bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated analysis of long non-coding RNAs and mRNAs associated with glaucoma in vitro
Authors: You Mengling , Rong Rong , Zeng Zhou , Fan Cong , Li Haibo , Yang Qian , Ji Dan
Published: February 2023

Introduction

In recent years, the biological functions and important roles of long non-coding RNAs (lncRNAs) have been widely reported in many diseases. Although glaucoma is the leading cause of blindness worldwide, the specific mechanisms of lncRNAs in the pathogenesis and progression of glaucoma remain unclear. Our research aims to elucidate the differentially expressed lncRNAs and mRNAs in glaucoma and to provide a basis for further exploration of the specific mechanism of action of lncRNAs in the progression of glaucoma.

Methods

We performed RNA sequencing on samples from a pressurized model of R28 cells and performed bioinformatics analyses on the sequencing results. The expression consistency of lncRNAs in clinical samples from patients with glaucoma or cataracts was detected using real-time quantitative polymerase chain reaction (RT-qPCR).

Results

RNA sequencing results showed that lncRNAs in cluster 5 were upregulated with increasing stress after typing all significantly altered lncRNAs using k-means in a cellular stress model. KEGG analysis indicated that they were associated with neurodegenerative diseases. Differentially expressed lncRNAs were verified by RT-qPCR, and the lncRNA expression levels of AC120246.2 and XLOC_006247 were significantly higher in the aqueous humor (AH) of patients with glaucoma than in those with cataracts. For LOC102551819, there was almost no expression in the AH and trabecular meshwork in patients with glaucoma but high expression was observed in the iris.

Conclusion

Our research proposes potential diagnostic or intervention targets for clinical applications as well as a theoretical basis for more in-depth research on the function of lncRNAs in glaucoma.
New insights into the inter-organ crosstalk mediated by ChREBP
Authors: Carbinatti Thais , Régnier Marion , Parlati Lucia , Benhamed Fadila , Postic Catherine
Published: February 2023

Carbohydrate response element binding protein (ChREBP) is a glucose responsive transcription factor recognized by its critical role in the transcriptional control of glycolysis and de novo lipogenesis. Substantial advances in the field have revealed novel ChREBP functions. Indeed, due to its actions in different tissues, ChREBP modulates the inter-organ communication through secretion of peptides and lipid factors, ensuring metabolic homeostasis. Dysregulation of these orchestrated interactions is associated with development of metabolic diseases such as type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). Here, we recapitulate the current knowledge about ChREBP-mediated inter-organ crosstalk through secreted factors and its physiological implications. As the liver is considered a crucial endocrine organ, we will focus in this review on the role of ChREBP-regulated hepatokines. Lastly, we will discuss the involvement of ChREBP in the progression of metabolic pathologies, as well as how the impairment of ChREBP-dependent signaling factors contributes to the onset of such diseases.
Case report: Metastatic pancreatic neuroendocrine tumour associated with portal vein thrombosis; successful management with subsequent pregnancies
Authors: Sira Lívia , Zsíros Noémi , Bidiga László , Barna Sándor , Kanyári Zsolt , Nagy Edit B. , Guillaume Nicolas , Wild Damian , Rázsó Katalin , Andó Szilvia , Balogh István , Nagy Endre V. , Balogh Zoltán
Published: February 2023

Background

Splanchnic vein thrombosis due to co-existing metastatic pancreatic neuroendocrine tumour (pNET) and JAK2V617F mutation is a rare condition.

Case report

Here we present a case of a young woman with complete remission of a non-functioning grade 2 pNET with unresectable liver metastases, coexisting with JAK2V617F mutation. Splenectomy and distal pancreatectomy were performed. Neither surgical removal, nor radiofrequency ablation of the liver metastases was possible. Therefore, somatostatin analogue (SSA) and enoxaparine were started. Peptide receptor radionuclide therapy (PRRT) was given in 3 cycles 6-8 weeks apart. Genetic testing revealed no multiple endocrine neoplasia type 1 (MEN-1) gene mutations. After shared decision making with the patient, she gave birth to two healthy children, currently 2 and 4 years old. On pregnancy confirmation, SSA treatment was interrupted and resumed after each delivery. Ten years after the diagnosis of pNET, no tumour is detectable by MRI or somatostatin receptor scintigraphy. PRRT followed by continuous SSA therapy, interrupted only during pregnancies, resulted in complete remission and enabled the patient to complete two successful pregnancies.
Identification of biomarkers for the diagnosis of chronic kidney disease (CKD) with non-alcoholic fatty liver disease (NAFLD) by bioinformatics analysis and machine learning
Authors: Cao Yang , Du Yiwei , Jia Weili , Ding Jian , Yuan Juzheng , Zhang Hong , Zhang Xuan , Tao Kaishan , Yang Zhaoxu
Published: February 2023

Background

Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) are closely related to immune and inflammatory pathways. This study aimed to explore the diagnostic markers for CKD patients with NAFLD.

Methods

CKD and NAFLD microarray data sets were screened from the GEO database and analyzed the differentially expressed genes (DEGs) in GSE10495 of CKD date set. Weighted Gene Co-Expression Network Analysis (WGCNA) method was used to construct gene coexpression networks and identify functional modules of NAFLD in GSE89632 date set. Then obtaining NAFLD-related share genes by intersecting DEGs of CKD and modular genes of NAFLD. Then functional enrichment analysis of NAFLD-related share genes was performed. The NAFLD-related hub genes come from intersection of cytoscape software and machine learning. ROC curves were used to examine the diagnostic value of NAFLD related hub genes in the CKD data sets and GSE89632 date set of NAFLD. CIBERSORTx was also used to explore the immune landscape in GSE104954, and the correlation between immune infiltration and hub genes expression was investigated.

Results

A total of 45 NAFLD-related share genes were obtained, and 4 were NAFLD-related hub genes. Enrichment analysis showed that the NAFLD-related share genes were significantly enriched in immune-related pathways, programmed cell death, and inflammatory response. ROC curve confirmed 4 NAFLD-related hub genes in CKD training set GSE104954 and other validation sets. Then they were used as diagnostic markers for CKD. Interestingly, these 4 diagnostic markers of CKD also showed good diagnostic value in the NAFLD date set GSE89632, so these genes may be important targets of NAFLD in the development of CKD. The expression levels of the 4 diagnostic markers for CKD were significantly correlated with the infiltration of immune cells.

Conclusion

4 NAFLD-related genes (DUSP1, NR4A1, FOSB, ZFP36) were identified as diagnostic markers in CKD patients with NAFLD. Our study may provide diagnostic markers and therapeutic targets for CKD patients with NAFLD.
Metabonomic analysis of follicular fluid in patients with diminished ovarian reserve
Authors: Li Jianan , Zhang Zhourui , Wei Yiqiu , Zhu Pujia , Yin Tailang , Wan Qiongqiong
Published: February 2023

Background

Ovarian reserve is an important factor determining female reproductive potential. The number and quality of oocytes in patients with diminished ovarian reserve (DOR) are reduced, and even if in vitro fertilization-embryo transfer (IVF-ET) is used to assist their pregnancy, the clinical pregnancy rate and live birth rate are still low. Infertility caused by reduced ovarian reserve is still one of the most difficult clinical problems in the field of reproduction. Follicular fluid is the microenvironment for oocyte survival, and the metabolic characteristics of follicular fluid can be obtained by metabolomics technology. By analyzing the metabolic status of follicular fluid, we hope to find the metabolic factors that affect the quality of oocytes and find new diagnostic markers to provide clues for early detection and intervention of patients with DOR.

Methods

In this research, 26 infertile women with DOR and 28 volunteers with normal ovarian reserve receiving IVF/ET were recruited, and their follicular fluid samples were collected for a nontargeted metabonomic study. The orthogonal partial least squares discriminant analysis model was used to understand the separation trend of the two groups, KEGG was used to analyze the possible metabolic pathways involved in differential metabolites, and the random forest algorithm was used to establish the diagnostic model.

Results

12 upregulated and 32 downregulated differential metabolites were detected by metabolic analysis, mainly including amino acids, indoles, nucleosides, organic acids, steroids, phospholipids, fatty acyls, and organic oxygen compounds. Through KEGG analysis, these metabolites were mainly involved in aminoacyl-tRNA biosynthesis, tryptophan metabolism, pantothenate and CoA biosynthesis, and purine metabolism. The AUC value of the diagnostic model based on the top 10 metabolites was 0.9936.

Conclusion

The follicular fluid of patients with DOR shows unique metabolic characteristics. These data can provide us with rich biochemical information and a research basis for exploring the pathogenesis of DOR and predicting ovarian reserve function.
The roles of microRNAs in horticultural plant disease resistance
Authors: Zhang Aiai , Zhang Shunshun , Wang Feng , Meng Xianmin , Ma Yue , Guan Jiantao , Zhang Feng
Published: February 2023

The development of the horticultural industry is largely limited by disease and excessive pesticide application. MicroRNAs constitute a major portion of the transcriptomes of eukaryotes. Various microRNAs have been recognized as important regulators of the expression of genes involved in essential biological processes throughout the whole life cycle of plants. Recently, small RNA sequencing has been applied to study gene regulation in horticultural plants. In this review, we summarize the current understanding of the biogenesis and contributions of microRNAs in horticultural plant disease resistance. These microRNAs may potentially be used as genetic resources for improving disease resistance and for molecular breeding. The challenges in understanding horticultural plant microRNA biology and the possibilities to make better use of these horticultural plant gene resources in the future are discussed in this review.
Formation of the synaptonemal complex in a gynogenetic allodiploid hybrid fish
Authors: Wang Jing , Wang Wen , Li Jihong , Zhang Yirui , Luo Kaikun , Han Linmei , Xiang Caixia , Chai Mingli , Luo Ziye , Zhao Rurong , Liu Shaojun
Published: February 2023

Introduction: The correct pairing and separation of homologous chromosomes during meiosis is crucial to ensure both genetic stability and genetic diversity within species. In allodiploid organisms, synapsis often fails, leading to sterility. However, a gynogenetic allodiploid hybrid clone line (GDH), derived by crossing red crucian carp (Carassius auratus ♀) and common carp (Cyprinus carpio ♂), stably produces diploid eggs. Because the GDH line carries 100 chromosomes with 50 chromosomes from the red crucian carp (RCC; ♀, 2n = 2x = 100) and 50 chromosomes from the common carp (CC; C. carpio L., ♂, 2n = 2x = 100), it is interesting to study the mechanisms of homologous chromosome pairing during meiosis in GDH individuals.

Methods: By using fluorescence in situ hybridization (FISH) with a probe specific to the red crucian carp to label homologous chromosomes, we identified the synaptonemal complex via immunofluorescence assay of synaptonemal complex protein 3 (SCP3).

Results: FISH results indicated that, during early ovarian development, the GDH oogonium had two sets of chromosomes with only one set from Carassius auratus, leading to the failure formation of normal bivalents and the subsequently blocking of meiosis. This inhibition lasted at least 5 months. After this long period of inhibition, pairs of germ cells fused, doubling the chromosomes such that the oocyte contained two sets of chromosomes from each parent. After chromosome doubling at 10 months old, homologous chromosomes and the synaptonemal complex were identified.

Discussion: Causally, meiosis proceeded normally and eventually formed diploid germ cells. These results further clarify the mechanisms by which meiosis proceeds in hybrids.
Cross-reactivity influences changes in human influenza A virus and Epstein Barr virus specific CD8 memory T cell receptor alpha and beta repertoires between young and old
Authors: Clark Fransenio , Gil Anna , Thapa Ishwor , Aslan Nuray , Ghersi Dario , Selin Liisa K.
Published: February 2023

Older people have difficulty controlling infection with common viruses such as influenza A virus (IAV), RNA virus which causes recurrent infections due to a high rate of genetic mutation, and Epstein Barr virus (EBV), DNA virus which persists in B cells for life in the 95% of people that become acutely infected. We questioned whether changes in epitope-specific memory CD8 T cell receptor (TCR) repertoires to these two common viruses could occur with increasing age and contribute to waning immunity. We compared CD8 memory TCR alpha and beta repertoires in two HLA-A2+ EBV- and IAV-immune donors, young (Y) and older (O) donors to three immunodominant epitopes known to be cross-reactive, IAV-M158-66 (IAV-M1), EBV-BMLF1280-288 (EBV-BM), and EBV-BRLF1109-117 (EBV-BR). We, therefore, also designed these studies to examine if TCR cross-reactivity could contribute to changes in repertoire with increasing age. TCR high throughput sequencing showed a significant difference in the pattern of TRBV usage between Y and O. However, there were many more differences in AV and AJ usage, between the age groups suggesting that changes in TCRα usage may play a greater role in evolution of the TCR repertoire emphasizing the importance of studying TRAV repertoires. With increasing age there was a preferential retention of TCR for all three epitopes with features in their complementarity-determining region (CDR3) that increased their ease of generation, and their cross-reactive potential. Young and older donors differed in the patterns of AV/AJ and BV/BJ pairings and usage of dominant CDR3 motifs specific to all three epitopes. Both young and older donors had cross-reactive responses between these 3 epitopes, which were unique and differed from the cognate responses having features that suggested they could interact with either ligand. There was an increased tendency for the classic IAV-M1 specific clone BV19-IRSS-JB2.7/AV27-CAGGGSQGNLIF-AJ42 to appear among the cross-reactive clones, suggesting that the dominance of this clone may relate to its cross-reactivity with EBV. These results suggest that although young and older donors retain classic TCR features for each epitope their repertoires are gradually changing with age, maintaining TCRs that are cross-reactive between these two common human viruses, one with recurrent infections and the other a persistent virus which frequently reactivates.
Case report: Spontaneous remission in lung carcinoma with a late relapse after adjuvant immunotherapy: Exceptional tumor micro-environment
Authors: Chen Yan , Guan Wenhui , Zhong Changhao , Deng Jiaxi , Hu Minjuan , Mo Wenwei , Xie Xiaohong , Li Shiyue , Zhou Chengzhi , Lin Xinqing
Published: February 2023

Spontaneous remission (SR) of local recurrence after adjuvant immunotherapy has rarely been reported, and the underlying mechanism is poorly understood. Herein, we reported a patient with stage cT2aN2M0 squamous cell lung carcinoma who received neoadjuvant and adjuvant treatment with nivolumab plus chemotherapy. The patient experienced a late relapse in the subcarinal lymph node seven months after the last dosage of treatment but achieved SR in the next three months without additional antitumor therapy. The complete response lasted for eleven months and counting. Notably, high copies of pathogenic microorganisms were detected in the patient’s bronchoalveolar lavage fluid along with the recurrence but disappeared after SR. The patient also experienced a lymph node puncture-induced fever but had no other symptoms. A longitudinal analysis of infiltrated immune cells in the recurrent lymph node was performed by multiplex immunofluorescence and whole transcriptome sequencing, which revealed that CD8+ T cells were recruited during the initial relapse, specifically in the stromal area, then migrated into the tumor tissue, and continued to increase after elimination of tumor cells. Meanwhile, the initial recruitment of CD8+ T cells was coupled with a higher proportion of B cells, and the abundant neutrophil population was synchronous with the infiltration of CD8+ T cells into tumor cells. This is the first report on an Non-small cell lung cancer (NSCLC) patient with a late relapse after adjuvant immune checkpoint inhibitor (ICI) therapy who achieved SR. Our case highlights the complexity and plasticity of antitumor immunity and is expected to help find efficient strategies against the resistance of ICI treatment.
Inflammatory myopathies and beyond: The dual role of neutrophils in muscle damage and regeneration
Authors: Torres-Ruiz Jiram , Alcalá-Carmona Beatriz , Alejandre-Aguilar Ricardo , Gómez-Martín Diana
Published: February 2023

Skeletal muscle is one of the most abundant tissues of the human body and is responsible for the generation of movement. Muscle injuries can lead to severe disability. Skeletal muscle is characterized by an important regeneration capacity, which is possible due to the interaction between the myoblasts and immune cells. Neutrophils are fundamental as inducers of muscle damage and as promoters of the initial inflammatory response which eventually allows the muscle repair. The main functions of the neutrophils are phagocytosis, respiratory burst, degranulation, and the production of neutrophil extracellular traps (NETs). An overactivation of neutrophils after muscle injuries may lead to an expansion of the initial damage and can hamper the successful muscle repair. The importance of neutrophils as inducers of muscle damage extends beyond acute muscle injury and recently, neutrophils have become more relevant as part of the immunopathogenesis of chronic muscle diseases like idiopathic inflammatory myopathies (IIM). This heterogeneous group of systemic autoimmune diseases is characterized by the presence of muscle inflammation with a variable amount of extramuscular features. In IIM, neutrophils have been found to have a role as biomarkers of disease activity, and their expansion in peripheral blood is related to certain clinical features like interstitial lung disease (ILD) and cancer. On the other hand, low density granulocytes (LDG) are a distinctive subtype of neutrophils characterized by an enhanced production of NETs. These cells along with the NETs have also been related to disease activity and certain clinical features like ILD, vasculopathy, calcinosis, dermatosis, and cutaneous ulcers. The role of NETs in the immunopathogenesis of IIM is supported by an enhanced production and deficient degradation of NETs that have been observed in patients with dermatomyositis and anti-synthetase syndrome. Finally, new interest has arisen in the study of other phenotypes of LDG with a phenotype corresponding to myeloid-derived suppressor cells, which were also found to be expanded in patients with IIM and were related to disease activity. In this review, we discuss the role of neutrophils as both orchestrators of muscle repair and inducers of muscle damage, focusing on the immunopathogenesis of IIM.
The diverse roles of C-type lectin-like receptors in immunity
Authors: Scur Michal , Parsons Brendon D. , Dey Sayanti , Makrigiannis Andrew P.
Published: February 2023

Our understanding of the C-type lectin-like receptors (CTLRs) and their functions in immunity have continued to expand from their initial roles in pathogen recognition. There are now clear examples of CTLRs acting as scavenger receptors, sensors of cell death and cell transformation, and regulators of immune responses and homeostasis. This range of function reflects an extensive diversity in the expression and signaling activity between individual CTLR members of otherwise highly conserved families. Adding to this diversity is the constant discovery of new receptor binding capabilities and receptor-ligand interactions, distinct cellular expression profiles, and receptor structures and signaling mechanisms which have expanded the defining roles of CTLRs in immunity. The natural killer cell receptors exemplify this functional diversity with growing evidence of their activity in other immune populations and tissues. Here, we broadly review select families of CTLRs encoded in the natural killer cell gene complex (NKC) highlighting key receptors that demonstrate the complex multifunctional capabilities of these proteins. We focus on recent evidence from research on the NKRP1 family of CTLRs and their interaction with the related C-type lectin (CLEC) ligands which together exhibit essential immune functions beyond their defined activity in natural killer (NK) cells. The ever-expanding evidence for the requirement of CTLR in numerous biological processes emphasizes the need to better understand the functional potential of these receptor families in immune defense and pathological conditions.
Identification and investigation of depression-related molecular subtypes in inflammatory bowel disease and the anti-inflammatory mechanisms of paroxetine
Authors: Ning Lijun , Wang Xinyuan , Xuan Baoqin , Ma Yanru , Yan Yuqing , Gao Ziyun , Tong Tianying , Cui Zhe , Chen Haoyan , Li Xiaobo , Hong Jie , Wang Zhenhua
Published: February 2023

Background

Up to 40 per cent of people with active inflammatory bowel disease (IBD) also suffer from mood disorders such as anxiety and depression. Notwithstanding, the fundamental biological pathways driving depression in IBD remain unknown.

Methods

We identified 33 core genes that drive depression in IBD patients and performed consensus molecular subtyping with the NMF algorithm in IBD. The CIBERSORT were employed to quantify the immune cells. Metabolic signature was characterized using the “IOBR” R package. The scoring system (D. score) based on PCA. Pre-clinical models are constructed using DSS.

Results

Using transcriptome data from the GEO database of 630 IBD patients, we performed a thorough analysis of the correlation between IBD and depression in this research. Firstly, the samples were separated into two different molecular subtypes (D. cluster1 and D. cluster2) based on their biological signatures. Moreover, the immunological and metabolic differences between them were evaluated, and we discovered that D. cluster2 most closely resembled IBD patients concomitant with depression. We also developed a scoring system to assess the IBD-related depression and predict clinical response to anti-TNF- therapy, with a higher D. score suggesting more inflammation and worse reaction to biological therapies. Ultimately, we also identified through animal experiments an antidepressant, paroxetine, has the added benefit of lowering intestinal inflammation by controlling microorganisms in the digestive tract.

Conclusions

This study highlights that IBD patients with or without depression show significant variations and antidepressant paroxetine may help reduce intestinal inflammation.
Effects of the radio electric asymmetric conveyer (REAC) on motor disorders: An integrative review
Authors: Machado Vinícius Gomes , Brun Ana Beatriz Sorgenfrei , Manffra Elisangela Ferretti
Published: February 2023

Introduction

The radio electric asymmetric conveyer (REAC) is a technology that has the purpose of restoring the cellular polarity triggering the rebalancing of the endogenous bioelectric field, which considering the neurological dysfunctions, affects the neural communication mechanisms. The studies published so far show that the REAC neuromodulation technology has positive effects in treating these dysfunctions, with the principles of endogenous bioelectricity as a basis to achieve these effects.

Objectives

This study aims to review the literature that explored the effects of REAC protocols on motor control and to identify which mechanisms would be involved.

Materials and methods

This integrative review considered studies that used REAC as a therapeutic intervention directed at human motor control and experimental research with animals that applied REAC to obtain effects related to motor behavior.

Results

Ten articles were included, eight clinical and two experimental studies. The clinical studies used the neuro postural optimization (NPO) protocol in 473 patients, of which 53 were healthy subjects, 91 were Alzheimer's disease patients, 128 were patients with atypical swallowing, 12 subjects with neurological diseases, and 189 were without the specification of disease. The experimental studies used the antalgic neuromodulation and neurodegeneration protocols in animal models.

Conclusion

The information integrated in this review made it possible to consider REAC technology a promising resource for treating motor control dysfunctions. It is possible to infer that the technology promotes functional optimization of neuronal circuits that may be related to more efficient strategies to perform motor tasks.
Exploring the common pathogenesis of Alzheimer’s disease and type 2 diabetes mellitus via microarray data analysis
Authors: Ye Xian-wen , Liu Meng-nan , Wang Xuan , Cheng Shui-qing , Li Chun-shuai , Bai Yu-ying , Yang Lin-lin , Wang Xu-xing , Wen Jia , Xu Wen-juan , Zhang Shu-yan , Xu Xin-fang , Li Xiang-ri
Published: February 2023

Background

Alzheimer’s Disease (AD) and Type 2 Diabetes Mellitus (DM) have an increased incidence in modern society. Although more and more evidence has supported that DM is prone to AD, the interrelational mechanisms remain fully elucidated.

Purpose

The primary purpose of this study is to explore the shared pathophysiological mechanisms of AD and DM.

Methods

Download the expression matrix of AD and DM from the Gene Expression Omnibus (GEO) database with sequence numbers GSE97760 and GSE95849, respectively. The common differentially expressed genes (DEGs) were identified by limma package analysis. Then we analyzed the six kinds of module analysis: gene functional annotation, protein–protein interaction (PPI) network, potential drug screening, immune cell infiltration, hub genes identification and validation, and prediction of transcription factors (TFs).

Results

The subsequent analyses included 339 common DEGs, and the importance of immunity, hormone, cytokines, neurotransmitters, and insulin in these diseases was underscored by functional analysis. In addition, serotonergic synapse, ovarian steroidogenesis, estrogen signaling pathway, and regulation of lipolysis are closely related to both. DEGs were input into the CMap database to screen small molecule compounds with the potential to reverse AD and DM pathological functions. L-690488, exemestane, and BMS-345541 ranked top three among the screened small molecule compounds. Finally, 10 essential hub genes were identified using cytoHubba, including PTGS2, RAB10, LRRK2, SOS1, EEA1, NF1, RAB14, ADCY5, RAPGEF3, and PRKACG. For the characteristic Aβ and Tau pathology of AD, RAPGEF3 was associated significantly positively with AD and NF1 significantly negatively with AD. In addition, we also found ADCY5 and NF1 significant correlations with DM phenotypes. Other datasets verified that NF1, RAB14, ADCY5, and RAPGEF3 could be used as key markers of DM complicated with AD. Meanwhile, the immune cell infiltration score reflects the different cellular immune microenvironments of the two diseases.

Conclusion

The common pathogenesis of AD and DM was revealed in our research. These common pathways and hub genes directions for further exploration of the pathogenesis or treatment of these two diseases.
LFP polarity changes across cortical and eccentricity in primary visual cortex
Authors: Khodaei Fereshteh , Sadati S. H. , Doost Mahyar , Lashgari Reza
Published: February 2023

Local field potentials (LFPs) can evaluate neural population activity in the cortex and their interaction with other cortical areas. Analyzing current source density (CSD) rather than LFPs is very significant due to the reduction of volume conduction effects. Current sinks are construed as net inward transmembrane currents, while current sources are net outward ones. Despite extensive studies of LFPs and CSDs, their morphology in different cortical layers and eccentricities are still largely unknown. Because LFP polarity changes provide a measure of neural activity, they can be useful in implanting brain-computer interface (BCI) chips and effectively communicating the BCI devices to the brain. We hypothesize that sinks and sources analyses could be a way to quantitatively achieve their characteristics in response to changes in stimulus size and layer-dependent differences with increasing eccentricities. In this study, we show that stimulus properties play a crucial role in determining the flow. The present work focusses on the primary visual cortex (V1). In this study, we investigate a map of the LFP-CSD in V1 area by presenting different stimulus properties (e.g., size and type) in the visual field area of Macaque monkeys. Our aim is to use the morphology of sinks and sources to measure the input and output information in different layers as well as different eccentricities. According to the value of CSDs, the results show that the stimuli smaller than RF’s size had lower strength than the others and the larger RF’s stimulus size showed smaller strength than the optimized stimulus size, which indicated the suppression phenomenon. Additionally, with the increased eccentricity, CSD’s strengths were increased across cortical layers.
Micronutrients and risks of three main urologic cancers: A mendelian randomization study
Authors: Lu Yi , Su Hao , Wang Yutao , Li Hongjun
Published: February 2023

Background

The effect of micronutrients on urologic cancers has been explored in observational studies. We conducted the two-sample mendelian randomization (TSMR) study to investigate whether micronutrients could causally influence the risk of urologic cancers.

Methods

Summary statistics for four micronutrients and three main urologic cancers outcomes were obtained from genome-wide association studies (GWAS). MR analyses were applied to explore the potential causal association between them. Sensitivity analyses using multiple methods were also conducted.

Results

Genetically predicted one SD increase in serum copper and iron concentrations was causally associated with increased risks of renal cell carcinoma (RCC) (OR = 3.021, 95%CI = 2.204–4.687, P < 0.001, male; OR = 2.231, 95%CI = 1.524-3.953, P < 0.001, female; OR = 1.595, 95%CI = 1.310–1.758, P = 0.0238, male; OR = 1.484, 95%CI = 1.197–2.337, P = 0.0210, female, respectively) and per SD increase in serum zinc levels was related to decreased risks of RCC (OR = 0.131, 95%CI = 0.0159–0.208, P < 0.001, male; OR = 0.124, 95%CI = 0.0434–0.356, P < 0.001, female). No significant results were observed between micronutrients and the risk of bladder cancer after Bonferroni correction. Additionally, per SD increase in serum zinc level was associated with a 5.8% higher risk of prostate cancer (PCa) [OR = 1.058, 95%CI = 1.002–1.116, P = 0.0403, inverse-variance weight (IVW)].

Conclusions

Micronutrients play a vital role in the development of urological tumors. Future studies are required to replicate the findings, explore the underlying mechanisms, and examine the preventive or therapeutic role of micronutrients in clinical settings.
The combination of hand grip strength and modified Glasgow prognostic score predicts clinical outcomes in patients with liver cancer
Authors: Chen Yue , Ruan Guo-Tian , Shi Jin-Yu , Liu Tong , Liu Chen-An , Xie Hai-Lun , Song Meng-Meng , Wang Zi-Wen , Hu Chun-Lei , Zhang He-Yang , Zhang Xiao-Wei , Tian Hai-Ying , Ge Yi-Zhong , Yang Ming , Liu Yu-Ying , Lin Shi-Qi , Liu Xiao-Yue , Zheng Xin , Wang Kun-Hua , Cong Ming-Hua , Shen Xian , Wang Xin , Deng Li , Shi Han-Ping
Published: February 2023

Purpose

Previous studies have shown that both hand grip strength (HGS) and the modified Glasgow Prognostic Score (mGPS) are associated with poor clinical outcomes in patients with liver cancer. In spite of this, no relevant studies have been conducted to determine whether the combination of HGS and mGPS can predict the prognosis of patients with liver cancer. Accordingly, this study sought to explore this possibility.

Methods

This was a multicenter study of patients with liver cancer. Based on the optimal HGS cutoff value for each sex, we determined the HGS cutoff values. The patients were divided into high and low HGS groups based on their HGS scores. An mGPS of 0 was defined as low mGPS, whereas scores higher than 0 were defined as high mGPS. The patients were combined into HGS-mGPS groups for the prediction of survival. Survival analysis was performed using Kaplan–Meier curves. A Cox regression model was designed and adjusted for confounders. To evaluate the nomogram model, receiver operating characteristic curves and calibration curves were used.

Results

A total of 504 patients were enrolled in this study. Of these, 386 (76.6%) were men (mean [SD] age, 56.63 [12.06] years). Multivariate analysis revealed that patients with low HGS and high mGPS had a higher risk of death than those with neither low HGS nor high mGPS (hazard ratio [HR],1.50; 95% confidence interval [CI],1.14–1.98; p = 0.001 and HR, 1.55; 95% CI, 1.14–2.12, p = 0.001 respectively). Patients with both low HGS and high mGPS had 2.35-fold increased risk of death (HR, 2.35; 95% CI, 1.52–3.63; p < 0.001). The area under the curve of HGS-mGPS was 0.623. The calibration curve demonstrated the validity of the HGS-mGPS nomogram model for predicting the survival of patients with liver cancer.

Conclusion

A combination of low HGS and high mGPS is associated with poor prognosis in patients with liver cancer. The combination of HGS and mGPS can predict the prognosis of liver cancer more accurately than HGS or mGPS alone. The nomogram model developed in this study can effectively predict the survival outcomes of liver cancer.
Prediction models for chronic postsurgical pain in patients with breast cancer based on machine learning approaches
Authors: Sun Chen , Li Mohan , Lan Ling , Pei Lijian , Zhang Yuelun , Tan Gang , Zhang Zhiyong , Huang Yuguang
Published: February 2023

Purpose

This study aimed to develop prediction models for chronic postsurgical pain (CPSP) after breast cancer surgery using machine learning approaches and evaluate their performance.

Methods

The study was a secondary analysis based on a high-quality dataset from a randomized controlled trial (NCT00418457), including patients with primary breast cancer undergoing mastectomy. The primary outcome was CPSP at 12 months after surgery, defined as modified Brief Pain Inventory > 0. The dataset was randomly split into a training dataset (90%) and a testing dataset (10%). Variables were selected using recursive feature elimination combined with clinical experience, and potential predictors were then incorporated into three machine learning models, including random forest, gradient boosting decision tree and extreme gradient boosting models for outcome prediction, as well as logistic regression. The performances of these four models were tested and compared.

Results

1152 patients were finally included, of which 22.1% developed CPSP at 12 months after breast cancer surgery. The 6 leading predictors were higher numerical rating scale within 2 days after surgery, post-menopausal status, urban medical insurance, history of at least one operation, under fentanyl with sevoflurane general anesthesia, and received axillary lymph node dissection. Compared with the multivariable logistic regression model, machine learning models showed better specificity, positive likelihood ratio and positive predictive value, helping to identify high-risk patients more accurately and create opportunities for early clinical intervention.

Conclusions

Our study developed prediction models for CPSP after breast cancer surgery based on machine learning approaches, which may help to identify high-risk patients and improve patients’ management after breast cancer.
Clinical management of molecular alterations identified by high throughput sequencing in patients with advanced solid tumors in treatment failure: Real-world data from a French hospital
Authors: Pinet Sandra , Durand Stéphanie , Perani Alexandre , Darnaud Léa , Amadjikpe Fifame , Yon Mathieu , Darbas Tiffany , Vergnenegre Alain , Egenod Thomas , Simonneau Yannick , Le Brun-Ly Valérie , Pestre Julia , Venat Laurence , Thuillier Frédéric , Chaunavel Alain , Duchesne Mathilde , Fermeaux Véronique , Guyot Anne , Lacorre Sylvain , Bessette Barbara , Lalloué Fabrice , Durand Karine , Deluche Elise
Published: February 2023

Background

In the context of personalized medicine, screening patients to identify targetable molecular alterations is essential for therapeutic decisions such as inclusion in clinical trials, early access to therapies, or compassionate treatment. The objective of this study was to determine the real-world impact of routine incorporation of FoundationOne analysis in cancers with a poor prognosis and limited treatment options, or in those progressing after at least one course of standard therapy.

Methods

A FoundationOneCDx panel for solid tumor or liquid biopsy samples was offered to 204 eligible patients.

Results

Samples from 150 patients were processed for genomic testing, with a data acquisition success rate of 93%. The analysis identified 2419 gene alterations, with a median of 11 alterations per tumor (range, 0–86). The most common or likely pathogenic variants were on TP53, TERT, PI3KCA, CDKN2A/B, KRAS, CCDN1, FGF19, FGF3, and SMAD4. The median tumor mutation burden was three mutations/Mb (range, 0–117) in 143 patients with available data. Of 150 patients with known or likely pathogenic actionable alterations, 13 (8.6%) received matched targeted therapy. Sixty-nine patients underwent Molecular Tumor Board, which resulted in recommendations in 60 cases. Treatment with genotype-directed therapy had no impact on overall survival (13 months vs. 14 months; p = 0.95; hazard ratio = 1.04 (95% confidence interval, 0.48–2.26)].

Conclusions

This study highlights that an organized center with a Multidisciplinary Molecular Tumor Board and an NGS screening system can obtain satisfactory results comparable with those of large centers for including patients in clinical trials.
Case report: A case of delayed cutaneous metastases from signet-ring cell mixed-type gastric cancer
Authors: Yao Shaohua , Zhou Peng , Li Yiqing , Li Qin
Published: February 2023

Background

Signet-ring cell gastric carcinoma is a highly malignant tumor, with the characteristics of strong invasiveness, rapid progression, a high degree of malignancy, and generally poor prognosis. The most common site of metastases is the abdominal organs, especially the liver, while delayed cutaneous metastases are rare.

Case presentation

We report a case of cutaneous metastases on the head, groin, and thigh, which recurred 7 years after signet-ring cell gastric carcinoma surgery. The patient was diagnosed with a 2.0×1.5×1.0cm tumor at the angle of stomach, and treated with Billroth II distal gastrectomy accompanied with D2 lymph node dissection. According the pathology, the stage was pT1N3M0. Then the patient received two cycles of oxaliplatin and tegafur chemotherapy, which was discontinued due to the inability to tolerate the side effects of chemotherapy. Seven years after the surgery, the patient initially presented with a fleshy mass on the head and beaded nodules in the groin; then, the mass gradually became larger, along with the thighs turning red, swollen, and crusty. Firstly, the patient was diagnosed with “lower extremity lymphangitis” and treated mostly with anti-inflammatory, promote lymphatic return, detumescence and elastic force cannula in vascular surgery department. However, the symptoms relieved insufficient. Finally, the skin biopsy indicates a signet-ring cell gastric carcinoma cutaneous metastasis. The whole-body PET-CT examination showed multiple nodules with increased metabolism. Then the patient was transferred to The Department of Oncology for further chemotherapy.

Conclusion

Our case highlights that gastric tumor recurrence and metastasis should be highly suspected when skin lesions appear in patients with signet-ring cell gastric carcinoma. At the same time, multidisciplinary consultation and close cooperation between surgeons, oncologists, and dermatologists are of great significance to the diagnosis and treatment of this disease.
Reduced radiation exposure to circulating blood cells in proton therapy compared with X-ray therapy in locally advanced lung cancer: Computational simulation based on circulating blood cells
Authors: Kim Nalee , Shin Jungwook , Ahn Sung Hwan , Pyo Hongryull , Noh Jae Myoung , Yang Kyungmi , Lee Woojin , Park Byoungsuk
Published: February 2023

Background

We estimated the dose of circulating blood cells (CBCs) in patients with locally advanced non-small cell lung cancer for predicting severe radiation-induced lymphopenia (SRIL) and compared pencil-beam scanning proton therapy (PBSPT) and intensity-modulated (photon) radiotherapy (IMRT).

Materials and methods

After reviewing 325 patients who received definitive chemoradiotherapy with PBSPT (n = 37) or IMRT (n = 164). SRIL was diagnosed when two or more events of an absolute lymphocyte count < 200 µL occurred during the treatment course. Dose information for the heart and lungs was utilized for the time-dependent computational dose calculation of CBCs.

Results

The dose distribution of CBCs was significantly lesser in the PBSPT group than that in the IMRT group. Overall, 75 (37.3%) patients experienced SRIL during the treatment course; 72 and 3 patients were treated with IMRT and PBSPT, respectively. SRIL was associated with poor progression-free and overall survival outcomes. Upon incorporating the dose information of CBCs for predicting SRIL, CBC D90% > 2.6 GyE was associated with the development of SRIL with the baseline lymphocyte count and target volume. Furthermore, PBSPT significantly reduced the dose of CBC D90% (odds ratio = 0.11; p = 0.004) compared with IMRT.

Conclusion

The results of this study demonstrate the significance of the dose distribution of CBCs in predicting SRIL. Furthermore, reducing the dose of CBCs after PBSPT minimized the risk of SRIL. Lymphocyte-sparing radiotherapy in PBSPT could improve outcomes, particularly in the setting of maintenance immunotherapy.
The role of virtual reality as adjunctive therapy to spinal cord stimulation in chronic pain: A feasible concept?
Authors: Noble Timothy , Boone Lyndon , El Helou Antonios
Published: February 2023

Spinal cord stimulation and virtual reality therapy are established and promising techniques, respectively, for managing chronic pain, each with its unique advantages and challenges. While each therapy has been the subject of significant research interest, the prospect of combining the two modalities to offer a synergistic effect in chronic pain therapy is still in its infancy. In this narrative review, we assess the state of the field combining virtual reality as an adjunctive therapy to spinal cord stimulation in chronic pain. We also review the broader field of virtual reality therapy for acute and chronic pain, considering evidence related to feasibility in the Canadian healthcare system from cost and patient satisfaction perspectives. While early results show promise, there are unexplored aspects of spinal cord stimulation combined with virtual reality therapy, particularly long-term effects on analgesia, anxiolysis, and implications on the effectiveness and longevity of spinal cord stimulation. The infrastructure for billing virtual reality as a consult service or therapy must also catch up if it is eventually used to supplement spinal cord stimulation for chronic pain.
Body size and brain volumetry in the rat following prolonged morphine administration in infancy and adulthood
Authors: Taylor Milo , Cheng Anya Brooke , Hodkinson Duncan Jack , Afacan Onur , Zurakowski David , Bajic Dusica
Published: February 2023

Background

Prolonged morphine treatment in infancy is associated with a high incidence of opioid tolerance and dependence, but our knowledge of the long-term consequences of this treatment is sparse. Using a rodent model, we examined the (1) short- and (2) long-term effects of prolonged morphine administration in infancy on body weight and brain volume, and (3) we evaluated if subsequent dosing in adulthood poses an increased brain vulnerability.

Methods

Newborn rats received subcutaneous injections of either morphine or equal volume of saline twice daily for the first two weeks of life. In adulthood, animals received an additional two weeks of saline or morphine injections before undergoing structural brain MRI. After completion of treatment, structural T2-weigthed MRI images were acquired on a 7 T preclinical scanner (Bruker) using a RARE FSE sequence. Total and regional brain volumes were manually extracted from the MRI images using ITK-SNAP (v.3.6). Regions of interest included the brainstem, the cerebellum, as well as the forebrain and its components: the cerebral cortex, hippocampus, and deep gray matter (including basal ganglia, thalamus, hypothalamus, ventral tegmental area). Absolute (cm3) and normalized (as % total brain volume) values were compared using a one-way ANOVA with Tukey HSD post-hoc test.

Results

Prolonged morphine administration in infancy was associated with lower body weight and globally smaller brain volumes, which was not different between the sexes. In adulthood, females had lower body weights than males, but no difference was observed in brain volumes between treatment groups. Our results are suggestive of no long-term effect of prolonged morphine treatment in infancy with respect to body weight and brain size in either sex. Interestingly, prolonged morphine administration in adulthood was associated with smaller brain volumes that differed by sex only in case of previous exposure to morphine in infancy. Specifically, we report significantly smaller total brain volume of female rats on account of decreased volumes of forebrain and cortex.

Conclusions

Our study provides insight into the short- and long-term consequences of prolonged morphine administration in an infant rat model and suggests brain vulnerability to subsequent exposure in adulthood that might differ with sex.
Protective effects and mechanisms of the Erzhi formula on glucocorticoid induced primary cortical neuron injury
Authors: Han Rui , Han Guoying , Yan Yiqi , Han Lifeng , Li Lin , Zhang Han
Published: February 2023

High concentrations of glucocorticoids (GC) can cross the blood-brain barrier into the brain parenchyma, triggering a stress state that can lead to a range of physiological changes. This study investigated whether Erzhi formula has neuroprotective effects against glucocorticoid damage by establishing a dexamethasone-induced primary cortical neuron injury model in vitro. The results showed that Erzhi formula could reduce dexamethasone-induced apoptosis in primary cultured cortical neurons and improve synaptic damage. Further, network pharmacological analysis revealed that Erzhi formula may exert antidepressant effects by multi-component, multi-target, and multi-pathway characteristics, in which Salidroside, Biochanin-A and other ingredients are key components, HSD11B1, NR3C1, and other proteins are key targets, and steroid metabolism may be a key process in its action. Moreover, our study found that the neuroprotective effect of Erzhi formula might be related to the 11β-HSD1-GC/glucocorticoid receptor (GR) signaling pathway. The Erzhi formula could significantly inhibit the activity of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in vitro using homogeneous time-resolved fluorescence. In addition to providing evidence for the pharmacological effects of the Erzhi formula, the present study lays down the foundation for subsequent experiments.