners and an assessment of the business models used. This document presents the results from the independent evaluation of the Dallas Area Rapid Transit (DART) First and Last Mile Solution MOD Sandbox Demonstration project. Evaluated were hypotheses that explored project impacts on travel behavior, user experiences, first and last mile to public transit accessibility, service quality for passengers with disabilities, and costs. The project improved first and last mile connectivity to DART transit, increased satisfaction among DART transit users, enhanced service for passengers with disabilities, and increased the geographic scope of DART transit service in the Plano area. In addition, wait and travel times for passengers with and without disabilities reflected similar distributions. The subsidy per rider of GoLink services was lower than the low-ridership fixed-route transit services that it replaced in Plano, but it was not lower than the subsidy for DART fixed-route transit in the overall Dallas region. DART project team members were interviewed to better understand challenges, barriers, successes, and broader lessons learned from the project, representing agency personnel from the offices of Innovation, Service Planning, Scheduling, Paratransit Operations, and Marketing. Lessons learned revealed the importance of having pre-planned, ready-to-go projects with committed partners, flexible contracting terms, metrics for adjusting spatial and temporal service coverage (including terminating service if appropriate), vehicle right-sizing, and understanding customer needs.

Background: Elevated expression of CAV1 in breast cancer increases tumor progression. Extracellular vesicles (EVs) from CAV1-expressing MDA-MB-231 breast cancer cells contain Tenascin C (TNC), but the relevance of TNC remained to be defined. Methods: EVs were characterized by nanotracking analysis, microscopy and western blotting. The uptake of EVs by cells was studied using flow cytometry. The effects of EVs on breast cancer cells were tested in migration, invasion, colony formation and in vivo assays. Results: EVs were taken up by cells; however, only those containing TNC promoted invasiveness. In vivo, EVs lacking TNC ceased to promote tumor growth. Conclusion: CAV1 and TNC contained in breast cancer cell-derived EVs were identified as proteins that favor progression of breast cancer. Caveolin-1 (CAV1) is a protein that in breast cancer increases with disease progression. Extracellular vesicles (EVs) from breast cancer cells with CAV1 also contain Tenascin C (TNC) protein, but the importance of TNC remained to be defined. EVs were identified by size, microscopy and protein analysis. The effects of EVs on breast cancer cells were studied using cells and experiments in animals. CAV1 expression promotes TNC inclusion into EVs, which increased the aggressiveness of recipient breast cancer cells. In animals, only EVs with TNC increased features associated with cancer spread, while EVs lacking TNC reduced tumor growth. [ABSTRACT FROM AUTHOR]

Thirty years after the passage of the Americans with Disabilities Act, people with disabilities still face significant barriers to transportation access. Nearly one-third of disabled people describe inadequate transportation as a problem in their lives, and many major transportation systems have large accessibility gaps. In the San Francisco Bay Area, home to Silicon Valley and the 2010s tech boom, new mobility services are particularly widespread. TNCs, for example, make up approximately 25% of peak-hour traffic in Downtown San Francisco. San Francisco also has a well-established bike-share system and was among the first cities in the country to see hundreds of scooters on its streets and sidewalks. In light of the prevalence of these services and the significant transportation needs of the disability community, this project examines perceptions of new mobility among disabled people in San Francisco and makes recommendations for improving transportation access for people with disabilities.

Laccases are industrially relevant enzymes. However, their range of applications is limited by their functioning and stability. Most of the currently known laccases function in acidic conditions at temperatures below 60 °C, but two-domain laccases (2D) oxidize some substrates in alkaline conditions and above 70 °C. In this study, we aim to establish the structural factors affecting the alkaline activity of the 2D laccase from Streptomyces griseoflavus (SgfSL). The range of methods used allowed us to show that the alkaline activity of SgfSL is influenced by the polar residues located close to the trinuclear center (TNC). Structural and functional studies of the SgfSL mutants Met199Ala/Asp268Asn and Met199Gly/Asp268Asn revealed that the substitution Asp268Asn (11 Å from the TNC) affects the orientation of the Asn261 (the second coordination sphere of the TNC), resulting in hydrogen-bond-network reorganization, which leads to a change in the SgfSL-activity pH profile. The combination of the Met199Gly/Arg240His and Asp268Asn substitutions increased the efficiency (kcat/KM) of the 2,6-DMP oxidation by 34-fold compared with the SgfSL. Our results extend the knowledge about the structure and functioning of 2D laccases' TNC active sites and open up new possibilities for the directed engineering of laccases. [ABSTRACT FROM AUTHOR]

Aim: Tenascin C (TNC) is a large extracellular matrix glycoprotein. It is involved in development and upregulated both during tissue repair and in several pathological conditions, including cardiovascular disease. Extracellular matrix proteins play a role in promoting exercise responses, leading to adaptation, regeneration, and repair. The main goal of this study was to investigate whether a short anaerobic effort leads to increased levels of TNC in serum. Methods: Thirty‐nine healthy men performed a Wingate test followed by a muscle biopsy. Myoblasts were isolated from the muscle biopsies and differentiated to myotubes ex vivo. TNC RNA was quantified in the biopsies, myotubes and myoblasts using RNA sequencing. Blood samples were drawn before and 5 min after the Wingate test. Serum TNC levels were measured using enzyme‐linked immunosorbent assay. Results: After the Wingate test, serum TNC increased on average by 23% [15–33], median [interquartile range]; PWilcoxon < 0.0001. This increase is correlated with peak power output and power drop, but not with VO2max. TNC RNA expression is higher in myoblasts and myotubes compared to skeletal muscle tissue. Conclusion: TNC is secreted systemically as a response to the Wingate anaerobic test in healthy males. The response was positively correlated with peak power and power drop, but not with VO2max which implicates a relation to mechanical strain and/or blood flow. With higher expression in undifferentiated myoblast cells than muscle tissue, it is likely that TNC plays a role in muscle tissue remodelling in humans. Our findings open for research on how TNC contributes to exercise adaptation. [ABSTRACT FROM AUTHOR]

We evaluate the impact of three proposed regulations of transportation network companies (TNCs) like Uber, Lyft and Didi: (1) A minimum wage for drivers, (2) a cap on the number of drivers or vehicles, and (3) a per-trip congestion tax. The impact is assessed using a queuing theoretic equilibrium model which incorporates the stochastic dynamics of the app-based ride-hailing matching platform, the ride prices and driver wages established by the platform, and the incentives of passengers and drivers. We show that a floor placed under driver earnings can push the ride-hailing platform to hire more drivers and offer more rides, at the same time that passengers enjoy faster rides and lower total cost, while platform rents are reduced. Contrary to standard competitive labor market theory, enforcing a minimum wage for drivers benefits both drivers and passengers, and promotes the efficiency of the entire system. This surprising outcome holds for almost all model parameters, and it occurs because the wage floor curbs TNC labor market power. In contrast to a wage floor, imposing a cap on the number of vehicles hurts drivers, because the platform reaps all the benefits of limiting supply. The congestion tax has the expected impact: fares increase, wages and platform revenue decrease. We also construct variants of the model to briefly discuss platform subsidy, platform competition, and autonomous vehicles.

We evaluate the impact of three proposed regulations of transportation network companies (TNCs) like Uber, Lyft and Didi: (1) A minimum wage for drivers, (2) a cap on the number of drivers or vehicles, and (3) a per-trip congestion tax. The impact is assessed using a queuing theoretic equilibrium model which incorporates the stochastic dynamics of the app-based ride-hailing matching platform, the ride prices and driver wages established by the platform, and the incentives of passengers and drivers. We show that a floor placed under driver earnings can push the ride-hailing platform to hire more drivers and offer more rides, at the same time that passengers enjoy faster rides and lower total cost, while platform rents are reduced. Contrary to standard competitive labor market theory, enforcing a minimum wage for drivers benefits both drivers and passengers, and promotes the efficiency of the entire system. This surprising outcome holds for almost all model parameters, and it occurs because the wage floor curbs TNC labor market power. In contrast to a wage floor, imposing a cap on the number of vehicles hurts drivers, because the platform reaps all the benefits of limiting supply. The congestion tax has the expected impact: fares increase, wages and platform revenue decrease. We also construct variants of the model to briefly discuss platform subsidy, platform competition, and autonomous vehicles.

Makorin-2 (Mkrn2) is an evolutionarily conserved gene whose biological functions are not fully known. Although recent studies have shed insights on the potential causes of male infertility, its underlining mechanisms still remain to be elucidated. We developed a Mrkn2 knockout mice model to study this gene and found that deletion of Mkrn2 in mice led to male infertility. Interestingly, the expression level of signal transducer and activator of the transcription (STAT)1 was significantly decreased in MKRN2 knockout testis and MEF cells. Co-IP assay showed an interaction between MKRN2 and STAT1. Moreover, our results further indicated that MKRN2 regulated the expression level of SIX4 and tenascin C (TNC) via the EBF transcription factor 2 (EBF2) in mice. The results of our study will provide insights into a new mechanism of male infertility. [ABSTRACT FROM AUTHOR]

Cardiac fibrosis and cardiomyocyte apoptosis are reparative processes after myocardial infarction (MI), which results in cardiac remodeling and heart failure at last. Tenascin-C (TNC) consists of four distinct domains, which is a large multimodular glycoprotein of the extracellular matrix. It is also a key regulator of proliferation and apoptosis in cardiomyocytes. As a significant m6A regulator, METTL3 binds m6A sites in mRNA to control its degradation, maturation, stabilization, and translation. Whether METTL3 regulates the occurrence and development of myocardial infarction through the m6A modification of TNC mRNA deserves our study. Here, we have demonstrated that overexpression of METTL3 aggravated cardiac dysfunction and cardiac fibrosis after 4 weeks after MI. Moreover, we also demonstrated that TNC resulted in cardiac fibrosis and cardiomyocyte apoptosis after MI. Mechanistically, METTL3 led to enhanced m6A levels of TNC mRNA and promoted TNC mRNA stability. Then, we mutated one m6A site "A" to "T", and the binding ability of METTL3 was reduced. In conclusion, METTL3 is involved in cardiac fibrosis and cardiomyocyte apoptosis by increasing m6A levels of TNC mRNA and may be a promising target for the therapy of cardiac fibrosis after MI. [ABSTRACT FROM AUTHOR]

The purpose of the article is to analyze the specific modern features of the transformation of the knowledge component of TNC. The methodological basis of the articles can be described by the variety of methods, such as comparative and synthesis methods, methods of abstract logical evaluation, system approaches, methods of detailing, groupings and generalizations, logic analysis, paired and multiple correlation techniques. The scientific-theoretical principles of building up the intellectual capital of TNCs, which are expressed in the concentration of technological priorities, the development and implementation of innovations, technologies, business models, and the formation of a holistic knowledge management system, are analyzed. Levels of knowledge utilization of TNCs are determined. The strategic vision of the TNC in the paradigm of the knowledge economy has been developed. The substantiated role of the intellectual component in the process of forming the competitive potential of TNCs, which is based on the identification of the latest features of corporate knowledge, which serve as a determining factor of economic growth, being in various forms of its manifestation: as a resource embodied (materialized) in technologies and equipment; as a constituent element of human capital, which interacts with the subjects' existing skills, experience, ability to reproduce and update knowledge, use it in their activities; as newly created knowledge, which is the result of research, development and other types of scientific activity of a fundamental and applied nature; as new goods that further contribute to the formation of new markets. The main theoretical and methodological provisions of the development of the knowledge component are formulated, the determinants of the formation of a new knowledge paradigm of TNCs are determined, and recommendations are provided for the strategic development of TNCs in the knowledge economy can be used by scientists, teachers, students, and economists who deal with the issues of the influence of the knowledge component on the development of TNCs. [ABSTRACT FROM AUTHOR]

Abstract Background Cord blood plays a very important role in stem cell transplantation and therapy with an emerging implication also in regenerative medicine. The number of cells available in a single cord blood unit (CBU), in particular, the CD34+ and total nucleated cell (TNC) content influences the transplantation clinical outcome. We analysed a very large series of CBUs, collected for private banking without any specific volume restriction, to deeply investigate the best predictors of cord blood stem cells content. Methods Maternal and neonatal clinic laboratory data of a total 2583 UCBs were obtained from the InScientiaFides cord blood bank based in Republic of San Marino. Univariate and multivariate analysis were conducted to better interpret the data and to build a predictive model to select, the CBU with high CD34+ content. Results Our univariate analysis shows that seasonality and the geographical area affects the quality of umbilical cord blood. Gestational age, babie’s gender and birth weight have a positive correlation with CB TNC content. The babie’s birth weight affects positively also CD34+ content and CBU volume while the cesarean delivery affect the CB volume only. Our predictive model, based on multivariate analysis, shows that male babie’s, gestational age lower to 39 weeks, cesarean delivery and CBUs with a content of TNC higher than 3.44 × 108 (group A) have a significant higher CD34+ content than group B (female babie’s, gestational age higher than 39 weeks and vaginal delivery). The group A have a 37.5% of CBUs with a concentration of CD34+ > 2 × 106, while no CBUs with high concentration of CD34+ were detect in group B. Conclusion This study, conducted on a very large series of CBUs without any specific volume constraint, highlighted the prenatal and maternal factors that significantly influence the quality of the CBU collected. Specifically, it highlights that volume is not the best predictor of CD34+ CBU content; for this reason it cannot be taken into consideration alone for the analysis of the collected samples. Our final aim is to identify relevant factors, immediately available, that help to choice UCB with high CD34+ cell content, especially in simultaneous deliveries.

The purpose of the article is to analyze the specific modern features of the transformation of the knowledge component of TNC. The methodological basis of the articles can be described by the variety of methods, such as comparative and synthesis methods, methods of abstract logical evaluation, system approaches, methods of detailing, groupings and generalizations, logic analysis, paired and multiple correlation techniques. The scientific-theoretical principles of building up the intellectual capital of TNCs, which are expressed in the concentration of technological priorities, the development and implementation of innovations, technologies, business models, and the formation of a holistic knowledge management system, are analyzed. Levels of knowledge utilization of TNCs are determined. The strategic vision of the TNC in the paradigm of the knowledge economy has been developed. The substantiated role of the intellectual component in the process of forming the competitive potential of TNCs, which is based on the identification of the latest features of corporate knowledge, which serve as a determining factor of economic growth, being in various forms of its manifestation: as a resource embodied (materialized) in technologies and equipment; as a constituent element of human capital, which interacts with the subjects' existing skills, experience, ability to reproduce and update knowledge, use it in their activities; as newly created knowledge, which is the result of research, development and other types of scientific activity of a fundamental and applied nature; as new goods that further contribute to the formation of new markets. The main theoretical and methodological provisions of the development of the knowledge component are formulated, the determinants of the formation of a new knowledge paradigm of TNCs are determined, and recommendations are provided for the strategic development of TNCs in the knowledge economy can be used by scientists, teachers, students, and economists who deal with the issues of the influence of the knowledge component on the development of TNCs.

We compare responses from an online survey among 700 customers of transportation network companies (TNC) in Boston and Philadelphia to investigate TNC's impact on vehicle ownership, trip making, and mode choice. We first use a qualitative comparative analysis to examine changes in respondents' travel behavior and vehicle ownership after adopting TNC. We then use a random parameter logit regression analysis to investigate customers' preferences between transit and TNC based on a choice experiment. We find that in both cities, TNC allows customers, including those who currently do not own a car, to either delay purchasing a car or forgo a car altogether. TNC enables customers across income levels to take trips that they otherwise would not have taken. Meanwhile, TNC substitutes for more than complementing transit. The random parameter logit analysis indicates that when choosing between TNC and transit, individuals in both cities consider waiting time and overall travel time for transit to be more burdensome than those for TNC. Bostonians perceive the time spent walking to and from transit to be less burdensome, and the time spent traveling in vehicle to be more burdensome than do Philadelphians. Differences in built environment, mode share within transit systems, and income likely contribute to respondents' different values of time between the two cities. Our paper is the first to compare individual trade-off between transit and TNC in two cities with different urban settings and transit services. The findings have implications on transit service planning, station area improvements, parking regulations, and traffic management. [ABSTRACT FROM AUTHOR]

Accumulating studies have demonstrated that hyperbaric oxygen (HBO) treatment alleviates spinal cord injury (SCI). However, the underlying mechanism by which HBO alleviates SCI remains to be elucidated. In this study, we performed genome-wide transcriptional profiling of the spinal cord between SCI mice and mice that received HBO treatment by high-throughput RNA sequencing at 1 week after SCI. We also compared genome-wide transcriptional profiles from SCI mice and sham-operated mice. We found 76 differentially co-expressed genes in sham-operated mice, SCI mice, and HBO-treated SCI mice. Using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we identified the biological characteristics of these differentially expressed genes from the perspectives of cell component, biological process, and molecular function. We also found enriched functional pathways including ferroptosis, calcium signaling pathway, serotonergic synapse, hypoxia-inducible factor-1 signaling pathway, cholinergic synapse, and neuroactive ligand-receptor interaction. We performed quantitative reverse transcription-polymerase chain reaction and validated that HBO treatment decreased the expression of Hspb1 (heat shock protein beta 1), Hmox1 (heme oxygenase 1), Ftl1 (ferritin light polypeptide 1), Tnc (tenascin C) and Igfbp3 (insulin-like growth factor binding protein 3) and increased the expression of Slc5a7 (solute carrier family 5 choline transporter member 7) after SCI. These results revealed the genome-wide transcriptional profile of the injured spinal cord after HBO treatment. Our findings contribute to a better understanding of the mechanism by which HBO treats SCI and may provide new targets for SCI intervention.

The role of ridesourcing services on vehicle ownership is an important research area, especially in the context of the environmental implications and long term sustainability of these services. However, evidence from literature so far is mixed, with studies reporting both an increase and reduction in ownership, sometimes in the same country. This research adds to the current knowledge by econometrically estimating the impacts of ridesourcing services on vehicle ownership in a large emerging economy, India. Using a cross-sectional timeseries data on vehicle registrations in 18 large cities in India over 17 years, we find a statistically significant reduction in vehicle ownership (compared to baseline) since the introduction of these services. The growth in vehicle ownership has reduced by around 7.7% in the cities together since the introduction of ridesourcing services and this impact appears to grow over time; but the overall ownership is still increasing.

Abstract Background Dermatofibrosarcoma protuberans (DFSP) is a superficial fibroblastic tumor characterized by high rate of local recurrence and low metastatic potential. Fibrosarcomatous transformation can rarely arise in DFSP either de novo or as recurrent, which represents a form of tumor progression and carries an increased risk of metastasis over classic DFSP. Cytogenetically, DFSP is characterized by a recurrent unbalanced chromosome translocation t (17;22)(q22;q13), leading to the formation of COL1A1-PDGFB fusion transcript that is present in more than 90% of cases. Alternative fusions involving the PDGFD with partners of COL6A3 or EMILIN2 have recently been documented in less than 2% of cases. Herein, we report a DFSP with fibrosarcomtous morphology harboring a novel TNC-PDGFD fusion. Case presentation A 54-year-old female presented with a slowly growing mass in the right thigh. Excision demonstrated a 2-cm ovoid, well-circumscribed, gray-white, mass. Microscopic examination revealed a partially encapsulated subcutaneous nodule without dermal connection. The neoplasm was composed of cellular and fairly uniform spindle cells with brisk mitoses, arranged in elongated fascicles and herringbone patterns, with focal collagenized stroma. The neoplastic cells were positive for CD34 and smooth muscle actin. Fluorescence in-situ hybridization analyses showed negative for COL1A1-PDGFB fusion as well as NTRK1/2/3 rearrangements. A subsequent RNA sequencing detected an in-frame fusion between exon 15 of TNC and exon 6 of PDGFD. This fusion was further confirmed by nested reverse transcription polymerase chain reaction amplification followed by Sanger sequencing. A diagnosis of fibrosarcomatous DFSP was rendered and the patient was in good status at a follow-up of 12 months after the operation. Conclusions We report a fibrosarcomatous DFSP with novel TNC-PDGFD fusion, which adds to the pathologic and genetic spectrum of PDGFD-rearranged DFSP.

Ride-hailing services have gained popularity in recent years due to attributes such as reduced travel costs, traffic congestion, and emissions. However, with the impact of COVID-19, the ride-hailing market is estimated to lose its fair share of an uprising as a transportation mode. During normal and critical circumstances, ride-hailing service users express their concerns, habits, and emotions through posting on social platforms such as Twitter. Hence, Twitter, as an emerging data source, is an effective and innovative digital platform to observe the rider’s behavior in ride-hailing services. This study hydrates large-scale Twitter reactions related to shared mobility to perform comparative sentiment and emotion analysis to understand the impact of COVID-19 on transportation network services in pre-pandemic and during pandemic conditions. Amid pandemic, negative tweets (34%) associated with ‘sad’ (15%) and ‘anger’ (15%) emotions were most prevalent in the dataset.

Introduction: Breast cancer is a heterogeneous disease. Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression, and is known for its aggressiveness. Materials and Methods: This retrospective study includes a series of 75 cases collected in the medical oncology department at CHU Hassan II in Fès from January 2020 to December 2023, out of a total of 380 localized TNBC cases. Results: A frequency peak was noted between ages 31 and 42, with 42.7% of patients still in reproductive age. Invasive ductal carcinoma was the predominant type, accounting for 100% of cases, with an average tumor size of 4.4 cm. Histopathological grades II and III were observed in 38.6% and 58.6% of cases, respectively. Primary surgical intervention was performed in 22.6% of patients (17 cases), while 74.6% (56 patients) underwent surgery post-chemotherapy. Neoadjuvant chemotherapy was administered to 77.3% (58 cases), with 23.33% receiving a dose-dense regimen and 76.67% receiving conventional chemotherapy. Adjuvant systemic chemotherapy was administered in 60% of cases, with 10.4% on a dose-dense regimen and 89.6% on a conventional regimen. An unfavorable progression was noted in 28.97% of cases, with 23.18% (16 cases) developing systemic metastases predominantly in bone (37.5%), lungs (31.25%), brain (18.75%), and liver (12.5%). Hematologic toxicity was the main side effect observed, accounting for 44.06% of the chemotherapy-related toxicity in our study. Adjuvant external radiotherapy at a dose of 42 Gray in 16 sessions (2.8 Gray per session) was administered in 82.6% of treated cases (62 patients). Conclusion: Triple-negative breast cancer is a subtype of breast cancer characterized by clinical, prognostic, and therapeutic polymorphism. [ABSTRACT FROM AUTHOR]

Piwi-interacting Ribonucleic acids (piRNAs) molecule is a wellknown subclass of small non-codingRNAmolecules that are mainly responsible for maintaining genome integrity, regulating gene expression, and germline stem cell maintenance by suppressing transposon elements. The piRNAs molecule can be used for the diagnosis of multiple tumor types and drug development. Due to the vital roles of the piRNA in computational biology, the identification of piRNAs has become an important area of research in computational biology. This paper proposes a two-layer predictor to improve the prediction of piRNAs and their function using deep learning methods. The proposed model applies various feature extraction methods to consider both structure information and physicochemical properties of the biological sequences during the feature extraction process. The outcome of the proposed model is extensively evaluated using the k-fold cross-validation method. The evaluation result shows that the proposed predictor performed better than the existing models with accuracy improvement of 7.59% and 2.81% at layer I and layer II respectively. It is anticipated that the proposed model could be a beneficial tool for cancer diagnosis and precision medicine. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma multiforme (GBM) is a common malignant brain tumor with high mortality. It is urgently necessary to develop a new treatment because traditional approaches have plateaued. Purpose: Here, we identified an immune-related gene (IRG)-based prognostic signature to comprehensively define the prognosis of GBM. Methods: Glioblastoma samples were selected from the Chinese Glioma Genome Atlas (CGGA). We retrieved IRGs from the ImmPort data resource. Univariate Cox regression and LASSO Cox regression analyses were used to develop our predictive model. In addition, we constructed a predictive nomogram integrating the independent predictive factors to determine the one-, two-, and 3-year overall survival (OS) probabilities of individuals with GBM. Additionally, the molecular and immune characteristics and benefits of ICI therapy were analyzed in subgroups defined based on our prognostic model. Finally, the proteins encoded by the selected genes were identified with liquid chromatography-tandemmass spectrometry and western blotting (WB). Results: Six IRGs were used to construct the predictive model. The GBM patients were categorized into a high-risk group and a low-risk group. High-risk group patients had worse survival than low-risk group patients, and stronger positive associations with multiple tumor-related pathways, such as angiogenesis and hypoxia pathways, were found in the high-risk group. The high-risk group also had a low IDH1 mutation rate, high PTEN mutation rate, low 1p19q co-deletion rate and low MGMT promoter methylation rate. In addition, patients in the high-risk group showed increased immune cell infiltration, more aggressive immune activity, higher expression of immune checkpoint genes, and less benefit from immunotherapy than those in the low-risk group. Finally, the expression levels of TNC and SSTR2 were confirmed to be significantly associated with patient prognosis by proteinmass spectrometry and WB. Conclusion: Herein, a robust predictive model based on IRGs was developed to predict the OS of GBM patients and to aid future clinical research. [ABSTRACT FROM AUTHOR]

[Display omitted] • Between 2012 and 2018, bus ridership in the US declined 15% and rail ridership declined 3%. • We identify the factors responsible and quantify the contribution of each. • Expanded transit service and land-use changes would have led to higher ridership but were offset by other factors. • Ride-hailing is the biggest contributor to transit ridership decline. • Higher fares, incomes, teleworking and car ownership, and lower gas prices also contribute. Between 2012 and 2018, bus ridership in the United States declined 15% and rail ridership declined 3%. These losses are widespread and in contrast to trends in other countries. Using data from 215 Metropolitan Statistical Areas (MSAs) prior to the COVID-19 pandemic, we identify the factors responsible for this decline and quantify the contribution of each. We show that expanded transit service and land-use changes increased ridership 4.7% on bus and 10.7% on rail. However, losses due to other factors exceed these gains. Ride-hailing is the biggest contributor to transit ridership decline over this period, reducing bus ridership by 10%. Ride-hailing's effect on rail varies by metropolitan area size: it has little effect on rail ridership in the largest metropolitan areas but decreases rail ridership 10% in mid-sized metropolitan areas. Lower gas prices and higher fares contribute to lower transit ridership, as do higher incomes, more teleworking and higher car ownership. By providing a clear understanding of the causes of transit ridership decline, our research provides the foundation on which communities can craft an effective response to the problem. [ABSTRACT FROM AUTHOR]

Background: Cord blood plays a very important role in stem cell transplantation and therapy with an emerging implication also in regenerative medicine. The number of cells available in a single cord blood unit (CBU), in particular, the CD34+ and total nucleated cell (TNC) content influences the transplantation clinical outcome. We analysed a very large series of CBUs, collected for private banking without any specific volume restriction, to deeply investigate the best predictors of cord blood stem cells content. Methods: Maternal and neonatal clinic laboratory data of a total 2583 UCBs were obtained from the InScientiaFides cord blood bank based in Republic of San Marino. Univariate and multivariate analysis were conducted to better interpret the data and to build a predictive model to select, the CBU with high CD34+ content. Results: Our univariate analysis shows that seasonality and the geographical area affects the quality of umbilical cord blood. Gestational age, babie's gender and birth weight have a positive correlation with CB TNC content. The babie's birth weight affects positively also CD34+ content and CBU volume while the cesarean delivery affect the CB volume only. Our predictive model, based on multivariate analysis, shows that male babie's, gestational age lower to 39 weeks, cesarean delivery and CBUs with a content of TNC higher than 3.44 × 108 (group A) have a significant higher CD34+ content than group B (female babie's, gestational age higher than 39 weeks and vaginal delivery). The group A have a 37.5% of CBUs with a concentration of CD34+ > 2 × 106, while no CBUs with high concentration of CD34+ were detect in group B. Conclusion: This study, conducted on a very large series of CBUs without any specific volume constraint, highlighted the prenatal and maternal factors that significantly influence the quality of the CBU collected. Specifically, it highlights that volume is not the best predictor of CD34+ CBU content; for this reason it cannot be taken into consideration alone for the analysis of the collected samples. Our final aim is to identify relevant factors, immediately available, that help to choice UCB with high CD34+ cell content, especially in simultaneous deliveries. [ABSTRACT FROM AUTHOR]

Why does the Chinese economic modernization strategy include transnationalization of Chinese enterprises, the creation of numerous Small and Medium Foreign Affiliates (SMFAs)? The research hypothesis suggests that in the context of globalization, modernization requires influencing other participants in the global economy beyond national borders. SMFAs are able to transform the structure of the economy of the PRC and host countries to ensure demand for national innovations and highly skilled labor. The literature review highlights the challenges of modernizing the national economy in the context of globalization, as well as the advantages of TNCs and participation in global value chains (GVCs). However, the question of the connection between catchup development and transnationalization of local business, especially small and medium-sized ones, has been understudied. The novelty of the study is in the analysis of the sectoral and geographical structure of the foreign activities of Chinese TNCs and the analysis of the problems of the participation of Chinese TNCs in Western global value chains (GVCs). The main findings reveal that the creation of SMFAs is a response to the challenges of globalization, which impede the modernization of the Chinese economy. Powerful state support to SMFAs makes them dependent, and thus the government is able to direct the goals of private enterprises in accordance with the national interests. The major field of Chinese SMFAs is the promotion of products manufactured in the PRC in the American and European markets, and it contributes to the development of the national innovation system, redistributes the added value in favor of national manufacturers, and stimulates the development of hightech industries of the PRC. In developing countries SMFAs are represented by trade and manufacturing outlets within the “Belt and Road Initiative” They come after the infrastructural projects of large business, grouped in clusters, have strong coordination with other Chinese TNCs, and create Chinese GVCs. The main role of Chinese SMFAs in the modernization of the PRC economy is to ensure national interests, including industrial sovereignty and the growth of wellbeing of citizens as the basis of innovative demand. In the modern international labor division, this is achieved by a shift to high valueadded operations, accompanied by a struggle for the markets of developed countries and for sites for the low valueadded operations inside Chinese GVCs in developing countries.

Ride-hailing has redefined vehicle access and has the potential to reduce travel difficulties for transit-poor areas and people with poor access to private and public transportation resources. Due to the lack of data, current studies lack a holistic understanding of how transportation resources serve different social groups and places in the ride-hailing era in low-density areas. This study uses multiple sources of data in Austin, Texas to understand: (1) how ride-hailing usage, transit supply, and vehicle ownership distribute across neighborhoods with different densities, income, and racial and ethnic compositions; (2) who are ride-hailing users among those with and without private vehicles, and how their ride-hailing usage and attitudes towards ride-hailing versus transit differ. Our study has shown that the ride-hailing services have provided residents living in low-income, low-density neighborhoods, and neighborhoods with a majority of Hispanics with an alternative transportation mode. However, residents living in low-density and low-income neighborhoods still use ride-hailing services less frequently than those living in high-density and high-income neighborhoods. The user survey further shows that ride-hailing users without private vehicles tend to be racial and minorities or younger people with higher education attainments. Ride-hailing services provide people with a convenient and safe transportation mode, regardless of their vehicle ownership. Our study shows the importance of ride-hailing in mitigating the social and spatial disparity and the opportunity of integrating ride-hailing and transit in transportation planning in low-density areas. • This study uses multiple data sources to study neighborhood and individual-level transportatation dirstributions. • Frequent ride-hailing usage, dense transit supply, and high share of zero-vehicle owners concentrate in downtown Austin. • Ride-hailing services support daily transportation for transport disadvantaged areas and people in Austin. • Ride-hailing services have the potential to integrate with public transit systems in low-density areas. [ABSTRACT FROM AUTHOR]

The article describes the specifics of the relationship between the state and big corporations (chaebol). There are analyzed the economic changes of the Republic of Korea, related to the world economy globalization and scientific and technical revolution. Many aspects of this global restructuring of the economy have their own history. The relationship between the state and large chaebol corporations played a significant role in these changes. Special attention in the article is focused on the analysis of the relations system between the state and large enterprises in the Republic of Korea during the period 1960-1980 and the transformation of the relations at the beginning of the 21st century. There were quite a lot of difficulties in the relations between the state and the chaebols, but the timely response to the changes of the world economy has borne fruit. It should be noted that the state and the chaebol have repeatedly reformed their relations and found consensus. As a result, such corporations as Hyundai, Samsung, LG, Hesong and others moved to the category of multinational companies (TNCs). Large corporations and business groups in different parts of the world differ among themselves in a number of economic, political and socio-cultural features, but the relationship between the state and the chaebols in the Republic of Korea deserves special attention from developing countries. [ABSTRACT FROM AUTHOR]

Municipal governments struggle with providing accessible mobility for constituents without overburdening them with service costs. While transit offers many advantages, the cost of providing services can be prohibitive. Transportation Network Companies (TNCs) are a mobility alternative. This research answers the following question: Can TNCs be economically feasible as a replacement for bus? U.S. Federal Transit Administration (FTA) National Transit Database (NTD) data was evaluated finding that while TNCs could replace transit in some instances (23% of cases for an exclusive TNC option; 45% of cases for shared TNCs) most of the time bus will be more cost effective. Three agency characteristics were identified to anticipate TNC cost effectiveness: ridership, service area density, and average bus operating speeds. Overall, while TNCs are unlikely to be able to replace transit completely in most cases, their flexibility allows public entities to be more creative when making mobility policy and operational decisions. [ABSTRACT FROM AUTHOR]