bluuebunny/crossref_metadata_2025 huggingface dataset:
SAP-expressing T peripheral helper cells identify systemic lupus erythematosus patients with lupus nephritis
Authors: Gartshteyn Yevgeniya , Geraldino-Pardilla Laura , Khalili Leila , Bukhari Shoiab , Lerrer Shalom , Winchester Robert J. , Askanase Anca D. , Mor Adam
Published: March 2024

Introduction

T follicular (TFH) and peripheral helper (TPH) cells have been increasingly recognized as a pathogenic subset of CD4 T cells in systemic lupus erythematosus (SLE). The SLAM Associated Protein (SAP) regulates TFH and TPH function by binding to the co-stimulatory signaling lymphocyte activation molecule family (SLAMF) receptors that mediate T cell - B cell interactions. SAP and SLAMF are critical for TPH-dependent B cell maturation into autoantibody-producing plasma cells that characterize SLE pathogenesis. We hypothesized that SAP-expressing TPH cells are involved in the pathogenesis of lupus nephritis (LN).

Methods

Peripheral blood mononuclear cells (PBMC) were isolated using density gradient separation from whole blood. Cells were stained for cell surface markers, followed by permeabilization and staining of intracellular SAP for spectral flow cytometry analysis. We also analyzed SAP expression from renal infiltrating LN T cells using the available single-cell RNA sequencing (scRNA seq) Accelerated Medicines Partnership (AMP) SLE dataset.

Results

PBMC from 30 patients with SLE (34 ± 10 years old, 83% female), including 10 patients with LN, were analyzed. We found an increase in total SAP-positive CD4 and CD8 T cells in SLE compared with controls (55.5 ± 2.6 vs. 41.3 ± 3.4, p=0.007, and 52.5 ± 3.0 vs. 39.2 ± 2.8, p=0.007 respectively). In CD4 T cells, the highest SAP expression was in the TPH subset. The frequency of SAP+TPH in circulation correlated with disease activity; SLE patients with renal disease had higher levels of circulating SAP+TPH that remained significant after adjusting for age, sex, race, low complements, and elevated anti-dsDNA (p=0.014). scRNA-seq data of renal infiltrating T cells in LN identified SAP expression to localize to the TFH-like CD4 cluster and GZMK+ CD8 cluster. Increased SAP expression in LN was associated with the differential expression of SLAMF3 and SLAMF7 and granzyme K and EOMES. The existence of two predominant SAP-expressing subsets, the TFH-like CD4 T cells, and GZMK+ effector CD8 T cells, was verified using scRNA-seq data from a human transcriptomic atlas of fifteen major organs.

Conclusion

The expansion of SAP-expressing T helper cells was associated with LN in our cohort and verified using scRNA-seq data of renal infiltrating T cells. Improved SLAM and SAP signaling understanding can identify new therapeutic targets in LN.
A genome-wide cross-trait analysis identifies shared loci and causal relationships of obesity and lipidemic traits with psoriasis
Authors: Wu Yuan , Huang Mengfen , Chen Xueru , Wu Jingjing , Li Li , Wei Jianan , Lu Chuanjian , Han Ling , Lu Yue
Published: March 2024

Background

Obesity and dyslipidemia, major global health concerns, have been linked to psoriasis, but previous studies faced methodological limitations and their shared genetic basis remains unclear. This study examines various obesity-related and lipidemic traits as potential contributors to psoriasis development, aiming to clarify their genetic associations and potential causal links.

Methods

Summary statistics from genome-wide association studies (GWAS) conducted for obesity-related traits (body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for the body mass index (WHRadjBMI)) and lipidemic traits (high-density lipoprotein (HDL), LDL, triglyceride (TG), total Cholesterol (TC), apolipoprotein A1 (apoA1), apolipoprotein B (apoB), and apolipoprotein E (apoE)) and psoriasis, all in populations of European ancestry, were used. We quantified genetic correlations, identified shared loci and explored causal relationship across traits.

Results

We found positive genetic correlation between BMI and psoriasis (rg=0.22, p=2.44×10-18), and between WHR and psoriasis (rg=0.19, p=1.41×10-12). We further found the positive genetic correlation between psoriasis and WHRadjBMI(rg=0.07, p=1.81×10-2) the genetic correlation, in while the effect of BMI was controlled for. We identified 14 shared loci underlying psoriasis and obesity-related traits and 43 shared loci between psoriasis and lipidemic traits via cross-trait meta-analysis. Mendelian randomization (MR) supported the causal roles of BMI (IVW OR=1.483, 95%CI=1.333-1.649), WHR (IVW OR=1.393, 95%CI=1.207-1.608) and WHRadjBMI (IVW OR=1.18, 95%CI=1.047-1.329) in psoriasis, but not observe any significant association between lipidemic traits and the risk of psoriasis. Genetic predisposition to psoriasis did not appear to affect the risk of obesity and lipidemic traits.

Conclusions

An intrinsic link between obesity-related traits and psoriasis has been demonstrated. The genetic correlation and causal role of obesity-related traits in psoriasis highlight the significance of weight management in both the prevention and treatment of this condition.
Phenotype and function of MAIT cells in patients with alveolar echinococcosis
Authors: Li Jintian , Zhao Hanyue , Lv Guodong , Aimulajiang Kalibixiati , Li Liang , Lin Renyong , Aji Tuerganaili
Published: March 2024

Mucosal-associated invariant T (MAIT) cells are a subpopulation of unconventional T cells widely involved in chronic liver diseases. However, the potential role and regulating factors of MAIT cells in alveolar echinococcosis (AE), a zoonotic parasitic disease by Echinococcus multilocularis (E. multilocularis) larvae chronically parasitizing liver organs, has not yet been studied. Blood samples (n=29) and liver specimens (n=10) from AE patients were enrolled. The frequency, phenotype, and function of MAIT cells in peripheral blood and liver tissues of AE patients were detected by flow cytometry. The morphology and fibrosis of liver tissue were examined by histopathology and immunohistochemistry. The correlation between peripheral MAIT cell frequency and serologic markers was assessed by collecting clinicopathologic characteristics of AE patients. And the effect of in vitro stimulation with E. multilocularis antigen (Emp) on MAIT cells. In this study, MAIT cells are decreased in peripheral blood and increased in the close-to-lesion liver tissues, especially in areas of fibrosis. Circulating MAIT exhibited activation and exhaustion phenotypes, and intrahepatic MAIT cells showed increased activation phenotypes with increased IFN-γ and IL-17A, and high expression of CXCR5 chemokine receptor. Furthermore, the frequency of circulating MAIT cells was correlated with the size of the lesions and liver function in patients with AE. After excision of the lesion site, circulating MAIT cells returned to normal levels, and the serum cytokines IL-8, IL-12, and IL-18, associated with MAIT cell activation and apoptosis, were altered. Our results demonstrate the status of MAIT cell distribution, functional phenotype, and migration in peripheral blood and tissues of AE patients, highlighting their potential as biomarkers and therapeutic targets.
Adoptive T cell therapy for solid tumors: current landscape and future challenges
Authors: Albarrán Víctor , San Román María , Pozas Javier , Chamorro Jesús , Rosero Diana Isabel , Guerrero Patricia , Calvo Juan Carlos , González Carlos , García de Quevedo Coral , Pérez de Aguado Patricia , Moreno Jaime , Cortés Alfonso , Soria Ainara
Published: March 2024

Adoptive cell therapy (ACT) comprises different strategies to enhance the activity of T lymphocytes and other effector cells that orchestrate the antitumor immune response, including chimeric antigen receptor (CAR) T-cell therapy, T-cell receptor (TCR) gene-modified T cells, and therapy with tumor-infiltrating lymphocytes (TILs). The outstanding results of CAR-T cells in some hematologic malignancies have launched the investigation of ACT in patients with refractory solid malignancies. However, certain characteristics of solid tumors, such as their antigenic heterogeneity and immunosuppressive microenvironment, hamper the efficacy of antigen-targeted treatments. Other ACT modalities, such as TIL therapy, have emerged as promising new strategies. TIL therapy has shown safety and promising activity in certain immunogenic cancers, mainly advanced melanoma, with an exciting rationale for its combination with immune checkpoint inhibitors. However, the implementation of TIL therapy in clinical practice is hindered by several biological, logistic, and economic challenges. In this review, we aim to summarize the current knowledge, available clinical results, and potential areas of future research regarding the use of T cell therapy in patients with solid tumors
Therapeutic potential of procathepsin L-inhibiting and progesterone-entrapping dimethyl-β-cyclodextrin nanoparticles in treating experimental sepsis
Authors: Qiang Xiaoling , Chen Weiqiang , Zhu Cassie Shu , Li Jianhua , Qi Timothy , Lou Li , Wang Ping , Tracey Kevin J. , Wang Haichao
Published: March 2024

The pathogenic mechanisms of bacterial infections and resultant sepsis are partly attributed to dysregulated inflammatory responses sustained by some late-acting mediators including the procathepsin-L (pCTS-L). It was entirely unknown whether any compounds of the U.S. Drug Collection could suppress pCTS-L-induced inflammation, and pharmacologically be exploited into possible therapies. Here, we demonstrated that a macrophage cell-based screening of a U.S. Drug Collection of 1360 compounds resulted in the identification of progesterone (PRO) as an inhibitor of pCTS-L-mediated production of several chemokines [e.g., Epithelial Neutrophil-Activating Peptide (ENA-78), Monocyte Chemoattractant Protein-1 (MCP-1) or MCP-3] and cytokines [e.g., Interleukin-10 (IL-10) or Tumor Necrosis Factor (TNF)] in primary human peripheral blood mononuclear cells (PBMCs). In vivo, these PRO-entrapping 2,6-dimethal-β-cyclodextrin (DM-β-CD) nanoparticles (containing 1.35 mg/kg PRO and 14.65 mg/kg DM-β-CD) significantly increased animal survival in both male (from 30% to 70%, n = 20, P = 0.041) and female (from 50% to 80%, n = 30, P = 0.026) mice even when they were initially administered at 24 h post the onset of sepsis. This protective effect was associated with a reduction of sepsis-triggered accumulation of three surrogate biomarkers [e.g., Granulocyte Colony Stimulating Factor (G-CSF) by 40%; Macrophage Inflammatory Protein-2 (MIP-2) by 45%; and Soluble Tumor Necrosis Factor Receptor I (sTNFRI) by 80%]. Surface Plasmon Resonance (SPR) analysis revealed a strong interaction between PRO and pCTS-L (KD = 78.2 ± 33.7 nM), which was paralleled with a positive correlation between serum PRO concentration and serum pCTS-L level (ρ = 0.56, P = 0.0009) or disease severity (Sequential Organ Failure Assessment, SOFA; ρ = 0.64, P = 0.0001) score in septic patients. Our observations support a promising opportunity to explore DM-β-CD nanoparticles entrapping lipophilic drugs as possible therapies for clinical sepsis.
Collapsing glomerulopathy is likely a major contributing factor for worse allograft survival in patients receiving kidney transplants from black donors
Authors: DiFranza Lanny T. , Daniel Emily , Serban Geo , Thomas Steven M. , Santoriello Dominick , Ratner Lloyd E. , D’Agati Vivette D. , Vasilescu Elena-Rodica , Husain Syed Ali , Batal Ibrahim
Published: March 2024

Although a few registry-based studies have shown associations between receiving kidney allografts from Black donors and shorter allograft survival, detailed, large, single-center studies accounting for common confounding factors are lacking. Furthermore, pathologic alterations underlying this potential disparity have not been systematically studied. We performed a retrospective clinical-pathological study of kidney transplant recipients who received kidney allografts from either Black (n = 407) or White (n = 1,494) donors at Columbia University Irving Medical Center from 2005 to 2018, with median follow-up of 4.5 years post-transplantation. Black donor race was independently associated with allograft failure (adjusted HR = 1.34, p = 0.02) and recipients of kidney allografts from Black donors had a higher incidence of collapsing glomerulopathy [7.4% vs. 1.9%, OR = 4.17, p < 0.001]. When causes of allograft failure were examined, only allograft failure following development of collapsing glomerulopathy was more frequent in recipients of allografts from Black donors [15% vs. 5%, OR = 3.16, p = 0.004]. Notably, when patients who developed collapsing glomerulopathy were excluded from analysis, receiving kidney allografts from Black donors was not independently associated with allograft failure (adjusted HR = 1.24, p = 0.10). These findings revealed that, compared with recipients of kidney allografts from White donors, recipients of kidneys from Black donors have modestly shorter allograft survival and a higher probability of developing collapsing glomerulopathy, which negatively impacts allograft outcome. Identification of collapsing glomerulopathy risk factors may help decrease this complication and improve allograft survival, which optimally may reduce racial disparities post-transplantation.
Long-term saline water irrigation affected soil carbon and nitrogen cycling functional profiles in the cotton field
Authors: Zhou Shuang , Wang Guangshuai , Han Qisheng , Zhang Junpeng , Dang Hongkai , Ning Huifeng , Gao Yang , Sun Jingsheng
Published: March 2024

Saline water irrigation (SWI) plays an important role in alleviating water resource shortages. At the same time, the salt input of irrigation water affects soil microorganisms which participate in various ecological processes of terrestrial ecosystems. However, the responses of soil microbial functional potential to long-term SWI remains unclear. Therefore, Metagenomics method was utilized in cotton fields under long-term SWI to reveal the microbial functional profiles associated with soil carbon and nitrogen cycles. Results indicated that SWI impacted the microbial functional profiles of soil carbon and nitrogen cycles in the cotton fields significantly. Especially, irrigation water salinity inhibited the relative abundances of sacC and vanB, which are soil carbon degradation genes. SWI also affected the functional gene abundance of nitrogen degradation, dissimilatory nitrate reduction, and nitrification. Moreover, SWI significantly increased the abundance of Candidatus_Cloacimonetes in both carbon and nitrogen cycles. In the discussion, we used person analysis found that soil salinity, pH, and ammonium nitrogen were important factors affecting the abundance of functional genes and microbial taxa. Overall, this study indicated that long-term SWI significantly influenced specific microbial functional genes and taxa abundance, which may lead to predictable outcomes for soil carbon and nitrogen cycling, and is of great importance in exploring the impact of SWI on soil environments.
Research reviews and prospects of gut microbiota in liver cirrhosis: a bibliometric analysis (2001–2023)
Authors: Zhu Xiaofei , Zhou Ziyuan , Pan Xiaxia
Published: March 2024

Introduction

The gut-liver axis has emerged as a focal point in chronic liver disorders, prompting more research into the role of the gut microbiota in liver cirrhosis. In individuals with liver cirrhosis, changes in the structure and function of the gut microbiota are closely tied to clinical prognosis. However, there is a scarcity of bibliometric evaluations conducted in this particular field.

Methods

This study is aiming to conduct a complete analysis of the knowledge structure and centers pertaining to gut microbiota in liver cirrhosis using bibliometric methods. Publications on gut microbiota and liver cirrhosis from 2001 to 2023 are sourced from the Web of Science Core Collection. For the bibliometric analysis, we employ VOSviewer, CiteSpace, and the R package “bibliometrix”.

Results

Our study encompasses a comprehensive collection of 3109 articles originating from 96 countries, with notable contributions from leading nations such as the United States and China. The quantity of publications concerning the gut microbiota of liver cirrhosis rises annually. The University of California San Diego, Virginia Commonwealth University, Zhejiang University are the primary research institutions. World Journal of Gastroenterology publishes the most papers in this field, while hepatology is the most frequently co-cited journal. These publications come from a total of 15,965 authors, and the most prolific authors are Bajaj Jasmohan S., Schnabl Bernd and Gillevet Patrick M., while the most co-cited authors are Bajaj Jasmohan S., Younossi Zobair M., and Reiner Wiest. In addition, “dysbiosis”, “gut microbiota”, “intestinal barrier”, “fecal microbiota transplantation”, and “complement-system” are the primary keywords of research trends in recent years.

Discussion

This study offering a comprehensive insight into the research dynamics surrounding gut microbiota in patients with liver cirrhosis. It delineates the current research frontiers and hotspots, serving as a valuable guide for scholars.
SARS-CoV-2 mutant spectra as variant of concern nurseries: endless variation?
Authors: Martínez-González Brenda , Soria María Eugenia , Mínguez Pablo , Lorenzo-Redondo Ramón , Salar-Vidal Llanos , López-García Alberto , Esteban-Muñoz Mario , Durán-Pastor Antoni , Somovilla Pilar , García-Crespo Carlos , de Ávila Ana Isabel , Gómez Jordi , Esteban Jaime , Fernández-Roblas Ricardo , Gadea Ignacio , Domingo Esteban , Perales Celia
Published: March 2024

Introduction

SARS-CoV-2 isolates of a given clade may contain low frequency genomes that encode amino acids or deletions which are typical of a different clade.

Methods

Here we use high resolution ultra-deep sequencing to analyze SARS-CoV-2 mutant spectra.

Results

In 6 out of 11 SARS-CoV-2 isolates from COVID-19 patients, the mutant spectrum of the spike (S)-coding region included two or more amino acids or deletions, that correspond to discordant viral clades. A similar observation is reported for laboratory populations of SARS-CoV-2 USA-WA1/2020, following a cell culture infection in the presence of remdesivir, ribavirin or their combinations. Moreover, some of the clade-discordant genome residues are found in the same haplotype within an amplicon.

Discussion

We evaluate possible interpretations of these findings, and reviewed precedents for rapid selection of genomes with multiple mutations in RNA viruses. These considerations suggest that intra-host evolution may be sufficient to generate minority sequences which are closely related to sequences typical of other clades. The results provide a model for the origin of variants of concern during epidemic spread─in particular Omicron lineages─that does not require prolonged infection, involvement of immunocompromised individuals, or participation of intermediate, non-human hosts.
The roles of SARP family regulators involved in secondary metabolism in Streptomyces
Authors: Yan Yusi , Xia Haiyang
Published: March 2024

Streptomyces species are best known for their ability to produce abundant secondary metabolites with versatile bioactivities and industrial importance. These metabolites are usually biosynthesized through metabolic pathways encoded by cluster-situated genes. These genes are also known as biosynthetic gene clusters (BGCs) of secondary metabolites. The expression of BGCs is intricately controlled by pyramidal transcriptional regulatory cascades, which include various regulators. Streptomyces antibiotic regulatory proteins (SARPs), a genus-specific family of regulators, are widely distributed and play important roles in regulating the biosynthesis of secondary metabolites in Streptomyces. Over the past decade, the biological functions of SARPs have been extensively investigated. Here, we summarized the recent advances in characterizing the roles of SARPs involved in Streptomyces secondary metabolism from the following three aspects. First, the classification and domain organization of SARPs were summarized according to their size variation. Second, we presented a detailed description of the regulatory mechanisms and modes of action of SARPs involved in secondary metabolism. Finally, the biotechnological application of SARPs was illustrated by improving the production of target secondary metabolites and discovering novel bioactive natural products. This review will help researchers to comprehensively understand the roles of SARPs in secondary metabolite biosynthesis in Streptomyces, which will contribute to building a solid foundation for their future application in synthetic biology.
Association between dietary inflammatory index and cognitive impairment among American elderly: a cross-sectional study
Authors: Zhang Yu , Peng Yuanyuan , Deng Wei , Xiang Qian , Zhang Wang , Liu Maohang
Published: March 2024

Background

It has been shown that inflammation may be associated with cognitive impairment (CI). Diet modulates inflammation. However, there is currently a scarcity of epidemiological studies exploring the connection between the inflammatory potential of diet and CI. The objective was to investigate the correlation between the dietary inflammatory index (DII) and cognitive impairment in older adults in the United States.

Methods

The present investigation utilized a cross-sectional dataset obtained from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. Dietary intake data was used to calculate DII scores, which were then used to categorize participants into quartiles. Participants’ cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Individuals who scored in the lowest quartile on any of these tests were classified as exhibiting low cognitive performance. The association between DII and cognitive impairment was investigated by multivariate logistic regression, smooth curve fitting, and subgroup analysis.

Results

A total of 947 older adults were enrolled in the study. Following the adjustment of confounding variables, DII scores exhibited a significant and positive correlation with low cognitive performance, as measured by AFT (OR 1.15, 95% CI 1.02–1.28, p = 0.02) and the DSST (OR 1.38, 95% CI 1.13–1.68, p = 0.004). Compared with the lowest quartile of DII, the highest weighted odds ratio of cognitive impairment based on AFT was observed in the fourth quartile group (OR 1.89, 95% CI 1.05–3.38, p = 0.03). Similarly, a comparable pattern was evident in DSST (OR 4.30, 95% CI 1.85–9.98, p = 0.003). Additionally, the smooth curve fitting results showed a nonlinear relationship between DII and cognitive decline evaluated by DSST (p for nonlinearity = 0.016). No interaction effects between cognitive impairment and age or gender were observed in relation to all cognitive test scores.

Conclusion

This research reveals a positive link between diet with higher inflammatory potential and cognitive decline among elderly individuals in America. However, additional studies on dietary interventions are necessary to explore the cause-and-effect relationship.
Suppression head impulse test in children—experiences in a tertiary paediatric vestibular centre
Authors: Dasgupta Soumit , Crunkhorn Rosa , Wong John , McMahon Annie , Ratnayake Sudhira , Manzari Leonardo
Published: March 2024

The suppression head impulse paradigm (SHIMP) involves suppression of the vestibulo-ocular reflex (VOR) and anticompensatory saccades generated thereof. SHIMP is gaining importance to understand vestibular compensation with its different parameters (VOR gain/peak saccadic velocity PSV/latency of saccades). SHIMP studies are emerging in adults, but pediatric studies have hardly been performed. This study is a retrospective case note audit over a period of 2 months in a tertiary pediatric vestibular center in the United Kingdom to investigate whether SHIMP is safe/robust to be used in children conforming to existing standards/norms in normal children and whether it yields any meaningful inferences in pediatric vestibular hypofunction. This is the largest pediatric SHIMP study to date. A total of 44 referred children (6–18 years, female children>male children) with a range of complaints from dizziness, imbalance, motor incoordination, postural instability, and hearing loss were included, and their SHIMP parameters were measured. All children underwent comprehensive functional/objective audiovestibular assessments. Two groups were defined—Group A with normal vestibular function and Group B with abnormal vestibular function. The normal population showed an average SHIMP VOR gain of 0.98+/−0.08 and latency of overt saccades at 215.68+/–46.16 milliseconds agreeing with published evidence. The PSV of overt saccades was 315.39+/−56.30/s, and there was a gain asymmetry of 7.42+/−4.68 between the sides. Statistically significant differences with moderate/large effect sizes were observed between the groups in terms of VOR gain and PSV but not in saccade latencies. Covert saccades were rare in SHIMP, while overt saccades were observed in 100% of children. VOR gain difference between the head impulse paradigm (HIMP) and the SHIMP was significant as well. We observed statistically significant differences in side asymmetry of VOR gain between the groups. Furthermore, we identified a group of children with cerebellar lesions where overt saccades in SHIMP were rather low in number. Further research is recommended to investigate pediatric PSV, asymmetry, and inability to generate overt saccades that may suggest useful means to assess compensation and central function. We conclude that SHIMP yields valuable information and is a safe, easy to perform, and a reliable test that should be used in children to supplement HIMP.
Combining detrended cross-correlation analysis with Riemannian geometry-based classification for improved brain-computer interface performance
Authors: Racz Frigyes Samuel , Kumar Satyam , Kaposzta Zalan , Alawieh Hussein , Liu Deland Hu , Liu Ruofan , Czoch Akos , Mukli Peter , Millán José del R.
Published: March 2024

Riemannian geometry-based classification (RGBC) gained popularity in the field of brain-computer interfaces (BCIs) lately, due to its ability to deal with non-stationarities arising in electroencephalography (EEG) data. Domain adaptation, however, is most often performed on sample covariance matrices (SCMs) obtained from EEG data, and thus might not fully account for components affecting covariance estimation itself, such as regional trends. Detrended cross-correlation analysis (DCCA) can be utilized to estimate the covariance structure of such signals, yet it is computationally expensive in its original form. A recently proposed online implementation of DCCA, however, allows for its fast computation and thus makes it possible to employ DCCA in real-time applications. In this study we propose to replace the SCM with the DCCA matrix as input to RGBC and assess its effect on offline and online BCI performance. First we evaluated the proposed decoding pipeline offline on previously recorded EEG data from 18 individuals performing left and right hand motor imagery (MI), and benchmarked it against vanilla RGBC and popular MI-detection approaches. Subsequently, we recruited eight participants (with previous BCI experience) who operated an MI-based BCI (MI-BCI) online using the DCCA-enhanced Riemannian decoder. Finally, we tested the proposed method on a public, multi-class MI-BCI dataset. During offline evaluations the DCCA-based decoder consistently and significantly outperformed the other approaches. Online evaluation confirmed that the DCCA matrix could be computed in real-time even for 22-channel EEG, as well as subjects could control the MI-BCI with high command delivery (normalized Cohen's κ: 0.7409 ± 0.1515) and sample-wise MI detection (normalized Cohen's κ: 0.5200 ± 0.1610). Post-hoc analysis indicated characteristic connectivity patterns under both MI conditions, with stronger connectivity in the hemisphere contralateral to the MI task. Additionally, fractal scaling exponent of neural activity was found increased in the contralateral compared to the ipsilateral motor cortices (C4 and C3 for left and right MI, respectively) in both classes. Combining DCCA with Riemannian geometry-based decoding yields a robust and effective decoder, that not only improves upon the SCM-based approach but can also provide relevant information on the neurophysiological processes behind MI.
How stroke-related dysphagia relates to quality of life: the mediating role of nutritional status and psychological disorders, and the moderating effect of enteral nutrition mode
Authors: Zeng Hongji , Zeng Xi , Xiong Nana , Wang Lichun , Yang Ying , Wang Liugen , Li Heping , Zhao Weijia
Published: March 2024

Background

Although stroke-related dysphagia has been shown to influence quality of life (QOL), the underlying mechanisms have yet to be uncovered.

Objective

This study aims to investigate the mediating role of nutritional status and psychological disorders in the relationship between stroke-related dysphagia and QOL in stroke patients and explore the moderating effect of enteral nutrition mode.

Methods

In 2022, A questionnaire survey using stratified random sampling was conducted on 5,322 stroke patients with dysphagia, including Functional Oral Intake Scale (FOIS), Swallowing Quality of Life Questionnaire, Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) to assess dysphagia, QOL and psychological disorders, respectively, for each participant. Records of serum albumin, Hemoglobin, Total serum protein, serum prealbumin and Body mass index were enrolled to assess nutritional status.

Results

FOIS demonstrated a significant positive predictive effect on QOL. Nutritional status and psychological disorders (PHQ-9 and GAD-7) mediated the relationship between FOIS and QOL. Nutritional status-psychological disorders showed a chain mediation effect in the relationship between FOIS and QOL. The moderating effect of enteral nutrition mode was observed.

Conclusion

The mediating role of nutritional status and psychological disorders with moderating effect of enteral nutrition mode in the relationship between dysphagia and QOL in stroke patients was found.
Exploring the interactions between metabolic dysfunction-associated fatty liver disease and micronutrients: from molecular mechanisms to clinical applications
Authors: Liu Yuan , Qin Xiang , Chen Tianzhu , Chen Mengyao , Wu Liyan , He Beihui
Published: March 2024

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) has emerged as a significant global health concern, representing a major cause of liver disease worldwide. This condition spans a spectrum of histopathologic stages, beginning with simple fatty liver (MAFL), characterized by over 5% fat accumulation, and advancing to metabolic (dysfunction)-associated steatohepatitis, potentially leading to hepatocellular carcinoma. Despite extensive research, there remains a substantial gap in effective therapeutic interventions. This condition’s progression is closely tied to micronutrient levels, crucial for biological functions like antioxidant activities and immune efficiency. The levels of these micronutrients exhibit considerable variability among individuals with MAFLD. Moreover, the extent of deficiency in these nutrients can vary significantly throughout the different stages of MAFLD, with disease progression potentially exacerbating these deficiencies. This review focuses on the role of micronutrients, particularly vitamins A, D, E, and minerals like iron, copper, selenium, and zinc, in MAFLD’s pathophysiology. It highlights how alterations in the homeostasis of these micronutrients are intricately linked to the pathophysiological processes of MAFLD. Concurrently, this review endeavors to harness the existing evidence to propose novel therapeutic strategies targeting these vitamins and minerals in MAFLD management and offers new insights into disease mechanisms and treatment opportunities in MAFLD.
Prognostic nomogram in patients with right-sided colon cancer after colectomy: a surveillance, epidemiology, and end results–based study
Authors: Qin Tiantian , Yu Chenyue , Dong Yuying , Zheng Mingming , Wang Xiaoxuan , Shen Xuning
Published: March 2024

Objective

This study aimed to develop and validate a nomogram for predicting overall survival (OS) in patients undergoing surgery for right-sided colon cancer (RCC).

Methods

We collected 25,203 patients with RCC from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided them into 7:3 training and internal validation set. Utilizing the Cox proportional hazards regression model, we constructed a nomogram based on prognostic risk factors. Furthermore, for external validation, we retrospectively followed up with 228 patients from Jiaxing First Hospital and assessed and calibrated the nomogram using the C-index and calibration curves.

Results

After identifying independent prognostic factors through univariate and multivariate analyses, a nomogram was developed. The c-index values of this nomogram differed as follows: 0.851 (95% CI: 0.845-0.857) in the training set, 0.860 (95% CI: 0.850-0.870) in the internal validation set, and 0.834 (95% CI: 0.780-0.888) in the external validation set, indicating the model’s strong discriminative ability. Calibration curves for 1-year, 3-year, and 5-year overall survival (OS) probabilities exhibited a high level of consistency between predicted and actual survival rates. Furthermore, Decision Curve Analysis (DCA) demonstrated that the new model consistently outperformed the TNM staging system in terms of net benefit.

Conclusion

We developed and validated a survival prediction model for patients with RCC. This novel nomogram outperforms the traditional TNM staging system and can guide clinical practitioners in making optimal clinical decisions.
Case report: An atypical case of uterine adenosarcoma with extensive bizarre stromal cells and amplification of MDM2
Authors: Xiao Xiaoling , He Ying
Published: March 2024

Polypoid lesions in the uterus are very common. There are a lot of benign lesions and malignant tumor should be considered. Adenosarcoma, one of the differential diagnoses, is a rare mixed epithelial and mesenchymal tumor consisting of benign epithelial components and sarcoma stroma. Here, we present a case of atypical adenosarcoma that has never been reported. This tumor was composed of benign endometrial epithelium and hyperplastic stroma with extensive bizarre stromal cells. But the cleft-like spaces and papillary stomal fronds which were the typical histological images of adenosarcoma were absent. These stomal cells, including bizarre cells, were positive for vimentin, CD10, ER, PR, cyclin D1 and P16 but were immunonegative for caldesmon. Furthermore, this tumor harbored amplification of MDM2, as revealed by fluorescence in situ hybridization testing (FISH) and next-generation DNA sequencing (NGS).
DDX58 deficiency leads to triple negative breast cancer chemotherapy resistance by inhibiting Type I IFN-mediated signalling apoptosis
Authors: Cao Shiyu , Long Xinyi , Xiao Lin , Zhang Peichuan , Shen Mengjia , Chen Fei , Bao Chunjuan , Zhong Xiaorong , Luo Ting , Ye Feng
Published: March 2024

Introduction

Triple-negative breast cancer (TNBC) is characterized by its aggressive nature and absence of specific therapeutic targets, necessitating the reliance on chemotherapy as the primary treatment modality. However, the drug resistance poses a significant challenge in the management of TNBC. In this study, we investigated the role of DDX58 (DExD/H-box helicase 58), also known as RIG-I, in TNBC chemoresistance.

Methods

The relationship between DDX58 expression and breast cancer prognosis was investigated by online clinical databases and confirmed by immunohistochemistry analysis. DDX58 was knockout by CRISPR-Cas9 system (DDX58-KO), knockdown by DDX58-siRNA (DDX58-KD), and stably over expressed (DDX58-OE) by lentivirus. Western blotting, immunofluorescence and qPCR were used for related molecules detection. Apoptosis was analyzed through flow cytometry (Annexin V/7AAD apoptosis assay) and Caspase 3/7 activity assay.

Results

Patients with lower expression of DDX58 led to lower rate of pathological complete response (pCR) and worse prognosis by online databases and hospital clinical data. DDX58-KD cells showed multiple chemo-drugs resistance (paclitaxel, doxorubicin, 5-fluorouracil) in TNBC cell lines. Similarly, DDX58-KO cells also showed multiple chemo-drugs resistance in a dosage-dependent manner. In the CDX model, tumours in the DDX58-KO group had a 25% reduction in the tumour growth inhibition rate (IR) compared to wild-type (WT) group after doxorubicin (Dox) treatment. The depletion of DDX58 inhibited proliferation and promoted the migration and invasion in MDA-MB-231 cells. The findings of our research indicated that DDX58-KO cells exhibit a reduction in Dox-induced apoptosis both in vivo and in vitro. Mechanistically, Dox treatment leads to a significant increase in the expression of double-stranded RNAs (dsRNAs) and activates the DDX58-Type I interferon (IFN) signaling pathway, ultimately promoting apoptosis in TNBC cells.

Discussion

In the process of TNBC chemotherapy, the deficiency of DDX58 can inhibit Dox-induced apoptosis, revealing a new pathway of chemotherapy resistance, and providing a possibility for developing personalized treatment strategies based on DDX58 expression levels.
Sarcopenia accompanied by systemic inflammation can predict clinical outcomes in patients with head and neck cancer undergoing curative therapy
Authors: Kasahara Ken , Kono Takeyuki , Sato Yoichiro , Ueno Masafumi , So Hirotaka , Fuse Yoshimitsu , Shinden Seiichi , Ozawa Hiroyuki
Published: March 2024

Objectives

Evaluation of sarcopenia accompanied by systemic inflammation status is a more beneficial prognostic marker than sarcopenia alone in various cancers. However, few studies have focused on this combination in patients with head and neck squamous cell cancer (HNSCC). In this study, we investigated how the combination of sarcopenia and systemic inflammation could affect survival in patients with HNSCC. Moreover, we explored which systemic inflammation markers could be better prognostic indicators when accompanied by sarcopenia.

Materials and methods

We retrospectively reviewed the medical records of patients with HNSCC treated between 2012 and 2016. Sarcopenia was defined by the skeletal muscle area measured on a computed tomography image slice at the level of the third cervical vertebra. The neutrophil/lymphocyte, platelet/lymphocyte, and lymphocyte/monocyte ratios (NLR, PLR, and LMR, respectively) were used as systemic inflammation markers that were combined with sarcopenia to evaluate prognosis.

Results

A total of 100 patients were enrolled, and 71 patients were considered sarcopenia. Patients with sarcopenia had significantly lower LMR and higher NLR and PLR. They also showed worse overall survival (OS) and progression-free survival (PFS). The comparative assessment of multiple combination patterns of sarcopenia and systemic inflammation indices proved that sarcopenia plus LMR considered as most reliable indicator for prognosis in HNSCC patients. Sarcopenia plus low LMR was a significantly poor prognostic factor both for OS and PFS with greater HR values than sarcopenia alone.

Conclusions

The combination of sarcopenia and LMR was considered the most sensitive prognostic factor in patients with HNSCC, suggesting it might be beneficial for identifying poor outcome risks.
Laparoscopic pyeloplasty for newborns with severe hydronephrosis
Authors: Shi Tong , Lao Weihua , Ouyang Keyu , Chen Yueqing , Zhang Yikui , Luo Jiayao , Chen Shuhan
Published: March 2024

Aim

We aimed to investigate the short-term efficacy and safety of laparoscopic pyeloplasty for treating newborns with severe hydronephrosis due to ureteropelvic junction obstruction (UPJO).

Methods

A retrospective analysis was performed on 16 newborn patients with severe neonatal hydronephrosis who underwent laparoscopic pyeloplasty at our hospital from January 2021 to November 2022. All patients were regularly followed up. Laparoscopic pyeloplasty with double J stent placement was performed after the presence of severe hydronephrosis was confirmed.

Results

Among the 16 pediatric patients (13 males, 3 females), the left side was affected in 13 cases and the right side in 3. The average age at surgery was 9.50 (8.50–12.00) days, with an average weight of 3.30 ± 0.95 kg. Laparoscopic pyeloplasty was performed in all cases without the need for open conversion. The mean surgery duration was 292.06 ± 73.60 min, with minimal blood loss (2.50, 2.00–5.00 ml). Postoperative hospital stays averaged 13.44 ± 4.70 days. No anastomotic leakage occurred, and follow-ups at 1, 3, 6, and 12 months showed no stent displacement, except for one case where the stent was removed at 1 month, and the others at 3 months. There were no cases of worsened hydronephrosis, except for one with renal atrophy at the 6-month follow-up. Changes in renal pelvis anteroposterior diameter exhibited a time effect (F = 49.281, P < 0.001), with significant differences at 1, 3, 6, and 12 months postoperatively compared to preoperative values (P < 0.05). Notably, differences were observed between 6 and 3 months, as well as between 12 and 3 months postoperatively (P < 0.05). Similarly, renal parenchymal thickness changes showed a time effect Pediatric urology, Guangdong Women and Children Hospital, Guangzhou, China (F = 49.281, P < 0.001), with significant differences at 1, 3, 6, and 12 months postoperatively compared to preoperative values (P < 0.05). Significant differences were also noted between 6 and 1 month, as well as between 12 and 1 month postoperatively (P < 0.05). There was one case of urinary tract infection after surgery, and no case of recurrence was observed.

Conclusion

Severe neonatal hydronephrosis must be treated promptly. Laparoscopic pyeloplasty is a safe and feasible treatment with minimal complications for newborn patients with severe hydronephrosis due to UPJO.
Model-based exploration of the rationality of off-label use of cetirizine in Chinese pediatric patients: a prospective cohort study
Authors: Liu Wei , Tan Zhiyuan , Yang Ping , Yu Zhiheng , Yao Xueting , Zhou Pengxiang , Liu Ling , Zhou Wei
Published: March 2024

Aims: Cetirizine is frequently administered at an increased dosage in clinical practice and recommended by several guidelines. Nonetheless, the pharmacokinetic (PK) profile and real-world safety data remain insufficient in the Chinese pediatric population. The objective of the current study is to develop a population pharmacokinetic (PPK) model for cetirizine in Chinese pediatric patients and to investigate the rationale behind its off-label usage.

Methods: A prospective cohort study was conducted, enrolling children who had been diagnosed with allergic diseases and prescribed cetirizine. The outcomes were safety and pharmacokinetic (PK) parameters. Cetirizine concentrations were measured using a pre-established analytical method. Subsequently, a PK model was developed, followed by model evaluation and simulation. The developed PK model was employed to investigate the drug exposure differences across various age groups and to simulate scenarios of potential overdose.

Results: Sixty-three children were enrolled, and 24 of them received a cetirizine dose exceeding the recommended dosage. A PPK model, based on published literature, served as the basis of our analysis, with adjustment made to estimate certain parameters. The final model evaluation and validation indicated accurate predictive performance and robust parameter estimation. Simulations conducted for the label-dose among age 1–12 indicated median maximum concentration at steady state (Cmax,ss) of 7 year old children could be the highest. The model was also used to predict the off-label dose scenarios and overdose patient to support the clinical decision. There were no adverse drug reactions in either group.

Conclusion: This study provides evidence-based and model-based exploration for optimizing cetirizine usage in Chinese pediatric patients. The cetirizine PPK model showed accurate predictive performance and could be utilized to simulate individual patient exposure in real-world clinical scenarios.
Sedum aizoon L.: a review of its history, traditional uses, nutritional value, botany, phytochemistry, pharmacology, toxicology, and quality control
Authors: Wang Bai-Ling , Ge Zhen-Kai , Qiu Jing-Ran , Luan Si-Qi , Hao Xin-Cai , Zhao Yong-Heng
Published: March 2024

In China, Russia, Mongolia, Japan, North Korea, and Mexico, Sedum aizoon L. (S. aizoon) is used as an edible plant. Up to now, over 234 metabolites, including phenolic acids, flavonoids, triterpenes, phytosterols, and alkaloids, among others, have been identified. In addition to its antioxidant, anti-inflammatory, anti-fatigue, antimicrobial, anti-cancer, and hemostatic activities, S. aizoon is used for the treatment of cardiovascular disease. This paper provides an overview of the history, botany, nutritional value, traditional use, phytochemistry, pharmacology, toxicology, and quality control of S. aizoon.
Identification of key genes increasing susceptibility to atrial fibrillation in nonalcoholic fatty liver disease and the potential mechanisms: mitochondrial dysfunction and systemic inflammation
Authors: Zhong Baiyin , Xie Zhonghui , Zhang Jianhong , Xie Xing , Xie Yuankang , Xie Binhui , Wang Jing , Liu Chuanbin
Published: March 2024

Background: Non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) are major health burdens, with emerging evidence suggesting NAFLD as a significant risk factor for AF, but the mechanism is remain unclear.

Methods: In this study, we analyzed gene expression data from NAFLD (GSE89632) and AF (GSE75092) datasets from the Gene Expression Omnibus. We identified co-upregulated and co-downregulated genes between NAFLD and AF, assessed diagnostic potential of specific genes, conducted immune infiltration analysis, and performed molecular docking studies with sodium glucose co-transporter 2 inhibitors (SGLT2i).

Results: We identified eight co-upregulated and 31 co-downregulated genes between NAFLD and AF. Genes such as AMOT, PDE11A, TYMS, TMEM98, and PTGS2 demonstrated substantial diagnostic potential for identifying NAFLD patients at risk of AF. Immune infiltration analysis discovered an elevated presence of CD8 T cells, γδ T cells, and M2 macrophages in NAFLD livers, linking systemic inflammation to NAFLD and AF. Additionally, studies have shown that a connection between mitochondrial dysfunction and several hub genes like DGAT1, TYMS, and PTGS2, suggesting that mitochondrial disturbances may underpin the systemic inflammation in NAFLD, which possibly exacerbating AF. Molecular docking studies indicated that empagliflozin's binding affinity with key genes such as DGAT1, TYMS, and PTGS2 presents a novel therapeutic avenue for NAFLD-associated AF.

Conclusion: Our study firstly discovered that AMOT, PDE11A, TYMS, TMEM98, and PTGS2 are associated with NAFLD-related AF and hold strong diagnostic values. Our study also indicates that mitochondrial dysfunction and systemic inflammation may be potential mechanisms bridging NAFLD and AF. Additionally, we identified empagliflozin as a potentially effective therapeutic agent for NAFLD-related AF at the molecular structure level. These novel insights contribute to the further understanding, diagnosis, and intervention of NAFLD-related AF.