bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-omics analysis revealed the role of CYP1A2 in the induction of mechanical allodynia in type 1 diabetes
Authors: Chen Hongjin , Liao Chenlong , Yang Xiaosheng , Zhou Han , Wu Yiwei , Sun Qiuyang , Li Shuo , Zhang Wenchuan
Published: March 2023

Background: Mechanical allodynia (MA) is one of the leading clinical symptoms of painful diabetic peripheral neuropathy (PDPN), which is a primary reason for non-traumatic amputations, foot ulceration, and gait abnormalities in patients with diabetes. However, the pathogenic mechanisms of MA have not yet been fully elucidated, and there is no effective treatment. This study aims to study the potential pathogenetic mechanisms of MA and to provide targets for the therapy of MA.

Methods: A single intraperitoneal injection of streptozotocin induced type 1 diabetes in rat models. Subsequently, rats were divided into the control group, the diabetic group without MA, and the diabetic group with MA based on weekly behavioral assays. The differentially expressed lipids in the sciatic nerve of each group were detected using untargeted lipidomics, and the differentially expressed genes in the sciatic nerve of each group were detected by transcriptomics. The pathogenesis of MA was predicted using integrated analysis and validated by immunofluorescence staining and transmission electron microscopy.

Results: Untargeted lipidomics revealed the accumulation of a more severe lipid in MA rats. Transcriptomics results suggested that differentially expressed genes in MA rats were primarily related to lipid droplets and myelin sheath. Integrated analysis results indicated that the downregulation of Cytochrome P450 1A2 (CYP1A2) expression was closely linked to lipid metabolism disorders. Immunofluorescence staining demonstrated that down-regulation of CYP1A2 expression occurred in MA rats. Transmission electron microscopy results showed that more severe lipid droplet accumulation and myelin sheath degeneration occurred in MA rats.

Conclusion: Our findings imply that the downregulation of CYP1A2 expression leads to disorders of lipid metabolism and further leads to lipid droplet accumulation and myelin sheath degeneration, which might ultimately lead to the development of MA. Therefore, our study contributes to promoting the understanding of the molecular mechanisms of MA and providing potential targets for the clinical treatment of MA.
Identification of berberine as a potential therapeutic strategy for kidney clear cell carcinoma and COVID-19 based on analysis of large-scale datasets
Authors: Zheng Zhihua , Li Xiushen , Nie Kechao , Wang Xiaoyu , Liang Wencong , Yang Fuxia , Zheng Kairi , Zheng Yihou
Published: March 2023

Background

Regarding the global coronavirus disease 2019 (COVID)-19 pandemic, kidney clear cell carcinoma (KIRC) has acquired a higher infection probability and may induce fatal complications and death following COVID-19 infection. However, effective treatment strategies remain unavailable. Berberine exhibits significant antiviral and antitumour effects. Thus, this study aimed to provide a promising and reliable therapeutic strategy for clinical decision-making by exploring the therapeutic mechanism of berberine against KIRC/COVID-19.

Methods

Based on large-scale data analysis, the target genes, clinical risk, and immune and pharmacological mechanisms of berberine against KIRC/COVID-19 were systematically investigated.

Results

In total, 1,038 and 12,992 differentially expressed genes (DEGs) of COVID-19 and KIRC, respectively, were verified from Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively, and 489 berberine target genes were obtained from official websites. After intersecting, 26 genes were considered potential berberine therapeutic targets for KIRC/COVID-19. Berberine mechanism of action against KIRC/COVID-19 was revealed by protein-protein interaction, gene ontology, and Kyoto Encyclopedia of Genes and Genomes with terms including protein interaction, cell proliferation, viral carcinogenesis, and the PI3K/Akt signalling pathway. In COVID-19 patients, ACOX1, LRRK2, MMP8, SLC1A3, CPT1A, H2AC11, H4C8, and SLC1A3 were closely related to disease severity, and the general survival of KIRC patients was closely related to ACOX1, APP, CPT1A, PLK1, and TYMS. Additionally, the risk signature accurately and sensitively depicted the overall survival and patient survival status for KIRC. Numerous neutrophils were enriched in the immune system of COVID-19 patients, and the lives of KIRC patients were endangered due to significant immune cell infiltration. Molecular docking studies indicated that berberine binds strongly to target proteins.

Conclusion

This study demonstrated berberine as a potential treatment option in pharmacological, immunological, and clinical practice. Moreover, its therapeutic effects may provide potential and reliable treatment options for patients with KIRC/COVID-19.
Optimal LC-MS metabolomic profiling reveals emergent changes to monocyte metabolism in response to lipopolysaccharide
Authors: Leacy Emma , Batten Isabella , Sanelli Laetitia , McElheron Matthew , Brady Gareth , Little Mark A. , Khouri Hania
Published: March 2023

Introduction

Immunometabolism examines the links between immune cell function and metabolism. Dysregulation of immune cell metabolism is now an established feature of innate immune cell activation. Advances in liquid chromatography mass spectrometry (LC-MS) technologies have allowed discovery of unique insights into cellular metabolomics. Here we have studied and compared different sample preparation techniques and data normalisation methods described in the literature when applied to metabolomic profiling of human monocytes.

Methods

Primary monocytes stimulated with lipopolysaccharide (LPS) for four hours was used as a study model. Monocytes (n=24) were freshly isolated from whole blood and stimulated for four hours with lipopolysaccharide (LPS). A methanol-based extraction protocol was developed and metabolomic profiling carried out using a Hydrophilic Interaction Liquid Chromatography (HILIC) LC-MS method. Data analysis pipelines used both targeted and untargeted approaches, and over 40 different data normalisation techniques to account for technical and biological variation were examined. Cytokine levels in supernatants were measured by ELISA.

Results

This method provided broad coverage of the monocyte metabolome. The most efficient and consistent normalisation method was measurement of residual protein in the metabolite fraction, which was further validated and optimised using a commercial kit. Alterations to the monocyte metabolome in response to LPS can be detected as early as four hours post stimulation. Broad and profound changes in monocyte metabolism were seen, in line with increased cytokine production. Elevated levels of amino acids and Krebs cycle metabolites were noted and decreases in aspartate and β-alanine are also reported for the first time. In the untargeted analysis, 154 metabolite entities were significantly altered compared to unstimulated cells. Pathway analysis revealed the most prominent changes occurred to (phospho-) inositol metabolism, glycolysis, and the pentose phosphate pathway.

Discussion

These data report the emergent changes to monocyte metabolism in response to LPS, in line with reports from later time points. A number of these metabolites are reported to alter inflammatory gene expression, which may facilitate the increases in cytokine production. Further validation is needed to confirm the link between metabolic activation and upregulation of inflammatory responses.
Pancreatic cancer: Emerging field of regulatory B-cell-targeted immunotherapies
Authors: Senturk Zeynep Nur , Akdag Isilay , Deniz Bahar , Sayi-Yazgan Ayca
Published: March 2023

Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is characterized by a high mortality rate and poor prognosis. Current treatments for PDAC, are ineffective due to a prominent immunosuppressive PDAC tumor microenvironment (TME). Although B lymphocytes are highly infiltrated into PDAC, the importance of B lymphocytes in tumorigenesis is largely neglected. B cells play a dual role in the PDAC tumor microenvironment, acting as either anti-tumorigenic or pro-tumorigenic depending on where they are localized. Tumor-infiltrating B cells, which reside in ectopic lymph nodes, namely tertiary lymphoid structures (TLS), produce anti-tumor antibodies and present tumor antigens to T cells to contribute to cancer immunosurveillance. Alternatively, regulatory B cells (Bregs), dispersed inside the TME, contribute to the dampening of anti-tumor immune responses by secreting anti-inflammatory cytokines (IL-10 and IL-35), which promote tumor growth and metastasis. Determining the role of Bregs in the PDAC microenvironment is thus becoming increasingly attractive for developing novel immunotherapeutic approaches. In this minireview, we shed light on the emerging role of B cells in PDAC development and progression, with an emphasis on regulatory B cells (Bregs). Furthermore, we discussed the potential link of Bregs to immunotherapies in PDAC. These current findings will help us in understanding the full potential of B cells in immunotherapy.
Firefighters’ exposure to per-and polyfluoroalkyl substances (PFAS) as an occupational hazard: A review
Authors: Mazumder Nur-Us-Shafa , Hossain Md Tanjim , Jahura Fatema Tuj , Girase Arjunsing , Hall Andrew Stephen , Lu Jingtian , Ormond R. Bryan
Published: March 2023

The term “firefighter” and “cancer” have become so intertwined in the past decade that they are now nearly inseparable. Occupational exposure of firefighters to carcinogenic chemicals may increase their risk of developing different types of cancer. PFAS are one of the major classes of carcinogenic chemicals that firefighters are exposed to as occupational hazard. Elevated levels of PFAS have been observed in firefighters’ blood serum in recent studies. Possible sources of occupational exposure to PFAS include turnout gear, aqueous film-forming foam, and air and dust at both the fire scene and fire station. Preliminary discussion on PFAS includes definition, classification, and chemical structure. The review is then followed by identifying the sources of PFAS that firefighters may encounter as an occupational hazard. The structural properties of the PFAS used in identified sources, their degradation, and exposure pathways are reviewed. The elevated level of PFAS in the blood serum and how this might associate with an increased risk of cancer is discussed. Our review shows a significant amount of PFAS on turnout gear and their migration to untreated layers, and how turnout gear itself might be a potential source of PFAS exposure. PFAS from aqueous film-forming foams (AFFF), air, and dust of fire stations have been already established as potential exposure sources. Studies on firefighters’ cancer suggest that firefighters have a higher cancer risk compared to the general population. This review suggests that increased exposure to PFAS as an occupational hazard could be a potential cancer risk for firefighters.
Development and implementation of a continuing medical education program on non-alcoholic fatty liver disease for primary care practitioners in Europe
Authors: Papadakis Sophia , Anastasaki Marilena , Gergianaki Irini , Koek Ger , Mendive Juan , Anastasiou Foteini , Heyens Leen , Garcia-Retortillo Montserrat , Muris Jean , Lionis Christos
Published: March 2023

Background

Primary care has a crucial role to play in the prevention, early detection, referral, and risk factor management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NAFLD/NASH). In 2021, a team of European collaborators developed a continuing medical education (CME) program on NAFLD/NASH that consolidates evidence and clinical best practices tailored to the primary care setting. This article reports on the methodology used to design and develop the CME and the results of a feasibility study.

Methods

An expert advisory group representing both European specialists and general practitioners supported the design of the CME to be implemented in three European settings (Greece, Spain, and Netherlands). The CME features four training modules and problem-based learning using clinical case studies. The CME was tested regarding feasibility and acceptability among a sample of primary care providers (PCPs) in Greece (n = 28) with measurements occurring before, immediately after, and 1 month following the training. Outcome measures included satisfaction with the CME, changes in PCPs’ knowledge, attitudes, confidence, and self-reported clinical practices related to NAFLD/NASH.

Results

The CME is available as an open-access e-learning course on the European Society for Primary Care Gastroenterology education platform1 in English, Greek, Spanish, and Dutch. The feasibility study documented high levels of satisfaction, with 96% of PCPs reporting they were extremely or very satisfied with the overall training. Statistically significant increases in PCPs’ confidence in NAFLD/NASH-related clinical practices were documented between the pre- and post-assessments. At the follow-up, 62% of GPs reported that the CME had changed their clinical practices related to NAFLD/NASH to a great extent.

Conclusion

This CME intervention developed by experts and tailored to PCPs in European settings may serve as an asset for increasing knowledge, confidence, and practice behaviors related to NAFLD/NASH.
The Neolithic site “La Marmotta”: DNA metabarcoding to identify the microbial deterioration of waterlogged archeological wood
Authors: Beccaccioli Marzia , Moricca Claudia , Faino Luigi , Reale Rita , Mineo Mario , Reverberi Massimo
Published: March 2023

Introduction

The evaluation of biological degradation of waterlogged archeological wood is crucial to choose the conservative and protective treatments to be applied to the wooden material. The waterlogged environmental conditions are characterized by oxygen scarcity, only allowing the growth of adapted microbes capable to degrade the organic wooden material, mainly erosion bacteria and soft-rot fungi. In this work, we characterized and evaluated the biodegradation state and the microbial communities of wooden fragments preserved in storage tanks. These were preserved by waterlogging within the Neolithic village “La Marmotta,” currently found under the Bracciano Lake (Lazio, Italy).

Methods

The waterlogged wood samples were first identified taxonomically with an optical microscope, also allowing an evaluation of their preservation state. The microbial community was then evaluated through the sequencing of Internal Transcribed Spacer sequences for fungi and 16S for bacteria with the Oxford Nanopore Technologies (ONT) MinION platform.

Results

The identified microbial community appears to be consistent with the waterlogged samples, as many bacteria attributable to the erosion of wood and ligninolytic fungi have been sequenced.

Discussion

The reported results highlight the first use of targeted metabarcoding by ONT applied to study the biodeterioration of waterlogged archeological wood.
First report of coexistence of blaKPC-2-, blaNDM-1- and mcr-9-carrying plasmids in a clinical carbapenem-resistant Enterobacter hormaechei isolate
Authors: Yuan Qian , Xia Peiyuan , Xiong Lirong , Xie Linli , Lv Shan , Sun Fengjun , Feng Wei
Published: March 2023

Introduction

Colistin is regarded as one of the last-resort antibiotics against severe infections caused by carbapenem-resistant Enterobacteriaceae. Strains with cooccurrence of mcr-9 and carbapenemase genes are of particular concern. This study aimed to investigate the genetic characteristics of a blaKPC-2-carrying plasmid, blaNDM-1-carrying plasmid and mcr-9-carrying plasmid coexisting in a carbapenem-resistant Enterobacter hormaechei isolate.

Methods

E. hormaechei strain E1532 was subjected to whole-genome sequencing, and the complete nucleotide sequences of three resistance plasmids identified in the strain were compared with related plasmid sequences. The resistance phenotypes mediated by these plasmids were analyzed by plasmid transfer, carbapenemase activity and antimicrobial susceptibility testing.

Results

Whole-genome sequencing revealed that strain E1532 carries three different resistance plasmids, pE1532-KPC, pE1532-NDM and pE1532-MCR. pE1532-KPC harboring blaKPC-2 and pE1532-NDM harboring blaNDM-1 are highly identical to the IncR plasmid pHN84KPC and IncX3 plasmid pNDM-HN380, respectively. The mcr-9-carrying plasmid pE1532-MCR possesses a backbone highly similar to that of the IncHI2 plasmids R478 and p505108-MDR, though their accessory modules differ. These three coexisting plasmids carry a large number of resistance genes and contribute to high resistance to almost all antibiotics tested, except for amikacin, trimethoprim/sulfamethoxazole, tigecycline and polymyxin B. Most of the plasmid-mediated resistance genes are located in or flanked by various mobile genetic elements, facilitating horizontal transfer of antibiotic resistance genes.

Discussion

This is the first report of a single E. hormaechei isolate with coexistence of three resistance plasmids carrying mcr-9 and the two most common carbapenemase genes, blaKPC-2 and blaNDM-1. The prevalence and genetic features of these coexisting plasmids should be monitored to facilitate the establishment of effective strategies to control their further spread.
Identification of anoikis-related genes classification patterns and immune infiltration characterization in ischemic stroke based on machine learning
Authors: Qin Xiaohong , Yi Shangfeng , Rong Jingtong , Lu Haoran , Ji Baowei , Zhang Wenfei , Ding Rui , Wu Liquan , Chen Zhibiao
Published: March 2023

Introduction

Ischemic stroke (IS) is a type of stroke that leads to high mortality and disability. Anoikis is a form of programmed cell death. When cells detach from the correct extracellular matrix, anoikis disrupts integrin junctions, thus preventing abnormal proliferating cells from growing or attaching to an inappropriate matrix. Although there is growing evidence that anoikis regulates the immune response, which makes a great contribution to the development of IS, the role of anoikis in the pathogenesis of IS is rarely explored.

Methods

First, we downloaded GSE58294 set and GSE16561 set from the NCBI GEO database. And 35 anoikis-related genes (ARGs) were obtained from GSEA website. The CIBERSORT algorithm was used to estimate the relative proportions of 22 infiltrating immune cell types. Next, consensus clustering method was used to classify ischemic stroke samples. In addition, we used least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE) and random forest (RF) algorithms to screen the key ARGs in ischemic stroke. Next, we performed receiver operating characteristics (ROC) analysis to assess the accuracy of each diagnostic gene. At the same time, the nomogram was constructed to diagnose IS by integrating trait genes. Then, we analyzed the correlation between gene expression and immune cell infiltration of the diagnostic genes in the combined database. And gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis were performed on these genes to explore differential signaling pathways and potential functions, as well as the construction and visualization of regulatory networks using NetworkAnalyst and Cytoscape. Finally, we investigated the expression pattern of ARGs in IS patients across age or gender.

Results

Our study comprehensively analyzed the role of ARGs in IS for the first time. We revealed the expression profile of ARGs in IS and the correlation with infiltrating immune cells. And The results of consensus clustering analysis suggested that we can classify IS patients into two clusters. The machine learning analysis screened five signature genes, including AKT1, BRMS1, PTRH2, TFDP1 and TLE1. We also constructed nomogram models based on the five risk genes and evaluated the immune infiltration correlation, gene-miRNA, gene-TF and drug-gene interaction regulatory networks of these signature genes. The expression of ARGs did not differ by sex or age.

Discussion

This study may provide a beneficial reference for further elucidating the pathogenesis of IS, and render new ideas for drug screening, individualized therapy and immunotherapy of IS.
Construction and evaluation of Alzheimer’s disease diagnostic prediction model based on genes involved in mitophagy
Authors: Pei Yongyan , Chen Sijia , Zhou Fengling , Xie Tao , Cao Hua
Published: March 2023

Introduction

Alzheimer’s disease (AD) is a common neurodegenerative disease. The concealment of the disease is the difficulty of its prevention and treatment. Previous studies have shown that mitophagy is crucial to the development of AD. However, there is a lack of research on the identification and clinical significance of mitophagy-related genes in AD. Therefore, the purpose of this study was to identify the mitophagy-related genes with the diagnostic potential for AD and establish a diagnostic model for AD.

Methods

Firstly, we download the AD gene expression profile from Gene Expression Omnibus (GEO). Limma, PPI, functional enrichment analysis and WGCNA were used to screen the differential expression of mitophagy-related AD gene. Then, machine learning methods (random forest, univariate analysis, support vector machine, LASSO regression and support vector machine classification) were used to identify diagnostic markers. Finally, the diagnostic model was established and evaluated by ROC, multiple regression analysis, nomogram, calibration curve and other methods. Moreover, multiple independent datasets, AD cell models and AD clinical samples were used to verify the expression level of characteristic genes in the diagnostic model.

Results

In total, 72 differentially expressed mitophagy-related related genes were identified, which were mainly involved in biological functions such as autophagy, apoptosis and neurological diseases. Four mitophagy-related genes (OPTN, PTGS2, TOMM20, and VDAC1) were identified as biomarkers. A diagnostic prediction model was constructed, and the reliability of the model was verified by receiver operating characteristic (ROC) curve analysis of GSE122063 and GSE63061. Then, we combine four mitophagy-related genes with age to establish a nomogram model. The ROC, C index and calibration curve show that the model has good prediction performance. Finally, multiple independent datasets, AD cell model samples and clinical peripheral blood samples confirmed that the expression levels of four mitophagy-related genes were consistent with the results of bioinformatics analysis.

Discussion

The analysis results and diagnostic model of this study are helpful for the follow-up clinical work and mechanism research of AD.
Ex vivo, in situ perfusion protocol for human brain fixation compatible with microscopy, MRI techniques, and anatomical studies
Authors: Insausti Ricardo , Insausti Ana María , Muñoz López Mónica , Medina Lorenzo Isidro , Arroyo-Jiménez Maria del Mar , Marcos Rabal María Pilar , de la Rosa-Prieto Carlos , Delgado-González José Carlos , Montón Etxeberria Javier , Cebada-Sánchez Sandra , Raspeño-García Juan Francisco , Iñiguez de Onzoño María Mercedes , Molina Romero Francisco Javier , Benavides-Piccione Ruth , Tapia-González Silvia , Wisse Laura E. M. , Ravikumar Sadhana , Wolk David A. , DeFelipe Javier , Yushkevich Paul , Artacho-Pérula Emilio
Published: March 2023

We present a method for human brain fixation based on simultaneous perfusion of 4% paraformaldehyde through carotids after a flush with saline. The left carotid cannula is used to perfuse the body with 10% formalin, to allow further use of the body for anatomical research or teaching. The aim of our method is to develop a vascular fixation protocol for the human brain, by adapting protocols that are commonly used in experimental animal studies. We show that a variety of histological procedures can be carried out (cyto- and myeloarchitectonics, histochemistry, immunohistochemistry, intracellular cell injection, and electron microscopy). In addition, ex vivo, ex situ high-resolution MRI (9.4T) can be obtained in the same specimens. This procedure resulted in similar morphological features to those obtained by intravascular perfusion in experimental animals, provided that the postmortem interval was under 10 h for several of the techniques used and under 4 h in the case of intracellular injections and electron microscopy. The use of intravascular fixation of the brain inside the skull provides a fixed whole human brain, perfectly fitted to the skull, with negligible deformation compared to conventional techniques. Given this characteristic of ex vivo, in situ fixation, this procedure can probably be considered the most suitable one available for ex vivo MRI scans of the brain. We describe the compatibility of the method proposed for intravascular fixation of the human brain and fixation of the donor’s body for anatomical purposes. Thus, body donor programs can provide human brain tissue, while the remainder of the body can also be fixed for anatomical studies. Therefore, this method of human brain fixation through the carotid system optimizes the procurement of human brain tissue, allowing a greater understanding of human neurological diseases, while benefiting anatomy departments by making the remainder of the body available for teaching purposes.
Case report: Fatal cerebral herniation caused by hypoglycemic due to mistaking glibenclamide in children
Authors: Song Chunlan , Jia Wanyu , Shi Shengli , Li Peng
Published: March 2023

In recent years, the prevalence of diabetes in China has significantly increased, and glibenclamide is widely used as a basic hypoglycemic drug in China's primary clinical practice. There are many left-behind children in the grass-roots areas in China and various dangerous incidents of children taking drugs by mistake continue to occur. This article reports a case of cerebral edema and fatal cerebral hernia caused by hypoglycemia induced by mistakenly ingesting glibenclamide in a child. This is the first reported case in China of a child who died from brain herniation caused by accidental administration of glibenclamide. This case reminded that clinicians must comprehensively consider the cause of convulsions and coma in children with unknown causes, ask the history in detail and cannot ignore the risk of hypoglycemic convulsions and coma. When hypoglycemic is detected, high concentration of glucose should be given promptly to normalize blood glucose. When dealing with unexplained convulsions and comatose children, clinical pediatricians must be alert to the possibility of accidental medication.
3D network with channel excitation and knowledge distillation for action recognition
Authors: Hu Zhengping , Mao Jianzeng , Yao Jianxin , Bi Shuai
Published: March 2023

Modern action recognition techniques frequently employ two networks: the spatial stream, which accepts input from RGB frames, and the temporal stream, which accepts input from optical flow. Recent researches use 3D convolutional neural networks that employ spatiotemporal filters on both streams. Although mixing flow with RGB enhances performance, correct optical flow computation is expensive and adds delay to action recognition. In this study, we present a method for training a 3D CNN using RGB frames that replicates the motion stream and, as a result, does not require flow calculation during testing. To begin, in contrast to the SE block, we suggest a channel excitation module (CE module). Experiments have shown that the CE module can improve the feature extraction capabilities of a 3D network and that the effect is superior to the SE block. Second, for action recognition training, we adopt a linear mix of loss based on knowledge distillation and standard cross-entropy loss to effectively leverage appearance and motion information. The Intensified Motion RGB Stream is the stream trained with this combined loss (IMRS). IMRS surpasses RGB or Flow as a single stream; for example, HMDB51 achieves 73.5% accuracy, while RGB and Flow streams score 65.6% and 69.1% accuracy, respectively. Extensive experiments confirm the effectiveness of our proposed method. The comparison with other models proves that our model has good competitiveness in behavior recognition.
An optimal model of long-term post-stroke care
Authors: Sarzyńska-Długosz Iwona
Published: March 2023

Stroke is a major healthcare challenge that is increasing worldwide. The burden of stroke is significant for the affected individuals as well as for the general population; high-quality care is needed to reduce its negative impacts. This article synthesized information from systematic reviews, guidelines, and primary literature on stroke care and post-stroke rehabilitation and proposes an optimal strategy for long-term post-stroke care. It also highlights the unmet needs of patients who experienced a stroke in terms of early diagnosis of complications and adequate, comprehensive therapy.
Neurodegenerative disease and antioxidant biomarkers: A bidirectional Mendelian randomization study
Authors: Zhang Qianqian , Li Qingyang , Zhao Huihui , Shu Mingzhu , Luo Maotao , Li Yanan , Ding Yu , Shi Shiyu , Cheng Xi , Niu Qi
Published: March 2023

Objective

Previous observational studies have suggested that antioxidant imbalance is correlated with neurodegenerative diseases, while its cause–effect remains unclear. Thus, the goal of the present study is to explore the causal relationship between 11 antioxidant biomarkers and 3 most common neurodegenerative diseases [Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Parkinson’s disease (PD)].

Methods

A bidirectional Mendelian randomization (MR) study was performed to investigate the causal effects by using 3 main methods (Variance Weighted (IVW), Weighted Median (WM), and MR-Egger regression) in the European population. The data of 11 antioxidant biomarkers were obtained from the open database by the most up-to-date Genome-Wide Association Studies (GWAS), the summary statistics of PD and ALS were obtained from the International Parkinson’s Disease Genomics Consortium (IPDGC) (33,674 cases, and 449,056 controls), and the International Amyotrophic Lateral Sclerosis Genomics Consortium (IALSC) (20,806 cases and 59,804 controls), respectively. For AD, we specifically used two recently published GWAS data, one from the International Genomics of Alzheimer’s Project (IGAP) (21,982 cases and 41,944 controls), and the other from a large meta-analysis (71,880 cases and 383,378 controls) as validation data.

Results

Based on the Bonferroni correction p < 0.0015, there was no significant causal evidence for the antioxidant biomarkers on neurodegenerative diseases, however, the reverse analysis found that AD was significantly related to the decrease in retinol (IVW: beta = −0.023, p = 0.0007; WM: beta = −0.025, p = 0.0121), while the same analysis was carried out between the AD validation database and retinol, the results were consistent (IVW: beta = −0.064, p = 0.025). Moreover, AD on Glutathione S-transferase (GST), PD on Glutathione Peroxidase (GPX) as well as PD on uric acid (UA) also indicated potential causal-and-effect associations (IVW: p = 0.025; p = 0.027; p = 0.021, respectively).

Conclusions

There was no sufficient evidence that antioxidant imbalance has a significant causal effect on neurodegenerative diseases. However, this study revealed that genetically predicted AD was significantly related to the decrease in retinol, which provides a new insight into previous research and indicates the possibility to regard retinol as potential biomarker for the diagnosis and progress of AD.
On closed-loop brain stimulation systems for improving the quality of life of patients with neurological disorders
Authors: Belkacem Abdelkader Nasreddine , Jamil Nuraini , Khalid Sumayya , Alnajjar Fady
Published: March 2023

Emerging brain technologies have significantly transformed human life in recent decades. For instance, the closed-loop brain-computer interface (BCI) is an advanced software-hardware system that interprets electrical signals from neurons, allowing communication with and control of the environment. The system then transmits these signals as controlled commands and provides feedback to the brain to execute specific tasks. This paper analyzes and presents the latest research on closed-loop BCI that utilizes electric/magnetic stimulation, optogenetic, and sonogenetic techniques. These techniques have demonstrated great potential in improving the quality of life for patients suffering from neurodegenerative or psychiatric diseases. We provide a comprehensive and systematic review of research on the modalities of closed-loop BCI in recent decades. To achieve this, the authors used a set of defined criteria to shortlist studies from well-known research databases into categories of brain stimulation techniques. These categories include deep brain stimulation, transcranial magnetic stimulation, transcranial direct-current stimulation, transcranial alternating-current stimulation, and optogenetics. These techniques have been useful in treating a wide range of disorders, such as Alzheimer's and Parkinson's disease, dementia, and depression. In total, 76 studies were shortlisted and analyzed to illustrate how closed-loop BCI can considerably improve, enhance, and restore specific brain functions. The analysis revealed that literature in the area has not adequately covered closed-loop BCI in the context of cognitive neural prosthetics and implanted neural devices. However, the authors demonstrate that the applications of closed-loop BCI are highly beneficial, and the technology is continually evolving to improve the lives of individuals with various ailments, including those with sensory-motor issues or cognitive deficiencies. By utilizing emerging techniques of stimulation, closed-loop BCI can safely improve patients' cognitive and affective skills, resulting in better healthcare outcomes.
Novel electrotactile brain-computer interface with somatosensory event-related potential based control
Authors: Savić Andrej M. , Novičić Marija , Ðorđević Olivera , Konstantinović Ljubica , Miler-Jerković Vera
Published: March 2023

Objective

A brain computer interface (BCI) allows users to control external devices using non-invasive brain recordings, such as electroencephalography (EEG). We developed and tested a novel electrotactile BCI prototype based on somatosensory event-related potentials (sERP) as control signals, paired with a tactile attention task as a control paradigm.

Approach

A novel electrotactile BCI comprises commercial EEG device, an electrical stimulator and custom software for EEG recordings, electrical stimulation control, synchronization between devices, signal processing, feature extraction, selection, and classification. We tested a novel BCI control paradigm based on tactile attention on a sensation at a target stimulation location on the forearm. Tactile stimuli were electrical pulses delivered at two proximal locations on the user’s forearm for stimulating branches of radial and median nerves, with equal probability of the target and distractor stimuli occurrence, unlike in any other ERP-based BCI design. We proposed a compact electrical stimulation electrodes configuration for delivering electrotactile stimuli (target and distractor) using 2 stimulation channels and 3 stimulation electrodes. We tested the feasibility of a single EEG channel BCI control, to determine pseudo-online BCI performance, in ten healthy subjects. For optimizing the BCI performance we compared the results for two classifiers, sERP averaging approaches, and novel dedicated feature extraction/selection methods via cross-validation procedures.

Main results

We achieved a single EEG channel BCI classification accuracy in the range of 75.1 to 88.1% for all subjects. We have established an optimal combination of: single trial averaging to obtain sERP, feature extraction/selection methods and classification approach.

Significance

The obtained results demonstrate that a novel electrotactile BCI paradigm with equal probability of attended (target) and unattended (distractor) stimuli and proximal stimulation sites is feasible. This method may be used to drive restorative BCIs for sensory retraining in stroke or brain injury, or assistive BCIs for communication in severely disabled users.
Altered isotropic volume fraction in gray matter after sleep deprivation and its association with visuospatial memory: A neurite orientation dispersion and density imaging study
Authors: Lin Jia-Hui , Chen Xu-Hui , Wu Ye , Cao Yun-Bin , Chen Hua-Jun , Huang Nao-Xin
Published: March 2023

Background and aims

Diffusion magnetic resonance imaging (dMRI) studies have revealed microstructural abnormalities in white matter resulting from sleep deprivation (SD). This study aimed to adopt neurite orientation dispersion and density imaging (NODDI) to investigate the effect of SD on gray matter (GM) microstructural properties and its association to visuospatial memory (VSM).

Methods

Twenty-four healthy women underwent two sessions of dMRI scanning and visuospatial ability assessment by Complex Figure Test (CFT), once during rested wakefulness (RW) and once after 24 h of SD. We calculated NODDI metrics, including intracellular volume fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fraction (ISO). Differences in NODDI-related metrics between RW and SD were determined using a voxel-wise paired t-test. We identified an association between NODDI metrics and CFT results using Spearman’s correlation coefficient.

Results

Sleep deprivation worsened subjects’ performance in the delayed-CFT trial. We observed no significant difference in ICVF and ODI between RW and SD. After SD, subjects showed decreases in ISO, primarily in the prefrontal cortex and temporal lobe, while exhibiting ISO increases in the anterior and posterior cerebellar lobe and cerebellar vermis. Furthermore, ISO change in the left superior, middle and inferior frontal gyrus was significantly correlated with completion time change in delayed-CFT trial performance.

Conclusion

Our results suggested that SD hardly affected the density and spatial organization of neurites in GM, but the extra-neurite water molecule diffusion process was affected (perhaps resulting from neuroinflammation), which contributed to VSM dysfunction.
Telemedicine efficacy and satisfaction of patients and headache specialists in migraine management
Authors: Liu Qinlin , Liu Fang , Yu Xiran , Zang Jiali , Tan Ge
Published: March 2023

Background

Migraine follow-up is difficult for outpatients, especially after the COVID-19 pandemic, we tried to identify the most appropriate telemedicine methods for migraine in terms of efficacy, safety, patient compliance, and patient and physician satisfaction.

Methods

Migraine patients were screened from the Headache Center of the First Affiliated Hospital of Chongqing Medical University from September 2019 to December 2021 and randomly classified into an outpatient group and four telemedicine groups: social software, telephone, E-mail, and short message. Headache specialists followed up with the patients 3 and 6 months after their visit and asked about their satisfaction with the follow-up in each instance, as were the headache specialists.

Results

A total of 147 migraine patients were included, of whom 65 completed the follow-up. After 3 and 6 months of follow-up, the proportion of patients whose monthly headache frequency decreased by over 50% in the social-software, telephone, and E-mail groups was no different from that in the outpatient group. A similar result was obtained from evaluations with the Visual Analog Scale, the Headache Impact Test and the Migraine Disability Assessment compared with baseline in social software and telephone groups. The compliance in social-software group was not worse than that in the outpatient group. The proportion of patients in the E-mail group who completed the follow-up and the proportion of patients in the telephone group who consistently took preventive medication were significantly lower than those in the outpatient group. After 6 months, the majority of patients in the outpatient, social-software, and telephone groups and headache specialists in the outpatient, social-software groups were satisfied with the follow-up, while fewer patients in the E-mail group and fewer specialists in the telephone and E-mail group showed their satisfaction.

Conclusion

Compared with outpatient visits, it is safe and effective to use social software and telephone to follow up on migraine patients, and E-mail and short-message follow-up have lower feasibility. Migraine patients prefer social-software and telephone follow-up, while specialists prefer social-software follow-up.
The little brain and the seahorse: Cerebellar-hippocampal interactions
Authors: Froula Jessica M. , Hastings Shayne D. , Krook-Magnuson Esther
Published: March 2023

There is a growing appreciation for the cerebellum beyond its role in motor function and accumulating evidence that the cerebellum and hippocampus interact across a range of brain states and behaviors. Acute and chronic manipulations, simultaneous recordings, and imaging studies together indicate coordinated coactivation and a bidirectional functional connectivity relevant for various physiological functions, including spatiotemporal processing. This bidirectional functional connectivity is likely supported by multiple circuit paths. It is also important in temporal lobe epilepsy: the cerebellum is impacted by seizures and epilepsy, and modulation of cerebellar circuitry can be an effective strategy to inhibit hippocampal seizures. This review highlights some of the recent key hippobellum literature.
Effects of high-frequency repetitive transcranial magnetic stimulation on the nutritional status of patients in a persistent vegetative state: A pilot study
Authors: Liu Xuan-Wei , Zhao Na-Na , Pang Tao , Wen Qiong , Xiao Peng , Zeng Ke-Xue , Wang Dan-Ning , Chen Jia-Min , Wang Yu-Long , Yu Hai-Bo
Published: March 2023

Purpose

This paper presents a preliminary study on whether repetitive transcranial magnetic stimulation (rTMS) can modulate the nutritional status of persistent vegetative state (PVS) patients (the primary endpoint) by regulating the intestinal flora and the metabolites, with the correlation between them also investigated.

Methods

Seventy-six patients with PVS were selected and divided into the observation group (n = 38) and the control group (n = 38) by random numerical grouping. All subjects’ stool samples were examined for metabolites and analyzed regarding the short-chain fatty acids (SCFAs) content. All subjects’ serum albumin, prealbumin, and hemoglobin levels were measured before and after the treatment. Nutrition risk screening 2002 was performed on all the subjects before and after the treatment and on the 30th and 90th days of the follow-up.

Results

(1) Intestinal flora structure: the Chao index, Ace index, and Shannon index of the observation group and the control group were significantly higher (p < 0.05), while the Simpson index was significantly lower (p < 0.05) following the treatment. (2) Metabolites of the intestinal flora: the observation group had significantly higher levels of acetic acid, butyric acid, and valeric acid (p < 0.05), as well as lower levels of propionic acid (p < 0.05) following the treatment. (3) Nutritional status (the primary endpoint): following the treatment, the above serum nutritional indices were significantly higher in both groups (p < 0.05), while the indices of the observation group were significantly higher than those of the control group (p < 0.05).

Conclusion

The rTMS method may improve the nutritional status of patients with PVS by regulating the structure of the intestinal flora and affecting the level of SCFAs through the microbiota–gut–brain axis. The possible mechanism involves how high-frequency rTMS can cause increased excitation in the frontal lobe of the right side of the brain, thus regulating the 5-hydroxytryptamine and norepinephrine levels.
Prognostic value of inflammatory markers and clinical features for survival in advanced or metastatic esophageal squamous cell carcinoma patients receiving anti-programmed death 1 treatment
Authors: Da Liangshan , Qu Ziting , Zhang Congjun , Shen Yuanyuan , Huang Wei , Zhang Yiyin , Gu Kangsheng
Published: March 2023

Purpose

This study aims to assess the prognostic value of inflammatory markers and clinical features in advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients receiving anti-programmed death 1 (PD-1) treatment.

Methods

Based on receiver operating characteristic curve (ROC) analysis, Youden’s indexes were applied to determine the cut-off values for inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocye ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Wilcoxon test was conducted to evaluate the changes in above inflammatory markers. Kaplan-Meier method was utilized to estimate progression-free survival (PFS) and overall survival (OS), and the Log-rank test was used to compare the different survival between groups. Univariate and multivariate Cox regression analyses were performed to assess the prognostic value of inflammatory markers and clinical features.

Results

162 advanced or metastatic ESCC patients receiving anti-PD-1 treatment were enrolled in this retrospective study. The cut-off values of NLR, dNLR, MLR, PLR, and SII were 4.748, 2.214, 0.309, 250.505, and 887.895, respectively. NLR, dNLR, PLR, and SII declined significantly among the partial response (PR) (P<0.001, P<0.001, P=0.036, P<0.001), objective response rate (ORR) (P<0.001, P<0.001, P=0.036, P<0.001), and disease control rate (DCR) (P<0.001, P<0.001, P=0.038, P<0.001) groups, respectively. Significant increases were found in NLR (P<0.001), dNLR (P<0.001), MLR (P=0.001), and SII (P=0.024) when anti-PD-1 treatment failed. Multivariate Cox regression analysis indicated that NLR (P<0.001, P=0.002), lymph node metastasis (P=0.013, P=0.001), Eastern Cooperative Oncology Group Performance Status (ECOG PS) (P=0.008, P=0.002), and treatment lines (P=0.037, P=0.048) were significant prognostic indicators of PFS and OS. Additionally, SII (P=0.016) was also significantly related to OS in ESCC patients. The risk score model showed that low risk patients prolonged PFS and OS than those with middle or high risk (P<0.001, P<0.001).

Conclusion

Inflammatory markers can reflect short-term outcomes of anti-PD-1 treatment for ESCC patients. NLR, lymph node metastases, ECOG PS, and treatment lines are significant prognostic indicators for PFS and OS. And the risk score model constructed based on the above factors has favourable prognostic predictive value.
YB1 participated in regulating mitochondrial activity through RNA replacement
Authors: Gong Weipeng , Zhang Song
Published: March 2023

As a relic of ancient bacterial endosymbionts, mitochondria play a central role in cell metabolism, apoptosis, autophagy, and other processes. However, the function of mitochondria-derived nucleic acids in cellular signal transduction has not been fully elucidated. Here, our work has found that Y-box binding protein 1 (YB1) maintained cellular autophagy at a moderate level to inhibit mitochondrial oxidative phosphorylation. In addition, mitochondrial RNA was leaked into cytosol under starvation, accompanied by YB1 mitochondrial relocation, resulting in YB1-bound RNA replacement. The mRNAs encoded by oxidative phosphorylation (OXPHOS)-associated genes and oncogene HMGA1 (high-mobility group AT-hook 1) were competitively replaced by mitochondria-derived tRNAs. The increase of free OXPHOS mRNAs released from the YB1 complex enhanced mitochondrial activity through facilitating translation, but the stability of HMGA1 mRNA was impaired without the protection of YB1, both contributing to breast cancer cell apoptosis and reactive oxygen species production. Our finding not only provided a new potential target for breast cancer therapy but also shed new light on understanding the global landscape of cellular interactions between RNA-binding proteins and different RNA species.