bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluorescence quenching-based immunological probe for ticagrelor monitoring
Authors: Zhang Shengshuo , Cheng Yueqing , Gao Yujie , Zou Yujie , Xiao Weiling , Li Tianyi , Li Mei , Yu Bowen , Dong Jinhua
Published: November 2023

Introduction: Ticagrelor is extensively utilized for the treatment of acute coronary syndromes (ACS), but its platelet aggregation inhibitory effects can potentially result in tissue bleeding, posing a serious risk to patients’ lives.

Methods: In this study, we developed highly sensitive full length anti-ticagrelor Quenchbodies (Q-bodies) for fast monitoring of ticagrelor both in solution and serum for the first time. Ticagrelor coupled with N- hydroxysuccinimide (Ticagrelor-NHS) ester was also designed and synthesized for interaction and biological activity detection.

Results: Both ATTO-labeled MEDI2452 (2452A) Q-body and TAMRA-labeled IgG 152 (152T) Q-body demonstrated efficient detection of ticagrelor and its active metabolite (TAM). The 2452A Q-body exhibited a broader detection range, while the 152T Q-body displayed a lower limit of detection (LOD). Under physiological conditions (Ticagrelor:TAM, 3:1), the concentration of ticagrelor was further measured, yielding LOD values of 4.65 pg/mL and 2.75 pg/mL for the two Q-bodies, with half-maximal effect concentrations of 8.15 ng/mL and 3.0 ng/mL, respectively.

Discussion: Compared with traditional liquid chromatography-mass spectrometry (LC-MS) methods, anti-ticagrelor Q-bodies have higher sensitivity and detection speed. It enabled the completion of analysis within 3 min, facilitating rapid preoperative detection of blood drug concentration in ACS to determine the feasibility of surgery and mitigate the risk of intraoperative and postoperative hemorrhage. The swift detection of ticagrelor holds promise for enhancing individualized drug administration, preventing adverse reactions, and providing preoperative guidance.
Characterization of the enzyme kinetics of EMP and HMP pathway in Corynebacterium glutamicum: reference for modeling metabolic networks
Authors: Yang Liu , Li Junyi , Zhang Yaping , Chen Linlin , Ouyang Zhilin , Liao Daocheng , Zhao Fengguang , Han Shuangyan
Published: November 2023

The model of intracellular metabolic network based on enzyme kinetics parameters plays an important role in understanding the intracellular metabolic process of Corynebacterium glutamicum, and constructing such a model requires a large number of enzymological parameters. In this work, the genes encoding the relevant enzymes of the EMP and HMP metabolic pathways from Corynebacterium glutamicum ATCC 13032 were cloned, and engineered strains for protein expression with E.coli BL21 and P.pastoris X33 as hosts were constructed. The twelve enzymes (GLK, GPI, TPI, GAPDH, PGK, PMGA, ENO, ZWF, RPI, RPE, TKT, and TAL) were successfully expressed and purified by Ni2+ chelate affinity chromatography in their active forms. In addition, the kinetic parameters (Vmax, Km, and Kcat) of these enzymes were measured and calculated at the same pH and temperature. The kinetic parameters of enzymes associated with EMP and the HMP pathway were determined systematically and completely for the first time in C.glutamicum. These kinetic parameters enable the prediction of key enzymes and rate-limiting steps within the metabolic pathway, and support the construction of a metabolic network model for important metabolic pathways in C.glutamicum. Such analyses and models aid in understanding the metabolic behavior of the organism and can guide the efficient production of high-value chemicals using C.glutamicum as a host.
Vascular aging and cardiovascular disease: pathophysiology and measurement in the coronary arteries
Authors: Cheng Daniel C. Y. , Climie Rachel E. , Shu Matthew , Grieve Stuart M. , Kozor Rebecca , Figtree Gemma A.
Published: November 2023

Age is a key risk factor for cardiovascular disease, including atherosclerosis. However, pathophysiological disease processes in the arteries are not an inevitable feature of aging. Large cohort studies with arterial phenotyping along with clinical and demographic data are essential to better understand factors related to the susceptibility or resilience to age-related vascular pathophysiology in humans. This review explores the mechanisms by which vascular structure and function alters with age, and how these changes relate to cardiovascular pathophysiology and disease. Features of vascular aging in the coronary arteries have historically been difficult to quantify pre-mortem due to their size and location. However, non-invasive imaging modalities including CT Coronary Angiogram are now being used to assess coronary vascular age, and further advances in imaging analysis such as the CT Fat Attenuation Index will help provide further measurement of features associated with coronary vascular aging. Currently, markers of vascular aging are not used as therapeutic targets in routine clinical practice, but non-pharmacological interventions including aerobic exercise and low salt diet, as well as anti-hypertensives have been demonstrated to reduce arterial stiffness. Advances in imaging technology, both in acquisition and advanced analysis, as well as harmonisation of measurements for researchers across the globe will be invaluable in understanding what constitutes healthy vascular aging and in identifying features of vascular aging that are associated with coronary artery disease and its adverse outcomes. Assessing such images in large cohorts can facilitate improved definitions of resilient and susceptible phenotypes to vascular aging in the coronary arteries. This is a critical step in identifying further risk factors and biomarkers within these groups and driving forward the development of novel therapies aimed at slowing or stopping age-related vascular changes in the coronary arteries.
Assessing health science students’ gaming experience: a cross-sectional study
Authors: Rodríguez-Roca Beatriz , Calatayud Estela , Gomez-Soria Isabel , Marcén-Román Yolanda , Cuenca-Zaldivar Juan Nicolas , Andrade-Gómez Elena , Subirón-Valera Ana Belén
Published: November 2023

Background

Digital gamification applied to university students enrolled in health-related degrees is considered an innovative and beneficial tool that complements traditional teaching.

Objectives

To analyze the enjoyment experience obtained by university students in the Faculty of Health Sciences and to know the gender differences after participating in a digital game.

Design

Cross-sectional descriptive study.

Participants

A total of 156 university students from the Faculty of Health Sciences, University of Zaragoza.

Methods

The activity of a digital game took place in the academic year 2021–2022 and was carried out as a teaching innovation project with the final approval of the University of Zaragoza. The tools used were the Spanish version of the Gameful Experience Scale and a self-administered questionnaire on satisfaction and suitability reported by the activity.

Results

A total of 156 students participated with an age of 21.2 ± 6.2 years. The highest score is the enjoyment dimension (4 ± 0.7), and the lowest score is the negative affect dimension (1.5 ± 0.9). Cronbach’s alpha for the whole Gameful Experience Scale was 0.95. There were significant differences in three dimensions of the Gameful Experience Scale: male students had more enjoyment than female students (p = 0.05), enjoyed a greater sense of domination (p = 0.01), and had fewer negative effects (p = 0.0). In the highest corresponding positions it was used for other topics such as learning (m 4.4; SD 0.5), motivation to learn (m 4.1; SD 0.8) or helping memorize concepts (m 4.4).4; SD 0.5).

Conclusion

Gender influences student satisfaction after carrying out a gamification activity, especially after a digital game. The dimensions in which gender differences were found were fun, absence of negative effects, and dominance.
Distinctive biochemistry profiles associated with hyperuricemia between Tibetans and Hans in China
Authors: Ren Xue-Wen , Chen Kang , Wu Jue , Yang Zhang-Lin , Ji Tao , Zhang Qing-Hong
Published: November 2023

Purpose

We sought to identify distinct risk factors for hyperuricemia in native Tibetan and immigrant Han populations in Tibet, China.

Methods

Three cohorts of male participants aged between 20 and 40 years were enrolled in this study. Biochemical parameters including serum uric acid (UA), fasting plasma glucose, insulin, lactate dehydrogenase (LDH), thyroxin, blood cell count, aminotransferase, and lipid profiles were analyzed. The association of risk factors with UA levels was evaluated using a multivariable line regression model. The effect of UA level on the biochemical parameters between the Hans and Tibetans was evaluated by two-way ANOVA.

Results

The prevalence of hyperuricemia (≥420 μmol/L) was 24.8% (62/250) in the Hans, similar to 23.8% (29/136) in the Tibetans. In the regression analysis, the risk factors that were significantly associated with UA in Hans did not apply to Tibetans. Tibetans had higher fasting insulin (P<0.05) and LDH (P<0.01) levels, in contrast with lower levels of triglycerides (P<0.05), total cholesterol (P<0.01), and low-density lipoprotein-cholesterol (P<0.01) than Hans in normal UA populations. Biochemistry analysis revealed lower albumin levels (P<0.001) and higher levels of all aminotransaminase and especially alkaline phosphatase (P<0.01) in Tibetans than in Hans in both populations. Compared with Hans, Tibetans had lower serum levels of urea, creatinine, and electrolytes in the normal UA population, which were further exacerbated in the high UA population. Tibetans had comparable white blood cell counts as Hans in both normal and high UA populations. In contrast, the red blood cell count and hemoglobin concentration were much lower in Tibetans than in Hans under high UA conditions.

Conclusions

The distinctive biochemistry between Tibetans and Hans may underlie the different etiologies of hyperuricemia in Tibet, China.
Associations between body composition profile and hypertension in different fatty liver phenotypes
Authors: Huang Xiaoyin , Zeng Yuchen , Ma Mingyang , Xiang Liangguang , Liu Qingdan , Xiao Ling , Feng Ruimei , Li Wanxin , Zhang Xiaoling , Lin Moufeng , Hu Zhijian , Zhao Hongwei , Du Shanshan , Ye Weimin
Published: November 2023

Background

It is currently unclear whether and how the association between body composition and hypertension varies based on the presence and severity of fatty liver disease (FLD).

Methods

FLD was diagnosed using ultrasonography among 6,358 participants. The association between body composition and hypertension was analyzed separately in the whole population, as well as in subgroups of non-FLD, mild FLD, and moderate/severe FLD populations, respectively. The mediation effect of FLD in their association was explored.

Results

Fat-related anthropometric measurements and lipid metabolism indicators were positively associated with hypertension in both the whole population and the non-FLD subgroup. The strength of this association was slightly reduced in the mild FLD subgroup. Notably, only waist-to-hip ratio and waist-to-height ratio showed significant associations with hypertension in the moderate/severe FLD subgroup. Furthermore, FLD accounted for 17.26% to 38.90% of the association between multiple body composition indicators and the risk of hypertension.

Conclusions

The association between body composition and hypertension becomes gradually weaker as FLD becomes more severe. FLD plays a significant mediating role in their association.
Association between the neutrophil-to-lymphocyte ratio and cognitive impairment: a meta-analysis of observational studies
Authors: Hung Kuo-Chuan , Liu Chien-Cheng , Wu Jheng-Yan , Ho Chun-Ning , Lin Ming-Chung , Hsing Chung-Hsi , Chen I-Wen
Published: November 2023

Background

Systemic inflammation is one of the underlying mechanisms of cognitive impairment. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a systemic inflammation indicator. This meta-analysis aimed to evaluate the association between high NLR and cognitive impairment (CI) risk.

Method

A comprehensive systematic search was conducted to identify eligible studies published until May 30, 2023. The reference group comprised patients with the lowest NLR level, whereas the exposure group comprised those with the highest NLR level. The main outcome was to examine the relationship between NLR and CI risk. The secondary outcome included the association between patient characteristics or comorbidities and CI risk.

Results

This meta-analysis included 11 studies published between 2018 and 2023, involving 10,357 patients. Patients with CI had a higher NLR than those without (mean difference=0.35, 95% confidence interval [CI]: 0.26–0.44, p < 00001, I2 = 86%). Consistently, pooled results revealed an association between high NLR and CI risk (odds ratio [OR]=2.53, 95% CI:1.67–3.82, p<0.0001, I2 = 84%). Furthermore, aging (mean difference =4.31 years, 95% CI:2.83–5.8, p < 0.00001, I2 = 92%), diabetes (OR=1.59, 95% CI:1.35–1.88, p < 0.00001, I2 = 66%), and hypertension (OR=1.36, 95% CI:1.19–1.57, p < 0.00001, I2 = 0%) were significant risk factors for CI. However, no significant associations were observed between CI and male gender (OR = 0.84, 95% CI:0.64–1.11, p = 0.22, I2 = 81%), body mass index (mean = −0.32 kg/m2, 95% CI: −0.82, 0.18, p = 0.2, I2 = 82%), alcohol consumption (OR = 1.11, 95% CI:0.95−1.3, p = 1.35, I2 = 0%), and smoking (OR = 0.99, 95% CI:0.87–1.13, p = 0.86, I2 = 0%). Meta-regression found that diabetes and hypertension, but not age, significantly moderated the association between NLR and CI.

Conclusion

This meta-analysis showed a significant association between high NLR and increased CI risk. Moreover, meta-regression identified diabetes and hypertension, but not age, as significant moderating factors in the relationship between NLR and CI. To validate and strengthen these findings, further large-scale studies are required.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023430384, identifier CRD42023430384.
Techno-economic and environmental evaluation of the production of biodiesel from rice-straw in China
Authors: Hu Yixuan , Chen Jiajun , Tian Hong , Hu Zhangmao
Published: November 2023

Rice straw (RS) is the residue obtained during the rice processing process, and is recognized as one of the most abundant biomass resources in the world. Approximately 800 million to 1 billion tons of rice straw are produced globally every year, and most of them are considered general waste and typically end up in landfills or incineration. This approach wastes resources and can also lead to environmental pollution. In the current study, the RS was used as the source of biodiesel production and a comprehensive process model of the RS valorization process was developed to evaluate the energy flow, production efficiency, production costs, and greenhouse gas emissions in Hunan Province, China. The evaluation results showed that the energy efficiency of biodiesel production from rice straw and the overall energy efficiency of the rice straw valorization process are reported as 52.1% and 56.1%, respectively. The minimum selling price of biodiesel, which is CNY 3.03/kg, is considerably lower than the current market prices for similar products in China. The largest proportion of the production cost of biodiesel is the cost of natural gas, followed by utilities, capital, transportation, plant maintenance and overheads, consumables, labor, and waste disposal. For the current RS valorization plant with a 5000 kg/h RS feed rate, the investment payback times are 8.9 yr and 7.1 yr when the biodiesel is sold at the lowest (CNY 4/kg) and highest (CNY 4.6/kg) market price, respectively. Environmental analysis shows that the greenhouse gas emissions intensity of biodiesel production is 75.8 g CO2eq/MJ, which is only about 52% of traditional fossil diesel and indicating that biodiesel is an environmentally friendly energy source.
Research on the influence factors of accident severity of new energy vehicles based on ensemble learning
Authors: Zhang Zixuan , Niu Zhenxing , Li Yan , Ma Xuejun , Sun Shaofeng
Published: November 2023

With the deepening of the concept of green, low-carbon, and sustainable development, the continuous growth of the ownership of new energy vehicles has led to increasing public concerns about the traffic safety issues of these vehicles. In order to conduct research on the traffic safety of new energy vehicles, three sampling methods, namely, Synthetic Minority Over-sampling Technique (SMOTE), Edited Nearest Neighbours (ENN), and SMOTE-ENN hybrid sampling, were employed, along with cost-sensitive learning, to address the problem of imbalanced data in the UK road traffic accident dataset. Three algorithms, eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), and Categorical Boosting (CatBoost), were selected for modeling work. Lastly, the evaluation criteria used for model selection were primarily based on G-mean, with AUC and accuracy as secondary measures. The TreeSHAP method was applied to explain the interaction mechanism between accident severity and its influencing factors in the constructed models. The results showed that LightGBM had a more stable overall performance and higher computational efficiency. XGBoost demonstrated a balanced combination of computational efficiency and model performance. CatBoost, however, was more time-consuming and showed less stability with different datasets. Studies have found that people using fewer protective means of transportation (bicycles, motorcycles) and vulnerable groups such as pedestrians are susceptible to serious injury and death.
Predicting the response of three common subtropical tree species in China to climate change
Authors: Jin Songheng , Chi Yi , Li Xueqin , Shu Pengzhou , Zhu Mengxun , Yuan Zheng , Liu Yang , Chen Wenjing , Han Yini
Published: November 2023

Introduction

Climate is crucial factor influencing species distribution, and with global climate change, the potential geographic distribution of species will also alter. In this study, three subtropical tree species (Cunninghamia lanceolata, Pinus taiwanensis, and Quercus glauca) of great ecological values were selected as research objects.

Methods

We applied a maximum entropy (MaxEnt) to predict their potential distributions under different climate scenarios in both present and future conditions based on 37 environmental factors. Jackknife test was used in key factors affecting species distribution. In addition, we explored the key environmental variables that affect their distributions and revealed the evolutionary patterns and migration trends of these tree species under future climate.

Results

The main findings are as follows: (1) Winter temperature, winter precipitation, and annual temperature range are identified as the key environmental variables affecting the potential geographic distribution of the three tree species; moreover, precipitation-related factors have a greater impact than temperature-related factors; (2) Currently suitable habitats for these three tree species are primarily located in subtropical China with decreasing suitability from south to north; (3) Under future climate conditions, the area of potentially suitable habitat for C. lanceolata continues to expand, while P. taiwanensis and Q. glauca tend to experience a reduction due to increasing greenhouse gas emissions over time; and (4) The centroid of suitable habitat for C. lanceolata shifts northward under future climate change, while the centroid of P. taiwanensis and Q. glauca move southward along with shrinking suitable habitat area.

Discussion

Our predictions highlight a high risk of habitat loss of Q. glauca under climate change, recommending management and conservation references for these three commonly used afforestation species under current and future climate change scenarios in China.
Personalized medicine in a community health system: the NorthShore experience
Authors: David Sean P. , Dunnenberger Henry M. , Choi Sarah , DePersia Allison , Ilbawi Nadim , Ward Christopher , Wake Dyson T. , Khandekar Janardan D. , Shannon Yvette , Hughes Kristen , Miller Nicholas , Mangold Kathy A. , Sabatini Linda M. , Helseth Donald L. , Xu Jianfeng , Sanders Alan , Kaul Karen L. , Hulick Peter J.
Published: November 2023

Genomic and personalized medicine implementation efforts have largely centered on specialty care in tertiary health systems. There are few examples of fully integrated care systems that span the healthcare continuum. In 2014, NorthShore University HealthSystem launched the Center for Personalized Medicine to catalyze the delivery of personalized medicine. Successful implementation required the development of a scalable family history collection tool, the Genetic and Wellness Assessment (GWA) and Breast Health Assessment (BHA) tools; integrated pharmacogenomics programming; educational programming; electronic medical record integration; and robust clinical decision support tools. To date, more than 225,000 patients have been screened for increased hereditary conditions, such as cancer risk, through these tools in primary care. More than 35,000 patients completed clinical genetic testing following GWA or BHA completion. An innovative program trained more than 100 primary care providers in genomic medicine, activated with clinical decision support and access to patient genetic counseling services and digital healthcare tools. The development of a novel bioinformatics platform (FLYPE) enabled the incorporation of genomics data into electronic medical records. To date, over 4,000 patients have been identified to have a pathogenic or likely pathogenic variant in a gene with medical management implications. Over 33,000 patients have clinical pharmacogenomics data incorporated into the electronic health record supported by clinical decision support tools. This manuscript describes the evolution, strategy, and successful multispecialty partnerships aligned with health system leadership that enabled the implementation of a comprehensive personalized medicine program with measurable patient outcomes through a genomics-enabled learning health system model that utilizes implementation science frameworks.
The Global Compact on Refugees: inadequate substitute or useful complement?
Authors: Arnold-Fernández Emily E.
Published: November 2023

The Global Compact on Refugees is touted by its supporters as a soft law instrument that advances solutions for refugees in a way that complements the fundamental human rights protections afforded by the hard law Refugee Convention. In practice, however, the Global Compact appears to have replaced the Refugee Convention as the centerpiece of multilateral dialogue about states' actions vis-à-vis refugees. This paper argues that the substitution of the Global Compact for the Refugee Convention is problematic from a human rights perspective because the Global Compact makes very little provision for refugees' rights and interests, instead focusing on the rights and interests of states. The Compact thus exerts a gravitational pull that distances the forced displacement response sector from the objective of realizing refugees' human rights. To counter this, the paper suggests a need for increased attention and deeper investment in bolstering the use of human rights treaty mechanisms and processes to enforce refugees' human rights.
Appraising the causal relationship between thyroid function and rheumatoid arthritis: a two-sample bidirectional Mendelian randomization study
Authors: Gu Peng , Pu Bin , Ma YangCheng , Yue Dan , Xin Qiao , Li HaiShan , Liu Teng , Zheng XiaoHui , Ouyang ChongZhi
Published: November 2023

Background

Hypothyroidism and hyperthyroidism are observationally associated with rheumatoid arthritis (RA), but causality is unclear. To evaluate the causal relationship between thyroid function and RA, we conducted a two-Sample bidirectional Mendelian Randomization (MR) study.

Methods

Single nucleotide polymorphisms associated with six phenotypes were selected from the FinnGen biobank database, The ThyroidOmics Consortium database, and the IEU Open GWAS database. For the forward MR analysis, we selected hypothyroidism (N=213,390), Graves’ disease (GD) (N=199,034), other types of hyperthyroidism (N=190,799), free thyroxine (FT4, N=49,269), and thyroid-stimulating hormone (TSH, N=54,288) as the five related thyroid function phenotypes for exposure, with RA (N=58,284) as the outcome. Reverse MR analysis selected RA as the exposure and five phenotypes of thyroid function as the outcome. The Inverse variance weighting (IVW) method was used as the primary analysis method, supplemented by weighted median (WM) and MR-Egger methods. Cochran’s Q test, MR-PRESSO, MR-Egger regression methods, and leave-one-out analysis were employed to assess sensitivity and pleiotropy.

Results

Forward MR evidence indicates that genetic susceptibility to hypothyroidism is associated with an increased risk of RA (ORIvw=1.758, P=7.61×10-5). Reverse MR evidence suggests that genetic susceptibility to RA is associated with an increased risk of hypothyroidism (ORIvw=1.274, P=3.88×10-20), GD (ORIvw=1.269, P=8.15×10-05), and other types of hyperthyroidism (ORIvw=1.141, P=1.80×10-03). There is no evidence to support a forward or reverse causal relationship between genetic susceptibility to RA and FT4, TSH.

Conclusion

Our results provide genetic evidence supporting bidirectional causal relationships between thyroid function and RA. These findings inform preventive strategies and interventions targeting RA and thyroid dysfunction.
The Simple prEservatioN of Single cElls method for cryopreservation enables the generation of single-cell immune profiles from whole blood
Authors: Satpathy Sarthak , Thomas Beena E. , Pilcher William J. , Bakhtiari Mojtaba , Ponder Lori A. , Pacholczyk Rafal , Prahalad Sampath , Bhasin Swati S. , Munn David H. , Bhasin Manoj K.
Published: November 2023

Introduction

Current multistep methods utilized for preparing and cryopreserving single-cell suspensions from blood samples for single-cell RNA sequencing (scRNA-seq) are time-consuming, requiring trained personnel and special equipment, so limiting their clinical adoption. We developed a method, Simple prEservatioN of Single cElls (SENSE), for single-step cryopreservation of whole blood (WB) along with granulocyte depletion during single-cell assay, to generate high quality single-cell profiles (SCP).

Methods

WB was cryopreserved using the SENSE method and peripheral blood mononuclear cells (PBMCs) were isolated and cryopreserved using the traditional density-gradient method (PBMC method) from the same blood sample (n=6). The SCPs obtained from both methods were processed using a similar pipeline and quality control parameters. Further, entropy calculation, differential gene expression, and cellular communication analysis were performed to compare cell types and subtypes from both methods.

Results

Highly viable (86.3 ± 1.51%) single-cell suspensions (22,353 cells) were obtained from the six WB samples cryopreserved using the SENSE method. In-depth characterization of the scRNA-seq datasets from the samples processed with the SENSE method yielded high-quality profiles of lymphoid and myeloid cell types which were in concordance with the profiles obtained with classical multistep PBMC method processed samples. Additionally, the SENSE method cryopreserved samples exhibited significantly higher T-cell enrichment, enabling deeper characterization of T-cell subtypes. Overall, the SENSE and PBMC methods processed samples exhibited transcriptional, and cellular communication network level similarities across cell types with no batch effect except in myeloid lineage cells.

Discussion

Comparative analysis of scRNA-seq datasets obtained with the two cryopreservation methods i.e., SENSE and PBMC methods, yielded similar cellular and molecular profiles, confirming the suitability of the former method’s incorporation in clinics/labs for cryopreserving and obtaining high-quality single-cells for conducting critical translational research.
The autoinflammation-associated NLRC4V341A mutation increases microbiota-independent IL-18 production but does not recapitulate human autoinflammatory symptoms in mice
Authors: Eeckhout Elien , Asaoka Tomoko , Van Gorp Hanne , Demon Dieter , Girard-Guyonvarc’h Charlotte , Andries Vanessa , Vereecke Lars , Gabay Cem , Lamkanfi Mohamed , van Loo Geert , Wullaert Andy
Published: November 2023

Background

Autoinflammation with infantile enterocolitis (AIFEC) is an often fatal disease caused by gain-of-function mutations in the NLRC4 inflammasome. This inflammasomopathy is characterized by macrophage activation syndrome (MAS)-like episodes as well as neonatal-onset enterocolitis. Although elevated IL-18 levels were suggested to take part in driving AIFEC pathology, the triggers for IL-18 production and its ensuing pathogenic effects in these patients are incompletely understood.

Methods

Here, we developed and characterized a novel genetic mouse model expressing a murine version of the AIFEC-associated NLRC4V341A mutation from its endogenous Nlrc4 genomic locus.

Results

NLRC4V341A expression in mice recapitulated increased circulating IL-18 levels as observed in AIFEC patients. Housing NLRC4V341A-expressing mice in germfree (GF) conditions showed that these systemic IL-18 levels were independent of the microbiota, and unmasked an additional IL-18-inducing effect of NLRC4V341A expression in the intestines. Remarkably, elevated IL-18 levels did not provoke detectable intestinal pathologies in NLRC4V341A-expressing mice, even not upon genetically ablating IL-18 binding protein (IL-18BP), which is an endogenous IL-18 inhibitor that has been used therapeutically in AIFEC. In addition, NLRC4V341A expression did not alter susceptibility to the NLRC4-activating gastrointestinal pathogens Salmonella Typhimurium and Citrobacter rodentium.

Conclusion

As observed in AIFEC patients, mice expressing a murine NLRC4V341A mutant show elevated systemic IL-18 levels, suggesting that the molecular mechanisms by which this NLRC4V341A mutant induces excessive IL-18 production are conserved between humans and mice. However, while our GF and infection experiments argue against a role for commensal or pathogenic bacteria, identifying the triggers and mechanisms that synergize with IL-18 to drive NLRC4V341A-associated pathologies will require further research in this NLRC4V341A mouse model.
Advancing CAR-based immunotherapies in solid tumors: CAR- macrophages and neutrophils
Authors: Liang Yanling , Xu Qumiao , Gao Qianqian
Published: November 2023

Macrophages and neutrophils are the main components of the innate immune system and play important roles in promoting angiogenesis, extracellular matrix remodeling, cancer cell proliferation, and metastasis in the tumor microenvironment (TME). They can also be harnessed to mediate cytotoxic tumor killing effects and orchestrate effective anti-tumor immune responses with proper stimulation and modification. Therefore, macrophages and neutrophils have strong potential in cancer immunotherapy. In this review, we briefly outlined the applications of macrophages or neutrophils in adoptive cell therapies, and focused on chimeric antigen receptor (CAR)-engineered macrophages (CAR-Ms) and neutrophils (CAR-Ns). We summarized the construction strategies, the preclinical and clinical studies of CAR-Ms and CAR-Ns. In the end, we briefly discussed the limitations and challenges of CAR-Ms and CAR-Ns, as well as future research directions to extend their applications in treating solid tumors.
COVID-19 and trained immunity: the inflammatory burden of long covid
Authors: Gu Jienan , Liu Qianhui , Zhang Jiale , Xu Shijie
Published: November 2023

Severe COVID-19 elicits excessive inflammation mediated by innate immune cells like monocytes. Recent evidence reveals extensive epigenetic changes in monocytes during recovery from severe COVID-19, including increased chromatin accessibility at genes related to cytokine production and leukocyte activation. These changes likely originate from the reprogramming of upstream hematopoietic stem and progenitor cells (HSPCs) and represent “trained immunity”. HSPC-to-monocyte transmission of epigenetic memory may explain the persistence of these monocyte alterations despite their short lifespan. IL-6 appears pivotal for imprinting durable epigenetic modifications in monocytes during acute infection, with IL-1β potentially playing a contributory role. The poised inflammatory phenotype of monocytes post-COVID-19 may drive chronic inflammation and tissue damage, contributing to post-acute sequelae of COVID-19 symptoms. COVID-19 could also exacerbate inflammation-related diseases, such multisystem inflammatory syndromes, by altering innate immune tendencies via hematopoietic epigenetic reprogramming. Further clinical investigations quantifying inflammatory mediators and mapping epigenetic changes in HSPCs/monocytes of recovering patients are warranted. Research should also examine whether COVID-19 elicits transgenerational inheritance of epigenetic alterations. Elucidating mechanisms underlying COVID-19-induced monocyte reprogramming and developing interventions targeting key inflammatory regulators like IL-6 may mitigate the sustained inflammatory burden imposed by the aberrant trained immunity post-COVID-19.
Genome-resolved metagenomics provides insights into the microbial-mediated sulfur and nitrogen cycling in temperate seagrass meadows
Authors: Liu Pengyuan , Zou Songbao , Zhang Haikun , Liu Qing , Song Zenglei , Huang Yanyan , Hu Xiaoke
Published: November 2023

The presence of seagrasses facilitates numerous microbial-mediated biogeochemical cycles, with sulfur- and nitrogen-cycling microorganisms playing crucial roles as regulators. Despite efforts to comprehend the diversity of microbes in seagrass ecosystems, the metabolic functions of these benthic microorganisms in seagrass sediments remain largely unknown. Using metagenomics, we provide insights into the sulfur- and nitrogen-cycling pathways and key metabolic capacities of microorganisms in both Z. japonica-colonized and unvegetated sediments over a seasonal period. Taxonomic analysis of N and S cycling genes revealed that δ- and γ- proteobacteria dominated the benthic sulfate-reducing bacteria, while α- and γ-proteobacteria played a significant role in the sulfur-oxidation processes. The proteobacterial lineages were also major contributors to the benthic nitrogen cycling. However, at a finer taxonomic resolution, microbial participants in different processes were observed to be highly diverse and mainly driven by environmental factors such as temperature and salinity. The gene pools of sulfur and nitrogen cycles in the seagrass sediments were dominated by genes involved in sulfide oxidation (fccA) and hydroxylamine oxidation (hao), respectively. Seagrass colonization elevated the relative abundance of genes responsible for sulfite production (phsC), hydroxylamine oxidation (hao), and nitrogen fixation (nifK), but suppressed sulfur oxidation (soxXYZ) and denitrification (nosZ and nirS). The prevalence of proteobacterial lineages functioned with versatile capabilities in both sulfur and nitrogen cycles in seagrass ecosystems, highlighting tight couplings between these processes, which was further supported by the recovery of 83 metagenome-assembled genomes (MAGs). These findings broaden our understanding of the biogeochemical processes that are mediated by microorganisms in seagrass ecosystems.
Colorimetric sensing of uric acid based on sawdust-deposited silver nanoparticles via an eco-friendly and cost-effective approach
Authors: Nishan Umar , Khan Noaman , Muhammad Nawshad , Afridi Saifullah , Badshah Amir , Shah Mohibullah , Asad Muhammad , Ullah Raheed , Niamat Haris , Ullah Riaz , A. Ali Essam , Ojha Suvash Chandra
Published: November 2023

Uric acid is directly linked to gout, arthritis, neurological, cardiovascular, and kidney-related disorders. It is a byproduct obtained from the breakdown of purines and a significant indicator of hyperuricemia observed in both urine and blood. In the absence of any enzyme, it's quite difficult to develop a novel, cost-effective, and clinical method for uric acid detection. Herein, we report a very simple, low-cost, and non-enzymatic method for the selective identification and quantification of uric acid using green synthesized silver nanoparticles (Ag NPs). The desired Ag NPs were synthesized by the hydrothermal method using Erythrina suberosa sawdust as a deagglomeration agent and Psidium guajava extract as a reductant. The synthesis of the sensing platform, i.e., sawdust-deposited Ag NPs, was confirmed through different techniques such as UV-Vis spectrophotometer, FTIR, XRD, EDX, and scanning electron microscopy (SEM). Sawdust can offer a good, environmentally friendly, and cost-effective strategy to overcome the problem of agglomeration in nanoparticles. The enzyme mimic, with the help of H2O2, oxidizes the colorless 3,3′,5,5′-tetramethylbenzidine (TMB) to oxidized TMB with a blue-green color. The addition of uric acid reduces the oxidized TMB to a colorless product, resulting in a colorimetric change. For quality improvement, different reaction parameters, including pH, time, TMB, and NPs concentration, were optimized. Our proposed sensor responds in linear ranges of 0.04–0.360 μM, with a limit of quantification of 0.01 μM and a limit of detection of 0.004 μM. The suggested enzyme mimic detected uric acid in blood samples, with particular specificity in the presence of competitive analytes.
Case report: Oxaliplatin-induced idiopathic non-cirrhotic portal hypertension: a case report and literature review
Authors: Ye Jiayuan , Xie Yilian , Xu Yaojiang , Chen Nan , Tu Yifei
Published: November 2023

Oxaliplatin has become a widely used agent in neoadjuvant chemotherapy for gastrointestinal tract tumors and is an integral part of the therapeutic approach for managing colorectal cancer recurrences and metastases, resulting in a more favorable prognosis for patients. Nevertheless, oxaliplatin can give rise to idiopathic non-cirrhotic portal hypertension (INCPH). The emergence of INCPH can disrupt tumor chemotherapy and incite persistent adverse reactions in later stages, significantly complicating clinical management. Consequently, we have presented a case report of INCPH induced by oxaliplatin chemotherapy with the aim of advancing the diagnosis and treatment of this condition, with a particular focus on the clinical manifestations. This study has ascertained that the condition is primarily attributed to complications related to portal hypertension, such as gastrointestinal bleeding, splenomegaly, and hypersplenism. The pathological features primarily involve hepatic sinus dilation and congestion, portal obstruction, absence, stenosis, shunting, localized venous and perisinusoidal fibrosis, as well as hepatocellular atrophy. Treatment primarily concentrates on strategies typically employed for cirrhosis. Endoscopic ligation, sclerotherapy, and non-selective beta-blockers (NSBBs) can be selected to prevent and treat variceal hemorrhage. Transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation can also be chosen for severe cases. Notably, despite the timely discontinuation of oxaliplatin, most patients continue to experience disease progression, ultimately resulting in a poor prognosis due to either tumor advancement or the ongoing progression of portal hypertension. This emphasizes the importance for physicians to be aware of and consider the risk of INCPH when prescribing oxaliplatin.
Neuropathic post-COVID pain symptomatology is not associated with serological biomarkers at hospital admission and hospitalization treatment in COVID-19 survivors
Authors: Fernández-de-las-Peñas César , Guijarro Carlos , Velasco-Arribas María , Torres-Macho Juan , Franco-Moreno Ana , Truini Andrea , Pellicer-Valero Oscar , Arendt-Nielsen Lars
Published: November 2023

Objective

Evidence suggests that individuals who had survived to coronavirus disease, 2019 (COVID-19) could develop neuropathic post-COVID pain. This study investigated the association of serological biomarkers and treatments received during hospitalization with development of neuropathic-associated symptoms.

Methods

One hundred and eighty-three (n = 183) previously hospitalized COVID-19 survivors during the first wave of the pandemic were assessed in a face-to-face interview 9.4 months after hospitalization. Nineteen serological biomarkers, hospitalization data, and treatment during hospitalization were obtained from medical records. Neuropathic pain symptoms (Self-Report Leeds Assessment of Neuropathic Scale), sleep quality (Pittsburgh Sleep Quality Index), pain catastrophizing (Pain Catastrophizing Scale) and anxiety/depressive levels (Hospital Anxiety and Depression Scale) were assessed.

Results

The prevalence of post-COVID pain was 40.9% (n = 75). Fifteen (20%) patients reported neuropathic symptoms. Overall, no differences in hospitalization data and serological biomarkers were identified according to the presence or not of neuropathic-associated symptoms. Patients with post-COVID pain had the highest neutrophil count, and post hoc analysis revealed that patients with neuropathic post-COVID associated symptoms had lower neutrophil count (p = 0.04) compared with those without neuropathic pain, but differences were small and possible not clinically relevant. No differences in fatigue, dyspnea, brain fog, anxiety or depressive levels, poor sleep, or pain catastrophism between patients with and without neuropathic symptoms were found.

Conclusion

It seems that neuropathic-like post-COVID pain symptoms are not associated with neither of assessed serological biomarkers at hospital admission nor hospitalization treatments received in this cohort of hospitalized COVID-19 survivors.
Structural connectivity of cytoarchitectonically distinct human left temporal pole subregions: a diffusion MRI tractography study
Authors: Sasaki Takeshi , Makris Nikos , Shenton Martha E. , Savadjiev Peter , Rathi Yogesh , Eckbo Ryan , Bouix Sylvain , Yeterian Edward , Dickerson Bradford C. , Kubicki Marek
Published: November 2023

The temporal pole (TP) is considered one of the major paralimbic cortical regions, and is involved in a variety of functions such as sensory perception, emotion, semantic processing, and social cognition. Based on differences in cytoarchitecture, the TP can be further subdivided into smaller regions (dorsal, ventrolateral and ventromedial), each forming key nodes of distinct functional networks. However, the brain structural connectivity profile of TP subregions is not fully clarified. Using diffusion MRI data in a set of 31 healthy subjects, we aimed to elucidate the comprehensive structural connectivity of three cytoarchitectonically distinct TP subregions. Diffusion tensor imaging (DTI) analysis suggested that major association fiber pathways such as the inferior longitudinal, middle longitudinal, arcuate, and uncinate fasciculi provide structural connectivity to the TP. Further analysis suggested partially overlapping yet still distinct structural connectivity patterns across the TP subregions. Specifically, the dorsal subregion is strongly connected with wide areas in the parietal lobe, the ventrolateral subregion with areas including constituents of the default-semantic network, and the ventromedial subregion with limbic and paralimbic areas. Our results suggest the involvement of the TP in a set of extensive but distinct networks of cortical regions, consistent with its functional roles.
Research on system of ultra-flat carrying robot based on improved PSO algorithm
Authors: Zhu Jinghao , Wu Jun , Chen Zhongxiang , Cao Libo , Yang Minghai , Xu Wu
Published: November 2023

Ultra-flat carrying robots (UCR) are used to carry soft targets for functional safety road tests of intelligent driving vehicles and should have superior control performance. For the sake of analyzing and upgrading the motion control performance of the ultra-flat carrying robot, this paper develops the mathematical model of its motion control system on the basis of the test data and the system identification method. Aiming at ameliorating the defects of the standard particle swarm optimization (PSO) algorithm, namely, low accuracy, being susceptible to being caught in a local optimum, and slow convergence when dealing with the parameter identification problems of complex systems, this paper proposes a refined PSO algorithm with inertia weight cosine adjustment and introduction of natural selection principle (IWCNS-PSO), and verifies the superiority of the algorithm by test functions. Based on the IWCNS-PSO algorithm, the identification of transfer functions in the motion control system of the ultra-flat carrying robot was completed. In comparison with the identification results of the standard PSO and linear decreasing inertia weight (LDIW)-PSO algorithms, it indicated that the IWCNS-PSO has the optimal performance, with the number of iterations it takes to reach convergence being only 95 and the fitness value being only 0.117. The interactive simulation model was constructed in MATLAB/Simulink, and the critical proportioning method and the IWCNS-PSO algorithm were employed respectively to complete the tuning and optimization of the Proportional-Integral (PI) controller parameters. The results of simulation indicated that the PI parameters optimized by the IWCNS-PSO algorithm reduce the adjustment time to 7.99 s and the overshoot to 13.41% of the system, and the system is significantly improved with regard to the control performance, which basically meets the performance requirements of speed, stability, and accuracy for the control system. In conclusion, the IWCNS-PSO algorithm presented in this paper represents an efficient system identification method, as well as a system optimization method.
Roles of microRNA-124 in traumatic brain injury: a comprehensive review
Authors: Wu Panxing , He Bao , Li Xiaoliang , Zhang Hongwei
Published: November 2023

Traumatic brain injury (TBI) is a prominent global cause of mortality due to the limited availability of effective prevention and treatment strategies for this disorder. An effective molecular biomarker may contribute to determining the prognosis and promoting the therapeutic efficiency of TBI. MicroRNA-124 (miR-124) is most abundantly expressed in the brain and exerts different biological effects in a variety of diseases by regulating pathological processes of apoptosis and proliferation. Recently, increasing evidence has demonstrated the association between miR-124 and TBI, but there is still a lack of relevant literature to summarize the current evidence on this topic. Based on this review, we found that miR-124 was involved as a regulatory factor in cell apoptosis and proliferation, and was also strongly related with the pathophysiological development of TBI. MiR-124 played an essential role in TBI by interacting with multiple biomolecules and signaling pathways, such as JNK, VAMP-3, Rela/ApoE, PDE4B/mTOR, MDK/TLR4/NF-κB, DAPK1/NR2B, JAK/STAT3, PI3K/AKT, Ras/MEK/Erk. The potential benefits of upregulating miR-124 in facilitating TBI recovery have been identified. The advancement of miRNA nanocarrier system technology presents an opportunity for miR-124 to emerge as a novel therapeutic target for TBI. However, the specific mechanisms underlying the role of miR-124 in TBI necessitate further investigation. Additionally, comprehensive large-scale studies are required to evaluate the clinical significance of miR-124 as a therapeutic target for TBI.