bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic inflammation response index as a prognostic predictor in patients with acute ischemic stroke: A propensity score matching analysis
Authors: Dang Hui , Mao Wenjuan , Wang Shanshan , Sha Jing , Lu Mingjia , Cong Li , Meng Xuegang , Li Hongyan
Published: January 2023

Background

Acute ischemic stroke (AIS), the most common type of stroke, is a major cause of morbidity and mortality worldwide. A growing number of studies have demonstrated that inflammation is a critical mechanism in AIS. Being an easily available and effective inflammatory marker, the systemic inflammation response index (SIRI) shows a high association with mortality in patients with cancer and intracerebral hemorrhage. In this study, we evaluated the potential prognostic role of SIRI in critically ill patients with AIS.

Methods

Clinic data were extracted from the Medical Information Mart data for the Intensive Care IV (MIMIC-IV) database. The optimal cutoff value of SIRI was determined by X-tile software. The primary outcome was the 90-day all-cause mortality, and the secondary outcomes were 30-day and 1-year all-cause mortality of patients with AIS. Cox proportional hazards regression analyses were used to assess the association between SIRI levels and all-cause mortality, and survival curves were estimated using the Kaplan–Meier method. Furthermore, a 1:1 propensity score matching (PSM) method was performed to balance the influence of potential confounding factors.

Results

A total of 2,043 patients were included in our study. X-tile software indicated that the optimal cutoff value of the SIRI for 90-day mortality was 4.57. After PSM, 444 pairs of score-matched patients were generated. Cox proportional hazard model showed that after adjusting for possible confounders, high SIRI level (≥4.57) was independently associated with the 90-day all-cause mortality in the cohort before PSM (HR = 1.56, 95% CI: 1.30–1.89, p < 0.001) and the PSM subset (HR = 1.47, 95% CI: 1.16–1.86, p = 0.001). The survival curves showed that patients with SIRI ≥4.57 had a significantly lower 90-day survival rate in the cohort before PSM (56.7 vs. 77.3%, p < 0.001) and the PSM subset (61.0 vs. 71.8%, p = 0.001). Consistently, AIS patients with high SIRI levels (≥4.57) presented a significantly high risk of 30-day and 1-year all-cause mortality before and after PSM.

Conclusion

A higher SIRI (≥4.57) was associated with a higher risk of 90-day, 30-day, and 1-year mortality and was an independent risk factor of mortality in patients with acute ischemic stroke.
Impact of polycyclic aromatic hydrocarbon exposure on cognitive function and neurodegeneration in humans: A systematic review and meta-analysis
Authors: Humphreys Jessica , Valdés Hernández Maria del C.
Published: January 2023

Introduction

This article documents an emerging body of evidence concerning the neurological effect of polycyclic aromatic hydrocarbon (PAH) exposure with regard to cognitive function and increased risk of neurodegeneration.

Methods

Two electronic databases, PubMed and Web of Science, were systematically searched.

Results

The 37/428 studies selected included outcomes measuring cognitive function, neurobehavioral symptoms of impaired cognition, and pathologies associated with neurodegeneration from pre-natal (21/37 studies), childhood (14/37 studies), and adult (8/37 studies) PAH exposure. Sufficient evidence was found surrounding pre-natal exposure negatively impacting child intelligence, mental development, average overall development, verbal IQ, and memory; externalizing, internalizing, anxious, and depressed behaviors; and behavioral development and child attentiveness. Evidence concerning exposure during childhood and as an adult was scarce and highly heterogeneous; however, the presence of neurodegenerative biomarkers and increased concentrations of cryptic “self” antigens in serum and cerebrospinal fluid samples suggest a higher risk of neurodegenerative disease. Associations with lowered cognitive ability and impaired attentiveness were found in children and memory disturbances, specifically auditory memory, verbal learning, and general memory in adults.

Discussion

Although evidence is not yet conclusive and further research is needed, the studies included supported the hypothesis that PAH exposure negatively impacts cognitive function and increases the risk of neurodegeneration in humans, and recommends considering the introduction of a variable “rural vs. urban” as covariate for adjusting analyses, where the neurological functions affected (as result of our review) are outcome variables.
Pediatric dumbbell-shaped orbital schwannoma with extension to the cranial cavity: A case report and literature review
Authors: Shao Yongjia , Xi Qian , Cheng Ailan , Qian Minghui , Chu Shuguang
Published: January 2023

Orbital schwannomas are rare in children, especially those with intracranial extension. Herein, our report refers to a 12-year-old boy who had a cranial-orbital mass with a dumbbell-like appearance. The total neoplasms was successfully removed via a transcranial approach, and the pathological diagnostic result was schwannoma. Neither radiotherapy nor chemotherapy was performed after surgery, and no recurrences were observed for 3 months. Our report suggests that orbital schwannomas should be differentiated from other types of orbital tumors with sufficient evidence and that complete surgical resection remains the first choice to cure this disease.
Efficacy of Chinese herbal medicine on poststroke depression in animal models: A systematic review and meta-analysis
Authors: Li Li , Huo Bixiu , Wang Yuan , Wang Yao , Gong Ying , Zhang Yun , Liu Tingting , Sha Guiming , Zheng Tianru
Published: January 2023

Background

Poststroke depression (PSD) is a common complication that can seriously affect patients' functional recovery and quality of life after a stroke. Various side effects have been found to be associated with the pharmacological therapies used for PSD. Studies have shown that Chinese herbal medicine (CHM) can effectively improve PSD-like behavior and neurological function in clinical and animal studies. The efficacy of CHM on PSD in animal models has not been systematically analyzed.

Methods

The following electronic databases were searched for articles published up to September 2022: PubMed, Web of Science, the Cochrane Library, and Embase. Studies that reported the efficacy of CHM in animals with PSD and were written in English were included. Depression-like behavior and the neurological deficit score were assessed as measures of efficacy. The included studies assessed depression-like behavior using sucrose preference, open-field, forced swimming, and tail suspension tests, as well as body weight. The Review Manager version 5.4 and STATA version 13.1 software packages were used for the meta-analysis. The standardized mean difference (SMD) with 95% confidence intervals was used to assess all the outcomes. Subgroup analyses were performed to explore the sources of heterogeneity. The Egger's test and funnel plots were used to assess the potential publication bias. Sensitivity analyses were used to identify the stability of the results.

Results

A total of 14 studies, including 12 CHMs involving 442 rats, fulfilled the inclusion criteria for meta-analysis. The pooled results showed that CHM significantly alleviated neurological deficits (−1.72 SMD, −2.47– −0.97) and was efficacious in improving the depression-like behavior of rats in the sucrose preference (2.08 SMD, 1.33–2.84), open-field (2.85 SMD, 1.88–3.83), forced swimming (−1.83 SMD, −2.23−1.44), and tail suspension tests (−1.35 SMD, −1.94−0.76).

Conclusion

Our results suggest that CHM could significantly improve depression-like behavior and neurological function in animals with PSD. The current results should be interpreted with caution because only animal studies were included.
Sleep disturbance in post COVID-19 conditions: Prevalence and quality of life
Authors: Tedjasukmana Rimawati , Budikayanti Astri , Islamiyah Wardah Rahmatul , Witjaksono Anastasia Melissa Ayu Larasati , Hakim Manfaluthy
Published: January 2023

Post COVID-19 conditions are complaints and symptoms in patients with a history of probable or confirmed COVID-19 after 3 months of the onset of COVID-19 and last at least 2 months. About 10–20% of people may experience post COVID-19 conditions, one of which is sleep disturbance. There is a wide range of prevalence of sleep disturbances from 6% to more than 70%. An online survey of the post COVID-19 conditions in various countries showed that 78.58% of subjects had sleep disturbances, including insomnia, sleep-disordered breathing, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, parasomnias, and sleep-related movement disorders. Sleep disturbance can be found starting from 2 weeks until 48 weeks or more after discharge or after having a negative COVID-19 test results. Women aged < 50 years old with severe COVID-19 infection reported a worse outcome. Several mechanisms may cause sleep disturbance in post COVID-19 condition, namely persistent viral infection and inflammation, immunity dysregulation, and mitochondrial dysfunction. Several studies discovered sleep disturbance was a major problem that affected different domains of QoL in post COVID-19 conditions. Significant correlation was found between several dimensions of SF-36 with moderate-to-severe insomnia in post COVID-19 conditions. Therefore, sleep disturbance is a major problem in post COVID-19 conditions and may affect patients' QoL, and the existence of sleep disturbance should be a concern in post COVID-19 conditions period. Further research is required to determine the prevalence based on agreed definition as well as methods to assess this condition and its impact on QoL.
Diagnosis of comorbid migraine without aura in patients with idiopathic/genetic epilepsy based on the gray zone approach to the International Classification of Headache Disorders 3 criteria
Authors: Atalar Arife Çimen , Özge Aynur , Türk Bengi Gül , Ekizoğlu Esme , Kurt Gök Duygu , Baykan Betül , Ayta Semih , Erdoğan Füsun Ferda , Yeni Seher Naz , Taşdelen Bahar ,   IDEM Study Group, Velioğlu Sibel K.
Published: January 2023

Background

Migraine without aura (MwoA) is a very frequent and remarkable comorbidity in patients with idiopathic/genetic epilepsy (I/GE). Frequently in clinical practice, diagnosis of MwoA may be challenging despite the guidance of current diagnostic criteria of the International Classification of Headache Disorders 3 (ICHD-3). In this study, we aimed to disclose the diagnostic gaps in the diagnosis of comorbid MwoA, using a zone concept, in patients with I/GEs with headaches who were diagnosed by an experienced headache expert.

Methods

In this multicenter study including 809 consecutive patients with a diagnosis of I/GE with or without headache, 163 patients who were diagnosed by an experienced headache expert as having a comorbid MwoA were reevaluated. Eligible patients were divided into three subgroups, namely, full diagnosis, zone I, and zone II according to their status of fulfilling the ICHD-3 criteria. A Classification and Regression Tree (CART) analysis was performed to bring out the meaningful predictors when evaluating patients with I/GEs for MwoA comorbidity, using the variables that were significant in the univariate analysis.

Results

Longer headache duration (<4 h) followed by throbbing pain, higher visual analog scale (VAS) scores, increase of pain by physical activity, nausea/vomiting, and photophobia and/or phonophobia are the main distinguishing clinical characteristics of comorbid MwoA in patients with I/GE, for being classified in the full diagnosis group. Despite being not a part of the main ICHD-3 criteria, the presence of associated symptoms mainly osmophobia and also vertigo/dizziness had the distinguishing capability of being classified into zone subgroups. The most common epilepsy syndromes fulfilling full diagnosis criteria (n = 62) in the CART analysis were 48.39% Juvenile myoclonic epilepsy followed by 25.81% epilepsy with generalized tonic-clonic seizures alone.

Conclusion

Longer headache duration, throbbing pain, increase of pain by physical activity, photophobia and/or phonophobia, presence of vertigo/dizziness, osmophobia, and higher VAS scores are the main supportive associated factors when applying the ICHD-3 criteria for the comorbid MwoA diagnosis in patients with I/GEs. Evaluating these characteristics could be helpful to close the diagnostic gaps in everyday clinical practice and fasten the diagnostic process of comorbid MwoA in patients with I/GEs.
Case report: KPTN gene-related syndrome associated with a spectrum of neurodevelopmental anomalies including severe epilepsy
Authors: Horn Svea , Danyel Magdalena , Erdmann Nina , Boschann Felix , Gunnarsson Cecilia , Biskup Saskia , Juengling Jerome , Potratz Cornelia , Prager Christine , Kaindl Angela M.
Published: January 2023

Biallelic variants in the kaptin gene KPTN were identified recently in individuals with a novel syndrome referred to as autosomal recessive intellectual developmental disorder 41 (MRT41). MRT41 is characterized by developmental delay, predominantly in language development, behavioral abnormalities, and epilepsy. Only about 15 affected individuals have been described in the literature, all with primary or secondary macrocephaly. Using exome sequencing, we identified three different biallelic variants in KPTN in five affected individuals from three unrelated families. In total, two KPTN variants were already reported as a loss of function variants. A novel splice site variant in KPTN was detected in two unrelated families of this study. The core phenotype with neurodevelopment delay was present in all patients. However, macrocephaly was not present in at least one patient. In total, two patients exhibited developmental and epileptic encephalopathies with generalized tonic-clonic seizures that were drug-resistant in one of them. Thus, we further delineate the KPTN-related syndrome, especially emphasizing the severity of epilepsy phenotypes and difficulties in treatment in patients of our cohort.
Systems-level decoding reveals the cognitive and behavioral profile of the human intraparietal sulcus
Authors: Boeken Ole Jonas , Markett Sebastian
Published: January 2023

Introduction

The human intraparietal sulcus (IPS) covers large portions of the posterior cortical surface and has been implicated in a variety of cognitive functions. It is, however, unclear how cognitive functions dissociate between the IPS's heterogeneous subdivisions, particularly in perspective to their connectivity profile.

Methods

We applied a neuroinformatics driven system-level decoding on three cytoarchitectural distinct subdivisions (hIP1, hIP2, hIP3) per hemisphere, with the aim to disentangle the cognitive profile of the IPS in conjunction with functionally connected cortical regions.

Results

The system-level decoding revealed nine functional systems based on meta-analytical associations of IPS subdivisions and their cortical coactivations: Two systems–working memory and numeric cognition–which are centered on all IPS subdivisions, and seven systems–attention, language, grasping, recognition memory, rotation, detection of motions/shapes and navigation–with varying degrees of dissociation across subdivisions and hemispheres. By probing the spatial overlap between systems-level co-activations of the IPS and seven canonical intrinsic resting state networks, we observed a trend toward more co-activation between hIP1 and the front parietal network, between hIP2 and hIP3 and the dorsal attention network, and between hIP3 and the visual and somatomotor network.

Discussion

Our results confirm previous findings on the IPS's role in cognition but also point to previously unknown differentiation along the IPS, which present viable starting points for future work. We also present the systems-level decoding as promising approach toward functional decoding of the human connectome.
A standardized protocol for manually segmenting stroke lesions on high-resolution T1-weighted MR images
Authors: Lo Bethany P. , Donnelly Miranda R. , Barisano Giuseppe , Liew Sook-Lei
Published: January 2023

Although automated methods for stroke lesion segmentation exist, many researchers still rely on manual segmentation as the gold standard. Our detailed, standardized protocol for stroke lesion tracing on high-resolution 3D T1-weighted (T1w) magnetic resonance imaging (MRI) has been used to trace over 1,300 stroke MRI. In the current study, we describe the protocol, including a step-by-step method utilized for training multiple individuals to trace lesions (“tracers”) in a consistent manner and suggestions for distinguishing between lesioned and non-lesioned areas in stroke brains. Inter-rater and intra-rater reliability were calculated across six tracers trained using our protocol, resulting in an average intraclass correlation of 0.98 and 0.99, respectively, as well as a Dice similarity coefficient of 0.727 and 0.839, respectively. This protocol provides a standardized guideline for researchers performing manual lesion segmentation in stroke T1-weighted MRI, with detailed methods to promote reproducibility in stroke research.
Canonical template tracking: Measuring the activation state of specific neural representations
Authors: Palenciano Ana F. , Senoussi Mehdi , Formica Silvia , González-García Carlos
Published: January 2023

Multivariate analyses of neural data have become increasingly influential in cognitive neuroscience since they allow to address questions about the representational signatures of neurocognitive phenomena. Here, we describe Canonical Template Tracking: a multivariate approach that employs independent localizer tasks to assess the activation state of specific representations during the execution of cognitive paradigms. We illustrate the benefits of this methodology in characterizing the particular content and format of task-induced representations, comparing it with standard (cross-)decoding and representational similarity analyses. Then, we discuss relevant design decisions for experiments using this analysis approach, focusing on the nature of the localizer tasks from which the canonical templates are derived. We further provide a step-by-step tutorial of this method, stressing the relevant analysis choices for functional magnetic resonance imaging and magneto/electroencephalography data. Importantly, we point out the potential pitfalls linked to canonical template tracking implementation and interpretation of the results, together with recommendations to mitigate them. To conclude, we provide some examples from previous literature that highlight the potential of this analysis to address relevant theoretical questions in cognitive neuroscience.
An RBF neural network based on improved black widow optimization algorithm for classification and regression problems
Authors: Liu Hui , Zhou Guo , Zhou Yongquan , Huang Huajuan , Wei Xiuxi
Published: January 2023

Introduction

Regression and classification are two of the most fundamental and significant areas of machine learning.

Methods

In this paper, a radial basis function neural network (RBFNN) based on an improved black widow optimization algorithm (IBWO) has been developed, which is called the IBWO-RBF model. In order to enhance the generalization ability of the IBWO-RBF neural network, the algorithm is designed with nonlinear time-varying inertia weight.

Discussion

Several classification and regression problems are utilized to verify the performance of the IBWO-RBF model. In the first stage, the proposed model is applied to UCI dataset classification, nonlinear function approximation, and nonlinear system identification; in the second stage, the model solves the practical problem of power load prediction.

Results

Compared with other existing models, the experiments show that the proposed IBWO-RBF model achieves both accuracy and parsimony in various classification and regression problems.
Aberrant neurovascular coupling in Leber’s hereditary optic neuropathy: Evidence from a multi-model MRI analysis
Authors: Ji Yi , Wang Ling , Ding Hao , Tian Qin , Fan Ke , Shi Dapeng , Yu Chunshui , Qin Wen
Published: January 2023

The study aimed to investigate the neurovascular coupling abnormalities in Leber’s hereditary optic neuropathy (LHON) and their associations with clinical manifestations. Twenty qualified acute Leber’s hereditary optic neuropathy (A-LHON, disease duration ≤ 1 year), 29 chronic Leber’s hereditary optic neuropathy (C-LHON, disease duration > 1 year), as well as 37 healthy controls (HCs) were recruited. The neurovascular coupling strength was quantified as the ratio between regional homogeneity (ReHo), which represents intrinsic neuronal activity and relative cerebral blood flow (CBF), representing microcirculatory blood supply. A one-way analysis of variance was used to compare intergroup differences in ReHo/CBF ratio with gender and age as co-variables. Pearson’s Correlation was used to clarify the association between ReHo, CBF, and neurovascular coupling strength. Furthermore, we applied linear and exponential non-linear regression models to explore the associations among ReHo/CBF, disease duration, and neuro-ophthalmological metrics. Compared with HCs, A_LHON, and C_LHON patients demonstrated a higher ReHo/CBF ratio than the HCs in the bilateral primary visual cortex (B_CAL), which was accompanied by reduced CBF while preserved ReHo. Besides, only C_LHON had a higher ReHo/CBF ratio and reduced CBF in the left middle temporal gyrus (L_MTG) and left sensorimotor cortex (L_SMC) than the HCs, which was accompanied by increased ReHo in L_MTG (p < 1.85e–3, Bonferroni correction). A-LHON and C-LHON showed a negative Pearson correlation between ReHo/CBF ratio and CBF in B_CAL, L_SMC, and L_MTG. Only C_LHON showed a weak positive correlation between ReHo/CBF ratio and ReHo in L_SMC and L_MTG (p < 0.05, uncorrected). Finally, disease duration was positively correlated with ReHo/CBF ratio of L_SMC (Exponential: Radj2 = 0.23, p = 8.66e–4, Bonferroni correction). No statistical correlation was found between ReHo/CBF ratio and neuro-ophthalmological metrics (p > 0.05, Bonferroni correction). Brain neurovascular “dyscoupling” within and outside the visual system might be an important neurological mechanism of LHON.
A transfer learning approach for multiclass classification of Alzheimer's disease using MRI images
Authors: Khan Rizwan , Akbar Saeed , Mehmood Atif , Shahid Farah , Munir Khushboo , Ilyas Naveed , Asif M. , Zheng Zhonglong
Published: January 2023

Alzheimer's is an acute degenerative disease affecting the elderly population all over the world. The detection of disease at an early stage in the absence of a large-scale annotated dataset is crucial to the clinical treatment for the prevention and early detection of Alzheimer's disease (AD). In this study, we propose a transfer learning base approach to classify various stages of AD. The proposed model can distinguish between normal control (NC), early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI), and AD. In this regard, we apply tissue segmentation to extract the gray matter from the MRI scans obtained from the Alzheimer's Disease National Initiative (ADNI) database. We utilize this gray matter to tune the pre-trained VGG architecture while freezing the features of the ImageNet database. It is achieved through the addition of a layer with step-wise freezing of the existing blocks in the network. It not only assists transfer learning but also contributes to learning new features efficiently. Extensive experiments are conducted and results demonstrate the superiority of the proposed approach.
Disturbed relationship between glucocorticoid receptor and 5-HT1AR/5-HT2AR in ADHD rats: A correlation study
Authors: Lin Xiaoxia , Huang Liang , Huang Huifang , Ke Zhongling , Chen Yanhui
Published: January 2023

Objective

This work is to investigate the alterations of the central 5-hydroxytryptamine (5-HT) system in spontaneously hypertensive rats (SHR) and the correlation with the behaviors of SHR, and to explore the effects of glucocorticoid intervention on the central 5-HT system and SHR behaviors.

Materials and methods

Three weeks old SHR were chosen as the attention-deficit hyperactivity disorder (ADHD) model and treated with glucocorticoid receptor (GR) agonist or inhibitor, whereas Wista Kyoto rats (WKY) were chosen as the normal control group. Open-field test and Làt maze test were used to evaluate the spontaneous activities and non-selective attention. The levels of 5-HT in the extracellular fluid specimens of the prefrontal cortex of rats were analyzed by high-performance liquid chromatography. The expressions of GR, 5-HT1A receptor (5-HT1AR), and 5-HT2A receptor (5-HT2AR) in the prefrontal cortex were analyzed through immunohistochemistry.

Results

Our study demonstrated that the 5-HT level was lower in the prefrontal cortex of SHR compared to that of WKY. The Open-field test and Làt maze test showed that GR agonist (dexamethasone, DEX) intervention ameliorated attention deficit and hyperactive behavior, whereas GR inhibitor (RU486) aggravated the disorders. With DEX, the expression levels of 5-HT and 5-HT2AR in the prefrontal cortex of SHR were significantly higher than those in the control group, whereas the expression level of 5-HT1AR was lower. However, the expression levels of 5-HT and 5-HT2AR were significantly decreased after the intervention with RU486, while the expression level of 5-HT1AR increased. Results showed that glucocorticoid was negatively correlated with 5-HT1AR and positively correlated with 5-HT2AR.

Conclusion

In the prefrontal cortex of ADHD rats, the down-regulation of 5-HT and 5-HT2AR expressions and the up-regulation of 5-HT1AR, compared with WYK rats, suggested a dysfunctional central 5-HT system in ADHD rats. The GR agonist can upregulate the expression of 5-HT and 5-HT2AR and downregulate the expression of 5-HT1AR in the prefrontal cortex of SHR as well as reduce the hyperactivity and attention deficit behavior in SHR, while the opposite was true for the GR inhibitor. It is suggested that the dysfunction of the 5-HT system in ADHD rats is closely related to glucocorticoid receptor activity.
Small molecules to perform big roles: The search for Parkinson's and Huntington's disease therapeutics
Authors: Pérez-Arancibia Rodrigo , Cisternas-Olmedo Marisol , Sepúlveda Denisse , Troncoso-Escudero Paulina , Vidal Rene L.
Published: January 2023

Neurological motor disorders (NMDs) such as Parkinson's disease and Huntington's disease are characterized by the accumulation and aggregation of misfolded proteins that trigger cell death of specific neuronal populations in the central nervous system. Differential neuronal loss initiates the impaired motor control and cognitive function in the affected patients. Although major advances have been carried out to understand the molecular basis of these diseases, to date there are no treatments that can prevent, cure, or significantly delay the progression of the disease. In this context, strategies such as gene editing, cellular therapy, among others, have gained attention as they effectively reduce the load of toxic protein aggregates in different models of neurodegeneration. Nevertheless, these strategies are expensive and difficult to deliver into the patients' nervous system. Thus, small molecules and natural products that reduce protein aggregation levels are highly sought after. Numerous drug discovery efforts have analyzed large libraries of synthetic compounds for the treatment of different NMDs, with a few candidates reaching clinical trials. Moreover, the recognition of new druggable targets for NMDs has allowed the discovery of new small molecules that have demonstrated their efficacy in pre-clinical studies. It is also important to recognize the contribution of natural products to the discovery of new candidates that can prevent or cure NMDs. Additionally, the repurposing of drugs for the treatment of NMDs has gained huge attention as they have already been through clinical trials confirming their safety in humans, which can accelerate the development of new treatment. In this review, we will focus on the new advances in the discovery of small molecules for the treatment of Parkinson's and Huntington's disease. We will begin by discussing the available pharmacological treatments to modulate the progression of neurodegeneration and to alleviate the motor symptoms in these diseases. Then, we will analyze those small molecules that have reached or are currently under clinical trials, including natural products and repurposed drugs.
Bibliometric and visual analysis of cerebral revascularization from 1999 to 2022
Authors: Zhang Ding , Li Xiaoqian , Jia Ni , Chen Wei , Hu Yueqiang
Published: January 2023

Background

Cerebral revascularization is a neurosurgical procedure used to restore the cerebral collateral circulation channel. This study examines the countries, institutions, authors, journals, keywords, and references related to the disease in the field of cerebral revascularization from 1999 to 2022 from a bibliometrics perspective, evaluates the changes of knowledge structure clustering and identifies the new hot spots and new research directions in this field.

Methods

The Web of Science Core Collection (WOSCC) database and the PICOS retrieval method were used to conduct a comprehensive search for articles and reviews pertaining to cerebral revascularization. The final filtered data were bibliometrically and visually drawn using Microsoft office 365, CiteSpace (v.6.1.R2), and VOSviewer (v.1.6.18).

Results

From 1999 to 2022, a total of 854 articles pertaining to cerebral revascularization, which originated from 46 nations, 482 institutions, and 686 researchers, were extracted from the WOSCC database, and the number of publications in this field of study was rising. The United States held the highest proportion in the ranking analysis of countries, institutions, authors, and journals. By analyzing co-citations, the scientific organization of this field and the development status of frontier fields were realized. Cerebral revascularization, moyamoya disease, extracranial intracranial bypass, and occlusion are the current research focal points in the field of cerebral revascularization. Hyperperfusion and vascular disorder may also become a new study focus in this discipline in the near future.

Conclusion

Using the method of bibliometrics, this study analyzed and reviewed the articles in the field of cerebral revascularization, which enabled scholars to better comprehend the dynamic process in this field and provided a foundation for future in-depth research.
Dendritic spine loss deep in the neocortex and dendrite distortion with diffusion disturbances occur early in experimental pneumococcal meningitis
Authors: Baronti Dario , Tomov Nikola , Hupp Sabrina , Mitchell Timothy J. , Iliev Asparouh I.
Published: January 2023

Introduction

Streptococcus pneumoniae (pneumococcus) meningitis is a serious disease with substantial lethality and long-term disability in survivors. Loss of synaptic staining in the superficial layers of the neocortex in rodent models and in humans, and pneumolysin (a major pneumococcal toxin)-dependent dendritic spine collapse in brain slices have been described. It remains unclear how deep in the neocortex more discrete changes are present, how soon after disease onset these changes occur, and whether other properties of dendrites are also affected.

Methods

Using a mouse model of pneumococcal meningitis, we studied changes in the neocortex shortly (3–6 h) after the onset of clinical symptoms via modified Golgi-Cox silver staining.

Results

Dendritic changes were present in areas with otherwise unchanged cell numbers and no signs of necrosis or other apparent neuronal pathology. Mature dendritic spines were reduced in the pyramidal neurons running through layers 1–5. Additionally, spine morphology changes (swelling, spine neck distortion), were also observed in the deeper layers 4 and 5 of the neocortex. Immature spines (filopodia) remained unchanged between groups, as well as the dendritic arborization of the analyzed neurons. In a third of the animals with meningitis, massive mechanical distortion of the primary dendrites of most of the pyramidal neurons through layers 1–5 was observed. This distortion was reproduced in acute brain slices after exposure to pneumolysin-containing bacterial lysates (S. pneumoniae D39 strain), but not to lysates of pneumolysin-deficient bacteria, which we explain by the tissue remodeling effect of the toxin. Experimental mechanical dendrite distortion in primary neural cultures demonstrated diminished FRAP diffusion of neuronally-expressed enhanced green fluorescent protein (eGFP), indicative of disturbed dendritic diffusion.

Discussion

Our work extends earlier knowledge of synaptic loss in the superficial cortical layers during meningitis to deeper layers. These changes occurred surprisingly early in the course of the disease, substantially limiting the effective therapeutic window. Methodologically, we demonstrate that the dendritic spine collapse readout is a highly reliable and early marker of neural damage in pneumococcal meningitis models, allowing for reduction of the total number of animals used per a group due to much lower variation among animals.
Ear-EEG sensitivity modeling for neural sources and ocular artifacts
Authors: Yarici Metin C. , Thornton Mike , Mandic Danilo P.
Published: January 2023

The ear-EEG has emerged as a promising candidate for real-world wearable brain monitoring. While experimental studies have validated several applications of ear-EEG, the source-sensor relationship for neural sources from across the brain surface has not yet been established. In addition, modeling of the ear-EEG sensitivity to sources of artifacts is still missing. Through volume conductor modeling, the sensitivity of various configurations of ear-EEG is established for a range of neural sources, in addition to ocular artifact sources for the blink, vertical saccade, and horizontal saccade eye movements. Results conclusively support the introduction of ear-EEG into conventional EEG paradigms for monitoring neural activity that originates from within the temporal lobes, while also revealing the extent to which ear-EEG can be used for sources further away from these regions. The use of ear-EEG in scenarios prone to ocular artifacts is also supported, through the demonstration of proportional scaling of artifacts and neural signals in various configurations of ear-EEG. The results from this study can be used to support both existing and prospective experimental ear-EEG studies and applications in the context of sensitivity to both neural sources and ocular artifacts.
Chemokine-like factor-like MARVEL transmembrane domain containing 6: Bioinformatics and experiments in vitro analyze in glioblastoma multiforme
Authors: Meng Haining , Li Shaohua , Li Qingshu , Wang Yuqin , Wang Guoan , Qu Yan
Published: January 2023

Introduction

Chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing 6 (CMTM6) is a protein localized to the cell membrane and is known for its ability to co-localize with PD-L1 on the plasma membrane, prevent PD-L1 degradation, and maintain PD-L1 expression on the cell membrane. CMTM6 is highly expressed and plays an important role in various tumors such as oral squamous cell carcinoma (OSCC) and colorectal cancer (CRC), however, its role in Glioblastoma multiforme (GBM) is unclear.

Methods

In this paper, to investigate the role of CMTM6 in GBM, we analyzed the expression of CMTM6 in GBM, the interaction with CMTM6 and the associated genes by bioinformatics. Importantly, we analyzed the expression of CMTM6 in GBM in relation to tumor-infiltrating lymphocytes (TILs), immunoinhibitors, immunostimulators, chemokines and chemokine receptors. We further analyzed the function of CMTM6 and performed in vitro experiments to verify it. Finally, the sensitivity of CMTM6 to drugs was also analyzed and the relationship between CMTM6 and the anticancer drug Piperlonguminine (PL) was verified in vitro.

Results

The results showed that CMTM6 was highly expressed in GBM and correlated with multiple genes. Furthermore, CMTM6 is closely related to the immune microenvironment and inflammatory response in GBM. Bioinformatic analysis of CMTM6 correlated with the function of GBM, and our experiments demonstrated that CMTM6 significantly promoted the migration of GBM cells and epithelial-mesenchymal transition (EMT), but had no significant effect on other functions. Interestingly, we found that in GBM, PL promotes the expression of CMTM6.

Discussion

In this paper, we have performed a detailed analysis and validation of the role of CMTM6 in GBM using bioinformatics analysis and in vitro experiments to demonstrate that CMTM6 may be a potential target for glioma therapy.
Circulating exosomal microRNA profiles in migraine patients receiving acupuncture treatment: A placebo-controlled clinical trial
Authors: Liu Lu , Qi Wenchuan , Wang Yanan , Ni Xixiu , Gao Shan , Zhou Ziyang , Chen Daohong , He Zhenxi , Sun Mingsheng , Wang Ziwen , Cai Dingjun , Zhao Ling
Published: January 2023

Background

Acupuncture has a long history of being used in Chinese medicine for the treatment of migraine. However, molecular biomarkers for diagnosis and prognosis of migraine and its treatment are lacking. This study aimed to explore whether acupuncture could regulate differentially expressed exosomal miRNAs between patients with migraine without aura (MWoA) and healthy controls (HCs) and to identify diagnostic biomarkers that helped differentiate MWoA patients from HCs and identify prognostic biomarkers that helped to predict the effect of acupuncture.

Methods

Here, we isolated serum exosomes from patients with MWoA and HCs before and after true and sham acupuncture treatment. Then, small RNA sequencing and bioinformatics analysis were performed to screen out key miRNAs specifically responding to acupuncture treatment. Pearson’s correlation analysis was used to evaluate the correlation between miRNAs and clinical phenotypes. Finally, we applied a machine learning method to identify diagnostic biomarkers of MWoA patients and identify prognostic biomarkers that helped to predict the effect of acupuncture.

Results

Small RNA sequencing identified 68 upregulated and 104 downregulated miRNAs in MWoA patients compared to those in HCs. Further, we identified eight upregulated and four downregulated miRNAs in migraine patients after true acupuncture treatment (trAMWoA), but not in the sham acupuncture treatment (shAMWoA) or HC group. Among them, hsa-miR-378a-5p was positively correlated with time unable to work, study, or do housework due to migraine (p < 0.05), whereas hsa-miR-605-3p was negatively correlated with the restrictive subscale of the migraine-specific quality of life questionnaire (MSQ) (p < 0.05). We then evaluated the diagnostic and prognostic potential of these 12 miRNAs in patients with MWoA. The combination of serum levels of exosomal hsa-miR-369-5p, hsa-miR-145-5p, and hsa-miR-5,010-3p could serve as diagnostic and prognostic biomarkers for MWoA patients following acupuncture treatment.

Conclusion

This is the first study on the serum exosomal miRNA profiles of migraineurs before and after acupuncture treatment. Our results improve our understanding of the molecular functions of miRNAs in MWoA. More importantly, they expand our view of evaluating the clinical outcomes of migraine patients treated with acupuncture, using exosomal RNA markers.

Clinical Trial Registration

Chinese Clinical Trial Registry, ChiCTR2000034417, July 2020.
Bioactive compounds, antioxidant activity, and mineral content of bróquil: A traditional crop of Brassica oleracea var. italica
Authors: Montaner Celia , Mallor Cristina , Laguna Sonia , Zufiaurre Raquel
Published: January 2023

Brassicaceae edible plants are rich in bioactive compounds and promote health benefits. However, there is less interest in expanding knowledge about the Brassica cultivars to date. In particular, underutilized species and local cultivars could constitute a source of agrodiversity in adapting to the territory with likely higher contents of nutraceutical compounds. In this context, Bróquil (Brassica oleracea var. italica) is a traditional Brassicaceae crop grown in the Spanish region of Aragón. Currently, it is cultivated mainly in family orchards for autoconsumption and, in minority, in small farms for local markets. This study evaluates a collection of 13 bróquil landraces from the Spanish Vegetable Genebank of the Agrifood Research and Technology Center of Zaragoza (BGHZ-CITA), describing their mineral contents, bioactive compounds, and antioxidant activities, including a broccoli commercial variety “Parthenon” as the control. The study reports data on the health-promoting nutrients and antioxidants of bróquil for the first time. Under our experimental conditions, we found that bróquil has a great variability for these compounds that showed on average similar or higher levels than the broccoli control. The different bróquil landraces also revealed variability in both intraccessions and interaccessions due to the lack of a formal breeding selection. Despite this variability, we highlight accession HB5 that corresponds to Headed Bróquil BGHZ6685. In particular, we can stand out its antioxidant activity of 87.07 ± 0.81%I, total phenolic content of 13.21 ± 0.53 mg GAE g−1 dw, total flavonoid content of 14.50 ± 1.29 mg QE g−1 dw, total glucosinolate content of 43.70 ± 1.09 mg SnE g−1 dw, and vitamin C content of 7.21 ± 0.13 mg AA g−1 dw. Regarding bróquil mineral composition, K was the highest macroelement (22.66–33.62 mg g−1 dw), followed by Ca, P, and S whose values were relatively lower compared to K. Mg and Na showed the lowest values. Among the microelements evaluated (Mn, Zn, and Fe), iron was the most abundant detected, higher in all bróquil accessions than in broccoli, except for one accession. Therefore, the results reported for bróquil landraces show promising nutritional quality. This could lead to an increase in agrobiodiversity and contribute to a more diversified and healthy diet.
Simiao Wan and its ingredients alleviate type 2 diabetes mellitus via IRS1/AKT2/FOXO1/GLUT2 signaling
Authors: Xia Ting , Xu Wen-Jie , Hu Yan-Nan , Luo Zhen-Ye , He Wen , Liu Chang-Shun , Tan Xiao-Mei
Published: January 2023

Background

Type 2 diabetes mellitus (T2DM) is a metabolic disease. Simiao Wan (SMW) is a commonly used clinical drug for hyperuricemia treatment. SMW has been confirmed to improve insulin resistance and is expected to be a novel hypoglycemic agent. However, the hypoglycemic bioactive ingredients and mechanisms of action of SMW are unclear.

Objective

To explore the hypoglycemic effects and reveal the mechanisms of SMW and bioactive ingredients (SMW-BI).

Study design and methods

The hypoglycemic effects of SMW and SMW-BI were verified in a mouse model of T2DM induced by streptozotocin (STZ) and a high-fat and high-sugar diet (HFSD). Network pharmacology was used to predict the mechanisms of SMW and SMW-BI. Histological analysis and real-time quantitative polymerase chain reaction (RT-qPCR) verified network pharmacology results. RT-qPCR results were further verified by immunofluorescence (IFC) and molecular docking. The correlation between proteins and biochemical indicators was analyzed by Spearman’s correlation.

Results

Chlorogenic acid, phellodendrine, magnoflorine, jateorhizine, palmatine, berberine, and atractydin were identified as SMW-BI. After 8 weeks of treatment, SMW and SMW-BI decreased the levels of fasting blood glucose (FBG), total cholesterol (TC), triacylglycerols (TG) and low-density lipoprotein cholesterol (LDL-C), increased the level of high-density lipoprotein cholesterol (HDL-C), alleviated weight loss, and increased serum insulin levels in T2DM mice. In addition, SMW and SMW-BI improved hepatocyte morphology in T2DM mice, decreased the number of adipocytes, and increased liver glycogen. Network pharmacological analysis indicated that SMW and SMW-BI may exert hypoglycemic by regulating insulin receptor substrate 1 (IRS1)/RAC-beta serine/threonine-protein kinase (AKT2)/forkhead box protein O1 (FOXO1)/glucose transporter type 2 (GLUT2) signaling. Moreover, correlation analysis showed that SMW and SMW-BI were associated with activation of IRS1, AKT2, and GLUT2, and inhibiting FOXO1. RT-qPCR revealed that SMW and SMW-BI could increase levels of IRS1, AKT2, and GLUT2 in the livers of T2DM mice and lower the level of FOXO1. Furthermore, immunofluorescence analysis showed that FOXO1 expression in the livers of T2DM mice decreased after oral administration of SMW and SMW-BI. Furthermore, molecular docking showed that SMW-BI could bind directly to IRS1 and AKT2.

Conclusion

SMW and SMW-BI are potential hypoglycemic drugs that alleviate T2DM by regulating IRS1/AKT2/FOXO1 signaling. Our study provides a research idea for screening the bioactive ingredients in traditional Chinese medicine (TCM).
Impacts of turmeric and its principal bioactive curcumin on human health: Pharmaceutical, medicinal, and food applications: A comprehensive review
Authors: El-Saadony Mohamed T. , Yang Tao , Korma Sameh A. , Sitohy Mahmoud , Abd El-Mageed Taia A. , Selim Samy , Al Jaouni Soad K. , Salem Heba M. , Mahmmod Yasser , Soliman Soliman M. , Mo’men Shaimaa A. A. , Mosa Walid F. A. , El-Wafai Nahed A. , Abou-Aly Hamed E. , Sitohy Basel , Abd El-Hack Mohamed E. , El-Tarabily Khaled A. , Saad Ahmed M.
Published: January 2023

The yellow polyphenolic pigment known as curcumin, originating from the rhizome of the turmeric plant Curcuma longa L., has been utilized for ages in ancient medicine, as well as in cooking and food coloring. Recently, the biological activities of turmeric and curcumin have been thoroughly investigated. The studies mainly focused on their antioxidant, antitumor, anti-inflammatory, neuroprotective, hepatoprotective, and cardioprotective impacts. This review seeks to provide an in-depth, detailed discussion of curcumin usage within the food processing industries and its effect on health support and disease prevention. Curcumin’s bioavailability, bio-efficacy, and bio-safety characteristics, as well as its side effects and quality standards, are also discussed. Finally, curcumin’s multifaceted uses, food appeal enhancement, agro-industrial techniques counteracting its instability and low bioavailability, nanotechnology and focused drug delivery systems to increase its bioavailability, and prospective clinical use tactics are all discussed.