bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating various composite sampling modes for detecting pathogenic SARS-CoV-2 virus in raw sewage
Authors: Li Ye , Ash Kurt T. , Joyner Dominique C. , Williams Daniel E. , Alamilla Isabella , McKay Peter J. , Iler Chris , Hazen Terry C.
Published: November 2023

Inadequate sampling approaches to wastewater analyses can introduce biases, leading to inaccurate results such as false negatives and significant over- or underestimation of average daily viral concentrations, due to the sporadic nature of viral input. To address this challenge, we conducted a field trial within the University of Tennessee residence halls, employing different composite sampling modes that encompassed different time intervals (1 h, 2 h, 4 h, 6 h, and 24 h) across various time windows (morning, afternoon, evening, and late-night). Our primary objective was to identify the optimal approach for generating representative composite samples of SARS-CoV-2 from raw wastewater. Utilizing reverse transcription-quantitative polymerase chain reaction, we quantified the levels of SARS-CoV-2 RNA and pepper mild mottle virus (PMMoV) RNA in raw sewage. Our findings consistently demonstrated that PMMoV RNA, an indicator virus of human fecal contamination in water environment, exhibited higher abundance and lower variability compared to pathogenic SARS-CoV-2 RNA. Significantly, both SARS-CoV-2 and PMMoV RNA exhibited greater variability in 1 h individual composite samples throughout the entire sampling period, contrasting with the stability observed in other time-based composite samples. Through a comprehensive analysis of various composite sampling modes using the Quade Nonparametric ANCOVA test with date, PMMoV concentration and site as covariates, we concluded that employing a composite sampler during a focused 6 h morning window for pathogenic SARS-CoV-2 RNA is a pragmatic and cost-effective strategy for achieving representative composite samples within a single day in wastewater-based epidemiology applications. This method has the potential to significantly enhance the accuracy and reliability of data collected at the community level, thereby contributing to more informed public health decision-making during a pandemic.
Role of the microtubules in the electrical activity of the primary cilium of renal epithelial cells
Authors: Scarinci Noelia , Gutierrez Brenda C. , Albarracín Virginia H. , Cantero María del Rocío , Cantiello Horacio F.
Published: November 2023

The primary cilium is a non-motile sensory organelle that transduces environmental cues into cellular responses. It comprises an axoneme, a core of nine doublet microtubules (MTs) coated by a specialized membrane populated by receptors, and a high density of ion channels. Dysfunctional primary cilia generate the pathogenesis of several diseases known as ciliopathies. However, the electrical role of MTs in ciliary signaling remains largely unknown. Herein, we determined by the patch clamp technique the electrical activity of cytoplasmic and axonemal MTs from wild-type LLC-PK1 renal epithelial cells. We observed electrical oscillations with fundamental frequencies at ∼39 Hz and ∼93 Hz in sheets of cytoplasmic MTs. We also studied in situ and isolated, intact and Triton X-permeabilized primary cilia, observing electrical oscillations with peak frequencies at either 29–49 Hz (non-permeabilized) or ∼40–49 Hz (permeabilized) and ∼93 Hz (both). We applied Empirical Mode Decomposition (EMD), Continuous Wavelet Transform (CWT), and Cross-Correlation Analysis (CCA) to assess the differences and the coherence in the Time-Frequency domains of electrical oscillations between cytoplasmic and axonemal MTs. The data indicate that axonemal and cytoplasmic MTs show different patterns of electrical oscillations preserving coherence at specific frequency peaks that may serve as electromagnetic communication between compartments. Further, the electrical behavior of axonemal MTs was modified by siRNA deletion of polycystin-2 (PC2), which lengthens primary cilia, thus linking ciliary channels to the morphological and electrical behavior of cilia in ciliopathies. The encompassed evidence indicates that the primary cilium behaves as an electrical antenna, with an excitable MT structure that produces electrical oscillations whose synchronization and propagation constitute a novel cell signaling mechanism.
Period2 is associated with immune cell infiltration and is a potential diagnostic and prognostic marker for hepatocellular carcinoma
Authors: Chen Xiaolin , Zhao Qiaosu , Wang Haibiao , Qiu Kaijie , Deng Xi , Xu Feng
Published: November 2023

Background: Hepatocellular carcinoma (HCC) health challenge worldwide. Many studies showed that circadian rhythms play a critical role in tumor development. This study aimed to investigate the role of the circadian gene period2 (PER2) in HCC development and explore the possible mechanisms involved.

Methods: From fresh HCC tissues and paired paracancerous tissues, we measured PER2 mRNA and protein expression levels and calculated the correlations between PER2 expression and clinicopathological parameters in patients with HCC. We used transcriptome data from The Cancer Genome Atlas to mine the PER2 gene, including single gene difference analysis, single gene co-expression analysis, gene set enrichment analysis, immune infiltration analysis, and methylation analysis to explore its role and mechanism in HCC occurrence and development.

Results: PER2 expression levels were significantly lower in HCC tissues than in the paired paracancerous tissues. PER2 expression in HCC significantly correlated with neural invasion, Child-Pugh classification, and China liver cancer staging stage in HCC patients. The differentially expressed genes associated with PER2 were significantly enriched in mitochondrial oxidative phosphorylation, transcriptional translation, amino acid metabolism, and other related pathways. PER2 expression levels significantly correlated with immune cell infiltration and immune checkpoint genes and positively correlated with TP53 expression in HCC tissues. The DNA methylation status in eight CpG islands of the PER2 gene was associated with HCC outcomes.

Conclusion: PER2 is a potential diagnostic and prognostic biomarker and a promising therapeutic target in HCC.
Potent VEGFR-2 inhibitors for resistant breast cancer: a comprehensive 3D-QSAR, ADMET, molecular docking and MMPBSA calculation on triazolopyrazine derivatives
Authors: Baammi Soukayna , El Allali Achraf , Daoud Rachid
Published: November 2023

More people are being diagnosed with resistant breast cancer, increasing the urgency of developing new effective treatments. Several lines of evidence suggest that blocking the kinase activity of VEGFR-2 reduces angiogenesis and slows tumor growth. In this study, we developed novel VEGFR-2 inhibitors based on the triazolopyrazine template by using comparative molecular field analysis (CoMFA) and molecular similarity indices (CoMSIA) models for 3D-QSAR analysis of 23 triazolopyrazine-based compounds against breast cancer cell lines (MCF -7). Both CoMFA (Q2 = 0.575; R2 = 0.936, Rpred2 = 0.956) and CoMSIA/SE (Q2 = 0.575; R2 = 0.936, Rpred2 = 0.847) results demonstrate the robustness and stability of the constructed model. Six novel compounds with potent inhibitory activity were carefully designed, and screening of ADMET properties revealed their good oral bioavailability and ability to diffuse through various biological barriers. When compared with the most active molecule in the data set and with Foretinib (breast cancer drug), molecular docking revealed that the six designed compounds had strengthened affinity (−8.9 to −10 kcal/mol) to VEGFR-2. Molecular Dynamics Simulations and MMPBSA calculations were applied to the selected compound T01 with the highest predicted inhibitory activity, confirming its stability in the active pocket of VEGFR-2 over 100 ns. The present results provided the basis for the chemical synthesis of new compounds with improved inhibitory properties against the breast cancer cell line (MCF -7).
Association between oral microbiome and seven types of cancers in East Asian population: a two-sample Mendelian randomization analysis
Authors: Feng Kexin , Ren Fei , Wang Xiang
Published: November 2023

Background: The oral microbiome has been intricately linked to various pathological conditions, notably cancer, though clear causal links remain elusive. This study aimed to investigate the potential causal relationships between the oral microbiome and seven major cancers: breast, lung, pancreatic, colorectal, gastric, ovarian, and prostate cancers, leveraging Mendelian randomization (MR).

Methods: A two-sample MR analysis was conducted using genome-wide association study (GWAS) data specific to oral microbiota in individuals of East Asian descent. Single nucleotide polymorphisms (SNPs) independent of confounders served as instrumental variables (IVs) to deduce causality. MR methodologies such as the inverse variance weighted (IVW) method, weighted median (WM) method, and Mendelian randomization-Egger (MR-Egger) method were employed. The study utilized datasets encapsulating a multitude of cancer cases and controls, focusing on Asian populations.

Results: Our analysis revealed intricate associations between specific bacterial genera of the oral microbiome and diverse cancers. Notably, Fusobacterium showed mixed associations with various cancers, while genera like Prevotella and Streptococcus exhibited nuanced roles across malignancies. The genus Aggregatibacter demonstrated a multifaceted influence, positively correlating with some cancers while inhibiting others.

Conclusion: Our findings underscore the profound implications of the oral microbiome in systemic malignancies, suggesting potential modulatory roles in cancer etiology. These insights, though preliminary, accentuate the need for deeper exploration and could pave the way for novel therapeutic strategies.
Examining the efficacy of a cardio-dance intervention on brain health and the moderating role of ABCA7 in older African Americans: a protocol for a randomized controlled trial
Authors: Gluck Mark A. , Gills Joshua L. , Fausto Bernadette A. , Malin Steven K. , Duberstein Paul R. , Erickson Kirk I. , Hu Liangyuan
Published: November 2023

Introduction

African Americans are two to three times more likely to be diagnosed with Alzheimer’s disease (AD) compared to White Americans. Exercise is a lifestyle behavior associated with neuroprotection and decreased AD risk, although most African Americans, especially older adults, perform less than the recommended 150 min/week of moderate-to-vigorous intensity exercise. This article describes the protocol for a Phase III randomized controlled trial that will examine the effects of cardio-dance aerobic exercise on novel AD cognitive and neural markers of hippocampal-dependent function (Aims #1 and #2) and whether exercise-induced neuroprotective benefits may be modulated by an AD genetic risk factor, ABCA7 rs3764650 (Aim #3). We will also explore the effects of exercise on blood-based biomarkers for AD.

Methods and analysis

This 6-month trial will include 280 African Americans (≥ 60 years), who will be randomly assigned to 3 days/week of either: (1) a moderate-to-vigorous cardio-dance fitness condition or (2) a low-intensity strength, flexibility, and balance condition for 60 min/session. Participants will complete health and behavioral surveys, neuropsychological testing, saliva and venipuncture, aerobic fitness, anthropometrics and resting-state structural and functional neuroimaging at study entry and 6 months.

Discussion

Results from this investigation will inform future exercise trials and the development of prescribed interventions that aim to reduce the risk of AD in African Americans.
Case report: Mononeuropathy multiplex of extranodal natural killer/T-cell lymphoma misdiagnosed as systemic vasculitis
Authors: Shi Jiayu , Niu Jingwen , Wu Di , Zhang Lei , Huang Yangyu , Zhang Hui , Guan Hongzhi , Liu Mingsheng , Guan Yuzhou
Published: November 2023

Background

Extranodal NK/T-cell lymphoma (ENKTL) is an aggressive non-Hodgkin lymphoma that typically develops in the upper aerodigestive tract.

Case presentation

We encountered an ENKTL patient who presented with purpura-like rashes and foot drops as initial symptoms and later developed other peripheral nerve involvement. The nerve conduction study of both the motor nerve and the sensory nerve showed axonal damage resembling mononeuropathy multiplex. Although the initial response to steroids was encouraging, the patient's symptoms reappeared and aggravated. A biopsy of the abdominal subcutaneous fat tissue with additional immunohistochemistry revealed neoplastic NK/T lymphocytes.

Conclusion

We reported the first case presented as mononeuropathy multiplex as the initial clinical manifestation in ENKTL patients. Lymphoma should be considered in the diagnosis of atypical mononeuropathy in multiplex patients.
Bibliometric and visual analysis of spinal cord injury-associated macrophages from 2002 to 2023
Authors: Zhao Yan , Xia Qiuqiu , Zong Hui , Wang Yanyang , Dong Huaize , Zhu Lu , Xia Jiyue , Mao Qiming , Weng Zijing , Liao Wenbo , Xin Zhijun
Published: November 2023

Background

Spinal cord injury (SCI) triggers motor, sensory, and autonomic impairments that adversely damage patients' quality of life. Its pathophysiological processes include inflammation, oxidative stress, and apoptosis, although existing treatment options have little success. Macrophages have a vital function in controlling inflammation in SCI, with their M1-type and M2-type macrophages dominating early inflammatory effects and late brain tissue repair and regeneration, respectively. However, there is a dearth of rigorous bibliometric study in this sector to explore its dynamics and trends. This study intends to examine the current status and trends of macrophage usage in SCI using bibliometric methodologies, which may drive novel therapeutic options.

Methods

In this study, the Web of Science Core Collection (WOSCC) was utilized to collect publications and reviews on macrophages in SCI from 2002 to 2023. Bibliometrics and visualization analyses were performed by VOSviewer, CiteSpace, the R package “bibliometrix”, and online analytic platforms. These analyses covered a variety of aspects, including countries and institutions, authors and co-cited authors, journals and co-cited journals, subject categories, co-cited references, and keyword co-occurrences, in order to provide insights into the research trends and hotspots in this field.

Results

1,775 papers were included in the study, comprising 1,528 articles and 247 reviews. Our research analysis demonstrates that the number of relevant studies in this sector is expanding, specifically the number of publications in the United States and China has risen dramatically. However, there are fewer collaborations between institutions in different nations, and international cooperation needs to be reinforced. Among them, Popovich PG became the leader in the field, and significant journals include Experimental Neurology, Journal of Neurotrauma, and Journal of Neuroscience. Research hotspots involve macrophage polarization, microglia, astrocytes, signaling, cytokines, inflammation, and neuroprotection.

Conclusions

This analysis gives, for the first time, a comprehensive overview of bibliometric studies on macrophages in SCI over the past 20 years. This study not only gives an extensive picture of the knowledge structure but also indicates trends in the subject. The systematic summarization gives a complete and intuitive understanding of the link between spinal cord damage and macrophages and provides a great reference for future related studies.
Study protocol for FIBROKIT: a new tool for fibromyalgia diagnosis and patient follow-up
Authors: del Amo Laura Lucena , Durán-González Elena , Ramírez-Tejero Jorge A. , Martínez-Lara Antonio , Cotán David
Published: November 2023

Fibromyalgia (FM) is a complex disease that is characterized by chronic musculoskeletal pain and has great economic impact. FM prevalence is about 2% to 4% worldwide, affecting mainly middle-aged women, and its complex pathophysiology complicates diagnosis, treatment and the findings of solid biomarkers. Previous studies have suggested an association between the disease and oxidative stress, mitochondrial metabolism, intestinal microbiota and inflammation, providing sufficient data to support the multifactorial origin of FM. Hence, the objective of this randomized, prospective, low-interventional, double-blinded and placebo-controlled clinical trial is the development of a specific panel of FM biomarkers and the evaluation of their response to a six-month nutritional intervention based on the Mediterranean diet supplemented with extra virgin olive oil (EVOO). For this purpose, the experimental design implies the recruitment of a large cohort of female Spanish patients. Middle-aged women who meet the diagnostic criteria for FM according to the American College of Rheumatology (ACR) will be eligible, along with age-matched healthy women. Both groups will be randomly divided into placebo (olive oil, OO) and treatment groups (extra virgin olive oil, EVOO), and will provide samples at the beginning (T0), after 3 months of nutritional intervention (T1), at the end of the nutritional intervention in 6 months (T2), and 6 months after the end of nutritional intervention (TF), being enrolled for 1 year. Data will be collected through health questionnaires, and whole blood and stool samples will be taken and analyzed. Blood will be used for western-blotting and proteomic analysis of mitochondrial homeostasis and plasma proteome, while stool will undergo metagenomic analysis, respectively. This study represents the first low-interventional investigation with more than 200 participants focused on exploring the association of oxidative stress, mitochondrial metabolism, intestinal microbiota and related pathways with a nutritional intervention in the context of FM. As a result, the outcomes of this study will significantly contribute to the development of a comprehensive and robust panel of diagnostic biomarkers, and will shed some light on their modulation with non-pharmacological therapies such as nutrition.

Clinical trial registration: https://clinicaltrials.gov/study/NCT05921409, identifier: NCT05921409.
A comprehensive two-sample Mendelian randomization analysis of trigeminal neuralgia and modifiable risk factors
Authors: Wei Xingrong , Zhou Hao , Zhang Shuguang , Hu Xueqian , Wei Zhenqin , Li Yang
Published: November 2023

Objective

To conduct a comprehensive search and causality study of potential modifiable risk factors for trigeminal neuralgia. To provide new ideas for subsequent treatment and management of patients with trigeminal neuralgia.

Methods

Data were obtained from large GWAS databases and then analyzed by Mendelian randomization analysis. The causal relationship between 36 potentially modifiable risk factors and trigeminal neuralgia was explored based on the results of the inverse variance weighting method(IVW). p < 0.05 was considered statistically significant.

Results

Years of schooling [OR (95%CI), 0.59(0.42–0.84), p = 0.003] to be a significant protective factor. Anxiety disorders [OR (95%CI), 1.62(1.05–2.48), p = 0.028], Depression [OR (95%CI), 1.53(1.03–2.28), p = 0.035] and Autoimmune [OR (95%CI), 1.16(1.01–1.32), p = 0.033] were significant risk factors. Sleep duration [OR (95%CI), 0.43(0.18–1.01), p = 0.051] was a close protective factor. Body mass index [OR (95%CI), 1.24(0.98–1.57), p = 0.077] was a close risk factor.

Conclusion

Mendelian randomization analysis shows Years of schooling and Sleep duration as protective factors. Anxiety disorders, Depression, Autoimmune, and Body mass index are risk factors. This will help in the research of diagnosis, treatment, and mechanism of trigeminal neuralgia. And reduce the prevalence of trigeminal neuralgia through positive psychological and lifestyle interventions.
Treating seronegative neuromyelitis optica spectrum disorder with inebilizumab: a case report
Authors: Lehrieder Dominik , Zapantis Nikolaos , Pham Mirko , Schuhmann Michael Klaus , Haarmann Axel
Published: November 2023

Background

Neuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory disease of the central nervous system that is often severely disabling from the outset. The lack of pathognomonic aquaporin 4 (AQP4) antibodies in seronegative NMOSD not only hinders early diagnosis, but also limits therapeutic options, in contrast to AQP4 antibody-positive NMOSD, where the therapeutic landscape has recently evolved massively.

Case presentation

We report a 56-year-old woman with bilateral optic neuritis and longitudinally extensive myelitis as the index events of a seronegative NMOSD, who was successfully treated with inebilizumab.

Conclusion

Treatment with inebilizumab may be considered in aggressive seronegative NMOSD. Whether broader CD19-directed B cell depletion is more effective than treatment with rituximab remains elusive.
Performance of plasma von Willebrand factor in acute traumatic brain injury: relations to severity, CT findings, and outcomes
Authors: Zeng Rong , Li Shaoping , Yu Jiangtao , Ma Haoli , Zhao Yan
Published: November 2023

Background

von Willebrand factor (VWF) has been widely recognized as a biomarker for endothelial cell activation in trauma and inflammation. Traumatic brain injury (TBI) is characterized by cerebral vascular injury and subsequent inflammation. The objective of this study was to investigate the correlation between VWF levels and clinical severity, as well as imaging abnormalities, in TBI patients. Additionally, the predictive value of VWF for patient outcomes was assessed.

Methods

We conducted a prospective study to recruit acute TBI patients who were admitted to the emergency department within 24 h. Healthy individuals from the medical examination center were recruited as the control group. This study aimed to compare the accuracy of VWF in discriminating TBI severity and imaging abnormalities with the Glasgow Coma Scale (GCS) and Rotterdam computed tomography (CT) scores. We also analyzed the predictive value of these outcomes using the Glasgow Outcome Scale (GOS) and 6-month mortality.

Results

The plasma concentration of VWF in TBI patients (84.7 ± 29.7 ng/ml) was significantly higher than in healthy individuals (40 ± 8.8 ng/ml). There was a negative correlation between VWF levels and GCS scores, as well as a positive correlation between VWF levels and Rotterdam CT scores. The area under the curve (AUC) for VWF in discriminating mild TBI was 0.76 (95% CI: 0.64, 0.88), and for predicting negative CT findings, it was 0.82 (95% CI: 0.72, 0.92). Meanwhile, the AUC of VWF in predicting mortality within 6 months was 0.70 (95% CI: 0.56, 0.84), and for a GOS score lower 4, it was 0.78 (95% CI: 0.67, 0.88). Combining VWF with either the GCS or Rotterdam CT score improved the prediction ability compared to using VWF alone.

Conclusion

VWF levels were significantly elevated in patients with TBI compared with healthy individuals. Furthermore, VWF levels demonstrated a negative correlation with GCS scores and a positive correlation with Rotterdam CT scores. In terms of predicting mortality, VWF alone was not sufficient, but its predictive power was enhanced when combined with either the Rotterdam CT score or GCS. These findings suggest that VWF may serve as a potential biomarker for assessing the severity and prognosis of TBI patients.
Early-stage effect of HIBD on neuro-motor function and organic composition of neurovascular units in neonatal rats
Authors: Mo Yanjun , Zeng Ying , Huo Luyao , Liu Gang , Tao Jingwei , Jiang Yu , Zhao Tuo , Zhou Zhuoluo , Mu Xiaohong
Published: November 2023

Objective

This study aimed to investigate the effects of neonatal hypoxic–ischemic brain damage (HIBD) on early-stage neuro-motor function, cerebral blood flow, and the neurovascular unit.

Methods

Twenty-four Sprague–Dawley newborn rats aged 7 days were obtained and randomly assigned to either the sham or the model group using a random number table. The HIBD model was established using the Rice-Vannucci method. After the induction of HIBD, the body weight of the rats was measured and their neuro-motor function was assessed. Further, cerebral blood flow perfusion was evaluated using laser speckle flow imaging, and immunofluorescent staining techniques were employed for examining the activation of specific markers and their morphological changes in different cell populations, which included vascular endothelial cells, neurons, astrocytes, and microglia within the motor cortex.

Results

After HIBD, the model group exhibited impaired neuro-motor function and growth. Cerebral blood flow perfusion decreased in both the hemispheres on day 1 and in the ipsilateral brain on day 4. However, no significant difference was observed between the two groups on day 7. Moreover, the CD31 and NeuN showed a sharp decline on day 1, which was followed by a gradual increase in the expression levels. The activated microglia and astrocytes formed clusters in the injured cortex. Notably, the regions with positive staining for Arg-1, Iba-1, CD68, and GFAP consistently displayed higher values in the model group as compared to that in the sham group. The total number of branch endpoints and microglia branches was higher in the model group than in the sham group. Immunofluorescent co-localization analysis revealed no co-staining between Iba-1 and Arg-1; however, the Pearson’s R-value for the co-localization of Iba-1 and CD68 was higher in the model group, which indicated an increasing trend of co-staining in the model group.

Conclusion

Early-stage neuro-motor function, cerebral blood flow, microvasculature, and neurons in neonatal rats exhibited a trend of gradual recovery over time. The activation and upregulation of neuroglial cells continued persistently after HIBD. Furthermore, the impact of HIBD on early-stage neuro-motor function in newborn rats did not synchronize with the activation of neuroglial cells. The recovery of neuro-motor function, microvasculature, and neurons occurred earlier than that of neuroglial cells.
MFA-UNet: a vessel segmentation method based on multi-scale feature fusion and attention module
Authors: Cao Juan , Chen Jiaran , Gu Yuanyuan , Liu Jinjia
Published: November 2023

Introduction

The accurate segmentation of retinal vessels is of utmost importance in the diagnosis of retinal diseases. However, the complex vessel structure often leads to poor segmentation performance, particularly in the case of microvessels.

Methods

To address this issue, we propose a vessel segmentation method composed of preprocessing and a multi-scale feature attention network (MFA-UNet). The preprocessing stage involves the application of gamma correction and contrast-limited adaptive histogram equalization to enhance image intensity and vessel contrast. The MFA-UNet incorporates the Multi-scale Fusion Self-Attention Module(MSAM) that adjusts multi-scale features and establishes global dependencies, enabling the network to better preserve microvascular structures. Furthermore, the multi-branch decoding module based on deep supervision (MBDM) replaces the original output layer to achieve targeted segmentation of macrovessels and microvessels. Additionally, a parallel attention mechanism is embedded into the decoder to better exploit multi-scale features in skip paths.

Results

The proposed MFA-UNet yields competitive performance, with dice scores of 82.79/83.51/84.17/78.60/81.75/84.04 and accuracies of 95.71/96.4/96.71/96.81/96.32/97.10 on the DRIVE, STARE, CHASEDB1, HRF, IOSTAR and FIVES datasets, respectively.

Discussion

It is expected to provide reliable segmentation results in clinical diagnosis.
Attention-based multi-semantic dynamical graph convolutional network for eeg-based fatigue detection
Authors: Liu Haojie , Liu Quan , Cai Mincheng , Chen Kun , Ma Li , Meng Wei , Zhou Zude , Ai Qingsong
Published: November 2023

Introduction

Establishing a driving fatigue monitoring system is of utmost importance as severe fatigue may lead to unimaginable consequences. Fatigue detection methods based on physiological information have the advantages of reliable and accurate. Among various physiological signals, EEG signals are considered to be the most direct and promising ones. However, most traditional methods overlook the functional connectivity of the brain and fail to meet real-time requirements.

Methods

To this end, we propose a novel detection model called Attention-Based Multi-Semantic Dynamical Graph Convolutional Network (AMD-GCN). AMD-GCN consists of a channel attention mechanism based on average pooling and max pooling (AM-CAM), a multi-semantic dynamical graph convolution (MD-GC), and a spatial attention mechanism based on average pooling and max pooling (AM-SAM). AM-CAM allocates weights to the input features, helping the model focus on the important information relevant to fatigue detection. MD-GC can construct intrinsic topological graphs under multi-semantic patterns, allowing GCN to better capture the dependency between physically connected or non-physically connected nodes. AM-SAM can remove redundant spatial node information from the output of MD-GC, thereby reducing interference in fatigue detection. Moreover, we concatenate the DE features extracted from 5 frequency bands and 25 frequency bands as the input of AMD-GCN.

Results

Finally, we conduct experiments on the public dataset SEED-VIG, and the accuracy of AMD-GCN model reached 89.94%, surpassing existing algorithms.

Discussion

The findings indicate that our proposed strategy performs more effectively for EEG-based driving fatigue detection.
Topological properties and connectivity patterns in brain networks of patients with refractory epilepsy combined with intracranial electrical stimulation
Authors: Sun Yulei , Shi Qi , Ye Min , Miao Ailiang
Published: November 2023

Objective

Although intracranial electrical stimulation has emerged as a treatment option for various diseases, its impact on the properties of brain networks remains challenging due to its invasive nature. The combination of intracranial electrical stimulation and whole-brain functional magnetic resonance imaging (fMRI) in patients with refractory epilepsy (RE) makes it possible to study the network properties associated with electrical stimulation. Thus, our study aimed to investigate the brain network characteristics of RE patients with concurrent electrical stimulation and obtain possible clinical biomarkers.

Methods

Our study used the GRETNA toolbox, a graph theoretical network analysis toolbox for imaging connectomics, to calculate and analyze the network topological attributes including global measures (small-world parameters and network efficiency) and nodal characteristics. The resting-state fMRI (rs-fMRI) and the fMRI concurrent electrical stimulation (es-fMRI) of RE patients were utilized to make group comparisons with healthy controls to identify the differences in network topology properties. Network properties comparisons before and after electrode implantation in the same patient were used to further analyze stimulus-related changes in network properties. Modular analysis was used to examine connectivity and distribution characteristics in the brain networks of all participants in study.

Results

Compared to healthy controls, the rs-fMRI and the es-fMRI of RE patients exhibited impaired small-world property and reduced network efficiency. Nodal properties, such as nodal clustering coefficient (NCp), betweenness centrality (Bc), and degree centrality (Dc), exhibited differences between RE patients (including rs-fMRI and es-fMRI) and healthy controls. The network connectivity of RE patients (including rs-fMRI and es-fMRI) showed reduced intra-modular connections in subcortical areas and the occipital lobe, as well as decreased inter-modular connections between frontal and subcortical regions, and parieto-occipital regions compared to healthy controls. The brain networks of es-fMRI showed a relatively weaker small-world structure compared to rs-fMRI.

Conclusion

The brain networks of RE patients exhibited a reduced small-world property, with a tendency toward random networks. The network connectivity patterns in RE patients exhibited reduced connections between cortical and subcortical regions and enhanced connections among parieto-occipital regions. Electrical stimulation can modulate brain network activity, leading to changes in network connectivity patterns and properties.
Autism spectrum disorder-specific changes in white matter connectome edge density based on functionally defined nodes
Authors: Weber Clara F. , Lake Evelyn M. R. , Haider Stefan P. , Mozayan Ali , Bobba Pratheek S. , Mukherjee Pratik , Scheinost Dustin , Constable Robert T. , Ment Laura , Payabvash Seyedmehdi
Published: November 2023

Introduction

Autism spectrum disorder (ASD) is associated with both functional and microstructural connectome disruptions. We deployed a novel methodology using functionally defined nodes to guide white matter (WM) tractography and identify ASD-related microstructural connectome changes across the lifespan.

Methods

We used diffusion tensor imaging and clinical data from four studies in the national database for autism research (NDAR) including 155 infants, 102 toddlers, 230 adolescents, and 96 young adults – of whom 264 (45%) were diagnosed with ASD. We applied cortical nodes from a prior fMRI study identifying regions related to symptom severity scores and used these seeds to construct WM fiber tracts as connectome Edge Density (ED) maps. Resulting ED maps were assessed for between-group differences using voxel-wise and tract-based analysis. We then examined the association of ASD diagnosis with ED driven from functional nodes generated from different sensitivity thresholds.

Results

In ED derived from functionally guided tractography, we identified ASD-related changes in infants (pFDR≤ 0.001–0.483). Overall, more wide-spread ASD-related differences were detectable in ED based on functional nodes with positive symptom correlation than negative correlation to ASD, and stricter thresholds for functional nodes resulted in stronger correlation with ASD among infants (z= −6.413 to 6.666,pFDR≤ 0.001–0.968). Voxel-wise analysis revealed wide-spread ED reductions in central WM tracts of toddlers, adolescents, and adults.

Discussion

We detected early changes of aberrant WM development in infants developing ASD when generating microstructural connectome ED map with cortical nodes defined by functional imaging. These were not evident when applying structurally defined nodes, suggesting that functionally guided DTI-based tractography can help identify early ASD-related WM disruptions between cortical regions exhibiting abnormal connectivity patterns later in life. Furthermore, our results suggest a benefit of involving functionally informed nodes in diffusion imaging-based probabilistic tractography, and underline that different age cohorts can benefit from age- and brain development-adapted image processing protocols.
Case report: A novel case of COVID-19 triggered tumefactive demyelinating lesions in one multiple sclerosis patient
Authors: Hu Jinghan , Huang Leiyun , Qiu Zengyun , Liu Yongzhen , Shen Kaiming , Tang Bin , Qian Jing
Published: November 2023

The epidemic of COVID-19 is mainly manifested by respiratory symptoms caused by SARS-CoV-2 infection. Recently, reports of central nervous system diseases caused or aggravated by SARS-CoV-2 infection are also increasing. Thus, the COVID-19 pandemic poses an unprecedented challenge to the diagnosis and management of neurological disorders, especially to those diseases which have overlapping clinical and radiologic features with each other. In this study, a 31-year-old female patient had been diagnosed with relapsing–remitting multiple sclerosis (RRMS) initially and subsequently developed tumefactive demyelinating lesions (TDLs) following an infection with SARS-CoV-2. After immunotherapy (glucocorticoid pulses), a significant improvement was observed in her both clinical and radiological characteristics. The patient was started on disease-modifying therapy (DMT) with teriflunomide after cessation of oral glucocorticoids. Following two months of DMT treatment, the imaging follow-up revealed that the patient’s condition continued to deteriorate. This case was characterized by the transformation of a multiple sclerosis patient (MS) infected with SARS-CoV-2 into TDLs and the ineffectiveness of DMT treatment, which added complexity to its diagnosis and treatment. The case also gave us a hint that SARS-CoV-2 has a potential contributory role in inducing or exacerbating demyelinating diseases of the central nervous system that warrants further investigation.
Identification and discovery of imaging genetic patterns using fusion self-expressive network in major depressive disorder
Authors: Pang Mengqian , Liu Xiaoyun , Hao Xiaoke , Wang Meiling , Xie Chunming , Zhang Li , Yuan Yonggui
Published: November 2023

Introduction

Major depressive disorder (MDD) is a prevalent mental illness, with severe symptoms that can significantly impair daily routines, social interactions, and professional pursuits. Recently, imaging genetics has received considerable attention for understanding the pathogenesis of human brain disorders. However, identifying and discovering the imaging genetic patterns between genetic variations, such as single nucleotide polymorphisms (SNPs), and brain imaging data still present an arduous challenge. Most of the existing MDD research focuses on single-modality brain imaging data and neglects the complex structure of brain imaging data.

Methods

In this study, we present a novel association analysis model based on a self-expressive network to identify and discover imaging genetics patterns between SNPs and multi-modality imaging data. Specifically, we first build the multi-modality phenotype network, which comprises voxel node features and connectivity edge features from structural magnetic resonance imaging (sMRI) and resting-state functional magnetic resonance imaging (rs-fMRI), respectively. Then, we apply intra-class similarity information to construct self-expressive networks of multi-modality phenotype features via sparse representation. Subsequently, we design a fusion method guided by diagnosis information, which iteratively fuses the self-expressive networks of multi-modality phenotype features into a single new network. Finally, we propose an association analysis between MDD risk SNPs and the multi-modality phenotype network based on a fusion self-expressive network.

Results

Experimental results show that our method not only enhances the association between MDD risk SNP rs1799913 and the multi-modality phenotype network but also identifies some consistent and stable regions of interest (ROIs) multi-modality biological markers to guide the interpretation of MDD pathogenesis. Moreover, 15 new potential risk SNPs highly associated with MDD are discovered, which can further help interpret the MDD genetic mechanism.

Discussion

In this study, we discussed the discriminant and convergence performance of the fusion self-expressive network, parameters, and atlas selection.
Generating Shigella that internalize into glioblastoma cells
Authors: Shipley Austin , Frampton Gabriel , Davies Bryan W. , Umlauf Benjamin J.
Published: November 2023

Introduction

The use of microorganisms as drug delivery systems to treat cancer has expanded recently, including FDA approval of certain viruses as oncolytics. Microorganisms have several unique benefits compared to traditional pharmacologic agents including dose independence, the ability to produce therapeutic proteins locally within the tumor, and simplicity of administration. However, current microbial delivery systems such as AAV9 and herpes virus have limited cassette sizes, minimal cancer cell selectivity, and low innate cytotoxicity. To address these issues, we sought to generate a strain of Shigella flexneri to selectively internalize into glioblastoma (GBM) brain tumor cells as an initial step to generating a bacterial-based drug delivery system.

Methods

We generated S. flexneri that selectively internalize into GBM cells using iterative co-cultured assays.

Results

After 50 rounds of co-culture, the new strain infected 95 percent of GBM cells in 2 hours. GBM-infecting Shigella demonstrate a 124-fold preference for internalizing in nine different GBM cell lines compared to Normal Astrocytes (NA) controls. Additionally, we developed an in-cell western to identify GBM-infecting Shigella clones that preferentially internalize in patient samples without iterative co-culture. Finally, we demonstrate internalization into GBM cells is mediated via a factor modified by myristoylation.

Discussion

In conclusion, here we present a novel bacterial platform that preferentially internalizes in brain tumor cells. This system provides numerous potential benefits over current interventions and other microbial strategies for treating brain tumors.
Case Report: Renal artery stenosis in children: ultrasound as a decisive diagnostic and therapy-accompanying technique!
Authors: Brasseler Maire , Finkelberg Ilja , Müntjes Carsten , Cetiner Metin
Published: November 2023

Introduction

Renal artery stenosis in children is rare, and the recommended diagnostic algorithm, including techniques such as catheter-based angiography, CT angiography, magnetic resonance angiography, and ultrasound, is controversial in pediatric cohorts.

Case presentation

We report a case of an 11-year-old girl with renal artery stenosis in whom ultrasonography played a decisive role in confirming the diagnosis and accompanying therapeutic percutaneous transluminal renal artery angioplasty.

Conclusion

Improved ultrasound techniques and the examiner’s experience contribute to improving renal artery stenosis diagnosis in children. In particular, localized sensitive blood flow velocity analysis indicates the advantages of ultrasound compared to other imaging modalities in renal artery stenosis. Therefore, ultrasound should be a focus of future study designs addressing the search for the best diagnostic algorithm.

The advantages of ultrasound techniques in pediatric patients with renal artery stenosis compared to other imaging modalities are highlighted.
Case Report: Neo-ostium creation with saphenous vein in a patient with anomalous origin of the right coronary artery
Authors: Temur Bahar , Özcan Zeynep Sıla , Başgöze Serdar , Aydın Selim , Güzelmeriç Füsun , Erek Ersin
Published: November 2023

Anomalous origin of the right coronary artery from the left sinus of Valsalva is a rare congenital anomaly. Most patients may be asymptomatic, but some may experience major cardiac events such as syncope, arrhythmias, and sudden cardiac death. We present a 16-year-old patient, who had several syncopes, with anomalous origin of the right coronary artery from the left coronary sinus, with an intramural and interarterial course between the pulmonary artery and the aorta. We describe a new surgical procedure of neo-ostium creation with a saphenous vein.
Case Report: Non-typhoidal Salmonella infections transmitted by reptiles and amphibians
Authors: Bernar Benoît , Gande Nina , Bernar Aline , Müller Thomas , Schönlaub Jörn
Published: November 2023

Non-typhoidal Salmonella infections (NTSI) can cause bacterial diarrhea, mostly leading to self-limiting gastroenteritis. However, in at-risk populations, NTSI can have severe complications. As transmission is most commonly foodborne, infection is rare in the breast- or bottle-fed very young. Another route is increasingly implicated, however, in newborns and infants especially: Contact with reptiles and amphibians. We describe infection with Salmonella enterica subsp. enterica ser. Monschaui (S. Monschaui), transmitted from bearded dragons, in a three-week-old boy. The boy initially appeared well, on the next morning deterioration was dramatic, with tachypnea, tachycardia, and mottled skin. Gram-negative sepsis was documented on day 2. His case prompted a review of published instances of reptile- and amphibian-associated salmonellosis (RAAS), summarized here. Association of S. Monschaui infection with exposure to reptiles and amphibians prompted inquiry into household pets. The parents had kept bearded dragons (Pogona sp.), the last of which died two weeks before the patient was born; confirmation of colonization with S. Monschaui was thus precluded. Among 63 reports (−5,000 cases) of RAAS or S. Monschaui, 62 appeared between 1995 and 2022, 10 were single case reports, and 53 were original articles with −5,000 cases; vectors included turtles, frogs, lizards, and snakes. RAAS is not a new phenomenon, but its incidence recently has risen due to the increased popularity of reptiles and amphibians as non-traditional pets. These animals can carry Salmonella sp. and transmit it to humans, posing a risk particularly to infants and other vulnerable persons. Risk mitigation requires that those bringing such pets into the home be informed of dangers associated with reptile and amphibian contact; that those selling reptiles and amphibians be mandated to inform customers comprehensively may be in order.
Performance of deamidated gliadin peptide antibodies as first screening for celiac disease in the general pediatric population
Authors: Al-Hussaini Abdulrahman , Al-Jurayyan Abdullah , Alharbi Sahar , Salman Bashir Muhammed , Troncone Riccardo
Published: November 2023

Background

Celiac serology has evolved, with the identification of newer antibodies against deamidated gliadin peptides (DGP) [e.g., anti-DGP, immunoglobulin A (IgA), and immunoglobulin G (IgG) types] with sensitivity and specificity in detecting celiac disease (CeD) that are equivalent to anti-tissue transglutaminase [anti-tissue transglutaminase (TTG) IgA]-based tests, particularly in populations with high pretest probability of CeD (prevalence of CeD > 50% of the population under study). This opens the possibility that anti-DGP assays can be used to identify CeD in the general population where the prevalence of CeD is very low (≈1%).

Objective

This study aimed (1) to determine the diagnostic performance of DGP antibodies-based serologic assays in identifying CeD during the screening of the general population and (2) to compare the levels of anti-DGP antibodies among CeD patients with mild and severe degrees of enteropathy.

Methods

Serology tests for DGP antibodies (DGP-IgA, DGP-IgG, and conjugate TTG/DGP antibodies) were performed on 104 serum samples of positive TTG-IgA (100 confirmed and four potential celiac patients) and a randomly selected 1,000 negative TTG-IgA serum samples collected during mass screening of children (aged 6–15 years) in 2014–2015.

Results

Sera from 32 of the 1,000 TTG-IgA negative serum specimens (3.2%) tested positive for one or more of the three anti-DGP serology tests. A total of 13 of the 32 anti-DGP seropositive patients had persistent positive results on follow-up samples in 2020 (1.3%). Eight of the 13 underwent endoscopy with biopsies, and only two had confirmed CeD (both DGP-IgG positive) (0.2%). The sensitivity and specificity of the serology assays were as follows: DGP-IgA (62.7%, 40%), DGP-IgG (80.4%, 100%), and conjugate TTG/DGP (96%, 10%). Based on receiver operating characteristic curves, the area under the curve for DGP-IgG (0.919; 95% CI −0.00406 to 0.114) was comparable to TTG-IgA (0.974; 95% CI 0.924–0.995) (P = 0.0679). Titers of antibodies to DGPs were significantly higher in children with severe intestinal damage than in those in children with mild lesions (P < 0.001).

Conclusion

The TTG-IgA assay remains the most reliable screening serology test for CeD in mass screening studies. The performance of TTG-IgA has improved marginally by adding DGP-IgG to the mass screening protocol. In CeD patients detected by mass screening, the anti-DGP antibody titer was significantly higher among patients with a severe degree of enteropathy as compared to the group with mild enteropathy.