bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of smart polymeric biomaterials in bone regeneration: a review
Authors: Xing Yanghui , Qiu Linhui , Liu Danqing , Dai Sihan , Sheu Chia-Lin
Published: August 2023

Addressing critical bone defects necessitates innovative solutions beyond traditional methods, which are constrained by issues such as immune rejection and donor scarcity. Smart polymeric biomaterials that respond to external stimuli have emerged as a promising alternative, fostering endogenous bone regeneration. Light-responsive polymers, employed in 3D-printed scaffolds and photothermal therapies, enhance antibacterial efficiency and bone repair. Thermo-responsive biomaterials show promise in controlled bioactive agent release, stimulating osteocyte differentiation and bone regeneration. Further, the integration of conductive elements into polymers improves electrical signal transmission, influencing cellular behavior positively. Innovations include advanced 3D-printed poly (l-lactic acid) scaffolds, polyurethane foam scaffolds promoting cell differentiation, and responsive polymeric biomaterials for osteogenic and antibacterial drug delivery. Other developments focus on enzyme-responsive and redox-responsive polymers, which offer potential for bone regeneration and combat infection. Biomaterials responsive to mechanical, magnetic, and acoustic stimuli also show potential in bone regeneration, including mechanically-responsive polymers, magnetic-responsive biomaterials with superparamagnetic iron oxide nanoparticles, and acoustic-responsive biomaterials. In conclusion, smart biopolymers are reshaping scaffold design and bone regeneration strategies. However, understanding their advantages and limitations is vital, indicating the need for continued exploratory research.
Comparative genomics and DNA methylation analysis of Pseudomonas aeruginosa clinical isolate PA3 by single-molecule real-time sequencing reveals new targets for antimicrobials
Authors: Li Zijiao , Zhou Xiang , Liao Danxi , Liu Ruolan , Zhao Xia , Wang Jing , Zhong Qiu , Zeng Zhuo , Peng Yizhi , Tan Yinling , Yang Zichen
Published: August 2023

Introduction

Pseudomonas aeruginosa (P.aeruginosa) is an important opportunistic pathogen with broad environmental adaptability and complex drug resistance. Single-molecule real-time (SMRT) sequencing technique has longer read-length sequences, more accuracy, and the ability to identify epigenetic DNA alterations.

Methods

This study applied SMRT technology to sequence a clinical strain P. aeruginosa PA3 to obtain its genome sequence and methylation modification information. Genomic, comparative, pan-genomic, and epigenetic analyses of PA3 were conducted.

Results

General genome annotations of PA3 were discovered, as well as information about virulence factors, regulatory proteins (RPs), secreted proteins, type II toxin-antitoxin (TA) pairs, and genomic islands. A genome-wide comparison revealed that PA3 was comparable to other P. aeruginosa strains in terms of identity, but varied in areas of horizontal gene transfer (HGT). Phylogenetic analysis showed that PA3 was closely related to P. aeruginosa 60503 and P. aeruginosa 8380. P. aeruginosa's pan-genome consists of a core genome of roughly 4,300 genes and an accessory genome of at least 5,500 genes. The results of the epigenetic analysis identified one main methylation sites, N6-methyladenosine (m6A) and 1 motif (CATNNNNNNNTCCT/AGGANNNNNNNATG). 16 meaningful methylated sites were picked. Among these, purH, phaZ, and lexA are of great significance playing an important role in the drug resistance and biological environment adaptability of PA3, and the targeting of these genes may benefit further antibacterial studies.

Disucssion

This study provided a detailed visualization and DNA methylation information of the PA3 genome and set a foundation for subsequent research into the molecular mechanism of DNA methyltransferase-controlled P. aeruginosa pathogenicity.
Virome analysis of an ectomycorrhizal fungus Suillus luteus revealing potential evolutionary implications
Authors: Liu Hanzhao , Zhang Yifei , Liu Yingying , Xiao Junbo , Huang Zijie , Li Yunfeng , Li Huaping , Li Pengfei
Published: August 2023

Suillus luteus is a widespread edible ectomycorrhizal fungus that holds significant importance in both ecological and economic value. Mycoviruses are ubiquitous infectious agents hosted in different fungi, with some known to exert beneficial or detrimental effects on their hosts. However, mycoviruses hosted in ectomycorrhizal fungi remain poorly studied. To address this gap in knowledge, we employed next-generation sequencing (NGS) to investigate the virome of S. luteus. Using BLASTp analysis and phylogenetic tree construction, we identified 33 mycovirus species, with over half of them belonging to the phylum Lenarviricota, and 29 of these viruses were novel. These mycoviruses were further grouped into 11 lineages, with the discovery of a new negative-sense single-stranded RNA viral family in the order Bunyavirales. In addition, our findings suggest the occurrence of cross-species transmission (CST) between the fungus and ticks, shedding light on potential evolutionary events that have shaped the viral community in different hosts. This study is not only the first study to characterize mycoviruses in S. luteus but highlights the enormous diversity of mycoviruses and their implications for virus evolution.
The price is not right
Authors: Chami Ralph , Fullenkamp Connel , González Gómez Andres , Hilmi Nathalie , Magud Nicolas E.
Published: August 2023

The 2015 Paris Agreement requires all nations to combat climate change and to adapt to its effects. Countries promise to reduce their greenhouse gas (GHG) emissions through their Nationally Determined Contributions. Pledges to reduce emissions, however, have implications for economic growth. We estimate the link between economic growth and CO2 pollution levels and find that this relationship is highly non-linear. A country's GHG emissions rise rapidly as its economic activity rises, relative to global activity, meaning that fast-growing countries contribute most heavily to current GHG emissions. Then, using real per-capita GDP as our metric, we estimate how much the carbon price should be in order to remove the economic growth benefit from excess GHG emissions. We find that the implied prices are far higher than the prices on any existing market for emissions as well as estimates of the social cost of carbon. Our findings also have important implications for the global dialogue regarding responsibility for climate mitigation as well as for the choice of policies to support mitigation efforts.
Data-driven non-parametric chance-constrained model predictive control for microgrids energy management using small data batches
Authors: Babić Leon , Lauricella Marco , Ceusters Glenn , Biskoping Matthias
Published: August 2023

This paper presents a stochastic model predictive control approach combined with a time-series forecasting technique to tackle the problem of microgrid energy management in the face of uncertainty. The data-driven non-parametric chance constraint method is used to formulate chance constraints for stochastic model predictive control, while removing the dependency on probability density assumptions of uncertain variables and retaining the linear structure of the resulting optimization problem. The proposed approach is suitable for implementation on systems with limited computational power or limited memory storage, thanks to its simple linear structure and its ability to provide accurate results within pre-defined confidence levels, even when using small data batches. The proposed forecasting and stochastic model predictive control approaches are applied on a numerical example featuring a small grid-connected microgrid with PV generation, a battery storage system, and a non-controllable load, showing the ability to reduce costs by reducing the confidence level, and to satisfy pre-defined confidence levels.
Community participation for reproductive, maternal, newborn and child health: insights from the design and implementation of the BornFyne-prenatal management system digital platform in Cameroon
Authors: Obegu Pamela , Nkangu Miriam , Ngo Ngo Valery , Wanda Franck , Kasonde Mwenya , Kibu Odette D. , Abong Nelly , Ndiforchu Victor , Fantaye Arone Wondwossen , Buh Amos , Gobina Ronald M. , Foretia Denis A. , Fobellah Nkengafack , Yaya Sanni
Published: August 2023

Introduction

Across communities in low-middle income countries, digital health is currently revolutionizing the delivery of health services, particularly in the field of reproductive, maternal, newborn, and child health (RMNCH) services. While studies have shown the effectiveness of mHealth in delivering RMNCH services, there is little information about factors that enhance mHealth services utilization in low-cost settings including stakeholders’ level of influence on the implementation of digital health intervention in sub–Saharan Africa. This paper seeks to describe important lessons on the levels of stakeholders’ direct or indirect influence on the design and implementation of the BornFyne-PNMS digital health platform to support RMNCH services.

Methods

A participatory research (PR) design approach was employed to explore stakeholders’ perspectives of a new initiative, through direct engagement of local priorities and perspectives. The process of introducing the digital application called the BornFyne-PNMS for district health delivery system and the community, and integrating it within the district health delivery system was guided by research-to-action, consistent with the PR approach. To explore stakeholders’ perspectives through a PR approach, we conducted a series of stakeholder meetings fashioned after focus group discussions.

Results

Issues around male involvement in the program, sensitization and equity concerns arose. Emergent challenges and proposed strategies for implementation from diverse stakeholders evidently enriched the design and implementation process of the project intervention. Stakeholder meetings informed the addition of variables on the mobile application that were otherwise initially omitted, which will further enhance the RMNCH electronic data collection for health information systems strengthening in Cameroon.

Discussion

This study charts a direction that is critical in digital health delivery of RMNCH in a rural and low-income community and describes the important iterative stakeholder input throughout the study. The strategy of stakeholders’ involvement in the BornFyne PNMS implementation charts a direction for ownership and sustainability in the strengthening of Cameroon's health information system.
Gender inequality in science, technology, engineering and mathematics: gendered time disparities in perceived and actual time spent in practical laboratory-based activities
Authors: Fernandez Daniela , White Sarah , Smith Helen C. M. , Connor Peter M. , Ryan Michelle
Published: August 2023

Lab-based activities provide essential skills for students within STEM disciplines, as lab activities provide students with research skills and science knowledge. Therefore, it is critical to note that female students have reported feeling less confident in conducting lab-based activities and report a lower sense of belonging in the lab. In two studies (N = 544) we examined gender differences in the time that students spent, and perceived they spent, on various laboratory-based activities. We predicted that female (vs. male) students in science, technology, engineering and mathematics (STEM) would both perceive, and actually spend, less time in practical, science-specific activities, such as using equipment, compared to observing or note-taking. Study 1a (N = 227) was an online, cross-sectional survey where university STEM students reported their perceptions of time spent during lab-based practical activities, and how satisfied they were with their time spent in these activities. Study 1b (N = 318) was an observational study of university practical lab sessions in STEM disciplines. Our findings demonstrated that female (vs. male) students (1) spent more time recording and taking notes during lab sessions, (2) did not perceive, yet actually spent, less time in the lab using equipment, and (3) were equally satisfied with their time in the lab using equipment. Together, these results suggest that women occupy stereotypically gendered roles in the STEM lab, spending less time on activities that are key for their professional development. Furthermore, the fact that students from disciplines with more female participation were more satisfied with their time spent in lab activities can promote the insidious effects of assessing gender participation and equality in STEM through numbers only. The differences in time spent in lab activities-yet the lack of acknowledge of these differences-opens the discussion about how women might be receiving reduced utility from their programmes, and that universities may not be delivering on their obligations to ensure equal access to teaching resource and opportunities.
Cost-effectiveness of active surveillance versus early surgery for thyroid micropapillary carcinoma based on diagnostic and treatment norms in China
Authors: Lai Min , Zhang Miao Miao , Qin Qing Qing , An Yu , Li Yan Ting , Yuan Wen Zhen
Published: August 2023

Objectives

In this study, we compared the cost-effectiveness comparison of the active surveillance (AS) and early surgery (ES) approaches for papillary thyroid microcarcinoma (PTMC) from the perspective of the Chinese healthcare system.

Methods

We performed a cost-effectiveness analysis using a Markov model of PTMC we developed to evaluate the incremental cost-effectiveness ratio of AS and ES. Our reference case was of a 40-year-old woman diagnosed with unifocal (<10 mm) PTMC. Relevant data were extracted after an extensive literature review, and the cost incurred in each state was determined using China Medicare data on payments for ES and AS. The willingness-to-pay threshold was set at ¥242,928/quality-adjusted life-year (QALY) gained. Sensitivity analyses were performed to account for any uncertainty in the model’s variables. Additional subgroup analyses were performed to determine whether AS was cost-effective when different initial monitoring ages were used.

Results

ES exhibited an effectiveness of 5.2 QALYs, whereas AS showed an effectiveness of 25.8 QALYs. Furthermore, the incremental cost-effectiveness ratio for ES versus AS was ¥1,009/QALY. The findings of all sensitivity analyses were robust. Compared with ES, AS was found to be the cost-effective strategy at initial monitoring ages of 20 and 60 years, with an incremental cost-effectiveness ratio of ¥3,431/QALY and −¥1,316/QALY at 20 and 60 years, respectively. AS was a more cost-effective strategy in patients with PTMC aged more than 60.

Conclusions

With respect to the norms of the Chinese healthcare system, AS was more cost-effective for PTMC over lifetime surveillance than ES. Furthermore, it was cost-effective even when the initial monitoring ages were different. In addition, if AS is incorporated into the management plan for PTMC in China at the earliest possible stage, a predicted savings of ¥10 × 108/year could be enabled for every 50,000 cases of PTMC, which indicates a good economic return for future management programs. The identification of such nuances can help physicians and patients determine the best and most individualized long-term management strategy for low-risk PTMC.
Network pharmacology- and molecular docking-based analyses of the antihypertensive mechanism of Ilex kudingcha
Authors: Liao Fei , Yousif Muhammad , Huang Ruya , Qiao Yanlong , Hu Yanchun
Published: August 2023

Herein, network pharmacology was used to identify the active components in Ilex kudingcha and common hypertension-related targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted, and molecular docking was performed to verify molecular dynamic simulations. Six active components in Ilex kudingcha were identified; furthermore, 123 target genes common to hypertension were identified. Topological analysis revealed the strongly associated proteins, with RELA, AKT1, JUN, TP53, TNF, and MAPK1 being the predicted targets of the studied traditional Chinese medicine. In addition, GO enrichment analysis revealed significant enrichment of biological processes such as oxidative stress, epithelial cell proliferation, cellular response to chemical stress, response to xenobiotic stimulus, and wound healing. Furthermore, KEGG enrichment analysis revealed that the genes were particularly enriched in lipid and atherosclerosis, fluid shear stress and atherosclerosis, and other pathways. Molecular docking revealed that the key components in Ilex kudingcha exhibited good binding potential to the target genes RELA, AKT1, JUN, TP53, TNF, and IL-6. Our study results suggest that Ilex kudingcha plays a role in hypertension treatment by exerting hypolipidemic, anti-inflammatory, and antioxidant effects and inhibiting the transcription of atherosclerosis-related genes.
Insulin signaling and its application
Authors: Le Thi Kim Chung , Dao Xuan Dat , Nguyen Dang Vung , Luu Duc Huy , Bui Thi Minh Hanh , Le Thi Huong , Nguyen Huu Thang , Le Tran Ngoan , Hosaka Toshio , Nguyen Thi Thu Thao
Published: August 2023

The discovery of insulin in 1921 introduced a new branch of research into insulin activity and insulin resistance. Many discoveries in this field have been applied to diagnosing and treating diseases related to insulin resistance. In this mini-review, the authors attempt to synthesize the updated discoveries to unravel the related mechanisms and inform the development of novel applications. Firstly, we depict the insulin signaling pathway to explain the physiology of insulin action starting at the receptor sites of insulin and downstream the signaling of the insulin signaling pathway. Based on this, the next part will analyze the mechanisms of insulin resistance with two major provenances: the defects caused by receptors and the defects due to extra-receptor causes, but in this study, we focus on post-receptor causes. Finally, we discuss the recent applications including the diseases related to insulin resistance (obesity, cardiovascular disease, Alzheimer’s disease, and cancer) and the potential treatment of those based on insulin resistance mechanisms.
Impact characteristics and erosion mechanism of solid particles in a centrifugal pump
Authors: Li Wei , Yang Yi , Wu Pu , Ji Leilei , Liu Mingjiang , Qi Handong , Li Shuo
Published: August 2023

To study the impact and erosion mechanism of solid particles in centrifugal pumps, the standard k–ε turbulence model and SIMPLE algorithm are adopted in this paper. Based on the discrete phase model (DPM) of the Lagrange method and McLaury erosion model, the flow impact characteristics and erosion mechanism of solid particles impacting the surface of flow passage components in a single-stage centrifugal pump were numerically simulated, and the test data were compared with the numerical simulation results of the external characteristics of the pump in clean water. The results show that the erosion mechanism of the pressure surface of the blade is mostly the impact erosion caused by high-speed particles with large impact angles, and the impact angle and impact velocity are larger near the tail of the pressure surface. The impact angle of solid particles on the shroud and hub is relatively small, but the erosion mechanism is still impact erosion. The erosion mechanism of the volute wall is mostly the cutting friction erosion caused by the low-velocity particles with small impact angles, and it is only impacted by the particles with large angles near the volute tongue, which is impact erosion. Overall, the average impact angle and impact velocity of the particles on the pressure surface of the blade are higher than those on the volute, so the erosion of the pressure surface is more serious than that of the volute in theory. The research results have certain theoretical reference value for improving the wear resistance of a centrifugal pump.
Smart grid energy storage capacity planning and scheduling optimization through PSO-GRU and multihead-attention
Authors: Xiao Ying , Zhang Lirong
Published: August 2023

The energy problem in today’s society is becoming increasingly prominent, and the smart grid has become one of the important ways to solve the energy problem. Smart grid energy storage capacity planning and scheduling optimization is an important issue in the smart grid, which can make the grid more efficient, reliable, and sustainable to meet energy demand better and protect the environment. The core of smart grid energy storage capacity planning and scheduling optimization is maximizing the use of energy storage devices to balance the difference between power supply and demand to ensure the grid operation’s stability. Traditional planning methods are usually based on experience and rules, have low precision, and cannot adapt to the dynamic changes in the long-term development of the power grid. Therefore, this paper proposes a method that combines PSO-GRU (particle swarm Optimization (PSO)-gated recurrent unit (GRU)) and Multihead-Attention to realize smart grid energy storage capacity planning. And scheduling optimization. First, PSO-GRU models and predicts power grid data by searching for the optimal GRU model parameters; second, Multihead-Attention improves the model’s performance through the self-attention mechanism. Finally, we use the method to determine the optimal energy storage capacity and dispatching scheme for the efficient operation of smart grids. Our experiments use real power grid datasets and compare them with other common methods. Experimental results show that our proposed method has higher accuracy and stability than other methods and can better adapt to the dynamic changes of the power grid. This indicates that our method has good feasibility and applicability in practical applications and is significant for realizing the efficient operation of smart grids and energy saving and emission reduction.
Study on rainfall infiltration characteristic parameters of unsaturated soil
Authors: Zhong Lijia , Wang Bo , Zhao Xuguang , Liu Fengyin , Miao Meng , Pu Cheng
Published: August 2023

The study of the rainfall infiltration mechanism of unsaturated soil has always been a hot issue in the field of geotechnical engineering. It is worth studying which parameters should be introduced to characterize the infiltration characteristics of unsaturated soil in the calculation and analysis of rainfall infiltration. In this paper, the Fredlund–Xing model was quoted in the SEEP/W module of the Geostudio software, and the transient numerical calculation of rainfall infiltration under the same rainfall duration T and different rainfall intensity I was carried out for a soil column. Three infiltration characteristic parameters were introduced: rainfall infiltration front depth WF, suction reduction depth MRn, and section infiltration rate IR. The variation of these three parameters and rainfall intensity I during rainfall were sorted out and analyzed; it is indicated that WF increases with the extension of rainfall duration. MRn decreases with the increase of suction reduction rate n%, and when the rainfall duration is 24 h, the maximum depth of the soil column affected by rainfall is approximately 35% of the total depth. IR is mainly affected by the rainfall intensity I and the saturation permeability coefficient ks. There is a limit value for the influence of I on WF, MRn, and IR, and the limit rainfall intensity under the calculation conditions in this paper is I = 2.5ks.
Regulation of tumor immunity and immunotherapy by the tumor collagen extracellular matrix
Authors: Flies Dallas B. , Langermann Solomon , Jensen Christina , Karsdal Morten A. , Willumsen Nicholas
Published: August 2023

It has been known for decades that the tumor extracellular matrix (ECM) is dysfunctional leading to loss of tissue architecture and promotion of tumor growth. The altered ECM and tumor fibrogenesis leads to tissue stiffness that act as a physical barrier to immune cell infiltration into the tumor microenvironment (TME). It is becoming increasingly clear that the ECM plays important roles in tumor immune responses. A growing body of data now indicates that ECM components also play a more active role in immune regulation when dysregulated ECM components act as ligands to interact with receptors on immune cells to inhibit immune cell subpopulations in the TME. In addition, immunotherapies such as checkpoint inhibitors that are approved to treat cancer are often hindered by ECM changes. In this review we highlight the ways by which ECM alterations affect and regulate immunity in cancer. More specifically, how collagens and major ECM components, suppress immunity in the complex TME. Finally, we will review how our increased understanding of immune and immunotherapy regulation by the ECM is leading towards novel disruptive strategies to overcome immune suppression.
IL-21 is required for the maintenance and pathogenesis of murine Vγ4+ IL-17-producing γδT cells
Authors: Ishikawa Junichi , Suto Akira , Abe Kazuya , Hayashi Yuki , Suga Kensuke , Tanaka Shigeru , Kageyama Takahiro , Iwata Arifumi , Suzuki Kazumasa , Suzuki Kotaro , Nakajima Hiroshi
Published: August 2023

Murine IL-17-producing γδT (γδT17) cells are divided into two subsets: natural γδT17 (nγδT17) cells, whose development is restricted to the fetal thymus, and inducible γδT17 cells, which require antigen exposure for their IL-17 production and are presumed to develop from Rorc+Il17a-CCR9+ immature γδT17 cells in the adult thymus and whose T cell receptor (TCR) is biased toward Vγ4. Although IL-23 is known to be involved in developing γδT17 cells, the roles of other cytokines, such as IL-21, which is involved in developing Th17 cells like IL-23, in the development, maintenance, and pathophysiology of γδT17 cells remain unknown. Here, we show that IL-21 is dispensable for the fetal thymic development of nγδT17 cells but is required for the peripheral maintenance of Vγ4+nγδT17 cells. Upon stimulation with γδTCR, IL-1 plus IL-21 induces the proliferation of Vγ4+nγδT17 cells via STAT3 as effectively as IL-1 plus IL-23. Using bone marrow chimeric mice, we demonstrated that immature γδT17 cells are produced de novo in the adult mice from donor adult bone marrow cells and that IL-21 is dispensable for their development. Instead, IL-21 is required to expand newly induced Vγ4+γδT17 cells in the periphery upon immunization. Finally, using adoptive transfer experiments of γδT17 cells, we found that IL-21 receptors on γδT17 cells are involved in maintaining Vγ4+γδT17 cells, subsequent infiltration of Th17 cells into the spinal cord, and exacerbation of experimental autoimmune encephalomyelitis. Collectively, IL-21 plays a vital role in the maintenance and pathogenesis of Vγ4+γδT17 cells.
Comparative transcriptomics of porcine liver-resident CD8αdim, liver CD8αhigh and circulating blood CD8αhigh NK cells reveals an intermediate phenotype of liver CD8αhigh NK cells
Authors: Hermans Leen , Denaeghel Sofie , Jansens Robert J. J. , De Pelsmaeker Steffi , Van Nieuwerburgh Filip , Deforce Dieter , Hegewisch-Solloa Everardo , Mace Emily M. , Cox Eric , Devriendt Bert , Favoreel Herman W.
Published: August 2023

Liver-resident NK (lrNK) cells have been studied in humans as well as in mice. Unfortunately, important differences have been observed between murine and human lrNK cells, complicating the extrapolation of data obtained in mice to man. We previously described two NK cell subsets in the porcine liver: A CD8αhigh subset, with a phenotype much like conventional CD8αhigh NK cells found in the peripheral blood, and a specific liver-resident CD8αdim subset which phenotypically strongly resembles human lrNK cells. These data suggest that the pig might be an attractive model for studying lrNK cell biology. In the current study, we used RNA-seq to compare the transcriptome of three porcine NK cell populations: Conventional CD8αhigh NK cells from peripheral blood (cNK cells), CD8αhigh NK cells isolated from the liver, and the liver-specific CD8αdim NK cells. We found that highly expressed transcripts in the CD8αdim lrNK cell population mainly include genes associated with the (adaptive) immune response, whereas transcripts associated with cell migration and extravasation are much less expressed in this subset compared to cNK cells. Overall, our data indicate that CD8αdim lrNK cells show an immature and anti-inflammatory phenotype. Interestingly, we also observed that the CD8αhigh NK cell population that is present in the liver appears to represent a population with an intermediate phenotype. Indeed, while the transcriptome of these cells largely overlaps with that of cNK cells, they also express transcripts associated with liver residency, in particular CXCR6. The current, in-depth characterization of the transcriptome of porcine liver NK cell populations provides a basis to use the pig model for research into liver-resident NK cells.
The combined signatures of telomere and immune cell landscape provide a prognostic and therapeutic biomarker in glioma
Authors: Han Xu , Yan Zihan , Fan Kaiyu , Guan Xueyi , Hu Bohan , Li Xiang , Ou Yunwei , Cui Bing , An Lingxuan , Zhang Yaohua , Gong Jian
Published: August 2023

Background

Gliomas, the most prevalent primary malignant tumors of the central nervous system in adults, exhibit slow growth in lower-grade gliomas (LGG). However, the majority of LGG cases progress to high-grade gliomas, posing challenges for prognostication. The tumor microenvironment (TME), characterized by telomere-related genes and immune cell infiltration, strongly influences glioma growth and therapeutic response. Therefore, our objective was to develop a Telomere-TME (TM-TME) classifier that integrates telomere-related genes and immune cell landscape to assess prognosis and therapeutic response in glioma.

Methods

This study encompassed LGG patients from the TCGA and CCGA databases. TM score and TME score were derived from the expression signatures of telomere-related genes and the presence of immune cells in LGG, respectively. The TM-TME classifier was established by combining TM and TME scores to effectively predict prognosis. Subsequently, we conducted Kaplan-Meier survival estimation, univariate Cox regression analysis, and receiver operating characteristic curves to validate the prognostic prediction capacity of the TM-TME classifier across multiple cohorts. Gene Ontology (GO) analysis, biological processes, and proteomaps were performed to annotate the functional aspects of each subgroup and visualize the cellular signaling pathways.

Results

The TM_low+TME_high subgroup exhibited superior prognosis and therapeutic response compared to other subgroups (P<0.001). This finding could be attributed to distinct tumor somatic mutations and cancer cellular signaling pathways. GO analysis indicated that the TM_low+TME_high subgroup is associated with the neuronal system and modulation of chemical synaptic transmission. Conversely, the TM_high+TME_low subgroup showed a strong association with cell cycle and DNA metabolic processes. Furthermore, the classifier significantly differentiated overall survival in the TCGA LGG cohort and served as an independent prognostic factor for LGG patients in both the TCGA cohort (P<0.001) and the CGGA cohort (P<0.001).

Conclusion

Overall, our findings underscore the significance of the TM-TME classifier in predicting prognosis and immune therapeutic response in glioma, shedding light on the complex immune landscape within each subgroup. Additionally, our results suggest the potential of integrating risk stratification with precision therapy for LGG.
The benefits of clustering in TNF receptor superfamily signaling
Authors: Vanamee Éva S. , Faustman Denise L.
Published: August 2023

The tumor necrosis factor (TNF) receptor superfamily is a structurally and functionally related group of cell surface receptors that play crucial roles in various cellular processes, including apoptosis, cell survival, and immune regulation. This review paper synthesizes key findings from recent studies, highlighting the importance of clustering in TNF receptor superfamily signaling. We discuss the underlying molecular mechanisms of signaling, the functional consequences of receptor clustering, and potential therapeutic implications of targeting surface structures of receptor complexes.
Removal of natural anti-αGal antibodies elicits protective immunity against Gram-negative bacterial infections
Authors: Olivera-Ardid Sara , Bello-Gil Daniel , Perez-Cruz Magdiel , Costa Cristina , Camoez Mariana , Dominguez M. Angeles , Ferrero-Alves Yara , Vaquero Jose Miguel , Khasbiullina Nailya , Shilova Nadezhda V. , Bovin Nicolai V. , Mañez Rafael
Published: August 2023

Antibody-dependent enhancement (ADE) of bacterial infections occurs when blocking or inhibitory antibodies facilitate the infectivity of pathogens. In humans, antibodies involved in ADE of bacterial infections may include those naturally produced against Galα1-3Galβ1-4GlcNAcβ (αGal). Here, we investigate whether eliminating circulating anti-αGal antibodies using a soluble αGal glycopolymer confers protection against Gram-negative bacterial infections. We demonstrated that the in vivo intra-corporeal removal of anti-αGal antibodies in α1,3-galactosyltransferase knockout (GalT-KO) mice was associated with protection against mortality from Gram-negative sepsis after cecal ligation and puncture (CLP). The improved survival of GalT-KO mice was associated with an increased killing capacity of serum against Escherichia coli isolated after CLP and reduced binding of IgG1 and IgG3 to the bacteria. Additionally, inhibition of anti-αGal antibodies from human serum in vitro increases the bactericidal killing of E. coli O86:B7 and multidrug-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa. In the case of E. coli O86:B7, there was also an improvement in bacteria opsonophagocytosis by macrophages. Both lytic mechanisms were related to a decreased binding of IgG2 to the bacteria. Our results show that protective immunity against Gram-negative bacterial pathogens can be elicited, and infectious diseases caused by these bacteria can be prevented by removing natural anti-αGal antibodies.
Therapeutic cancer vaccination against mutant calreticulin in myeloproliferative neoplasms induces expansion of specific T cells in the periphery but specific T cells fail to enrich in the bone marrow
Authors: Holmström Morten Orebo , Andersen Morten , Traynor Sofie , Ahmad Shamaila Munir , Lisle Thomas Landkildehus , Handlos Grauslund Jacob , Skov Vibe , Kjær Lasse , Ottesen Johnny T. , Gjerstorff Morten Frier , Hasselbalch Hans Carl , Andersen Mads Hald
Published: August 2023

Background

Therapeutic cancer vaccination against mutant calreticulin (CALR) in patients with CALR-mutant (CALRmut) myeloproliferative neoplasms (MPN) induces strong T-cell responses against mutant CALR yet fails to demonstrate clinical activity. Infiltration of tumor specific T cells into the tumor microenvironment is needed to attain a clinical response to therapeutic cancer vaccination.

Aim

Determine if CALRmut specific T cells isolated from vaccinated patients enrich in the bone marrow upon completion of vaccination and explore possible explanations for the lack of enrichment.

Methods

CALRmut specific T cells from four of ten vaccinated patients were expanded, enriched, and analyzed by T-cell receptor sequencing (TCRSeq). The TCRs identified were used as fingerprints of CALRmut specific T cells. Bone marrow aspirations from the four patients were acquired at baseline and at the end of trial. T cells were enriched from the bone marrow aspirations and analyzed by TCRSeq to identify the presence and fraction of CALRmut specific T cells at the two different time points. In silico calculations were performed to calculate the ratio between transformed cells and effector cells in patients with CALRmut MPN.

Results

The fraction of CALRmut specific T cells in the bone marrow did not increase upon completion of the vaccination trial. In general, the T cell repertoire in the bone marrow remains relatively constant through the vaccination trial. The enriched and expanded CALRmut specific T cells recognize peripheral blood autologous CALRmut cells. In silico analyses demonstrate a high imbalance in the fraction of CALRmut cells and CALRmut specific effector T-cells in peripheral blood.

Conclusion

CALRmut specific T cells do not enrich in the bone marrow after therapeutic cancer peptide vaccination against mutant CALR. The specific T cells recognize autologous peripheral blood derived CALRmut cells. In silico analyses demonstrate a high imbalance between the number of transformed cells and CALRmut specific effector T-cells in the periphery. We suggest that the high burden of transformed cells in the periphery compared to the number of effector cells could impact the ability of specific T cells to enrich in the bone marrow.
Arctic weather routing: a review of ship performance models and ice routing algorithms
Authors: Liu Quanhong , Wang Yangjun , Zhang Ren , Yan Hengqian , Xu Jing , Guo Yutong
Published: August 2023

With the accelerated melting of the Arctic sea ice, the opening of the Northeast Passage of the Arctic is becoming increasingly accessible. Nevertheless, the constantly changing natural environment of the Arctic and its multiple impacts on vessel navigation performance have resulted in a lack of confidence in the outcomes of polar automated route planning. This paper aims to evaluate the effectiveness of two distinct models by examining the advancements in two essential components of e-navigation, namely ship performance methods and ice routing algorithms. We also seek to provide an outlook on the future directions of model development. Furthermore, through comparative experiments, we have examined the existing research on ice path planning and pointed out promising research directions in future Arctic Weather Routing research.
Effects of temperature, salinity and diet on embryonic and early larval development in Littorina littorea (Gastropoda: Littorinimorpha)
Authors: Lillebjerka Tora , Malzahn Arne M. , Kjørsvik Elin , Hagemann Andreas
Published: August 2023

Introduction

The common periwinkle Littorina littorea is a delicacy in southern Europe. Enabling aquaculture production would be measure to avoid future over-harvesting and ensure a constant market supply.

Methods

However, knowledge gaps in reproductive biology needs to be filled to allow setting up rearing protocols.

Results

We investigated effects of temperature and salinity on embryonic development by incubating eggs at ten different temperatures in steps every 2°C, form 5 to 23°C) and four salinities (20 – 40). Embryonic development was clearly temperature dependent; eggs hatched after three days at the highest temperature while it took 16 days to hatch at the lowest temperature. Calculating effective day-degrees (DDeff) allowed expressing the thermal history of the embryogenesis and concluding that this species hatches on average at 61 (SD 3.7) DDeff. Larval growth- and developmental rates showed a different response to the temperature extremes as snails with the smallest shell lengths at hatch were found for the highest and lowest temperatures (204.5, SD = 11.6, and 202.9µm, SD = 13.7 respectively). Viable larvae only hatched at temperatures above 9°C. Larvae hatched at lower temperatures did not develop a shell or swimming lobes. Salinity and temperature significantly influenced time-to-hatch and hatching success; the lowest salinity (20PSU) lead to later hatching (80-100DDeff) and lower hatching success compared to higher salinities (25, 30, and 40, hatch around 40-50 DDeff). Neither hatch rate nor time-to-hatch showed differences among the higher salinities, suggesting a salinity threshold below 25. There was no significant interaction between salinity and temperature on time-to-hatch or hatching success. Larval diet had a significant effect on growth rates during the planktonic stage. Veliger larvae fed on two different live microalgae mono-diets (Dunaliella tertiolecta and Rhodomonas baltica) successfully passed their pelagic phase at the same time with no differences in growth rates, while veliger larvae fed on either of two preserved microalgae products (Nannochloropis sp. and Tetrasemis sp. frozen pastes) were not growing.

Discussion

We conclude that embryonal development can be successfully completed at temperatures between 7 and 20°C, while lower or higher temperatures should be avoided. Successfully hatched larvae can be fed on mono-microalgae diets until settlement.
Analysis of influencing factors and prediction of China’s Containerized Freight Index
Authors: Tu Xiaoying , Yang Yiling , Lin Yu , Ma Shiqun
Published: August 2023

China, as a major maritime nation, the China Containerized Freight Index (CCFI) serves as an objective reflection of the Chinese shipping market and an important indicator for understanding China’s shipping industry globally. The shipping market is a complex ecosystem influenced by various factors, including vessel supply and demand, cargo supply and demand relationships and prices, fuel prices, and competition from substitute and complementary markets. To analyze and study the state of the Chinese shipping market, we selected the CCFI as an indicator and collected data on six factors that may affect the overall shipping market. These factors include “ the China Coastal Bulk Freight Index(CCBFI)”, “the Baltic Dry Index(BDI)”, “the Yangtze River Container Freight Index”, “Global: Aluminum (minimum purity of 99.5%, London Metal Exchange (LME) spot price): UK landed price”, “Major Ports: Container Throughput”, and “Coal Price: US Central Appalachia: Coal Spot Price Index”. Then, we constructed an analyticaland predictive framework using Deep Neural Network (DNN), CatBoost regression model, and robust regression model to study the CCFI. Based on the R2 results of the three models, it is evident that DNN provides the best analytical and predictive performance for the CCFI, accurately forecasting its changes. Additionally, the robust regression model indicates that “Global: Aluminum (minimum purity of 99.5%, LME spot price): UK landed price” has the greatest impact on the CCFI. Finally, from a business perspective, we provide some suggestions for China’s container shipping industry.
Inter-rater reliability of the extended Composite Quality Score (CQS-2)
Authors: Mickenautsch Steffen , Rupf Stefan , Miletić Ivana , Strähle Ulf Tilman , Sturm Richard , Kimmie-Dhansay Faheema , Vidosusić Kata , Yengopal Veerasamy
Published: August 2023

Aim

To establish the inter-rater reliability of the Composite Quality Score (CQS-2) and to test the null hypothesis that it did not differ significantly from that of the first CQS version (CQS-1).

Materials and methods

Four independent raters were selected to rate 45 clinical trial reports using CQS-1 and CQS-2. The raters remained unaware of each other’s participation in this study until all rating had been completed. Each rater received only one rating template at a time in a random sequence for CQS-1 and CQS-2 rating. Raters completed each template and sent these back to the principal investigator. Each rater received their next template 2 weeks after submission of the completed previous template. The inter-rater reliabilities for the overall appraisal score of the CQS-1 and the CQS-2 were established by using the Brennan-Prediger coefficient (BPC). The coefficients of both CQS versions were compared by using the two-sample z-test. During secondary analysis, the BPCs for every criterion and each corroboration level for both CQS versions were established.

Results

The BPC for the CQS-1 was 0.85 (95% CI: 0.64–1.00) and for the CQS-2 it was 1.00 (95% CI: 0.94–1.00), suggesting a very high inter-rater reliability for both. The difference between the two CQS versions was statistically not significant (p = 0.17). The null hypothesis was accepted.

Conclusion

The CQS-2 is still under development, This study shows that it is associated with a very high inter-rater reliability, which did not statistically significantly differ from that of the CQS-1. The promising results of this study warrant further investigation in the applicability of the CQS-2 as an appraisal tool for prospective controlled clinical therapy trials.
Novel insights into genetic characteristics of blaGES-encoding plasmids from hospital sewage
Authors: Ota Yusuke , Prah Isaac , Mahazu Samiratu , Gu Yoshiaki , Nukui Yoko , Koike Ryuji , Saito Ryoichi
Published: August 2023

Introduction

The prevalence of Guiana extended-spectrum (GES)-type carbapenemase producers is increasing worldwide, and hospital water environments are considered as potential reservoirs. However, the genetic features underlying this resistance are not yet fully understood. This study aimed to characterize blaGES-encoding plasmids from a single-hospital sewage sample in Japan.

Methods

Carbapenemase producers were screened using carbapenemase-selective agar and polymerase chain reaction. Whole-genome sequencing analyzes were performed on the carbapenemase-producing isolates.

Results

Eleven gram-negative bacteria (four Enterobacter spp., three Klebsiella spp., three Aeromonas spp., and one Serratia spp.) with blaGES-24 (n = 6), blaGES-6 (n = 4), and blaGES-5 (n = 1) were isolated from the sewage sample. Five blaGES-24 and a blaGES-5 were localized in IncP-6 plasmids, whereas three blaGES-6 plasmids were localized in IncC plasmids with IncF-like regions. The remaining blaGES-6 and blaGES-24 were, respectively, localized on IncFIB-containing plasmids with IncF-like regions and a plasmid with an IncW-like replication protein. The IncP-6 and IncW-like plasmids had a close genetic relationship with plasmids from Japan, whereas the IncC/IncF-like and IncFIB/IncF-like plasmids were closely related to those from the United States and Europe. All blaGES genes were located on the class 1 integron cassette of the Tn3 transposon-related region, and the IncC/IncF-like plasmid carried two copies of the integron cassette. Eight of the eleven blaGES-encoding plasmids contained toxin-antitoxin system genes.

Discussion

The findings on the plasmids and the novel genetic content from a single wastewater sample extend our understanding regarding the diversity of resistance and the associated spread of blaGES, suggesting their high adaptability to hospital effluents. These findings highlight the need for the continuous monitoring of environmental GES-type carbapenemase producers to control their dissemination.
Responses of rumen microorganisms and metabolites to different roughage of domesticated Tibetan sheep
Authors: Ren Yue , Zhaxi Yangzhong , Ciwang Renzeng , Wang Zhengwen , Liu Mengjun
Published: August 2023

Tibetan sheep can utilize high fiber feeds well. However, the mechanisms of rumen microbiota and metabolites in response to different roughage in a housed environment are still unclear. We fed Tibetan sheep with three different roughage diets: 50% whole corn silage (TS), 50% wheatgrass group (TW), and 25% each of whole corn silage and wheatgrass (TM). Subsequently, meat traits, rumen contents 16S rRNA and metabolomics were studied. The results showed that feeding wheat straw to Tibetan sheep significantly increased the abundance of bacteria such as Ruminococcus and Succiniclasticum in the rumen. These microorganisms significantly increased metabolites such as beta-alanyl-L-lysine, butanoic acid and prostaglandin E2. Eventually, production performance, such as carcass weight and intramuscular fat and meat quality characteristics, such as color and tenderness were improved by altering the rumen’s amino acid, lipid and carbohydrate metabolism. This study demonstrated that including 25% wheatgrass and 25% whole corn silage in the diet improved the performance of Tibetan sheep, revealing the effect of the diet on the performance of Tibetan sheep through rumen microorganisms and metabolites.