bluuebunny/crossref_metadata_2025 huggingface dataset:
Controversial causal association between IGF family members and osteoporosis: a Mendelian randomization study between UK and FinnGen biobanks
Authors: Tang Jie , Zhao Chanjuan , Lin Sha , Li Xing , Zhu Binlu , Li Yifei
Published: January 2024

Objectives

Osteoporosis, a prevalent skeletal disorder characterized by reduced bone strength, is closely linked to the IGF system, crucial for skeletal metabolism. However, the precise nature of this relationship remains elusive. In this study, we employed Mendelian randomization (MR) to unravel the associations between genetically predicted serum IGF system member levels and osteoporosis.

Methods

A two-sample MR approach was employed to investigate these causal associations based on two individual datasets. Predictions of 14 serum levels of IGF system members were made using 11,036,163 relevant Single Nucleotide Polymorphisms (SNPs) within a cohort of 4,301 individuals of European descent. Genetic association estimates for osteoporosis were derived from two publicly available GWAS consortia: the Finnish consortium from the FinnGen biobank, comprising 212,778 individuals of Finnish descent (3,203 cases and 209,575 controls), and the UK consortium from the UK Biobank, including 337,159 individuals of European descent (5,266 cases and 331,893 controls).

Results

According to the UK dataset, IGF-1 levels were associated with a reduced risk of osteoporosis, as indicated by the weighted median method (Odds Ratio [OR] = 0.998, 95% CI = 0.997–1.000, P = 0.032). Additionally, higher levels of IGFBP-3 were linked to a decreased risk of osteoporosis using the Inverse-Variance Weighted (IVW) method (OR = 0.999, 95% CI = 0.998–1.000, P = 0.019), and CTGF levels exhibited a negative association with osteoporosis, as determined by the weighted median method (OR = 0.998, 95% CI = 0.996–0.999, P = 0.004). In the FinnGen dataset, IGF-1 and IGFBP-3 were not identified to be associated with osteoporosis. While, IGF-LR1 levels displayed a negative association with osteoporosis, according to the MR-Egger method (OR = 0.886, 95% CI = 0.795–0.987, P = 0.036), while CYR61 was linked to an increased risk of osteoporosis based on both the weighted median and IVW methods (OR = 1.154, 95% CI = 1.009–1.319, P = 0.037, and OR = 1.115, 95% CI = 1.022–1.215, P = 0.014, respectively).

Conclusion

This study provides compelling evidence that certain IGF family members play a role in the pathogenesis of osteoporosis between different datasets, indicating population specific causal effects between IGF family and osteoporosis. Although the results from both datasets demonstrated that IGF family involved in the pathogenesis of osteoporosis, but the responding key molecules might be various among different population. Subsequent research is warranted to evaluate the potential of these biomarkers as targets for osteoporosis prevention and treatment in specific population.
Promoting the use of bioenergy in developing nations: a CDM route to sustainable development
Authors: Dirisu Joseph O. , Salawu Enesi Y. , Ekpe Ikenna C. , Udoye Nduka E. , Falodun Oluwasegun E. , Oyedepo Sunday O. , Ajayi Oluseyi O. , Kale Sandip A.
Published: January 2024

The study focused on a forensic assessment of bioenergy utilization in developing countries, emphasizing how to improve bioenergy resources for a sustainable economy and development. First, a holistic review of energy sources and their impacts on sustainable development was highlighted. The study also looked at the relationships between various energy sources, both the supply and demand of energy, as the population statistics in developing countries. However, renewable energy is yet to be harnessed fully as it lagged by 0.7%. Shockingly, the African continent is backward in both the global energy supply and in tapping renewable energy sources, as only 6% is contributed. More so, applying a clean development mechanism (CDM) for energy utilization and control shows that net emission reduction and global temperature reduction of 1.5°C by 2030 is attainable. Thus, helping to realize low-cost and sustainable energy (SDG 7) and sustainable cities and communities (SDG11). Further, the assessment of the level of bioenergy availability and its utilization shows that 10% of the world’s energy is provided by bioenergy. Interestingly, it is available in every region in the form of biomass. The study is helpful for stakeholders, policymakers, and governments managing the affairs of the energy sector on the need to formulate policy that will guide effective bioenergy utilization and reduction in greenhouse gas emissions, especially in developing countries thereby, promoting sustainable economic growth.
Study on the fracture propagation law of deep shale reservoir under the influence of different number of fracturing clusters
Authors: Zeng Bo , Wu Mingyang , Su Yuliang , Guo Yintong , Feng Jiangrong , Gui Junchuan , Lu Jun
Published: January 2024

Deep reservoirs have a large difference in geo-stress, and compared to shallow reservoirs, multiple clusters of fracturing are usually required to effectively improve the quality of reservoir reconstruction. In this paper, considering the relevant geological parameters of a certain reservoir in the southwest, multi-cluster reservoir fracturing models under three-dimensional conditions based on the cohesive element modelling method are established. Then, the quantitative rules of fluid pressure, fracture length, fracture aperture, fracture area, tensile failure rate, and the fractal dimension of fracture morphology under different fracturing cluster numbers were revealed. The results show that compared to conventional fracturing, multi-cluster fracturing can significantly increase the number of main fractures and improve the effectiveness of reservoir reconstruction. As the number of clusters increases, the number of main fractures in the reservoir increases, but it can also lead to the increase of small opening fractures, which may be unfavourable for the pumping of proppant and subsequent mining. Meanwhile, based on the fractal dimension results of fracture morphology, it was found that under this simulation condition, the number of fracturing clusters had a significant impact on the fractal dimension of fracturing fractures before the fracturing of six clusters, while after the fracturing of six clusters, the impact of the number of fracturing clusters on the fractal dimension of fracturing fractures decreased. Therefore, when considering factors such as the complexity of fractures, multi-cluster fracturing does not necessarily result in more fracturing clusters being better but should be comprehensively considered for optimization. This study has certain reference significance for selecting the spacing between multiple fracturing clusters.
Synthesis and application of Al trimesate-based metal-organic framework: a critical review
Authors: Zheng Huifang , Chen Qian , Chen Zhijie , Ni Bing-Jie
Published: January 2024

This review comprehensively explores the synthesis and diverse applications of the Al trimesate-based metal-organic framework, MIL-96 (Al). It begins with an introduction to the structure and properties of MIL-96 (Al), followed by an in-depth discussion of various synthesis strategies, including hydrothermal, microwave irradiation, electrochemical, mechanochemical, and sonochemical methods. The paper then delves into environmental remediation applications, highlighting MIL-96 (Al)’s effectiveness in fluoride and heavy metal removal, as well as in the elimination of volatile organic compounds (VOCs) and CO2. The review further examines the role of MIL-96 (Al) in catalysis and its emerging significance in battery technology, showcasing its versatility and potential in sustainable energy solutions. Finally, the paper concludes with perspectives on future research directions, emphasizing the ongoing development and optimization of MIL-96 (Al) for environmental and energy-related applications.
A bibliometric review of zero waste in the built environment using VOSviewer: evolution, hotspots, and prospects
Authors: Linglin Zhou
Published: January 2024

The global construction industry presents a significant challenge to environmental sustainability, sparking increasing concerns regarding its environmental impact. Zero Waste (ZW) has become a comprehensive waste management approach within the construction sector. However, there is a notable absence of systematic reviews in this field. Bibliometrics has played a pivotal role in advancing new methodologies for systematic reviews. To address this gap, our study employs VOSviewer to systematically review the research domain of ZW, exploring research trends, international collaborations, primary authors, research domains, and literature. Our findings reveal a pronounced upward trend in research dedicated to achieving zero waste goals in the built environment, aligning with escalating global environmental concerns. Research in this realm has thrived notably in China, Australia, and England, with these countries contributing significantly to relevant studies. Co-occurrence analysis highlights key themes, such as construction waste reduction, sustainable construction, circular design, prefabrication, and Building Information Modelling (BIM). Notably, system dynamics and BIM have emerged as crucial modelling techniques. Moreover, this study emphasises the adoption of circular economy principles, the efficacy of prefabrication, and the role of BIM in waste management. Future research directions encompass exploring global variations, investigating the impact of technology, engaging stakeholders, and considering regulatory frameworks. Despite its limitations, this study underscores the mounting global interest in ZW research, providing a foundation for future exploration and collaboration in sustainable construction and environmental management.
A novel fast and efficient adaptive shuffled complex evolution algorithm for model parameter calibration
Authors: Liu Junxiang , Hong Haicheng , Fan Weinan , Chen Yilong
Published: January 2024

The research and optimization of hydrological forecasting models are among the most crucial components in the scope of water management and flood protection. Optimizing the calibration of hydrological forecasting models is crucial for forecasting performance. A rapid adaptive Shuffled Complex Evolution (SCE) method called Fast Adaptive SCE (FASCE) is proposed for calibrating model parameters. It builds upon the previously established SCE-UA, known for its effectiveness and robustness in the same calibration context. The robustness of the original SCE-UA is expanded upon, introducing a revised adaptive simplex search to bolster efficiency. Additionally, a new strategy for setting up the initial population base enhances explorative capacities. FASCE’s performance has been assessed alongside numerous methods from prior studies, demonstrating its effectiveness. Initial tests were conducted on a set of functions to assess FASCE’s efficacy. Findings revealed that FASCE could curtail the failure rate by a minimum of 80%, whereas the requirement for function evaluations fell between 30% and 60%. Two hydrological models - Support Vector Machine (SVM) and Xinanjiang rainfall-runoff model were employed to estimate the new algorithm’s performance. No failures were reported, and there was a reduction of at least 30% in function evaluations using FASCE. The outcomes from these studies affirm that FASCE can considerably reduce both the number of failures and the count of function evaluations required to reach the global maximum. Hence, FASCE emerges as a viable substitute for model parameter calibration.
Accelerating decline of wildfires in China in the 21st century
Authors: Lian Chenqin , Xiao Chiwei , Feng Zhiming , Ma Qin
Published: January 2024

Global wildfires have increased in frequency and intensity, especially in temperate regions, in the context of global warming. However, the spatiotemporal characteristics of wildfire frequency and intensity are still not well understood. Using Moderate Resolution Imaging Spectroradiometer (MODIS) Collection 6 (C6) wildfire products during 2003–2022, here, we analyzed the spatiotemporal patterns and evolutionary characteristics of the frequency and intensity of wildfires in China. The main conclusions are: (1) Over the past 20 years, the wildfire frequency and fire radiative power (FRP) have declined at rates of –1920/year (p < 0.001) and –76492 MW/year (p < 0.001), respectively, showing a highly significant downward trend, with declines of up to 63 and 81%. (2) Wildfires in China show a single peak pattern of high incidence in winter and spring, with the most frequent in March, followed by February and April. (3) The overall spatial distribution of wildfires in China is characterized by a bimodal distribution, with more in the south and less in the north. Wildfires are most abundant but less intense in the southern region(SR), fewer but most intense in the northeastern region(NER), and significantly influenced by El Niño in the southwestern region(SWR), with significant regional differences in wildfires in China. (4) The average FRP of wildfire spots presented a decreasing trend from 47 MW/spot in 2003 to only 25 MW/spot in 2022. This may be due to more dispersed wildfires, rather than concentrated wildfires. (5) The frequency and FRP of wildfires showed an overall negative correlation with the Standardized Precipitation Evapotranspiration Index (SPEI). Drought events (negative SPEI) have a significant effect on wildfires, especially in SR. This study demonstrates the effectiveness of current fire suppression policies in China in terms of disaster prevention and mitigation, and further provides data to further explore and analyze the impact of wildfires on the regional environment.
Factors driving carbon accumulation in forest biomass and soil organic carbon across natural forests and planted forests in China
Authors: Wang Tao , Dong Lingbo , Liu Zhaogang
Published: January 2024

Introduction

Forests play a pivotal role within the global carbon cycle. However, how to enhance carbon storage in existing forests remains unclear.

Methods

In this study, we conduct a comprehensive analysis of data from 2,948 forest sites across China. Utilizing structural equation modeling (SEM), we investigate the intricate relationship between climate, tree species diversity, stand structure, function traits, initial biomass carbon stocks (BCi), soil organic carbon stocks (Soil C content), and carbon accumulation in biomass (ΔBC) and soil organic carbon stocks (ΔSOC) within both natural forests (NF, n = 1,910) and planted forests (PF, n = 1,038).

Results

Our findings underscore the critical influence of tree species diversity and stand structure drivers of both direct and indirect carbon accumulation, with distinct drivers emerging based on the carbon pools in NF and PF. Specifically, increasing tree species diversity from its minimum to maximum value through management-results in a 14.798 tC/ha reduction in BC and 0.686 tC/ha in SOC in NF. Conversely, amplifies BC and SOC in PF by 0.338 tC/ha and 0.065 tC/ha, respectively. Enhancing stand structure-such as stand density-results in a 231.727 tC/ha reduction in BC and SOC in NF, and a 10.668 tC/ha in BC and 64.008 tC/ha increment in SOC in PF.

Discussion

Overall, our results indicate that higher tree species diversity, stand density and age-group limits further carbon accumulation in BC and SOC in current NF. In contrast, low tree species diversity and stand density limits the development of carbon storage potential in planted forests. To enhance carbon sequestration capacity, China should change its current policy of completely banning logging of natural forests. Natural forests need thinning and reduced tree species diversity, while planted forests should increase tree species diversity and stand density.
Enhanced phenylpropanoid metabolism underlies resistance to Fusarium oxysporum f. sp. vasinfectum race 4 infection in the cotton cultivar Pima-S6 (Gossypium barbadense L.)
Authors: Ojeda-Rivera Jonathan Odilón , Ulloa Mauricio , Pérez-Zavala Francisco G. , Nájera-González Héctor-Rogelio , Roberts Philip A. , Yong-Villalobos Lenin , Yadav Himanshu , Chávez Montes Ricardo A. , Herrera-Estrella Luis , Lopez-Arredondo Damar
Published: January 2024

Introduction:Fusarium oxysporum f. sp. vasinfectum (FOV) race 4 (FOV4) is a highly pathogenic soil-borne fungus responsible for Fusarium wilt in cotton (Gossypium spp.) and represents a continuing threat to cotton production in the southwest states of the United States, including California, New Mexico, and Texas. Pima (G. barbadense L.) cotton, which is highly valued for its fiber quality, has been shown to be more susceptible to this pathogen than Upland (G. hirsutum L.) cotton. Still, some Pima cultivars present resistance to FOV4 infection.

Methods: To gain insights into the FOV4-resistance mechanism, we performed comparative transcriptional and metabolomic analyses between FOV4-susceptible and FOV4-resistant Pima cotton entries. FOV4-resistant Pima-S6 and FOV4-susceptible Pima S-7 and Pima 3-79 cotton plants were infected with FOV4 in the greenhouse, and the roots harvested 11 days post-infection for further analysis.

Results: We found that an enhanced root phenylpropanoid metabolism in the resistant Pima-S6 cultivar determines FOV4-resistance. Gene-ontology enrichment of phenylpropanoid biosynthesis and metabolism categories correlated with the accumulation of secondary metabolites in Pima-S6 roots. Specifically, we found esculetin, a coumarin, an inhibitor of Fusarium’s growth, accumulated in the roots of Pima-S6 even under non-infected conditions. Genes related to the phenylpropanoid biosynthesis and metabolism, including phenylalanine ammonia-lyase 2 (PAL2) and pleiotropic drug resistance 12 (PDR12) transporter, were found to be upregulated in Pima-S6 roots.

Discussion: Our results highlight an essential role for the phenylpropanoid synthesis pathway in FOV4 resistance in Pima-S6 cotton. These genes represent attractive research prospects for FOV4-disease resistance and breeding approaches of other cotton cultivars of economic relevance.
nPCA: a linear dimensionality reduction method using a multilayer perceptron
Authors: Li Juzeng , Wang Yi
Published: January 2024

Background: Linear dimensionality reduction techniques are widely used in many applications. The goal of dimensionality reduction is to eliminate the noise of data and extract the main features of data. Several dimension reduction methods have been developed, such as linear-based principal component analysis (PCA), nonlinear-based t-distributed stochastic neighbor embedding (t-SNE), and deep-learning-based autoencoder (AE). However, PCA only determines the projection direction with the highest variance, t-SNE is sometimes only suitable for visualization, and AE and nonlinear methods discard the linear projection.

Results: To retain the linear projection of raw data and generate a better result of dimension reduction either for visualization or downstream analysis, we present neural principal component analysis (nPCA), an unsupervised deep learning approach capable of retaining richer information of raw data as a promising improvement to PCA. To evaluate the performance of the nPCA algorithm, we compare the performance of 10 public datasets and 6 single-cell RNA sequencing (scRNA-seq) datasets of the pancreas, benchmarking our method with other classic linear dimensionality reduction methods.

Conclusion: We concluded that the nPCA method is a competitive alternative method for dimensionality reduction tasks.
Differential expression of miRNAs revealed by small RNA sequencing in traumatic tracheal stenosis
Authors: Li Wentao , Wei Jinmei , Huang Pingping , Wei Yuhui , Chang Li , Liu Guangnan
Published: January 2024

Introduction: Traumatic tracheal stenosis (TTS) is a major cause of complex difficult airways, without clinically definitive efficacious drugs available. The aim of this study was to provide a general view of interactions between micro and messenger ribonucleic acids (miRNAs and mRNAs) and many potential mechanisms in TTS via small RNA sequencing.

Methods: In this study, the identification of miRNAs was completed using small RNA sequencing and samples from four TTS patients and four normal control cases. By using bioinformatics tools, such as miRanda and RNAhybrid, for identifying the candidate target genes of miRNAs with differential expression in each sample, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were employed for enriching the predicted target genes of miRNAs with differential expression based on the correspondence between miRNAs and their target genes. We detected the expression of the candidate miRNAs using quantitative real-time polymerase chain reaction (qRT-PCR).

Results: Twenty-four miRNAs with significant differential expression were identified, including 13 upregulated and 11 downregulated ones. Bioinformation technology was adopted to predict 2,496 target genes. These miRNA-target genes were shown to be primarily enriched in cells and organelles with catalytic activity and binding function, such as binding proteins, small molecules, and nucleotides. Finally, they were observed to process into TTS through the intercellular and signal regulation of related inflammatory signaling and fibrosis signaling pathways. QRT-PCR confirmed the upregulation of miR21-5p and miR214-3p and the downregulation of miR141-3p and miR29b-3p, which was expected to become a high-specific miRNA for TTS.

Conclusion: Among all the miRNAs detected, 24 miRNAs demonstrated differential expression between the TTS and normal control groups. A total of 2,496 target genes were predicted by bioinformation technology and enriched in inflammatory and fibrotic signaling pathways. These results provide new ideas for further studies and the selection of targets for TTS in the future.
Case report: A novel mutation in the EYA1 gene in a child with branchiootic syndrome with secretory otitis media and bilateral vestibular hypofunction
Authors: He Jun , Mahmoudi Ahmad , Gu Yu , Fu Jinfeng , Yuan Qiulin , Liu Wei
Published: January 2024

Branchiootic syndrome (BOS) is a rare, autosomal dominant syndrome characterized by malformations of the ear associated with hearing loss, second branchial arch anomalies, and the absence of renal anomalies. Herein, we report the case of an 8-year-old male patient with BOS. The proband also experiences mixed conductive and sensorineural hearing loss in the right ear, and severe-to-profound sensorineural hearing loss in the left ear. Preauricular pits, branchial fistulae, and cochlear hypoplasia were present bilaterally. Type III cup-shaped ear, and external auditory canal stenosis were detected in the right ear. Lateral semicircular canal-vestibule dysplasia was detected in the left ear. Moreover, the patient had unilateral secretory otitis media (SOM) in the right ear and bilateral vestibular hypofunction (VH), which has not been reported in previous studies. The patient’s hearing on the right side was restored to nearly normal after myringotomy. Whole exome sequencing identified a novel frameshift mutation in EYA1 (NM_000503.6): c.1697_1698delinT [p.(Lys566IlefsTer73)] in the proband, which was defined a “pathogenic” mutation according to American College of Medical Genetics and Genomics guidelines. This is the first report of a child presenting with BOS, SOM and VH, which expands the known clinical manifestations of this syndrome. We also observed a novel EYA1 gene mutation in this patient with BOS, which enriches the mutation map and provides a reference for genetic diagnosis of this syndrome.
Feasibility and acceptability of an HPV self-testing strategy: lessons from a research context to assess for ability to implement into primary care at a national level in Botswana
Authors: Luckett Rebecca , Ramogola-Masire Doreen , Harris Devon A. , Gompers Annika , Gaborone Kelebogile , Mochoba Lorato , Ntshese Lapelo , Mathoma Anikie , Kula Maduke , Shapiro Roger , Larson Elysia
Published: January 2024

Background

The WHO strategy for cervical cancer elimination strives to achieve 70% coverage with high-performance cervical screening. While few low- and middle-income countries have achieved this, high-risk human papillomavirus (hrHPV) self-testing creates the possibility to rapidly upscale access to high-performance cervical screening across resource settings. However, effective hrHPV screening requires linkage to follow-up, which has been variable in prior studies. This study developed and tested an implementation strategy aimed at improving screening and linkage to follow-up care in South East District in Botswana.

Methods

This study performed primary hrHPV self-testing; those with positive results were referred for a triage visit. Withdrawals for any reason, loss-to follow-up between hrHPV test and triage visit, and number of call attempts to give hrHPV results were also documented. Acceptability of the program to patients was measured as the proportion of patients who completed a triage visit when indicated, meeting the a priori threshold of 80%. Feasibility was defined as the proportion of participants receiving the results and attending follow-up. To assess the associations between participant characteristics and loss-to-follow-up we used log-binomial regressions to estimate risk ratios and 95% confidence intervals (CI).

Results

Enrollment of 3,000 women occurred from February 2021 to August 2022. In total, 10 participants withdrew and an additional 33 were determined ineligible after consent, leaving a final cohort of 2,957 participants who underwent self-swab hrHPV testing. Half (50%) of participants tested positive for hrHPV and nearly all (98%) of participants received their hrHPV results, primarily via telephone.  Few calls to participants were required to communicate results: 2,397 (82%) required one call, 386 (13%) required 2 calls, and only 151 (5%) required 3–5 calls. The median time from specimen collection to participant receiving results was 44 days (IQR, 27–65). Of all hrHPV positive participants, 1,328 (90%) attended a triage visit.

Discussion

In a large cohort we had low loss-to-follow-up of 10%, indicating that the strategy is acceptable. Telephonic results reporting was associated with high screening completion, required few calls to participants, and supports the feasibility of hrHPV self-testing in primary care followed by interval triage.
Macrophage SREBP1 regulates skeletal muscle regeneration
Authors: Oishi Yumiko , Koike Hiroyuki , Kumagami Naoki , Nakagawa Yoshimi , Araki Masaya , Taketomi Yoshitaka , Miki Yoshimi , Matsuda Shigeru , Kim Hyeree , Matsuzaka Takashi , Ozawa Hitoshi , Shimano Hitoshi , Murakami Makoto , Manabe Ichiro
Published: January 2024

Macrophages are essential for the proper inflammatory and reparative processes that lead to regeneration of skeletal muscle after injury. Recent studies have demonstrated close links between the function of activated macrophages and their cellular metabolism. Sterol regulatory element-binding protein 1 (SREBP1) is a key regulator of lipid metabolism and has been shown to affect the activated states of macrophages. However, its role in tissue repair and regeneration is poorly understood. Here we show that systemic deletion of Srebf1, encoding SREBP1, or macrophage-specific deletion of Srebf1a, encoding SREBP1a, delays resolution of inflammation and impairs skeletal muscle regeneration after injury. Srebf1 deficiency impairs mitochondrial function in macrophages and suppresses the accumulation of macrophages at sites of muscle injury. Lipidomic analyses showed the reduction of major phospholipid species in Srebf1-/- muscle myeloid cells. Moreover, diet supplementation with eicosapentaenoic acid restored the accumulation of macrophages and their mitochondrial gene expression and improved muscle regeneration. Collectively, our results demonstrate that SREBP1 in macrophages is essential for repair and regeneration of skeletal muscle after injury and suggest that SREBP1-mediated fatty acid metabolism and phospholipid remodeling are critical for proper macrophage function in tissue repair.
COVID-19 infection characteristics, risk factors and its potential impacts on Takayasu arteritis: a web-based survey in a large cohort
Authors: Kong Xiufang , Wang Jinghua , Fan Guihua , Huang Huijing , Sun Ying , Chen Huiyong , Ma Lili , Li Yanshan , Jiang Lindi
Published: January 2024

Objectives

To investigate the characteristics of COVID-19 and its impact on patients with Takayasu’s arteritis (TAK).

Methods

A web-based survey was administered to a TAK cohort and their co-residents in China during January 2023. Infection symptoms, post-acute sequelae of COVID-19 (PASC), potential impacts of COVID-19 on patients’ disease condition, treatment and immune-related parameters were analyzed. In addition, risk factors for COVID-19 and disease relapse after infection were explored.

Results

The infection rate was significantly lower in patients with TAK than in co-residents (79.13% vs 90.67%, p=0.025). TAK patients were more prone to gastrointestinal symptoms (17.78% vs 5.88%, p=0.024), sleep problems (25.15% vs 10.29%, p=0.011), and symptoms involving more than 2 organs (58.90% vs 35.29%, p=0.001) after infection. Although only 2.45% of TAK patients were hospitalized and none progressed to life-threatening conditions, they were more likely to suffer from PASC (26.38% vs 13.24%, p=0.029), especially active patients. Active disease after the pandemic was significantly lower in infected patients than uninfected patients (21/163, 12.88% vs. 11/43, 25.58%, p=0.041). The presence of multiple system symptoms was a risk factor for active TAK after infection [OR: 3.62 (95% CI 1.06-12.31), p=0.040]. Moreover, csDMARDs treatment was a risk factor for COVID-19 infection [OR: 3.68 (95% CI 1.56-8.66), p=0.002].

Conclusion

Although TAK patients with COVID-19 have more acute and post-acute symptoms, there is no adverse outcome and the risk of disease relapse does not increase. Patients treated with csDMARDs may be at higher risk of infection and deserve more clinical attention.
Vdelta1 T cells are more resistant than Vdelta2 T cells to the immunosuppressive properties of galectin-3
Authors: Schadeck Jan , Oberg Hans-Heinrich , Peipp Matthias , Hedemann Nina , Schamel Wolfgang W. , Bauerschlag Dirk , Wesch Daniela
Published: January 2024

Ovarian carcinomas have the highest lethality amongst gynecological tumors. A problem after primary resection is the recurrence of epithelial ovarian carcinomas which is often associated with chemotherapy resistance. To improve the clinical outcome, it is of high interest to consider alternative therapy strategies. Due to their pronounced plasticity, γδ T cells are attractive for T-cell-based immunotherapy. However, tumors might escape by the release of lectin galectin-3, which impairs γδ T-cell function. Hence, we tested the effect of galectin-3 on the different γδ T-cell subsets. After coculture between ovarian tumor cells and Vδ1 or Vδ2 T cells enhanced levels of galectin-3 were released. This protein did not affect the cytotoxicity of both γδ T-cell subsets, but differentially influenced the proliferation of the two γδ T-cell subsets. While increased galectin-3 levels and recombinant galectin-3 inhibited the proliferation of Vδ2 T cells, Vδ1 T cells were unaffected. In contrast to Vδ1 T cells, the Vδ2 T cells strongly upregulated the galectin-3 binding partner α3β1-integrin after their activation correlating with the immunosuppressive properties of galectin-3. In addition, galectin-3 reduced the effector memory compartment of zoledronate-activated Vδ2 T cells. Therefore, our data suggest that an activation of Vδ1 T-cell proliferation as part of a T-cell-based immunotherapy can be of advantage.
Enhancing bovine immune, antioxidant and anti-inflammatory responses with vitamins, rumen-protected amino acids, and trace minerals to prevent periparturient mastitis
Authors: Khan Muhammad Zahoor , Huang Bingjian , Kou Xiyan , Chen Yinghui , Liang Huili , Ullah Qudrat , Khan Ibrar Muhammad , Khan Adnan , Chai Wenqiong , Wang Changfa
Published: January 2024

Mastitis, the inflammatory condition of mammary glands, has been closely associated with immune suppression and imbalances between antioxidants and free radicals in cattle. During the periparturient period, dairy cows experience negative energy balance (NEB) due to metabolic stress, leading to elevated oxidative stress and compromised immunity. The resulting abnormal regulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with increased non-esterified fatty acids (NEFA) and β-hydroxybutyric acid (BHBA) are the key factors associated with suppressed immunity thereby increases susceptibility of dairy cattle to infections, including mastitis. Metabolic diseases such as ketosis and hypocalcemia indirectly contribute to mastitis vulnerability, exacerbated by compromised immune function and exposure to physical injuries. Oxidative stress, arising from disrupted balance between ROS generation and antioxidant availability during pregnancy and calving, further contributes to mastitis susceptibility. Metabolic stress, marked by excessive lipid mobilization, exacerbates immune depression and oxidative stress. These factors collectively compromise animal health, productive efficiency, and udder health during periparturient phases. Numerous studies have investigated nutrition-based strategies to counter these challenges. Specifically, amino acids, trace minerals, and vitamins have emerged as crucial contributors to udder health. This review comprehensively examines their roles in promoting udder health during the periparturient phase. Trace minerals like copper, selenium, and calcium, as well as vitamins; have demonstrated significant impacts on immune regulation and antioxidant defense. Vitamin B12 and vitamin E have shown promise in improving metabolic function and reducing oxidative stress followed by enhanced immunity. Additionally, amino acids play a pivotal role in maintaining cellular oxidative balance through their involvement in vital biosynthesis pathways. In conclusion, addressing periparturient mastitis requires a holistic understanding of the interplay between metabolic stress, immune regulation, and oxidative balance. The supplementation of essential amino acids, trace minerals, and vitamins emerges as a promising avenue to enhance udder health and overall productivity during this critical phase. This comprehensive review underscores the potential of nutritional interventions in mitigating periparturient bovine mastitis and lays the foundation for future research in this domain.
Microfluidic antibody profiling after repeated SARS-CoV-2 vaccination links antibody affinity and concentration to impaired immunity and variant escape in patients on anti-CD20 therapy
Authors: Priddey Ashley , Chen-Xu Michael Xin Hua , Cooper Daniel James , MacMillan Serena , Meisl Georg , Xu Catherine K. , Hosmillo Myra , Goodfellow Ian G. , Kollyfas Rafael , Doffinger Rainer , Bradley John R. , Mohorianu Irina I. , Jones Rachel , Knowles Tuomas P. J. , Smith Rona , Kosmoliaptsis Vasilis
Published: January 2024

Background

Patients with autoimmune/inflammatory conditions on anti-CD20 therapies, such as rituximab, have suboptimal humoral responses to vaccination and are vulnerable to poorer clinical outcomes following SARS-CoV-2 infection. We aimed to examine how the fundamental parameters of antibody responses, namely, affinity and concentration, shape the quality of humoral immunity after vaccination in these patients.

Methods

We performed in-depth antibody characterisation in sera collected 4 to 6 weeks after each of three vaccine doses to wild-type (WT) SARS-CoV-2 in rituximab-treated primary vasculitis patients (n = 14) using Luminex and pseudovirus neutralisation assays, whereas we used a novel microfluidic-based immunoassay to quantify polyclonal antibody affinity and concentration against both WT and Omicron (B.1.1.529) variants. We performed comparative antibody profiling at equivalent timepoints in healthy individuals after three antigenic exposures to WT SARS-CoV-2 (one infection and two vaccinations; n = 15) and in convalescent patients after WT SARS-CoV-2 infection (n = 30).

Results

Rituximab-treated patients had lower antibody levels and neutralisation titres against both WT and Omicron SARS-CoV-2 variants compared to healthy individuals. Neutralisation capacity was weaker against Omicron versus WT both in rituximab-treated patients and in healthy individuals. In the rituximab cohort, this was driven by lower antibody affinity against Omicron versus WT [median (range) KD: 21.6 (9.7–38.8) nM vs. 4.6 (2.3–44.8) nM, p = 0.0004]. By contrast, healthy individuals with hybrid immunity produced a broader antibody response, a subset of which recognised Omicron with higher affinity than antibodies in rituximab-treated patients [median (range) KD: 1.05 (0.45–1.84) nM vs. 20.25 (13.2–38.8) nM, p = 0.0002], underpinning the stronger serum neutralisation capacity against Omicron in the former group. Rituximab-treated patients had similar anti-WT antibody levels and neutralisation titres to unvaccinated convalescent individuals, despite two more exposures to SARS-CoV-2 antigen. Temporal profiling of the antibody response showed evidence of affinity maturation in healthy convalescent patients after a single SARS-CoV-2 infection, which was not observed in rituximab-treated patients, despite repeated vaccination.

Discussion

Our results enrich previous observations of impaired humoral immune responses to SARS-CoV-2 in rituximab-treated patients and highlight the significance of quantitative assessment of serum antibody affinity and concentration in monitoring anti-viral immunity, viral escape, and the evolution of the humoral response.
Anti-PD-L1 therapy altered inflammation but not survival in a lethal murine hepatitis virus-1 pneumonia model
Authors: Curran Colleen S. , Cui Xizhong , Li Yan , Jeakle Mark , Sun Junfeng , Demirkale Cumhur Y. , Minkove Samuel , Hoffmann Victoria , Dhamapurkar Rhea , Chumbris Symya , Bolyard Cameron , Iheanacho Akunna , Eichacker Peter Q. , Torabi-Parizi Parizad
Published: January 2024

Introduction

Because prior immune checkpoint inhibitor (ICI) therapy in cancer patients presenting with COVID-19 may affect outcomes, we investigated the beta-coronavirus, murine hepatitis virus (MHV)-1, in a lethal pneumonia model in the absence (Study 1) or presence of prior programmed cell death ligand-1 (PD-L1) antibody (PD-L1mAb) treatment (Study 2).

Methods

In Study 1, animals were inoculated intratracheally with MHV-1 or vehicle and evaluated at day 2, 5, and 10 after infection. In Study 2, uninfected or MHV-1-infected animals were pretreated intraperitoneally with control or PD-L1-blocking antibodies (PD-L1mAb) and evaluated at day 2 and 5 after infection. Each study examined survival, physiologic and histologic parameters, viral titers, lung immunophenotypes, and mediator production.

Results

Study 1 results recapitulated the pathogenesis of COVID-19 and revealed increased cell surface expression of checkpoint molecules (PD-L1, PD-1), higher expression of the immune activation marker angiotensin converting enzyme (ACE), but reduced detection of the MHV-1 receptor CD66a on immune cells in the lung, liver, and spleen. In addition to reduced detection of PD-L1 on all immune cells assayed, PD-L1 blockade was associated with increased cell surface expression of PD-1 and ACE, decreased cell surface detection of CD66a, and improved oxygen saturation despite reduced blood glucose levels and increased signs of tissue hypoxia. In the lung, PD-L1mAb promoted S100A9 but inhibited ACE2 production concomitantly with pAKT activation and reduced FOXO1 levels. PD-L1mAb promoted interferon-γ but inhibited IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) production, contributing to reduced bronchoalveolar lavage levels of eosinophils and neutrophils. In the liver, PD-L1mAb increased viral clearance in association with increased macrophage and lymphocyte recruitment and liver injury. PD-L1mAb increased the production of virally induced mediators of injury, angiogenesis, and neuronal activity that may play role in COVID-19 and ICI-related neurotoxicity. PD-L1mAb did not affect survival in this murine model.

Discussion

In Study 1 and Study 2, ACE was upregulated and CD66a and ACE2 were downregulated by either MHV-1 or PD-L1mAb. CD66a is not only the MHV-1 receptor but also an identified immune checkpoint and a negative regulator of ACE. Crosstalk between CD66a and PD-L1 or ACE/ACE2 may provide insight into ICI therapies. These networks may also play role in the increased production of S100A9 and neurological mediators in response to MHV-1 and/or PD-L1mAb, which warrant further study. Overall, these findings support observational data suggesting that prior ICI treatment does not alter survival in patients presenting with COVID-19.
Chimeric antigen-receptor (CAR) engineered natural killer cells in a chronic myeloid leukemia (CML) blast crisis model
Authors: Imeri Jusuf , Marcoux Paul , Huyghe Matthias , Desterke Christophe , Fantacini Daianne Maciely Carvalho , Griscelli Frank , Covas Dimas T. , de Souza Lucas Eduardo Botelho , Griscelli Annelise Bennaceur , Turhan Ali G.
Published: January 2024

During the last two decades, the introduction of tyrosine kinase inhibitors (TKIs) to the therapy has changed the natural history of CML but progression into accelerated and blast phase (AP/BP) occurs in 3-5% of cases, especially in patients resistant to several lines of TKIs. In TKI-refractory patients in advanced phases, the only curative option is hematopoietic stem cell transplantation. We and others have shown the relevance of the expression of the Interleukin-2-Receptor α subunit (IL2RA/CD25) as a biomarker of CML progression, suggesting its potential use as a therapeutic target for CAR-based therapies. Here we show the development of a CAR-NK therapy model able to target efficiently a blast crisis cell line (K562). The design of the CAR was based on the scFv of the clinically approved anti-CD25 monoclonal antibody (Basiliximab). The CAR construct was integrated into NK92 cells resulting in the generation of CD25 CAR-NK92 cells. Target K562 cells were engineered by lentiviral gene transfer of CD25. In vitro functionality experiments and in vivo leukemogenicity experiments in NSG mice transplanted by K562-CD25 cells showed the efficacy and specificity of this strategy. These proof-of-concept studies could represent a first step for further development of this technology in refractory/relapsed (R/R) CML patients in BP as well as in R/R acute myeloblastic leukemias (AML).
Tertiary lymphoid structures in autoimmune diseases
Authors: Dong Yuanji , Wang Ting , Wu Huaxiang
Published: January 2024

Tertiary lymphoid structures (TLSs) are organized lymphoid-like aggregations in non-lymphoid tissues. Tissues with chronic and persistent inflammation infiltration may drive and form ectopic germinal center-like structures, which are very common in autoimmune diseases, chronic infections, and tumor microenvironments. However, the mechanisms governing the formation of TLSs are still being explored. At present, it is not clear whether the formation of TLSs is associated with local uncontrolled immune inflammatory responses. While TLSs suggest a good prognosis in tumors, the opposite is true in autoimmune diseases. This review article will discuss the current views on initiating and maintaining TLSs and the potential therapeutic target in autoimmune diseases.
Endogenous complement-activating IgM is not required for primary antibody responses but promotes plasma cell differentiation and secondary antibody responses to a large particulate antigen in mice
Authors: Palm Anna-Karin E. , Westin Annika , Ayranci Diyar , Heyman Birgitta
Published: January 2024

Lack of complement factor C1q of the classical pathway results in severely impaired primary antibody responses. This is a paradox because antibodies, especially IgM, are the most efficient activators of the classical pathway and very little specific IgM will be present at priming. A possible explanation would be that natural IgM, binding with low affinity to the antigen, may suffice to activate complement. In support of this, mice lacking secretory IgM have an impaired antibody response, which can be rescued by transfer of non-immune IgM. Moreover, passive administration of specific IgM together with antigen enhances the antibody response in a complement-dependent fashion. To test the idea, we have used a knock-in mouse strain (Cμ13) carrying a point mutation in the IgM heavy chain, rendering the IgM unable to activate complement. Mutant mice backcrossed to BALB/c or C57BL/6 background were primed and boosted with a low dose of sheep red blood cells. Confirming earlier data, no impairment in early, primary IgM- or IgG-responses were seen in either of the Cμ13 strains. However, in one of the mutant strains, late primary IgG responses were impaired. A more pronounced effect was observed after boost, when the IgG response, the number of germinal center B cells and antibody secreting cells as well as the opsonization of antigen were impaired in mutant mice. We conclude that complement activation by natural IgM cannot explain the role of C1q in primary antibody responses, but that endogenous, specific, wildtype IgM generated after immunization feedback-enhances the response to a booster dose of antigen. Importantly, this mechanism can only partially explain the role of complement in the generation of antibody responses because the IgG response was much lower in C3- or complement receptor 1 and 2-deficient mice than in Cμ13 mice.
The immunomodulatory effects of mesenchymal stem cell-derived extracellular vesicles in Alzheimer's disease
Authors: Ye Yang , Gao Mingzhu , Shi Wentao , Gao Yan , Li Yilu , Yang Wenhui , Zheng Xiaomin , Lu Xiaojie
Published: January 2024

Neuroinflammation has been identified as another significant pathogenic factor in Alzheimer’s disease following Aβ amyloid deposition and tau protein hyperphosphorylation, activated in the central nervous system by glial cells in response to injury-related and pathogen-related molecular patterns. Moderate glial cell activity can be neuroprotective; however, excessive glial cell activation advances the pathology of Alzheimer’s disease and is accompanied by structural changes in the brain interface, with peripheral immune cells entering the brain through the blood-brain barrier, creating a vicious circle. The immunomodulatory properties of mesenchymal stem cells (MSCs) are primarily conveyed through extracellular vesicles (EVs). MSC-EVs participate in chronic inflammatory and immune processes by transferring nucleic acids, proteins and lipids from the parent cell to the recipient cell, thus MSC-EVs retain their immunomodulatory capacity while avoiding the safety issues associated with living cell therapy, making them a promising focus for immunomodulatory therapy. In this review, we discuss the modulatory effects of MSC-EVs on Alzheimer’s disease-associated immune cells and the mechanisms involved in their treatment of the condition. We have found a clinical trial of MSC-EVs in Alzheimer’s disease treatment and outlined the challenges of this approach. Overall, MSC-EVs have the potential to provide a safe and effective treatment option for Alzheimer’s disease by targeting neuroinflammation.