bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut microbiota and metabolic profiles in chronic intermittent hypoxia-induced rats: disease-associated dysbiosis and metabolic disturbances
Authors: Li Cong , Shi Song
Published: January 2024

Aim

Chronic intermittent hypoxia (CIH) is a key characteristic of obstructive sleep apnea (OSA) syndrome, a chronic respiratory disorder. The mechanisms of CIH-induced metabolic disturbance and histopathological damage remain unclear.

Methods

CIH-induced rats underwent daily 8-h CIH, characterized by oxygen levels decreasing from 21% to 8.5% over 4 min, remaining for 2 min, and quickly returning to 21% for 1 min. The control rats received a continuous 21% oxygen supply. The levels of hypersensitive C reactive protein (h-CRP), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), and nuclear factor kappa-B (NF-κB) were measured by ELISA. Histological analysis of the soft palates was conducted using HE staining. The microbial profiling of fecal samples was carried out by Accu16STM assay. Untargeted metabolomics of serum and soft palate tissue samples were analyzed by UPLC-MS. The protein expression of cAMP-related pathways in the soft palate was determined by Western blot.

Results

After 28 h of CIH induction, a significant increase in pro-inflammatory cytokines was observed in the serum, along with mucosal layer thickening and soft palate tissue hypertrophy. CIH induction altered the diversity and composition of fecal microbiota, specifically reducing beneficial bacteria while increasing harmful bacteria/opportunistic pathogens. Notably, CIH induction led to a significant enrichment of genera such as Dorea, Oscillibacter, Enteractinococcus, Paenibacillus, Globicatella, and Flaviflexus genera. Meanwhile, Additionally, CIH induction had a notable impact on 108 serum marker metabolites. These marker metabolites, primarily involving amino acids, organic acids, and a limited number of flavonoids or sterols, were associated with protein transport, digestion and absorption, amino acid synthesis and metabolism, as well as cancer development. Furthermore, these differential serum metabolites significantly affected 175 differential metabolites in soft palate tissue, mainly related to cancer development, signaling pathways, amino acid metabolism, nucleotide precursor or intermediate metabolism, respiratory processes, and disease. Importantly, CIH induction could significantly affect the expression of the cAMP pathway in soft palate tissue.

Conclusions

Our findings suggest that targeting differential metabolites in serum and soft palate tissue may represent a new approach to clinical intervention and treatment of OSA simulated by the CIH.
Oxidative balance score was negatively associated with the risk of metabolic syndrome, metabolic syndrome severity, and all-cause mortality of patients with metabolic syndrome
Authors: Xu Zhixiao , Lei Xiong , Chu Weiwei , Weng Luoqi , Chen Chengshui , Ye Ran
Published: January 2024

Background

The oxidative balance score (OBS), an encompassing scoring mechanism for assessing oxidative stress, is formulated based on nutritional and lifestyle components. The emergence of metabolic syndrome (MetS) is intricately linked to oxidative stress. Nonetheless, the correlation between OBS and MetS displays variability within distinct cohorts.

Objective

We worked on the relationships between OBS and the risk of MetS, MetS severity, and all-cause mortality of MetS patients.

Methods

A total of 11,171 adult participants were collected from the U.S. National Health Examination Survey (NHANES) 2007-2018. Employing survey-weighted logistic models, we evaluated the relationship between OBS and MetS risk. Furthermore, survey-weighted linear models were utilized to investigate the connection between OBS and MetS severity. Among the participants, 3,621 individuals had their survival status recorded, allowing us to employ Cox proportional hazards regression models in order to ascertain the association between OBS and the all-cause mortality within the subset of individuals with MetS. The OBS (where a higher OBS signified an increased prevalence of anti- or pro-oxidant exposures) weighed the 20 factors, while the MetS severity score weighed the five factors.

Results

After multivariable adjustment, individuals with elevated OBS were found to exhibit a decreased susceptibility to MetS [odds ratio (OR) 0.95; 95% CI 0.94-0.96]. The adjusted OR was 0.42 (95% CI 0.33-0.53) for MetS risk in the fourth OBS quartile compared with those in the first OBS quartile (P for trend < 0.001). A one-unit increase in OBS was linked to a 3% reduction in MetS severity score by 3% (mean difference, -0.03; 95% CI, -0.04 to -0.03). Moreover, increased OBS correlated with decreased hazard of all-cause mortality risk among MetS subjects (adjusted hazard ratio, 0.95; 95% CI, 0.93-0.98). These associations retained their strength even subsequent to the introduction of sensitivity analyses. There existed a statistically significant negative correlation between diet/lifestyle OBS and both MetS risk as well as MetS severity.

Conclusions

An inverse correlation was observed between OBS and the susceptibility to MetS, MetS severity, and all-cause mortality of MetS patients. Health outcomes for MetS patients were positively related to antioxidant diets and lifestyles.
Site selection and capacity determination of charging stations considering the uncertainty of users’ dynamic charging demands
Authors: Linjuan Zhang , Han Fu , Zhiheng Zhou , Shangbing Wang , Jinbin Zhang
Published: January 2024

Aiming at the problems of high investment and low efficiency in the planning and construction of electric vehicle (EV) charging stations in cities, an optimization model for site selection and capacity determination of charging stations considering the uncertainty of users’ dynamic charging demands is proposed. Firstly, based on the travel chain theory and the Origin-Destination (OD) matrix, the travel characteristics of EVs are studied, and the spatial and temporal distribution prediction model of EV charging load is established through the dynamic Dijkstra algorithm combined with the Monte Carlo method. Secondly, a site selection model for the charging station is established which takes the minimum annualized cost of the charging station operator and the annualized economic loss of the EV users as the goal. At the same time, the weighted Voronoi diagram and Adaptive Simulated Annealing Particle Swarm Optimization algorithm (ASPSO) are adopted to determine the optimal number/site selection and service scope of charging stations. Finally, an uncertain scenario set is introduced into the capacity determination model to describe the uncertainty of the users’ dynamic charging demands, and the robust optimization theory is utilized to solve the capacity of the charging station. A case study is carried out for the EV charging station planning problem in some urban areas of a northern city, and the validity of the model is verified.
Bi-level optimization configuration method for microgrids considering carbon trading and demand response
Authors: Lei Wang , Junping Zhou , Weijian Jiang , Yuling Xu
Published: January 2024

Under the background of the shortage of traditional energy and the increasingly serious environmental problems, this paper proposes a bi-level optimization configuration method for microgrids based on stepped carbon trading and price-based demand response. The stepped carbon trading mechanism is introduced into the planning model to clarify the impact of construction processes on land carbon emissions. Simultaneously, price-based demand response during system operation is introduced, guiding users to change the electricity consumption strategies to promote the consumption of renewable energy. Then, a bi-level optimal configuration framework is constructed. The upper level is optimized to allocate the capacity of the microgrid, with the lowest annual equivalent comprehensive cost as the objective function. The lower level is optimized for microgrid operation, with the minimum sum of the microgrid operation cost and carbon emission cost as the objective function. In view of the advantages of enhanced whale optimization algorithm (E-WOA) in solving multi-dimensional feature selection problems, E-WOA and CPLEX solver are combined to solve the bi-level optimization model for the first time. Simulation results show that after introducing a stepped carbon trading mechanism, the system carbon emissions decreased by 23.09%. Considering price-based demand response under the premise of introducing a stepped carbon trading mechanism, the total cost decreased by 3.57% and the carbon emissions decreased by 19.83%.
The propagation of hydraulic fracture in layered coal seam: a numerical simulation considering the interface thickness based on the distinct element method
Authors: Gao Hongye , Jia Baoshan , Lei Yun , Zheng Yongxiang , Shi Bin , Wei Haiyang , Zhang Tongjing , Wang Wei , Niu Qinghe
Published: January 2024

The intercalated layer of coal seam plays an important role in the propagation of hydraulic fracturing. To understand the role of the intercalated layer, a composite coal seam model considering the thickness of the intercalated layer was established. Based on the block distinct element method, the effects of rock structure (thickness of the coal seam and intercalated layer), rock properties (elastic modulus), and construction parameters (injection rate and fluid viscosity) on the penetration behavior of hydraulic fractures were analyzed. The results show that the intercalated layers influence the fracture deflection and have a hindering effect on fracture propagation. The thickness of the intercalated layer affects the stress on the bedding plane and the front edge of the fractures. On the contrary, the thickness of the coal seam mainly affects the penetration ability of hydraulic fractures and the extent of hydraulic fracture propagation. In addition, the elastic modulus of the intercalated layers and coal seams affects the hindering effect of the intercalated layer. The high injection rates reduce the hindering effect of the intercalated layer. When fracturing with a high-viscosity fluid, fractures are more likely to enter the intercalated layer. However, excessively high viscosity can make it difficult for fractures to penetrate the intercalated layer. This study can provide theoretical guidance for the fracturing of composite coal seams.
Gene drives, mosquitoes, and ecosystems: an interdisciplinary approach to emerging ethical concerns
Authors: Moreno Ricardo D. , Valera Luca , Borgoño Cristián , Castilla Juan Carlos , Riveros José Luis
Published: January 2024

Gene drives are genetic elements that in sexually reproducing organisms spread faster than those transmitted through a Mendelian fashion. Since gene drives can be engineered to modify different aspects of physiology and reproduction, they have been proposed as a new and revolutionary tool to control vector-borne diseases, particularly those transmitted by the genera Anopheles and Aedes (Culicidae), such as malaria, Dengue and Zika virus. This approach may impact on human health by lowering the transmission of such devastating diseases. However, the release of genetically modified mosquitos (or other species) into the environment raises a series of questions related to the still incipient technology and our present understanding of the complex structure and dynamics of terrestrial and aquatic ecosystems. Moreover, there are ethical concerns about human interventions in natural ecosystems that may eventually impact our way of living or the ecosystems themselves. This work is an interdisciplinary approach that analyzes from a biological, philosophical, and theological perspective the potential ecological impacts on natural environments of the release of genetically modified species, focusing on gene drive-modified mosquitos. It includes theological approach from a Catholic point of view (although it could be easily shared by other Christians) because we hold that world religions give valuable insights even though not everyone may share their groundings. We conclude that the focal problem is the relationship between humans and nature, and the release of genetically modified species may change this relationship unpredictably. However, given the complex interactions in ecosystems, new approaches such as Earth Stewardship principles could provide new and more widely accepted answers involving biological, philosophical, and theological concepts that will help engaging all relevant actors to make a better world.
Global trends in geospatial conservation planning: a review of priorities and missing dimensions
Authors: Cobb Gemma , Nalau Johanna , Chauvenet Alienor L. M.
Published: January 2024

Introduction

Biodiversity underpins resilient ecosystems that sustain life. Despite international conservation efforts, biodiversity is still declining due to ongoing anthropogenic threats. Protected areas have been widely adopted as a strategy for conserving biodiversity. The use of spatial conservation planning, which prioritizes areas for protection based on geo-referenced biodiversity and ecological information as well as cost of action and their feasibility, has gained popularity in the conservation discipline in the last few decades. However, there remain gaps between plans and implementation, and negative social impacts on local communities can occur, such as tension and conflict between differing priorities, perspectives, and views.

Methods

To better understand the state of the spatial conservation field and support translating research into practice, a mixed-method approach of bibliometric (n=4133 documents) and content analysis (n=2456 documents) was used to analyze and identify key research priorities, collaborative networks, and geographic and thematic patterns.

Results

We identified that research conducted by westernized nations dominated the field, with the United States, the United Kingdom, and Australia being responsible for almost two-thirds of the research globally, with research interest exponentially growing since 2010. Additionally, while there has been some refinement over time of algorithms and models, Zonation and Marxan methods developed in the 2000s remain the predominant choices of software, with a majority focus on marine ecosystems, birds, and mammals. We found a major gap in the use of social dimensions in spatial conservation case studies (only n=146; 6%).

Discussion

This gap highlights a lack of collaboration in conservation science between researchers and local communities who are affected by management decisions. We recommend including spatially explicit social dimensions from the onset of projects through participatory approaches, along with the acknowledgement by researchers of the importance of including diverse views in conservation planning to enhance implementation and outcomes that are relevant in local contexts. We suggest an increased reflection on types of data used for conservation but also on researchers’ personal values, biases, and positionality to encourage more ethical, applicable, and collaborative conservation science.
Machine learning and multi-omics data in chronic lymphocytic leukemia: the future of precision medicine?
Authors: Tsagiopoulou Maria , Gut Ivo G.
Published: January 2024

Chronic lymphocytic leukemia is a complex and heterogeneous hematological malignancy. The advance of high-throughput multi-omics technologies has significantly influenced chronic lymphocytic leukemia research and paved the way for precision medicine approaches. In this review, we explore the role of machine learning in the analysis of multi-omics data in this hematological malignancy. We discuss recent literature on different machine learning models applied to single omic studies in chronic lymphocytic leukemia, with a special focus on the potential contributions to precision medicine. Finally, we highlight the recently published machine learning applications in multi-omics data in this area of research as well as their potential and limitations.
Development of a targeted genotyping platform for reproducible results within tetraploid and hexaploid blueberry
Authors: Clare Shaun J. , Driskill Mandie , Millar Timothy R. , Chagné David , Montanari Sara , Thomson Susan , Espley Richard V. , Muñoz Patricio , Benevenuto Juliana , Zhao Dongyan , Sheehan Moira J. , Mengist Molla F. , Rowland Lisa J. , Ashrafi Hamid , Melmaiee Kalpalatha , Kulkarni Krishnanand P. , Babiker Ebrahiem , Main Dorrie , Olmstead James W. , Gilbert Jessica L. , Havlak Paul , Hung Hsiaoyi , Kniskern Joel , Percival David , Edger Patrick , Iorizzo Massimo , Bassil Nahla V.
Published: January 2024

Blueberry (Vaccinium spp.) is one of the most economically important berry crops worldwide. Validation of genetic mapping studies is often hindered by asynchronous marker technology. The development of a standardized genotyping platform that targets a specific set of polymorphic loci can be a practical solution to unify the scientific and breeding community toward blueberry improvement. The objective of this study was to develop and evaluate a targeted genotyping platform for cultivated blueberries that is affordable, reproducible, and sufficiently high density to warrant large-scale adoption for genomic studies. The Flex-Seq platform was developed in a two-step procedure that resulted in 22,000 loci that yielded 194,365 single nucleotide polymorphisms when assessed in a diversity set of 192 samples including cultivated and other related wild Vaccinium species. Locus recovery averaged 89.4% in the cultivated polyploid blueberry (northern highbush [NHB], southern highbush [SHB], and rabbiteye [RE]) and on average 88.8% were polymorphic. While recovery of these loci was lower in the other Vaccinium species assayed, recovery remained high and ranged between 60.8% and 70.4% depending on the taxonomic distance to the cultivated blueberry targeted in this platform. NHB had the highest mean number of variants per locus at 9.7, followed by RE with 9.1, SHB with 8.5, and a range between 7.7 and 8.5 in other species. As expected, the total number of unique-in-state haplotypes exceeded the total number of variants in the domesticated blueberries. Phylogenetic analysis using a subset of the SNPs and haplotypes mostly conformed to known relationships. The platform also offers flexibility about the number of loci, depth of sequencing for accurate dosage calling, loci and haplotype reconstruction from increased fragment length. This genotyping platform will accelerate the development and improvement of blueberry cultivars through genomic-assisted breeding tools.
Amelioration effect of 18β-Glycyrrhetinic acid on methylation inhibitors in hepatocarcinogenesis -induced by diethylnitrosamine
Authors: Khalil Hany , Nada Alaa H. , Mahrous Hoda , Hassan Amr , Rijo Patricia , Ibrahim Ibrahim A. , Mohamed Dalia D. , AL-Salmi Fawziah A. , Mohamed Doaa D. , Elmaksoud Ahmed I. Abd
Published: January 2024

Aim

suppression of methylation inhibitors (epigenetic genes) in hepatocarcinogenesis induced by diethylnitrosamine using glycyrrhetinic acid.

Method

In the current work, we investigated the effect of sole GA combined with different agents such as doxorubicin (DOX) or probiotic bacteria (Lactobacillus rhamanosus) against hepatocarcinogenesis induced by diethylnitrosamine to improve efficiency. The genomic DNA was isolated from rats’ liver tissues to evaluate either methylation-sensitive or methylation-dependent resection enzymes. The methylation activity of the targeting genes DLC-1, TET-1, NF-kB, and STAT-3 was examined using specific primers and cleaved DNA products. Furthermore, flow cytometry was used to determine the protein expression profiles of DLC-1 and TET-1 in treated rats’ liver tissue.

Results

Our results demonstrated the activity of GA to reduce the methylation activity in TET-1 and DLC-1 by 33.6% and 78%, respectively. As compared with the positive control. Furthermore, the association of GA with DOX avoided the methylation activity by 88% and 91% for TET-1 and DLC-1, respectively, as compared with the positive control. Similarly, the combined use of GA with probiotics suppressed the methylation activity in the TET-1 and DLC-1 genes by 75% and 81% for TET-1 and DLC-1, respectively. Also, GA and its combination with bacteria attenuated the adverse effect in hepatocarcinogenesis rats by altering potential methylomic genes such as NF-kb and STAT3 genes by 76% and 83%, respectively.

Conclusion

GA has an ameliorative effect against methylation inhibitors in hepatocellular carcinoma (HCC) by decreasing the methylation activity genes.
Understanding the podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy
Authors: Jiang Hong , Shen Zhirang , Zhuang Jing , Lu Chen , Qu Yue , Xu Chengren , Yang Shufen , Tian Xuefei
Published: January 2024

The glomerular filtration barrier, comprising the inner layer of capillary fenestrated endothelial cells, outermost podocytes, and the glomerular basement membrane between them, plays a pivotal role in kidney function. Podocytes, terminally differentiated epithelial cells, are challenging to regenerate once injured. They are essential for maintaining the integrity of the glomerular filtration barrier. Damage to podocytes, resulting from intrinsic or extrinsic factors, leads to proteinuria in the early stages and eventually progresses to chronic kidney disease (CKD). Immune-mediated podocyte injury is a primary pathogenic mechanism in proteinuric glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and lupus nephritis with podocyte involvement. An extensive body of evidence indicates that podocytes not only contribute significantly to the maintenance of the glomerular filtration barrier and serve as targets of immune responses but also exhibit immune cell-like characteristics, participating in both innate and adaptive immunity. They play a pivotal role in mediating glomerular injury and represent potential therapeutic targets for CKD. This review aims to systematically elucidate the mechanisms of podocyte immune injury in various podocyte lesions and provide an overview of recent advances in podocyte immunotherapy. It offers valuable insights for a deeper understanding of the role of podocytes in proteinuric glomerular diseases, and the identification of new therapeutic targets, and has significant implications for the future clinical diagnosis and treatment of podocyte-related disorders.
Glioblastoma with high O6-methyl-guanine DNA methyltransferase expression are more immunologically active than tumors with low MGMT expression
Authors: Kushihara Yoshihiro , Tanaka Shota , Kobayashi Yukari , Nagaoka Koji , Kikuchi Miyu , Nejo Takahide , Yamazawa Erika , Nambu Shohei , Kugasawa Kazuha , Takami Hirokazu , Takayanagi Shunsaku , Saito Nobuhito , Kakimi Kazuhiro
Published: January 2024

Background

Glioblastoma (GBM) is a highly lethal brain tumor. The effectiveness of temozolomide (TMZ) treatment in GBM is linked to the methylation status of O6-methyl-guanine DNA methyltransferase (MGMT) promoter. Patients with unmethylated MGMT promoter have limited treatment options available. Consequently, there is a pressing need for alternative therapeutic strategies for such patients.

Methods

Data, including transcriptomic and clinical information, as well as information on MGMT promoter methylation status in primary GBM, were obtained from The Cancer Genome Atlas (TCGA) (n=121) and Chinese Glioma Genome Atlas (CGGA) (n=83) datasets. Samples were categorized into high and low MGMT expression groups, MGMT-high (MGMT-H) and MGMT-low (MGMT-L) tumors. A comprehensive transcriptome analysis was conducted to explore the tumor-immune microenvironment. Furthermore, we integrated transcriptome data from 13 GBM patients operated at our institution with findings from tumor-infiltrating lymphocyte (TIL) cultures, specifically investigating their response to autologous tumors.

Results

Gene signatures associated with various immune cells, including CD8 T cells, helper T cells, B cells, and macrophages, were noted in MGMT-H tumors. Pathway analysis confirmed the enrichment of immune cell-related pathways. Additionally, biological processes involved in the activation of monocytes and lymphocytes were observed in MGMT-H tumors. Furthermore, TIL culture experiments showed a greater presence of tumor-reactive T cells in MGMT-H tumors compared to MGMT-L tumors. These findings suggest that MGMT-H tumors has a potential for enhanced immune response against tumors mediated by CD8 T cells.

Conclusion

Our study provides novel insights into the immune cell composition of MGMT-H tumors, which is characterized by the infiltration of type 1 helper T cells and activated B cells, and also the presence of tumor-reactive T cells evidenced by TIL culture. These findings contribute to a better understanding of the immune response in MGMT-H tumors, emphasizing their potential for immunotherapy. Further studies are warranted to investigate on the mechanisms of MGMT expression and antitumor immunity.
Recognition of pseudoinvasion in colorectal adenoma using spatial glycomics
Authors: Boyaval Fanny , Fariña-Sarasqueta Arantza , Boonstra Jurjen J. , Heijs Bram , Morreau Hans
Published: January 2024

Pseudoinvasion (PI) is a benign lesion in which cancer is mimicked in the colon by misplacement of dysplastic glands in the submucosa. Although there are morphological clues, the discrimination of PI from true invasion can be a challenge during pathological evaluation of colon adenomas. Both overdiagnosis and underdiagnosis can result in inadequate clinical decisions. This calls for novel tools to aid in cases where conventional methods do not suffice. We performed mass spectrometry imaging (MSI)-based spatial glycomics analysis on a cohort of formalin-fixed paraffin-embedded tissue (FFPE) material from 16 patients who underwent polypectomy. We used this spatial glycomic data to reconstruct the molecular histology of the tissue section using spatial segmentation based on uniform manifold approximation and projection for dimension reduction (UMAP). We first showed that the spatial glycomic phenotypes of the different morphological entities separated as distinct clusters in colon tissues, we separated true invasion from the other morphological entities. Then, we found that the glycomic phenotype in areas with suspected PI in the submucosa was strongly correlating with the corresponding glycomic phenotype of the adenomatous colon epithelium from the same tissue section (Pearson correlation distance average = 0.18). These findings suggest that using spatial glycomics, we can distinguish PI as having a molecular phenotype similar to the corresponding surface epithelium and true invasion as having a different phenotype even when compared to high-grade dysplasia. Therefore, when a novel molecular phenotype is found in the deepest submucosal region, this may be used as an argument in favor of true invasion.
Neutrophil extracellular traps and their implications in airway inflammatory diseases
Authors: Xuan Nanxia , Zhao Jie , Kang Zhiying , Cui Wei , Tian Bao-ping
Published: January 2024

Neutrophil extracellular traps (NETs) are essential for immune defense and have been increasingly recognized for their role in infection and inflammation. In the context of airway inflammatory diseases, there is growing evidence suggesting the involvement and significance of NETs. This review aims to provide an overview of the formation mechanisms and components of NETs and their impact on various airway inflammatory diseases, including acute lung injury/ARDS, asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. By understanding the role of NETs in airway inflammation, we can gain valuable insights into the underlying pathogenesis of these diseases and identify potential targets for future therapeutic strategies that either target NETs formation or modulate their harmful effects. Further research is warranted to elucidate the complex interactions between NETs and airway inflammation and to develop targeted therapies that can effectively mitigate their detrimental effects while preserving their beneficial functions in host defense.
Adult-onset neuronal intranuclear inclusion disease related retinal degeneration: a Chinese case series
Authors: Feng Chaoyi , Chen Qian , Luan Xinghua , Sun Ping , Cao Yuwen , Wu Jingying , Wang Shige , Sun Xinghuai , Cao Li , Tian Guohong
Published: January 2024

Purpose

To evaluate adult-onset neuronal intranuclear inclusion disease (NIID)-related retinopathy with guanine-guanine-cytosine repeat expansions in NOTCH2NLC.

Materials and methods

Neuro-ophthalmic evaluations, including best-corrected visual acuity, slit-lamp biomicroscopy, intraocular pressure (IOP), ultrasound biomicroscopy, pupillometry, fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), Humphrey visual field, full-field electroretinography (ERG), and multifocal ERG (mf-ERG) were performed in patients with gene-proven NIID.

Results

Nine patients (18 eyes) were evaluated, with a median age of 62 years (55–68) and only one man was included in our study. Six patients presented with decreased visual acuity or night blindness, whereas the other three were asymptomatic. The visual acuity was measured from 20/200 to 20/20. Miosis was present in eight patients, four of whom had ciliary process hypertrophy and pronation, and three of whom had shallow anterior chambers. Fundus photography, FAF, and OCT showed consistent structural abnormalities mainly started from peripapillary areas and localized in the outer layer of photoreceptors and inner ganglion cell layer. ERG and mf-ERG also revealed retinal dysfunction in the corresponding regions.

Conclusion

Patients with NIID showed both structural and functional retinopathies which were unique and different from common cone-rod dystrophy or retinitis pigmentosa. Patients with miosis may have a potential risk of an angle-closure glaucoma attack. Neuro-ophthalmic evaluations is essential for evaluating patients with NIID, even without visual symptom.
Identification of a novel B-cell epitope of the African swine fever virus p34 protein and development of an indirect ELISA for the detection of serum antibodies
Authors: Tian Yuanyuan , Liang Chao , Zhou Jingming , Sun Fanglin , Liu Yankai , Chen Yumei , Zhu Xifang , Liu Hongliang , Ding Peiyang , Liu Enping , Zhang Ying , Wu Sixuan , Wang Aiping
Published: January 2024

African swine fever (ASF) is a viral disease caused by the African swine fever virus that can be highly transmitted and lethal in domestic pigs. In the absence of a vaccine, effective diagnosis is critical for minimizing the virus’s spread. In recent years, with the decline of African swine fever virus (ASFV) virulence, antibody detection has become an important means of detection. ASFV nucleocapsid protein p34 is a mature hydrolytic product of pp220, which is highly conserved and has a high content in the structural protein of the virus. Prokaryotic cells were chosen to generate highly active and high-yield p34 protein, which was then used as an antigen for producing mouse monoclonal antibodies. The B-cell epitope 202QKELDKLQT210, which was highly conserved and found on the surface of the p34 protein, was first identified by an anti-p34 monoclonal antibody utilizing the peptide scanning technique and visualized in helix. This supported the viability of p34 protein detection even further. In addition, we established an indirect ELISA assay based on p34 to detect ASFV antibodies. The coincidence rate of this method with commercially available kits was shown to be 97.83%. Sensitivity analysis revealed that it could be detected in serum dilution as low as 1:6400, and there was no cross-reaction with other prevalent porcine epidemic diseases classical swine fever virus (CSFV), foot-and-mouth disease virus (FMDV), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine circovirus 2 (PCV2). In summary, the established ELISA method and anti-P34 monoclonal antibody have demonstrated that the p34 protein has a promising application prospect for the detection of African swine fever antibodies.
Identification and characterization of a critical loop for the high activity of alginate lyase VaAly2 from the PL7_5 subfamily
Authors: Du Muxuan , Li Xue , Qi Weipeng , Li Yingjie , Wang Lushan
Published: January 2024

As the major component in the cell wall of brown algae, alginates are degradable by alginate lyases via β-elimination. Alginate lyases can be categorized into various polysaccharide lyase (PL) families, and PL7 family alginate lyases are the largest group and can be divided into six subfamilies. However, the major difference among different PL7 subfamilies is not fully understood. In this work, a marine alginate lyase, VaAly2, from Vibrio alginolyticus ATCC 17749 belonging to the PL7_5 subfamily was identified and characterized. It displayed comparatively high alginolytic activities toward different alginate substrates and functions as a bifunctional lyase. Molecular docking and biochemical analysis suggested that VaAly2 not only contains a key catalyzing motif (HQY) conserved in the PL7 family but also exhibits some specific characters limited in the PL7_5 subfamily members, such as the key residues and a long loop1 structure around the active center. Our work provides insight into a loop structure around the center site which plays an important role in the activity and substrate binding of alginate lyases belonging to the PL7_5 subfamily.
Efficacy of diaphragmatic breathing exercise on respiratory, cognitive, and motor function outcomes in patients with stroke: a systematic review and meta-analysis
Authors: Abdullahi Auwal , Wong Thomson WL , Ng Shamay SM
Published: January 2024

Background

Stroke disrupts the functions carried out by the brain such as the control of movement, sensation, and cognition. Disruption of movement control results in hemiparesis that affects the function of the diaphragm. Impaired function of the diaphragm can in turn affect many outcomes such as respiratory, cognitive, and motor function. The aim of this study is to carry out a systematic review and meta-analysis to determine the efficacy of diaphragmatic breathing exercise on respiratory, cognitive, and motor outcomes after stroke.

Method

The study was registered in PROSPERO (CRD42023422293). PubMED, Embase, Web of Science (WoS), PEDro, Scopus, and CENTRAL databases were searched until September 2023. Only randomized controlled trials comparing diaphragmatic breathing exercise with a control were included. Information on the study authors, time since stroke, mean age, height, weight, sex, and the protocols of the experimental and control interventions including intensity, mean scores on the outcomes such as respiratory, cognitive, and motor functions were extracted. Cochrane risks of bias assessment tool and PEDro scale were used to assess the risks of bias and methodological quality of the studies. Narrative synthesis and meta-analysis were used to summarize the results, which were then presented in tables, risk-of-bias graph, and forest plots. The meta-analysis was carried out on respiratory function [forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, peak expiratory flow (PEF)] and motor function (trunk impairment, and internal and external oblique muscles activity).

Results

Six studies consisting of 151 participants were included. The results of the meta-analyses showed that diaphragmatic breathing exercise is only superior to the control at improving respiratory function, FVC (MD = 0.90, 95% CI = 0.76 to 1.04,P< 0.00001), FEV1 (MD = 0.32, 95% CI = 0.11 to 0.52,P= 0.002), and PEF (MD = 1.48, 95% CI = 1.15 to 1.81,P< 0.00001).

Conclusion

There is limited evidence suggesting that diaphragmatic breathing exercise may help enhance respiratory function, which may help enhance recovery of function post stroke.

Systematic Review Registration

PROSPERO, identifier CRD42023422293.
Neutrophil-to-lymphocyte ratio, white blood cell, and C-reactive protein predicts poor outcome and increased mortality in intracerebral hemorrhage patients: a meta-analysis
Authors: Guo Peixin , Zou Wei
Published: January 2024

Objective

Inflammation participates in the pathology and progression of secondary brain injury after intracerebral hemorrhage (ICH). This meta-analysis intended to explore the prognostic role of inflammatory indexes, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), white blood cell (WBC), and C-reactive protein (CRP) in ICH patients.

Methods

Embase, PubMed, Web of Science, and Cochrane Library were searched until June 2023. Two outcomes, including poor outcome and mortality were extracted and measured. Odds ratio (OR) and 95% confidence interval (CI) were presented for outcome assessment.

Results

Forty-six studies with 25,928 patients were included in this meta-analysis. The high level of NLR [OR (95% CI): 1.20 (1.13–1.27), p < 0.001], WBC [OR (95% CI): 1.11 (1.02–1.21), p = 0.013], and CRP [OR (95% CI): 1.29 (1.08–1.54), p = 0.005] were related to poor outcome in ICH patients. Additionally, the high level of NLR [OR (95% CI): 1.06 (1.02–1.10), p = 0.001], WBC [OR (95% CI): 1.39 (1.16–1.66), p < 0.001], and CRP [OR (95% CI): 1.02 (1.01–1.04), p = 0.009] were correlated with increased mortality in ICH patients. Nevertheless, PLR was not associated with poor outcome [OR (95% CI): 1.00 (0.99–1.01), p = 0.749] or mortality [OR (95% CI): 1.00 (0.99–1.01), p = 0.750] in ICH patients. The total score of risk of bias assessed by Newcastle-Ottawa Scale criteria ranged from 7–9, which indicated the low risk of bias in the included studies. Publication bias was low, and stability assessed by sensitivity analysis was good.

Conclusion

This meta-analysis summarizes that the high level of NLR, WBC, and CRP estimates poor outcome and higher mortality in ICH patients.
Interdisciplinary fetal-neonatal neurology training applies neural exposome perspectives to neurology principles and practice
Authors: Scher Mark S.
Published: January 2024

An interdisciplinary fetal-neonatal neurology (FNN) program over the first 1,000 days teaches perspectives of the neural exposome that are applicable across the life span. This curriculum strengthens neonatal neurocritical care, pediatric, and adult neurology training objectives. Teaching at maternal-pediatric hospital centers optimally merges reproductive, pregnancy, and pediatric approaches to healthcare. Phenotype–genotype expressions of health or disease pathways represent a dynamic neural exposome over developmental time. The science of uncertainty applied to FNN training re-enforces the importance of shared clinical decisions that minimize bias and reduce cognitive errors. Trainees select mentoring committee participants that will maximize their learning experiences. Standardized questions and oral presentations monitor educational progress. Master or doctoral defense preparation and competitive research funding can be goals for specific individuals. FNN principles applied to practice offer an understanding of gene–environment interactions that recognizes the effects of reproductive health on the maternal-placental-fetal triad, neonate, child, and adult. Pre-conception and prenatal adversities potentially diminish life-course brain health. Endogenous and exogenous toxic stressor interplay (TSI) alters the neural exposome through maladaptive developmental neuroplasticity. Developmental disorders and epilepsy are primarily expressed during the first 1,000 days. Communicable and noncommunicable illnesses continue to interact with the neural exposome to express diverse neurologic disorders across the lifespan, particularly during the critical/sensitive time periods of adolescence and reproductive senescence. Anomalous or destructive fetal neuropathologic lesions change clinical expressions across this developmental-aging continuum. An integrated understanding of reproductive, pregnancy, placental, neonatal, childhood, and adult exposome effects offers a life-course perspective of the neural exposome. Exosome research promises improved disease monitoring and drug delivery starting during pregnancy. Developmental origins of health and disease principles applied to FNN practice anticipate neurologic diagnoses with interventions that can benefit successive generations. Addressing health care disparities in the Global South and high-income country medical deserts require constructive dialogue among stakeholders to achieve medical equity. Population health policies require a brain capital strategy that reduces the global burden of neurologic diseases by applying FNN principles and practice. This integrative neurologic care approach will prolong survival with an improved quality of life for persons across the lifespan confronted with neurological disorders.
Long-term iron supplementation combined with vitamin B6 enhances maximal oxygen uptake and promotes skeletal muscle-specific mitochondrial biogenesis in rats
Authors: Zhou Lei , Mozaffaritabar Soroosh , Kolonics Attila , Kawamura Takuji , Koike Atsuko , Kéringer Johanna , Gu Yaodong , Karabanov Roman , Radák Zsolt
Published: January 2024

Introduction

Iron is an essential micronutrient that plays a crucial role in various biological processes. Previous studies have shown that iron supplementation is related to exercise performance and endurance capacity improvements. However, the underlying mechanisms responsible for these effects are not well understood. Recent studies have suggested the beneficial impact of iron supplementation on mitochondrial function and its ability to rescue mitochondrial function under adverse stress in vitro and rodents. Based on current knowledge, our study aimed to investigate whether the changes in exercise performance resulting from iron supplementation are associated with its effect on mitochondrial function.

Methods

In this study, we orally administered an iron-based supplement to rats for 30 consecutive days at a dosage of 0.66 mg iron/kg body weight and vitamin B6 at a dosage of 0.46 mg/kg.

Results

Our findings reveal that long-term iron supplementation, in combination with vitamin B6, led to less body weight gained and increased VO2 max in rats. Besides, the treatment substantially increased Complex I- and Complex II-driven ATP production in intact mitochondria isolated from gastrocnemius and cerebellum. However, the treatment did not change basal and succinate-induced ROS production in mitochondria from the cerebellum and skeletal muscle. Furthermore, the iron intervention significantly upregulated several skeletal muscle mitochondrial biogenesis and metabolism-related biomarkers, including PGC-1α, SIRT1, NRF-2, SDHA, HSL, MTOR, and LON-P. However, it did not affect the muscular protein expression of SIRT3, FNDC5, LDH, FIS1, MFN1, eNOS, and nNOS. Interestingly, the iron intervention did not exert similar effects on the hippocampus of rats.

Discussion

In conclusion, our study demonstrates that long-term iron supplementation, in combination with vitamin B6, increases VO2 max, possibly through its positive role in regulating skeletal muscle-specific mitochondrial biogenesis and energy production in rats.
Radiomics nomogram for preoperative differentiation of early-stage serous borderline ovarian tumors and serous malignant ovarian tumors
Authors: Yu Xinping , Zou Yuwei , Wang Lei , Yang Hongjuan , Jiao Jinwen , Yu Haiyang , Zhang Shuai
Published: January 2024

Objectives

This study aimed to construct a radiomics nomogram and validate its performance in the preoperative differentiation between early-stage (I and II) serous borderline ovarian tumors (SBOTs) and serous malignant ovarian tumors (SMOTs).

Methods

Data were collected from 80 patients with early-stage SBOTs and 102 with early-stage SMOTs (training set: n = 127; validation set: n = 55). Univariate and multivariate analyses were performed to identify the independent clinicoradiological factors. A radiomics signature model was constructed using radiomics features extracted from multidetector computed tomography images of the venous phase, in which the least absolute shrinkage and selection operator regression was employed to lessen the dimensionality of the data and choose the radiomics features. A nomogram model was established by combining independent clinicoradiological factors with the radiomics signature. The performance of nomogram calibration, discrimination, and clinical usefulness was evaluated using training and validation sets.

Results

In terms of clinicoradiological characteristics, age (p = 0.001), the diameter of the solid component (p = 0.009), and human epididymis protein 4 level (p < 0.001) were identified as the independent risk factors of SMOT, for which the area under the curves (AUCs) were calculated to be 0.850 and 0.836 in the training and validation sets, respectively. Nine features were finally selected to construct the radiomics signature model, which exhibited AUCs of 0.879 and 0.826 for the training and validation sets, respectively. The nomogram model demonstrated considerable calibration and discrimination with AUCs of 0.940 and 0.909 for the training and validation sets, respectively. The nomogram model displayed more prominent clinical usefulness than the clinicoradiological and radiomics signature models according to the decision curve analysis.

Conclusions

The nomogram model can be employed as an individualized preoperative non-invasive tool for differentiating early-stage SBOTs from SMOTs.
Preclinical characterization of CPL304110 as a potent and selective inhibitor of fibroblast growth factor receptors 1, 2, and 3 for gastric, bladder, and squamous cell lung cancer
Authors: Popiel Delfina , Stańczak Aleksandra , Skupińska Monika , Mikołajczyk Agata , Stańczak Paulina , Mituła Filip , Hucz-Kalitowska Joanna , Jastrzębska Kinga , Smuga Damian , Dominowski Jakub , Delis Monika , Mulewski Krzysztof , Pietruś Wojciech , Zdżalik-Bielecka Daria , Dzwonek Karolina , Lamparska-Przybysz Monika , Yamani Abdellah , Olejkowska Patrycja , Piórkowska Natalia , Dubiel Krzysztof , Wieczorek Maciej , Pieczykolan Jerzy
Published: January 2024

Fibroblast Growth Factor Receptors (FGFRs) are a family of receptor tyrosine kinases expressed on a plethora of cell membranes. They play crucial roles in both embryonic development and adult tissue functions. There is an increasing amount of evidence that FGFR-mediated oncogenesis is mainly related to gene amplification, activating mutations, or translocation in tumors of various histological types. Dysregulation of FGFRs has been implicated in a wide variety of neoplasms, such as bladder, gastric, and lung cancers. Given their functional significance, FGFRs emerge as promising targets for cancer therapy. Here, we introduce CPL304100, an innovative and highly potent FGFR1–3 kinase inhibitor demonstrating excellent in vitro biological activity. Comprehensive analyses encompassed kinase assays, cell line evaluations, PK/PD studies surface plasmon resonance studies, molecular docking, and in vivo testing in mouse xenografts. CPL304110 exhibited a distinctive binding profile to FGFR1/2/3 kinase domains, accompanied by a good safety profile and favorable ADMET parameters. Selective inhibition of tumor cell lines featuring active FGFR signaling was observed, distinguishing it from cell lines lacking FGFR aberrations (FGFR1, 2, and 3). CPL304110 demonstrated efficacy in both FGFR-dependent cell lines and patient-derived tumor xenograft (PDTX) in vivo models. Comparative analyses with FDA-approved FGFR inhibitors, erdafitinib and pemigatinib, revealed certain advantages of CPL304110 in both in vitro and in vivo assessments. Encouraging preclinical results led the way for the initiation of a Phase I clinical trial (01FGFR2018; NCT04149691) to further evaluate CPL304110 as a novel anticancer therapy.