bluuebunny/crossref_metadata_2025 huggingface dataset:
Confrontation of endolymphatic hydrops diagnosis on 3-Tesla MRI to clinical and audiovestibular findings in Meniere's disease
Authors: Diorflar Sarah , Guigou Caroline , Daguet Edouard , Bensimon Jean-Loup , Toupet Michel , Bozorg-Grayeli Alexis
Published: January 2023

Objective

The aim of this study was to compare different MRI diagnostic criteria for endolymphatic hydrops (EH) and to investigate the relation between audiovestibular and MRI findings in Meniere's disease (MD).

Materials and methods

Prospective cross-sectional cohort study in 2 referral centers included 76 patients with unilateral (n = 62) or bilateral (n = 14) MD. All patients underwent inner ear 3T-MRI 4 h (n = 52) or >24H (n = 24) following audiovestibular tests. T2-CISS and 3D-FLAIR images 4H after gadolinium were obtained. EH diagnosis was based on saccular morphology on coronal views (T2 and 3D-FLAIR), semi quantitative estimation of endolymphatic space enlargement, and saccule utricle ratio inversion (SURI) on 3D-FLAIR axial views.

Results

SURI was the best criterion related to the disease side (43 SURI+ on symptomatic ears, n = 77, vs. 6 SURI+ on asymptomatic ears, n = 53, p < 0.0001, Chi-2). Same-day MRI revealed relation between EH, hearing loss and caloric weakness which could not be detected on delayed MRI: SURI was associated with a higher pure-tone average (43 ± 4.1 dB in SURI+ ears, n = 42 vs. 23 ± 2.6 SURI-, n = 62, p < 0.0001, unpaired t-test,), and a higher proportion of vestibular caloric weakness (23/46 SURI+ ears vs. 4/62 SURI-, p < 0.001, Chi-2). Among all criteria, SURI combined to caloric weakness was the best predictor of the affected side in a logistic regression model.

Conclusion

SURI had the strongest relation to the side the disease and audio vestibular findings for unilateral, probable and definite meniere disease. A short delay between MRI and audio vestibular tests improved the coherence between the findings.
Rapid-onset dystonia-parkinsonism is associated with reduced cerebral blood flow without gray matter changes
Authors: Whitlow Christopher T. , Atcheson Kyle M. , Snively Beverly M. , Cook Jared F. , Kim Jeongchul , Haq Ihtsham U. , Sweadner Kathleen J. , Ozelius Laurie J. , Brashear Allison
Published: January 2023

Purpose

Previous research showed discrete neuropathological changes associated with rapid-onset dystonia-parkinsonism (RDP) in brains from patients with an ATP1A3 variant, specifically in areas that mediate motor function. The purpose of this study was to determine if magnetic resonance imaging methodologies could identify differences between RDP patients and variant-negative controls in areas of the brain that mediate motor function in order to provide biomarkers for future treatment or prevention trials.

Methods

Magnetic resonance imaging voxel-based morphometry and arterial spin labeling were used to measure gray matter volume and cerebral blood flow, respectively, in cortical motor areas, basal ganglia, thalamus, and cerebellum, in RDP patients with ATP1A3 variants (n = 19; mean age = 37 ± 14 years; 47% female) and variant-negative healthy controls (n = 11; mean age = 34 ± 19 years; 36% female).

Results

We report age and sex-adjusted between group differences, with decreased cerebral blood flow among patients with ATP1A3 variants compared to variant-negative controls in the thalamus (p = 0.005, Bonferroni alpha level < 0.007 adjusted for regions). There were no statistically significant between-group differences for measures of gray matter volume.

Conclusions

There is reduced cerebral blood flow within brain regions in patients with ATP1A3 variants within the thalamus. Additionally, the lack of corresponding gray matter volume differences may suggest an underlying functional etiology rather than structural abnormality.
Brain function effects of autonomous sensory meridian response (ASMR) video viewing
Authors: Sakurai Noriko , Nagasaka Kazuaki , Takahashi Shingo , Kasai Satoshi , Onishi Hideaki , Kodama Naoki
Published: January 2023

Background

Autonomous sensory meridian response (ASMR) is the sensation of tingling from audiovisual stimuli that leads to positive emotions. ASMR is used among young people to relax, induce sleep, reduce stress, and alleviate anxiety. However, even without experiencing tingling, ASMR is used by many young people to seek relaxation. Auditory stimulation in ASMR is thought to play the most important role among its triggers, and previous studies have used a mixture of auditory and visual stimulation and auditory stimulation. This is the first study to approach the differences between the effects of direct audiovisual and auditory stimulation from the perspective of brain function using functional magnetic resonance imaging (fMRI) and to clarify the effects of ASMR, which attracts many young people.

Methods

The subjects were 30 healthy subjects over 19 years old or older who had not experienced tingling. Brain function was imaged by fMRI while watching ASMR videos or listening to the sound files only. We administered a questionnaire based on a Likert scale to determine if the participants felt a “relaxed mood” and “tingling mood” during the task.

Results

Significant activation was found in the visual cortex for audiovisual stimulation and in the visual and auditory cortex for auditory stimulation. In addition, activation of characteristic sites was observed. The specific sites of activation for audiovisual stimulation were the middle frontal gyrus and the left nucleus accumbens, while the specific sites of activation for auditory stimulation were the bilateral insular cortices. The questionnaire showed no significant differences in either “relaxed mood” or “tingling mood” in response to auditory and visual stimulation or auditory stimulation alone.

Conclusion

The results of this study showed that there was a clear difference between auditory and audiovisual stimulation in terms of the areas of activation in the brain, but the questionnaire did not reveal any difference in the subjects’ mood. Audiovisual stimulation showed activation of the middle frontal gyrus and the nucleus accumbens, whereas auditory stimulation showed activation of the insular cortex. This difference in brain activation sites suggests a difference in mental health effects between auditory and audiovisual stimulation. However, future research on comparisons between those who experience tingling and those who do not, as well as investigations of physiological indices, and examination of the relationship with activated areas in the brain may show that ASMR is useful for mental health.
Methylmalonic acidemia: Neurodevelopment and neuroimaging
Authors: Chen Tao , Gao Yian , Zhang Shengdong , Wang Yuanyuan , Sui Chaofan , Yang Linfeng
Published: January 2023

Methylmalonic acidemia (MMA) is a genetic disease of abnormal organic acid metabolism, which is one of the important factors affecting the survival rate and quality of life of newborns or infants. Early detection and diagnosis are particularly important. The diagnosis of MMA mainly depends on clinical symptoms, newborn screening, biochemical detection, gene sequencing and neuroimaging diagnosis. The accumulation of methylmalonic acid and other metabolites in the body of patients causes brain tissue damage, which can manifest as various degrees of intellectual disability and severe neurological dysfunction. Neuroimaging examination has important clinical significance in the diagnosis and prognosis of MMA. This review mainly reviews the etiology, pathogenesis, and nervous system development, especially the neuroimaging features of MMA.
Periglomerular afferent innervation of the mouse renal cortex
Authors: Tyshynsky Roman , Sensarma Sulagna , Riedl Maureen , Bukowy John , Schramm Lawrence P. , Vulchanova Lucy , Osborn John W.
Published: January 2023

Recent studies using a novel method for targeted ablation of afferent renal nerves have demonstrated their importance in the development and maintenance of some animal models of hypertension. However, relatively little is known about the anatomy of renal afferent nerves distal to the renal pelvis. Here, we investigated the anatomical relationship between renal glomeruli and afferent axons identified based on transient receptor potential vanilloid 1 channel (TRPV1) lineage or calcitonin gene related peptide (CGRP) immunolabeling. Analysis of over 6,000 (10,000 was accurate prior to the removal of the TH data during the review process) glomeruli from wildtype C57BL/6J mice and transgenic mice expressing tdTomato in TRPV1 lineage cells indicated that approximately half of all glomeruli sampled were closely apposed to tdTomato+ or CGRP+ afferent axons. Glomeruli were categorized as superficial, midcortical, or juxtamedullary based on their depth within the cortex. Juxtamedullary glomeruli were more likely to be closely apposed by afferent axon subtypes than more superficial glomeruli. High-resolution imaging of thick, cleared renal slices and subsequent distance transformations revealed that CGRP+ axons closely apposed to glomeruli were often found within 2 microns of nephrin+ labeling of glomerular podocytes. Furthermore, imaging of thick slices suggested that CGRP+ axon bundles can closely appose multiple glomeruli that share the same interlobular artery. Based on their expression of CGRP or tdTomato, prevalence near glomeruli, proximity to glomerular structures, and close apposition to multiple glomeruli within a module, we hypothesize that periglomerular afferent axons may function as mechanoreceptors monitoring glomerular pressure. These anatomical findings highlight the importance of further studies investigating the physiological role of periglomerular afferent axons in neural control of renal function in health and disease.
Assessment of Treg-related lncRNAs in epilepsy
Authors: Sharifi Guive , Eghtedarian Reyhane , Taheri Mohammad , Hussen Bashdar Mahmud , Eslami Solat , Ghafouri-Fard Soudeh , Sayad Arezou
Published: January 2023

Recent studies have shown dysregulation of several groups of long non-coding RNAs in the context of epilepsy. According to evidence regarding the role of regulatory T cells in this disorder, we examined expression levels of regulatory T cell-related lncRNAs, namely TH2-LCR, RMRP, IFNG-AS1 (NEST), MAFTRR and FLICR in the blood of epileptic cases compared with controls. Expression of RMRP was lower in patients with refractory epilepsy compared with controls [expression ratio (95% CI) = 0.32 (0.13–0.8), adjusted p-value = 0.0008]. Besides, its expression was lower in refractory patients vs. non-refractory patients [expression ratio (95% CI) = 0.2 (0.1–0.41), adjusted p-value < 0.0001]. Expression of TH2-LCR was lower in refractory patients vs. controls [expression ratio (95% CI) = 0.4 (0.17–0.93), adjusted p-value = 0.0044] and in refractory patients vs. non-refractory ones [Expression ratio = 0.28 (0.19–0.58), p-value < 0.0001]. Expression of NEST was higher in total patients [expression ratio (95% CI) = 2.48 (1.15–5.27), adjusted p-value = 0.0012] and in both groups of patients compared with controls. However, its expression was not different between refractory and non-refractory cases. Similarly, FLICR and MAFTRR were over-expressed in total cases and both groups of patients compared with controls, but their expressions were similar between refractory and non-refractory cases. MAFTRR could differentiate between total epileptic cases and controls with AUC value of 0.8. This lncRNA could separate refractory and non-refractory cases from healthy controls with AUC values of 0.73 and 0.88, respectively. This study provides evidence for deregulation of regulatory T cell-related lncRNAs in epilepsy and their potential role as diagnostic markers in this condition.
Changes in French purchases of pulses during an FAO awareness campaign
Authors: Badji Ikpidi , Caillavet France , Amiot Marie Josephe
Published: January 2023

Background

Pulses can play a key role in a well-balanced diet and are now recognized for their health and sustainability benefits. However, consumption remains quite low, motivating promotion efforts such as the “International Year of Pulses” declared by the Food and Agriculture Organization (FAO) in 2016. The present study aims to evaluate the changes in the purchase of pulses before and after the FAO's awareness campaign promoting the consumption of pulses in France and investigate the potential differences across sub-populations.

Methods

Purchase data come from Kantar Worldpanel 2014–2017. First, in order to understand demand for pulses, the influence of sociodemographic variables on the purchase of pulses in different forms (raw, processed, ultra-processed) is analyzed using a Box-Cox heteroskedastic double-hurdle model. Then, changes in purchasing before and after the FAO campaign were estimated using a two-way fixed-effects model, controlling for price and sociodemographic variables.

Results

On that period, the purchasing of pulses increased by 8.4% overall. The increase was greater for younger participants (+11.8%), people living in urban areas with over 200,000 inhabitants (+8.4%), and lower-income households (+7.1%). The 8.4% increase observed indicated that there were gradual preference change in favor of pulses and the impact of the awareness campaign was to boost expenditure on pulses by a further 2%.

Conclusion

The FAO campaign coincided with an increase in the purchasing of pulses and may have had an enhancing effect. However, consumption still remains below the level advised by dietary guidelines. There is a need for more public information and communication on the health and sustainability benefits of pulses, the consumption of which can be promoted through supply and education interventions.

JEL codes

D12; Q18; I18.
Interactions between genetic and lifestyle factors on cardiometabolic disease-related outcomes in Latin American and Caribbean populations: A systematic review
Authors: Wuni Ramatu , Ventura Eduard F. , Curi-Quinto Katherine , Murray Claudia , Nunes Richard , Lovegrove Julie A. , Penny Mary , Favara Marta , Sanchez Alan , Vimaleswaran Karani Santhanakrishnan
Published: January 2023

Introduction

The prevalence of cardiometabolic diseases has increased in Latin American and the Caribbean populations (LACP). To identify gene-lifestyle interactions that modify the risk of cardiometabolic diseases in LACP, a systematic search using 11 search engines was conducted up to May 2022.

Methods

Eligible studies were observational and interventional studies in either English, Spanish, or Portuguese. A total of 26,171 publications were screened for title and abstract; of these, 101 potential studies were evaluated for eligibility, and 74 articles were included in this study following full-text screening and risk of bias assessment. The Appraisal tool for Cross-Sectional Studies (AXIS) and the Risk Of Bias In Non-Randomized Studies—of Interventions (ROBINS-I) assessment tool were used to assess the methodological quality and risk of bias of the included studies.

Results

We identified 122 significant interactions between genetic and lifestyle factors on cardiometabolic traits and the vast majority of studies come from Brazil (29), Mexico (15) and Costa Rica (12) with FTO, APOE, and TCF7L2 being the most studied genes. The results of the gene-lifestyle interactions suggest effects which are population-, gender-, and ethnic-specific. Most of the gene-lifestyle interactions were conducted once, necessitating replication to reinforce these results.

Discussion

The findings of this review indicate that 27 out of 33 LACP have not conducted gene-lifestyle interaction studies and only five studies have been undertaken in low-socioeconomic settings. Most of the studies were cross-sectional, indicating a need for longitudinal/prospective studies. Future gene-lifestyle interaction studies will need to replicate primary research of already studied genetic variants to enable comparison, and to explore the interactions between genetic and other lifestyle factors such as those conditioned by socioeconomic factors and the built environment. The protocol has been registered on PROSPERO, number CRD42022308488.

Systematic review registration

https://clinicaltrials.gov, identifier CRD420223 08488.
Libyan cancer patients at King Hussein Cancer Center for more than a decade, the current situation, and a future vision
Authors: Erashdi Madiha , Al-Ani Abdallah , Mansour Asem , Al-Hussaini Maysa
Published: January 2023

Background

Since 2011, the Libyan civil war crisis had affected all dimensions of livelihood including cancer care. This has resulted in a steady incline in the number of Libyan patients with cancer seeking oncologic care and management in Tunisia, Egypt and Jordan, among others. King Hussein Cancer Center (KHCC) has been one of the main destinations for Libyan patients with cancer for more than a decade.

Aim

We are reporting on the characteristics of Libyan patients with cancer presenting to KHCC during the past fourteen years.

Methods

We performed a retrospective chart review of all Libyan patients with cancer presenting to KHCC between 2006 and 2019.

Results

A total of 3170 records were included in the final analysis. The overall sample was predominantly adults (71%) with a male-to-female ratio of 1:1.2. Overall, the most common referred cancers to KHCC were breast (21%), hematolymphoid (HL) (17%), and gastrointestinal tract (GIT) (16.2%) cancers. Breast cancer was the most common among adult females (41.7%), GIT among adult males (23.6%), and HL among pediatrics (38.5%). Around 37.8% of patients presented with distant metastasis at their first encounter at KHCC, among which 14.7% were candidates for palliative care.

Conclusion

The sustenance of treatment for Libyan patients with cancer requires extensive collaboration between governmental and private sectors. The Libyan oncological landscape could benefit from national screening and awareness programs, twining programs and telemedicine, introduction of multidisciplinary boards, and the formulation of a national cancer registry. Adopting the successful models at KHCC can help to augment the oncology services within the Libyan healthcare sector.
Analysis of the potential association between ferroptosis and immune in hepatocellular carcinoma and their relationship with prognosis
Authors: Wen Kai , Yang Feng , Hu Lei , Shi Juanyi , Mui Sintim , Wang Weidong , Liao Hao , Li Huoming , Xiao Zhiyu , Yan Yongcong
Published: January 2023

Background

The development of targeted therapy and immunotherapy has enriched the treatment of hepatocellular carcinoma (HCC), however, have had poor or no reponse, or even no response. Previous research suggested that ferroptosis and tumor immune microenvironment (TIME) may have a fundamental impact on efficacy during HCC immunotherapy and targeted therapy. Therefore, there is a clinical need to develop a signature that categorizes HCC patients in order to make more accurate clinical decisions.

Methods

Clinical data and gene expression data of HCC patients were obtained from The Cancer Genome Atlas (TCGA) portal and International Cancer Genome Consortium (ICGC) portal. To identify ferroptosis-related immune-related genes (ferroptosis-related IRGs), Pearson correlation analysis was conducted. The ferroptosis-related IRGs prognostic signature (FIPS) was constructed using Univariate Cox and LASSO Cox algorithms. The predictive effectiveness of FIPS was evaluated using Receiver Operating Characteristic (ROC) curves and survivorship curve. The correlation ship between FIPS and TIME was evaluated using single-sample Gene Set Enrichment Analysis (ssGSEA) and CIBERSORT. The relationship between FIPS and immunotherapy responsiveness was evaluated using immunophenoscore. The expression level of 10 ferroptosis-related IRGs in normal liver tissues and HCC tissues was compared using immunohistochemistry. Finally, we established a nomogram (based on FIPS, TNM stage, and age) for clinical application.

Results

The FIPS was established with ten ferroptosis-related IRGs. The high-FIPS subgroup showed a poor clinical prognosis and an obviously higher proportion of HCC patients with advanced TNM stage, high WHO grade and high alpha fetoprotein(AFP) value. Analysis of TIME indicated that patients in the high-FIPS subgroup may be in immunosuppressed state. Meanwhile, we found that ferroptosis may be inhibited in the high-FIPS subgroup and this subgroup may be impervious to immunotherapy and sorafenib.

Conclusion

We constructed a novel potential prognostic signature for HCC patients that predicts overall survival, ferroptosis and immune status, sorafenib sensitivity, and immunotherapy responsiveness.
Acute promyelocytic leukemia with FIP1L1::RARA fusion gene: The clinical utility of transcriptome sequencing and bioinformatic analyses
Authors: Liu Guanghua , Long Jiangwen , Chen Yuyu , Li Lingqian , Huan Xisha , Long Panpan
Published: January 2023

Background

Acute promyelocytic leukemia (APL) is typically characterized by the presence of coagulopathy and the PML::RARA fusion gene. The FIP1L1::RARA has been reported as a novel fusion gene, but studies on its pathogenesis are limited.

Objectives

A FIP1L1::RARA fusion in a child finally diagnosed as APL was reported. RNA sequencing (RNA-seq) of six patients (three cases of acute lymphoblastic leukemia (ALL), one case of myelodysplastic syndrome (MDS), one case of acute megakaryoblastic leukemia (M7), and one case of APL with FIP1L1::RARA) were performed.

Methods

Transcriptome analysis of six patients was performed by RNA-seq. The heat map was used for showing the RNA expression profile, the volcano plot for identifying differential expression genes (DEGs), and the KEGG Orthology-Based Annotation System (KOBAS) online biological information database for KEGG pathway enrichment analysis.

Results

Obvious differences between APL with FIP1L1::RARA and hematologic malignancies were identified. 1060 common differentially expressed genes (co-DEGs) were detected between APL with FIP1L1::RARA vs ALL and APL with FIP1L1::RARA vs myeloid neoplasms (MDS, M7), the up-regulated genes were mainly mapped into platelet activation, cancer, AMPK signaling pathway, PI3K-Akt signaling pathway, and MAPK signaling pathway. The down-regulated genes were significantly associated with TNF signaling pathway, Rap1 signaling pathway, Age-RAGE signaling pathway, and apoptosis.

Conclusion

A FIP1L1::RARA fusion in a child finally diagnosed as APL was reported. RNA-seq may provide a new diagnostic method when RARA rearrangements fail to be identified by conventional methods. In the analysis of co-DEGs between case vs ALL and case vs myeloid neoplasms, the up-regulated and down-regulated genes were enriched in different signaling pathways. Further experimental studies are needed to identify pathogenesis and treatment for APL with FIP1L1::RARA.
Tumor-informed or tumor-agnostic circulating tumor DNA as a biomarker for risk of recurrence in resected colorectal cancer patients
Authors: Chan Hiu Ting , Nagayama Satoshi , Otaki Masumi , Chin Yoon Ming , Fukunaga Yosuke , Ueno Masashi , Nakamura Yusuke , Low Siew-Kee
Published: January 2023

Introduction

Circulating tumor DNA (ctDNA) has been increasingly recognized as a promising minimally-invasive biomarker that could identify patients with minimal residual disease and a high risk of recurrence after definitive treatment. In this study, we’ve compared the clinical utility and sensitivity of 2 different approaches to ctDNA analyses: tumor-informed and tumor-agnostic in the management of colorectal (CRC) patients. The clinical benefits of a single timepoint ctDNA analysis compared to serial ctDNA monitoring after definitive treatment were also evaluated to uncover the ideal surveillance protocol.

Methods

Patient-paired resected tumor tissues, peripheral blood cells, and a total of 127 pre-operative and serial plasma cell-free DNA (cfDNA) samples after definitive treatment from 38 CRC patients that had undergone curative intent surgery were analyzed using a commercial NGS cfDNA panel.

Results

Up to 84% (32/38) of the recruited patients were detected with at least 1 genomic alteration from the tumor tissues that could be monitored using the tumor-informed ctDNA approach and none of the detected alterations were clonal hematopoiesis (CH) related. In contrast, 37% (14/38) of patients were detected with at least 1 monitoring alteration after exclusion of CH mutations using the tumor-agnostic approach. Serial plasma samples after definitive therapy were available for 31 patients. In the landmark ctDNA analysis, 24% (7/29) of patients had detectable ctDNA and were more likely to relapse than ctDNA-negative patients (p < 0.05). The landmark analysis sensitivity and specificity for recurrence were 67% and 87%, respectively. The incorporation of longitudinal ctDNA analysis at 6-months intervals improved the sensitivity to 100%. The median variant allele frequency (VAF) of the ctDNA mutations detected during surveillance was 0.028% (range: 0.018-0.783), where up to 80% (8/10) of the mutations were detected at VAF lower than the tumor-agnostic detection limit of 0.1%. Utilizing the tumor-agnostic approach reduced the recurrence detection sensitivity to 67% (4/6). Serial ctDNA analyses predicted disease recurrence at a median of 5 months ahead of radiological imaging.

Conclusion

Longitudinal monitoring using tumor-informed ctDNA testing shows high analytical sensitivity, low probability of false-positive results due to CH mutations, and improved sensitivity in detecting recurrence which may modify the clinical management of CRC.
A novel cuproptosis-related LncRNA signature: Prognostic and therapeutic value for low grade glioma
Authors: Wen Jun , Zhao Wenting , Shu Xiaolei
Published: January 2023

Background

As a common primary intracranial tumor, the diagnosis and therapy of low-grade glioma (LGG) remains a pivotal barrier. Cuproptosis, a new way induces cell death, has attracted worldwide attention. However, the relationship between cuproptosis and LGG remains unknown. Our study is all about finding out if there are any genes related to coproptosis that can be used to predict the outcome of LGG.

Methods

RNA data and clinical information were selected from Cancer Genome Atlas (TCGA) datasets and the Genotype-Tissue Expression (GTEx), 5 lncRNAs (GAS5.AS1, MYLK.AS1, AC142472.1, AC011346.1, AL359643.3) were identified by Cox univariate and multivariate regression, as well as LASSO Cox regression. In the training and test sets, a dual validation of the predictive signature comprised of these 5 lncRNAs was undertaken. The findings demonstrate that the risk model is able to predict the survival regression of LGG patients and has a good performance in either the KM curve approach or the ROC curve. GO, GSEA and KEGG were carried out to explore the possible molecular processes that affecting the prognosis of LGG. The characteristics of immune microenvironment were investigated by using CIBERSORT, ESTIMATE and ssGSEA.

Results

We identified five lncRNAs related with cuproptosis that were closely associated with the prognosis of LGG and used these five lncRNAs to develop a risk model. Using this risk model, LGG patients were then divided into high-risk and low-risk groups. The two patient groups had significantly distinct survival characteristics. Analyses of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that the differential genes of the two patient groups were primarily concentrated in neural active ligand-receptor interaction and cytokine-cytokine receptor interaction. The ssGSEA score determined the information related to immune infiltration, and the two groups were differentially expressed in immune subpopulations such as T cells and B cells as well.

Conclusion

Our study discovered 5 cuproptosis-related lncRNAs which contribute to predicting patients’ survival of LGG and provide ideas for the exploration of new targets for LGG in the future.
Bacteria derived extracellular vesicles in the pathogenesis and treatment of gastrointestinal tumours
Authors: Ge Yang , Sun Fengyuan , Zhao Bo , Kong Fanyang , Li Zhaoshen , Kong Xiangyu
Published: January 2023

Extracellular vesicles are fundamentally significant in the communication between cells. Outer Membrane Vesicles(OMVs) are a special kind of EVs produced by Gram-negative bacteria, which are minute exosome-like particles budding from the outer membrane, which have been found to play essential roles in diverse bacterial life events, including regulation of microbial interactions, pathogenesis promotion, stress responses and biofilm formation. Recently, and more researches have explored the substantial potentials of EVs as natural functional nanoparticles in the bioengineering applications in infectious diseases, cardiovascular diseases, autoimmune diseases and neurological diseases, such as antibacterial therapy, cancer drugs and immunoadjuvants, with several candidates in clinical trials showing promising efficacy. However, due to the poor understanding of sources, membrane structures and biogenesis mechanisms of EVs, progress in clinical applications still remains timid. In this review, we summarize the latest findings of EVs, especially in gastrointestinal tract tumours, to provide a comprehensive introduction of EVs in tumorigenesis and therapeutics.
HiRAND: A novel GCN semi-supervised deep learning-based framework for classification and feature selection in drug research and development
Authors: Huang Yue , Rong Zhiwei , Zhang Liuchao , Xu Zhenyi , Ji Jianxin , He Jia , Liu Weisha , Hou Yan , Li Kang
Published: January 2023

The prediction of response to drugs before initiating therapy based on transcriptome data is a major challenge. However, identifying effective drug response label data costs time and resources. Methods available often predict poorly and fail to identify robust biomarkers due to the curse of dimensionality: high dimensionality and low sample size. Therefore, this necessitates the development of predictive models to effectively predict the response to drugs using limited labeled data while being interpretable. In this study, we report a novel Hierarchical Graph Random Neural Networks (HiRAND) framework to predict the drug response using transcriptome data of few labeled data and additional unlabeled data. HiRAND completes the information integration of the gene graph and sample graph by graph convolutional network (GCN). The innovation of our model is leveraging data augmentation strategy to solve the dilemma of limited labeled data and using consistency regularization to optimize the prediction consistency of unlabeled data across different data augmentations. The results showed that HiRAND achieved better performance than competitive methods in various prediction scenarios, including both simulation data and multiple drug response data. We found that the prediction ability of HiRAND in the drug vorinostat showed the best results across all 62 drugs. In addition, HiRAND was interpreted to identify the key genes most important to vorinostat response, highlighting critical roles for ribosomal protein-related genes in the response to histone deacetylase inhibition. Our HiRAND could be utilized as an efficient framework for improving the drug response prediction performance using few labeled data.
14-3-3 and Smad2/3 are crucial mediators of atypical-PKCs: Implications for neuroblastoma progression
Authors: Breedy S. , Ratnayake W.S. , Lajmi L. , Hill R. , Acevedo-Duncan M.
Published: January 2023

Neuroblastoma (NB) is a cancer that develops in the neuroblasts. It is the most common cancer in children under the age of 1 year, accounting for approximately 6% of all cancers. The prognosis of NB is linked to both age and degree of cell differentiation. This results in a range of survival rates for patients, with outcomes ranging from recurrence and mortality to high survival rates and tumor regression. Our previous work indicated that PKC-ι promotes cell proliferation in NB cells through the PKC-ι/Cdk7/Cdk2 cascade. We report on two atypical protein kinase inhibitors as potential therapeutic candidates against BE(2)-C and BE(2)-M17 cells: a PKC-ι-specific 5-amino-1-2,3-dihydroxy-4-(methylcyclopentyl)-1H-imidazole-4-carboxamide and a PKC-ζ specific 8-hydroxy-1,3,6-naphthalenetrisulfonic acid. Both compounds induced apoptosis and retarded the epithelial-mesenchymal transition (EMT) of NB cells. Proteins 14-3-3 and Smad2/3 acted as central regulators of aPKC-driven progression in BE(2)-C and BE(2)-M17 cells in relation to the Akt1/NF-κB and TGF-β pathways. Data indicates that aPKCs upregulate Akt1/NF-κB and TGF-β pathways in NB cells through an association with 14-3-3 and Smad2/3 that can be diminished by aPKC inhibitors. In summary, both inhibitors appear to be promising potential neuroblastoma therapeutics and merit further research.
Intraoperative oxygen tension and redox homeostasis in Pseudomyxoma peritonei: A short case series
Authors: Valenzuela-Molina Francisca , Bura Florina I. , Vázquez-Borrego Mari C. , Granados-Rodríguez Melissa , Rufián-Andujar Blanca , Rufián-Peña Sebastián , Casado-Adam Ángela , Sánchez-Hidalgo Juan Manuel , Rodríguez-Ortiz Lidia , Ortega-Salas Rosa , Martínez-López Ana , Michán Carmen , Alhama José , Arjona-Sánchez Álvaro , Romero-Ruiz Antonio
Published: January 2023

Introduction

Pseudomyxoma peritonei (PMP) is a rare malignant disease characterized by a massive multifocal accumulation of mucin within the peritoneal cavity. The current treatment option is based on complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. However, the recurrence is frequent with subsequent progression and death. To date, most of the studies published in PMP are related to histological and genomic analyses. Thus, the need for further studies unveiling the underlying PMP molecular mechanisms is urgent. In this regard, hypoxia and oxidative stress have been extensively related to tumoral pathologies, although their contribution to PMP has not been elucidated.

Methods

In this manuscript, we have evaluated, for the first time, the intratumoral real-time oxygen microtension (pO2mt) in the tumor (soft and hard mucin) and surrounding healthy tissue from five PMP patients during surgery. In addition, we measured hypoxia (Hypoxia Inducible Factor-1a; HIF-1α) and oxidative stress (catalase; CAT) markers in soft and hard mucin from the same five PMP patient samples and in five control samples.

Results

The results showed low intratumoral oxygen levels, which were associated with increased HIF-1α protein levels, suggesting the presence of a hypoxic environment in these tumors. We also found a significant reduction in CAT activity levels in soft and hard mucin compared with healthy tissue samples.

Discussion

In conclusion, our study provides the first evidence of low intratumoral oxygen levels in PMP patients associated with hypoxia and oxidative stress markers. However, further investigation is required to understand the potential role of oxidative stress in PMP in order to find new therapeutic strategies.
Trends in incidence and survival in patients with gastrointestinal neuroendocrine tumors: A SEER database analysis, 1977-2016
Authors: Liu Miao , Wei Lingge , Liu Wei , Chen Shupeng , Guan Meichao , Zhang Yingjie , Guo Ziyu , Liu Ruiqi , Xie Peng
Published: January 2023

Objectives

We aimed to determine trends in incidence and survival in patients with gastrointestinal neuroendocrine tumors (GI-NETs) from 1977 to 2016, and then analyze the potential risk factors including sex, age, race, grade, Socioeconomic status (SES), site, and stage.

Methods

Data were obtained from Surveillance, Epidemiology, and End Results Program (SEER) database. Kaplan-Meier survival analysis, relative survival rates (RSRs), and Cox proportional risk regression model were used to evaluate the relationship between these factors and prognosis.

Results

Compared with other sites, the small intestine and rectum have the highest incidence, and the appendix and rectum had the highest survival rate. The incidence was higher in males than in females, and the survival rate in males was close to females. Blacks had a higher incidence rate than whites, but similar survival rates. Incidence and survival rates were lower for G3&4 than for G1 and G2. Age, stage, and grade are risk factors.

Conclusions

This study described changes in the incidence and survival rates of GI-NETs from 1977 to 2016 and performed risk factor analyses related to GI-NETs.
Surgical management and outcomes of spinal metastasis of malignant adrenal tumor: A retrospective study of six cases and literature review
Authors: Ni Xiangzhi , Wang Jing , Cao Jiashi , Zhang Kun , Hou Shuming , Huang Xing , Song Yuanjin , Gao Xin , Xiao Jianru , Liu Tielong
Published: January 2023

Purpose

Spinal metastasis of malignant adrenal tumor (SMMAT) is an extremely rare and poorly understood malignant tumor originating from the adrenal gland. The objective of this study is to elucidate the clinical characteristics and discuss surgical management and outcomes of SMMAT.

Methods

Included in this study were six SMMAT patients who received surgical treatment in our center between February 2013 and May 2022. Their clinical data and outcomes were retrospectively analyzed to gain a better understanding of SMMAT. In addition, ten cases from the literature focusing on SMMAT were also reviewed.

Results

Surgery was performed successfully, and the associated symptoms were relieved significantly in all patients postoperatively. The mean follow-up duration was 26.2 (range 3-55) months. Two patients died of tumor recurrence 12 and 48 months after operation respectively. The other four patients were alive at the last follow-up.

Conclusions

The prognosis of SMMAT is usually poor. Preoperative embolization and early surgical radical resection can offer satisfactory clinical outcomes. The patient’s health status, preoperative neurological function, tumor location and the resection mode are potential prognostic factors of SMMAT.
CHD1, a multifaceted epigenetic remodeler in prostate cancer
Authors: Li Haoyan , Gigi Loraine , Zhao Di
Published: January 2023

Chromatin remodeling proteins contribute to DNA replication, transcription, repair, and recombination. The chromodomain helicase DNA-binding (CHD) family of remodelers plays crucial roles in embryonic development, hematopoiesis, and neurogenesis. As the founding member, CHD1 is capable of assembling nucleosomes, remodeling chromatin structure, and regulating gene transcription. Dysregulation of CHD1 at genetic, epigenetic, and post-translational levels is common in malignancies and other human diseases. Through interacting with different genetic alterations, CHD1 possesses the capabilities to exert oncogenic or tumor-suppressive functions in context-dependent manners. In this Review, we summarize the biochemical properties and dysregulation of CHD1 in cancer cells, and then discuss CHD1’s roles in different contexts of prostate cancer, with an emphasis on its crosstalk with diverse signaling pathways. Furthermore, we highlight the potential therapeutic strategies for cancers with dysregulated CHD1. At last, we discuss current research gaps in understanding CHD1’s biological functions and molecular basis during disease progression, as well as the modeling systems for biology study and therapeutic development.
Gene editing in the nematode parasite Nippostrongylus brasiliensis using extracellular vesicles to deliver active Cas9/guide RNA complexes
Authors: Hagen Jana , Ghosh Subhanita , Sarkies Peter , Selkirk Murray E.
Published: January 2023

Despite recent advances, animal-parasitic nematodes have thus far been largely refractory to genetic manipulation. We describe here a new approach providing proof of principle that CRISPR/Cas9-mediated gene editing of parasitic nematodes is achievable using vesicular stomatitis virus glycoprotein-pseudotyped extracellular vesicles for the delivery of Cas9-single guide ribonucleoprotein complexes. We demonstrate that extracellular vesicle-delivered ribonucleoproteins can be used to disrupt a secreted deoxyribonuclease in Nippostrogylus brasiliensis. Introduction of a repair template encoding multiple stop codons led to measurable reduction in expression of the targeted gene. Altered transcripts corresponding to the edited locus were detected by RT-PCR, demonstrating that vesicles can access cells of tissues actively expressing the gene of interest. These data provide evidence that this technique can be employed for targeted gene editing in N. brasiliensis, making this species genetically tractable for the first time, although further refinement will be necessary for routine and robust interrogation of gene function.
The potential value of exosomes as adjuvants for novel biologic local anesthetics
Authors: Zhang Yunmeng , Feng Shangzhi , Cheng Xin , Lou Kecheng , Liu Xin , Zhuo Ming , Chen Li , Ye Junming
Published: January 2023

The side effects of anesthetic drugs are a key preoperative concern for anesthesiologists. Anesthetic drugs used for general anesthesia and regional blocks are associated with a potential risk of systemic toxicity. This prompted the use of anesthetic adjuvants to ameliorate these side effects and improve clinical outcomes. However, the adverse effects of anesthetic adjuvants, such as neurotoxicity and gastrointestinal reactions, have raised concerns about their clinical use. Therefore, the development of relatively safe anesthetic adjuvants with fewer side effects is an important area for future anesthetic drug research. Exosomes, which contain multiple vesicles with genetic information, can be released by living cells with regenerative and specific effects. Exosomes released by specific cell types have been found to have similar effects as many local anesthetic adjuvants. Due to their biological activity, carrier efficacy, and ability to repair damaged tissues, exosomes may have a better efficacy and safety profile than the currently used anesthetic adjuvants. In this article, we summarize the contemporary literature about local anesthetic adjuvants and highlight their potential side effects, while discussing the potential of exosomes as novel local anesthetic adjuvant drugs.
Asymmetric localized states at a nonlinear interface of fractional systems with optical lattices
Authors: Zhou Shu , Zeng Jianhua , Qin Yali
Published: January 2023

We investigate the existence and stability of localized gap states at a non-linear interface of non-linear fractional systems in a one-dimensional photonic lattice. By using the direct numerical simulations and linear stability analysis, we obtain the stability of the asymmetric localized gap states in the first and second finite gaps. Our theoretical results show that the power of the localized gap states decrease gradually as the increase of propagation constant and the non-linear landscape (non-linear coefficient ratio between the left and right interface), providing insights into soliton physics in non-linear periodic systems with fractional-order diffraction.
RETRACTED: Analysis of rotating-symmetric frame and MHD for peristaltic multiphase flow: An exact solution
Authors: Fatima Nahid , Abdulkhaliq M. Alharbi Khalid , Ijaz Nouman , Riaz Arshad , El-Din ElSayed M. Tag
Published: January 2023

The rotational mechanism forms the basis of various cosmic and geophysical transports. In medical science, rotational blood flows have been related to healthy cardiac function. This study consists of a mathematical model representing magnetohydrodynamic effects on the two-phase pumping flow of a Ree–Eyring–Powell stress model in a rotating frame. The model is controlled by switching the system into a wave frame of reference for better analysis of the wave phenomenon. Moreover, a lubrication theory is applied to the resulting set of relations in order to get a more comprehensive form of the reduced mathematical model. In the end, an exact solution is found to discuss the substantial contents of the study. The data on velocity and stream function are presented diagrammatically to examine the theoretical behavior of various quantities under the variation of considerable physical factors. It is concluded from the graphs that axial and secondary velocities are decreasing against rotation, magnetic field, and fluid’s factor, but the same rise in the case of wall stiffness and particle concentration. In both industrial and biomedical applications, this type of flow measurement gives tomographic information on the multiphase flow process, which entails acquiring signal changes at the edges of objects like fluid pipes or blood vessels to determine how the objects are distributed within. This work is extendable by considering nanoparticles of various types to enhance the thermal conductivity of the flow.
“suMus,” a novel digital system for arm movement metrics and muscle energy expenditure
Authors: Gerhalter Teresa , Müller Christina , Maron Elke , Thielen Markus , Schätzl Teresa , Mähler Anja , Schütte Till , Boschmann Michael , Herzer René , Spuler Simone , Gazzerro Elisabetta
Published: January 2023

Objective: In the field of non-treatable muscular dystrophies, promising new gene and cell therapies are being developed and are entering clinical trials. Objective assessment of therapeutic effects on motor function is mandatory for economical and ethical reasons. Main shortcomings of existing measurements are discontinuous data collection in artificial settings as well as a major focus on walking, neglecting the importance of hand and arm movements for patients’ independence. We aimed to create a digital tool to measure muscle function with an emphasis on upper limb motility.

Methods: suMus provides a custom-made App running on smartwatches. Movement data are sent to the backend of a suMus web-based platform, from which they can be extracted as CSV data. Fifty patients with neuromuscular diseases assessed the pool of suMus activities in a first orientation phase. suMus performance was hence validated in four upper extremity exercises based on the feedback of the orientation phase. We monitored the arm metrics in a cohort of healthy volunteers using the suMus application, while completing each exercise at low frequency in a metabolic chamber. Collected movement data encompassed average acceleration, rotation rate as well as activity counts. Spearman rank tests correlated movement data with energy expenditure from the metabolic chamber.

Results: Our novel application “suMus,” sum of muscle activity, collects muscle movement data plus Patient-Related-Outcome-Measures, sends real-time feedback to patients and caregivers and provides, while ensuring data protection, a long-term follow-up of disease course. The application was well received from the patients during the orientation phase. In our pilot study, energy expenditure did not differ between overnight fasted and non-fasted participants. Acceleration ranged from 1.7 ± 0.7 to 3.2 ± 0.5 m/sec2 with rotation rates between 0.9 ± 0.5 and 2.0 ± 3.4 rad/sec. Acceleration and rotation rate as well as derived activity counts correlated with energy expenditure values measured in the metabolic chamber for one exercise (r = 0.58, p < 0.03).

Conclusion: In the analysis of slow frequency movements of upper extremities, the integration of the suMus application with smartwatch sensors characterized motion parameters, thus supporting a use in clinical trial outcome measures. Alternative methodologies need to complement indirect calorimetry in validating accelerometer-derived energy expenditure data.