bluuebunny/crossref_metadata_2025 huggingface dataset:
Medical Cannabis for the Treatment of Migraine in Adults: A Review of the Evidence
Authors: Okusanya Babasola O. , Lott Breanne E. , Ehiri John , McClelland Jean , Rosales Cecilia
Published: June 2022

Background

Medical cannabis (MC) has been hypothesized as an alternative therapy for migraines, given the undesirable side effects of current migraine medications. The objective of this review was to assess the effectiveness and safety of MC in the treatment of migraine in adults.

Methods

We searched PubMed, EMBASE, PsycINFO, CINAHL, and Web of Science for eligible studies in adults aged 18 years and older. Two reviewers independently screened studies for eligibility. A narrative synthesis of the included studies was conducted.

Results

A total of 12 publications involving 1,980 participants in Italy and the United States of America were included.

Medical cannabis significantly reduced nausea and vomiting associated with migraine attacks after 6 months of use. Also, MC reduced the number of days of migraine after 30 days, and the frequency of migraine headaches per month. MC was 51% more effective in reducing migraines than non-cannabis products. Compared to amitriptyline, MC aborted migraine headaches in some (11.6%) users and reduced migraine frequency. While the use of MC for migraines was associated with the occurrence of medication overuse headaches (MOH), and the adverse events were mostly mild and occurred in 43.75% of patients who used oral cannabinoid preparations.

Conclusions

There is promising evidence that MC may have a beneficial effect on the onset and duration of migraine headaches in adults. However, well-designed experimental studies that assess MC's effectiveness and safety for treating migraine in adults are needed to support this hypothesis.
Microscopic Transsphenoidal Resection of Giant Pituitary Adenomas: Analysis of the Factors Limiting the Degree of Resection in 73 Cases
Authors: Pei Zhijie , Wang Jiaxing , Mu Shuwen , Feng Tianshun , Wang Meina , Yu Shentong , Wei Liangfeng , Fang Yi , Wang Shousen
Published: June 2022

Purpose

To analyze the risk factors affecting the gross-total resection of giant pituitary adenomas using a transsphenoidal approach under a microscope to provide a reference basis for formulating an appropriate surgical strategy.

Methods

The clinical data of patients who underwent microscopic transsphenoidal resection of giant pituitary adenomas in a single center from January 2011 to December 2020 were retrospectively analyzed. Based on magnetic resonance imaging and surgical records, the predictive factors affecting the gross-total resection of giant pituitary adenomas under microscopy were determined through univariate and multivariate analyses.

Results

A total of 73 patients with giant pituitary adenomas underwent transsphenoidal microsurgery. Gross-total resection was performed in 19 cases (26%), subtotal resection in 31 cases (42%), partial resection in 21 cases (29%), and the degree of resection was <50% in only two cases (3%). After binary logistic analysis, it was found that it was more difficult to completely remove giant pituitary adenomas with a Knosp grade 3–4 [odds ratio (OR) = 0.214, 95% confidence interval (CI): 0.05–0.917; P = 0.038], greater proportion of tumor suprasellar volume (odds ratio = 0.937, 95% confidence interval: 0.898–0.978; P = 0.003), and intraoperative evidence of invasion of the cavernous sinus (odds ratio = 0.187, 95% CI: 0.039–0.898; P = 0.036).

Conclusion

It is difficult to remove a giant pituitary adenoma invading the cavernous sinus completely with a higher degree of invasion of the suprasellar region using microscopic transsphenoidal surgery. The combined application of multiple surgical methods can help to improve the degree of resection during a single operation.
Current Status and Future Opportunities in Modeling Clinical Characteristics of Multiple Sclerosis
Authors: Liu Joshua , Kelly Erin , Bielekova Bibiana
Published: June 2022

Development of effective treatments requires understanding of disease mechanisms. For diseases of the central nervous system (CNS), such as multiple sclerosis (MS), human pathology studies and animal models tend to identify candidate disease mechanisms. However, these studies cannot easily link the identified processes to clinical outcomes, such as MS severity, required for causality assessment of candidate mechanisms. Technological advances now allow the generation of thousands of biomarkers in living human subjects, derived from genes, transcripts, medical images, and proteins or metabolites in biological fluids. These biomarkers can be assembled into computational models of clinical value, provided such models are generalizable. Reproducibility of models increases with the technical rigor of the study design, such as blinding, control implementation, the use of large cohorts that encompass the entire spectrum of disease phenotypes and, most importantly, model validation in independent cohort(s). To facilitate the growth of this important research area, we performed a meta-analysis of publications (n = 302) that model MS clinical outcomes extracting effect sizes, while also scoring the technical quality of the study design using predefined criteria. Finally, we generated a Shiny-App-based website that allows dynamic exploration of the data by selective filtering. On average, the published studies fulfilled only one of the seven criteria of study design rigor. Only 15.2% of the studies used any validation strategy, and only 8% used the gold standard of independent cohort validation. Many studies also used small cohorts, e.g., for magnetic resonance imaging (MRI) and blood biomarker predictors, the median sample size was <100 subjects. We observed inverse relationships between reported effect sizes and the number of study design criteria fulfilled, expanding analogous reports from non-MS fields, that studies that fail to limit bias overestimate effect sizes. In conclusion, the presented meta-analysis represents a useful tool for researchers, reviewers, and funders to improve the design of future modeling studies in MS and to easily compare new studies with the published literature. We expect that this will accelerate research in this important area, leading to the development of robust models with proven clinical value.
Dysautonomia in COVID-19 Patients: A Narrative Review on Clinical Course, Diagnostic and Therapeutic Strategies
Authors: Carmona-Torre Francisco , Mínguez-Olaondo Ane , López-Bravo Alba , Tijero Beatriz , Grozeva Vesselina , Walcker Michaela , Azkune-Galparsoro Harkaitz , López de Munain Adolfo , Alcaide Ana Belen , Quiroga Jorge , del Pozo Jose Luis , Gómez-Esteban Juan Carlos
Published: June 2022

Introduction

On March 11, 2020, the World Health Organization sounded the COVID-19 pandemic alarm. While efforts in the first few months focused on reducing the mortality of infected patients, there is increasing data on the effects of long-term infection (Post-COVID-19 condition). Among the different symptoms described after acute infection, those derived from autonomic dysfunction are especially frequent and limiting.

Objective

To conduct a narrative review synthesizing current evidence of the signs and symptoms of dysautonomia in patients diagnosed with COVID-19, together with a compilation of available treatment guidelines.

Results

Autonomic dysfunction associated with SARS-CoV-2 infection occurs at different temporal stages. Some of the proposed pathophysiological mechanisms include direct tissue damage, immune dysregulation, hormonal disturbances, elevated cytokine levels, and persistent low-grade infection. Acute autonomic dysfunction has a direct impact on the mortality risk, given its repercussions on the respiratory, cardiovascular, and neurological systems. Iatrogenic autonomic dysfunction is a side effect caused by the drugs used and/or admission to the intensive care unit. Finally, late dysautonomia occurs in 2.5% of patients with Post-COVID-19 condition. While orthostatic hypotension and neurally-mediated syncope should be considered, postural orthostatic tachycardia syndrome (POTS) appears to be the most common autonomic phenotype among these patients. A review of diagnostic and treatment guidelines focused on each type of dysautonomic condition was done.

Conclusion

Symptoms deriving from autonomic dysfunction involvement are common in those affected by COVID-19. These symptoms have a great impact on the quality of life both in the short and medium to long term. A better understanding of the pathophysiological mechanisms of Post-COVID manifestations that affect the autonomic nervous system, and targeted therapeutic management could help reduce the sequelae of COVID-19, especially if we act in the earliest phases of the disease.
Safety and Clinical Efficacy of Mesenchymal Stem Cell Treatment in Traumatic Spinal Cord Injury, Multiple Sclerosis and Ischemic Stroke – A Systematic Review and Meta-Analysis
Authors: Kvistad Christopher Elnan , Kråkenes Torbjørn , Gjerde Cecilie , Mustafa Kamal , Rekand Tiina , Bø Lars
Published: June 2022

Background

Mesenchymal stem cells (MSCs) is an attractive candidate in regenerative research and clinical trials have assessed their therapeutic potential in different neurological conditions with disparate etiologies. In this systematic review, we aimed to assess safety and clinical effect of MSC treatment in traumatic spinal cord injury (TSCI), multiple sclerosis (MS) and ischemic stroke (IS).

Methods

A systematic search was performed 2021-12-10 in MEDLINE, EMBASE, Web of Science and Cochrane where clinical studies assessing MSC treatment in TSCI, MS or IS were included. Studies without control group were excluded for efficacy analysis, but included in the safety analysis. For efficacy, AIS score, EDSS score and mRS were used as clinical endpoints and assessed in a meta-analysis using the random effects model.

Findings

Of 5,548 identified records, 54 studies were included. Twenty-six studies assessed MSC treatment in TSCI, 14 in MS and nine in IS, of which seven, seven and five studies were controlled, respectively. There were seven serious adverse events (SAEs), of which four were related to the surgical procedure and included one death due to complications following the implantation of MSCs. Three SAEs were considered directly related to the MSC treatment and all these had a transient course. In TSCI, a meta-analysis showed no difference in conversion from AIS A to C and a trend toward more patients treated with MSCs improving from AIS A to B as compared to controls (p = 0.05). A subgroup analysis performed per protocol, showed more MSC treated patients improving from AIS A to C in studies including patients within 8 weeks after injury (p = 0.04). In MS and IS, there were no significant differences in clinical outcomes between MSC treated patients and controls as measured by EDSS and mRS, respectively.

Interpretation

MSC-treatment is safe in patients with TSCI, MS and IS, although surgical implantation of MSC led to one fatal outcome in TSCI. There was no clear clinical benefit of MSC treatment, but this is not necessarily a proof of inefficacy due to the low number of controlled studies. Future studies assessing efficacy of MSC treatment should aim to do this in randomized, controlled studies.
Multiple Autoimmune Syndromes Including Acute Disseminated Encephalomyelitis, Myasthenia Gravis, and Thyroiditis Following Messenger Ribonucleic Acid-Based COVID-19 Vaccination: A Case Report
Authors: Poli Khouloud , Poli Sven , Ziemann Ulf
Published: June 2022

The global pandemic has resulted from the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19). To control the spread of the pandemic, SARS-CoV-2 vaccines have been developed. Messenger ribonucleic acid (mRNA)-based COVID-19 vaccines have been the most widely used. We present the case of a 65-year-old patient, who was diagnosed with acute disseminated encephalomyelitis, ocular myasthenia gravis, and autoimmune thyroiditis, following his third mRNA COVID-19 vaccination. On admission, the patient showed mild left-sided hemiparesis, contralateral dissociated sensory loss, dizziness, and right-sided deafness. Brain MRI revealed multiple acute inflammatory contrast-enhancing periventricular and brainstem lesions with involvement of vestibulo-cerebellar tract and cochlear nuclei. Despite steroid pulse and intravenous immunoglobulin therapy, clinical symptoms and MRI lesions worsened, and additional signs of ocular myasthenia gravis and elevated but asymptomatic thyroid antibodies developed. After repeated plasma exchange, all clinical symptoms resolved. This is, to the best of our knowledge, the first case report of multiple autoimmune syndromes triggered by COVID-19 vaccination. The rare occurrence of such treatable autoimmune complications should not question the importance of vaccination programs during the COVID-19 pandemic.
High-Definition Transcranial Direct Current Stimulation of the Dorsolateral Prefrontal Cortex Modulates the Electroencephalography Rhythmic Activity of Parietal Occipital Lobe in Patients With Chronic Disorders of Consciousness
Authors: Han Jinying , Chen Chen , Zheng Shuang , Yan Xiaoxiang , Wang Changqing , Wang Kai , Hu Yajuan
Published: June 2022

Background

Disorders of consciousness (DOC) are a spectrum of pathologies affecting one’s ability to interact with the external world. At present, High-Definition Transcranial Direct Current Stimulation (HD-tDCS) is used in many patients with DOC as a non-invasive treatment, but electrophysiological research on the effect of HD-tDCS on patients with DOC is limited.

Objectives

To explore how HD-tDCS affects the cerebral cortex and examine the possible electrophysiological mechanisms underlying the effects of HD-tDCS on the cerebral cortex.

Methods

A total of 19 DOC patients were assigned to HD-tDCS stimulation. Each of them underwent 10 anodal HD-tDCS sessions of the left dorsolateral prefrontal cortex (DLPFC) over 5 consecutive days. Coma Recovery Scale-Revision (CRS-R) scores were recorded to evaluate the consciousness level before and after HD-tDCS, while resting-state electroencephalography (EEG) recordings were obtained immediately before and after single and multiple HD-tDCS stimuli. Depending on whether the CRS-R score increased after stimulation, we classified the subjects into responsive (RE) and non-responsive (N-RE) groups and compared the differences in power spectral density (PSD) between the groups in different frequency bands and brain regions, and also examined the relationship between PSD values and CRS-R scores.

Results

For the RE group, the PSD value of the parieto-occipital region increased significantly in the 6–8 Hz frequency band after multiple stimulations by HD-tDCS. After a single stimulation, an increase in PSD was observed at 10–13 and 13–30 Hz. In addition, for all subjects, a positive correlation was observed between the change in PSD value in the parieto-occipital region at 10–13 and 6–8 Hz frequency band and the change in CRS-R score after a single stimulation.

Conclusion

Repeated anodal HD-tDCS of the left DLPFC can improve clinical outcomes in patients with DOC, and HD-tDCS-related increased levels of consciousness were associated with increased parieto-occipital PSD.
NNMT: Mean-Field Based Analysis Tools for Neuronal Network Models
Authors: Layer Moritz , Senk Johanna , Essink Simon , van Meegen Alexander , Bos Hannah , Helias Moritz
Published: June 2022

Mean-field theory of neuronal networks has led to numerous advances in our analytical and intuitive understanding of their dynamics during the past decades. In order to make mean-field based analysis tools more accessible, we implemented an extensible, easy-to-use open-source Python toolbox that collects a variety of mean-field methods for the leaky integrate-and-fire neuron model. The Neuronal Network Mean-field Toolbox (NNMT) in its current state allows for estimating properties of large neuronal networks, such as firing rates, power spectra, and dynamical stability in mean-field and linear response approximation, without running simulations. In this article, we describe how the toolbox is implemented, show how it is used to reproduce results of previous studies, and discuss different use-cases, such as parameter space explorations, or mapping different network models. Although the initial version of the toolbox focuses on methods for leaky integrate-and-fire neurons, its structure is designed to be open and extensible. It aims to provide a platform for collecting analytical methods for neuronal network model analysis, such that the neuroscientific community can take maximal advantage of them.
On the Interplay Between the Medicine of Hildegard of Bingen and Modern Medicine: The Role of Estrogen Receptor as an Example of Biodynamic Interface for Studying the Chronic Disease's Complexity
Authors: Melino Sabrina , Mormone Elisabetta
Published: June 2022

Introduction

Hildegard of Bingen (1098-1179) interpreted the origins of chronic disease highlighting and anticipating, although only in a limited fashion, the importance that complex interactions among numerous genetic, internal milieu and external environmental factors have in determining the disease phenotype. Today, we recognize those factors, capable of mediating the transmission of messages between human body and environment and vice versa, as biodynamic interfaces.

Aim

We analyzed, in the light of modern scientific evidence, Hildegard of Bingen's medical approach and her original humoral theory in order to identify possible insights included in her medicine that could be referred to in the context of modern evidence-based medicine. In particular, the abbess's humoral theory suggests the identification of biodynamic interfaces with sex hormones and their receptors.

Findings

We found that the Hildegardian holistic vision of the organism-environment relationship can actually represent a visionary approach to modern endocrinology and that sex hormones, in particular estrogens, could represent an example of a biodynamic interface. Estrogen receptors are found in regions of the brain involved in emotional and cognitive regulation, controlling the molecular mechanism of brain function. Estrogen receptors are involved in the regulation of the hypothalamic-pituitary-adrenal axis and in the epigenetic regulation of responses to physiological, social, and hormonal stimuli. Furthermore, estrogen affects gene methylation on its own and related receptor promoters in discrete regions of the developing brain. This scenario was strikingly perceived by the abbess in the XIIth century, and depicted as a complex interplay among different humors and flegmata that she recognized to be sex specific and environmentally regulated.

Viewpoint

Considering the function played by hormones, analyzed through the last scientific evidence, and scientific literature on biodynamic interfaces, we could suggest Hildegardian insights and theories as the first attempt to describe the modern holistic, sex-based medicine.

Conclusion

Hildegard anticipated a concept of pathogenesis that sees a central role for endocrinology in sex-specific disease. Furthermore, estrogens and estrogen receptors could represent a good example of molecular interfaces capable of modulating the interaction between the organism internal milieu and the environmental factors.
HFAC Dose Repetition and Accumulation Leads to Progressively Longer Block Carryover Effect in Rat Sciatic Nerve
Authors: Rapeaux Adrien , Constandinou Timothy G.
Published: June 2022

This paper describes high-frequency nerve block experiments carried out on rat sciatic nerves to measure the speed of recovery of A fibres from block carryover. Block carryover is the process by which nerve excitability remains suppressed temporarily after High Frequency Alternative (HFAC) block is turned off following its application. In this series of experiments 5 rat sciatic nerves were extracted and prepared for ex-vivo stimulation and recording in a specially designed perfusion chamber. For each nerve repeated HFAC block and concurrent stimulation trials were carried out to observe block carryover after signal shutoff. The nerve was allowed to recover fully between each trial. Time to recovery from block was measured by monitoring for when relative nerve activity returned to within 90% of baseline levels measured at the start of each trial. HFAC block carryover duration was found to be dependent on accumulated dose by statistical test for two different HFAC durations. The carryover property of HFAC block on A fibres could enable selective stimulation of autonomic nerve fibres such as C fibres for the duration of carryover. Block carryover is particularly relevant to potential chronic clinical applications of block as it reduces power requirements for stimulation to provide the blocking effect. This work characterizes this process toward the creation of a model describing its behavior.
Facilitating Applications of SSVEP-Based BCIs by Within-Subject Information Transfer
Authors: Liu Xiaobing , Liu Bingchuan , Dong Guoya , Gao Xiaorong , Wang Yijun
Published: June 2022

The steady-state visual evoked potential based brain–computer interface (SSVEP–BCI) can provide high-speed alternative and augmentative communication in real-world applications. For individuals using a long-term BCI, within-subject (i.e., cross-day and cross-electrode) transfer learning could improve the BCI performance and reduce the calibration burden. To validate the within-subject transfer learning scheme, this study designs a 40-target SSVEP–BCI. Sixteen subjects are recruited, each of whom has performed experiments on three different days and has undergone the experiments of the SSVEP–BCIs based on the dry and wet electrodes. Several transfer directions, including the cross-day directions in parallel with the cross-electrode directions, are analyzed, and it is found that the transfer learning-based approach can maintain stable performance by zero training. Compared with the fully calibrated approaches, the transfer learning-based approach can achieve significantly better or comparable performance in different transfer directions. This result verifies that the transfer learning-based scheme is well suited for implementing a high-speed zero-training SSVEP–BCI, especially the dry electrode-based SSVEP–BCI system. A validation experiment of the cross-day wet-to-dry transfer, involving nine subjects, has shown that the average accuracy is 85.97 ± 5.60% for the wet-to-dry transfer and 77.69 ± 6.42% for the fully calibrated method with dry electrodes. By leveraging the electroencephalography data acquired on different days by different electrodes via transfer learning, this study lays the foundation for facilitating the long-term usage of the SSVEP–BCI and advancing the frontier of the dry electrode-based SSVEP–BCI in real-world applications.
Gut Microbes Regulate Innate Immunity and Epilepsy
Authors: Zhang Linhai , Li Shuang , Tai Zhenzhen , Yu Changyin , Xu Zucai
Published: June 2022

Epilepsy is a common chronic brain disease. There are many clinical methods to control epileptic seizures, such as anti-seizure medications (ASMs) or surgical removal of epileptogenic lesions. However, the pathophysiology of epilepsy is still unknown, making it difficult to control or prevent it. The host’s immune system monitors gut microbes, interacts with microbes through pattern recognition receptors such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs) expressed by innate immune cells, and activates immune responses in the body to kill pathogens and balance the relationship between microbes and host. In addition, inflammatory responses induced by the innate immune system are seen in animal models of epilepsy and temporal lobe epilepsy brain tissue to combat pathogens or injuries. This review summarizes the potential relationship between gut microbes, innate immunity, and epilepsy based on recent research to provide more hints for researchers to explore this field further.
Prediction of Speech Intelligibility by Means of EEG Responses to Sentences in Noise
Authors: Muncke Jan , Kuruvila Ivine , Hoppe Ulrich
Published: June 2022

Objective

Understanding speech in noisy conditions is challenging even for people with mild hearing loss, and intelligibility for an individual person is usually evaluated by using several subjective test methods. In the last few years, a method has been developed to determine a temporal response function (TRF) between speech envelope and simultaneous electroencephalographic (EEG) measurements. By using this TRF it is possible to predict the EEG signal for any speech signal. Recent studies have suggested that the accuracy of this prediction varies with the level of noise added to the speech signal and can predict objectively the individual speech intelligibility. Here we assess the variations of the TRF itself when it is calculated for measurements with different signal-to-noise ratios and apply these variations to predict speech intelligibility.

Methods

For 18 normal hearing subjects the individual threshold of 50% speech intelligibility was determined by using a speech in noise test. Additionally, subjects listened passively to speech material of the speech in noise test at different signal-to-noise ratios close to individual threshold of 50% speech intelligibility while an EEG was recorded. Afterwards the shape of TRFs for each signal-to-noise ratio and subject were compared with the derived intelligibility.

Results

The strongest effect of variations in stimulus signal-to-noise ratio on the TRF shape occurred close to 100 ms after the stimulus presentation, and was located in the left central scalp region. The investigated variations in TRF morphology showed a strong correlation with speech intelligibility, and we were able to predict the individual threshold of 50% speech intelligibility with a mean deviation of less then 1.5 dB.

Conclusion

The intelligibility of speech in noise can be predicted by analyzing the shape of the TRF derived from different stimulus signal-to-noise ratios. Because TRFs are interpretable, in a manner similar to auditory evoked potentials, this method offers new options for clinical diagnostics.
Real-World Visual Experience Alters Baseline Brain Activity in the Resting State: A Longitudinal Study Using Expertise Model of Radiologists
Authors: Su Jiaxi , Zhang Xiaoyan , Zhang Ziyuan , Wang Hongmei , Wu Jia , Shi Guangming , Jin Chenwang , Dong Minghao
Published: June 2022

Visual experience modulates the intensity of evoked brain activity in response to training-related stimuli. Spontaneous fluctuations in the restful brain actively encode previous learning experience. However, few studies have considered how real-world visual experience alters the level of baseline brain activity in the resting state. This study aimed to investigate how short-term real-world visual experience modulates baseline neuronal activity in the resting state using the amplitude of low-frequency (<0.08 Hz) fluctuation (ALFF) and a visual expertise model of radiologists, who possess fine-level visual discrimination skill of homogeneous stimuli. In detail, a group of intern radiologists (n = 32) were recruited. The resting-state fMRI data and the behavioral data regarding their level of visual expertise in radiology and face recognition were collected before and after 1 month of training in the X-ray department in a local hospital. A machine learning analytical method, i.e., support vector machine, was used to identify subtle changes in the level of baseline brain activity. Our method led to a superb classification accuracy of 86.7% between conditions. The brain regions with highest discriminative power were the bilateral cingulate gyrus, the left superior frontal gyrus, the bilateral precentral gyrus, the bilateral superior parietal lobule, and the bilateral precuneus. To the best of our knowledge, this study is the first to investigate baseline neurodynamic alterations in response to real-world visual experience using longitudinal experimental design. These results suggest that real-world visual experience alters the resting-state brain representation in multidimensional neurobehavioral components, which are closely interrelated with high-order cognitive and low-order visual factors, i.e., attention control, working memory, memory, and visual processing. We propose that our findings are likely to help foster new insights into the neural mechanisms of visual expertise.
Proteoglycan Sulphation in the Function of the Mature Central Nervous System
Authors: Fawcett James W. , Kwok Jessica C. F.
Published: June 2022

Chondroitin sulphate and heparan sulphate proteoglycans (CSPGS and HSPGs) are found throughout the central nervous system (CNS). CSPGs are ubiquitous in the diffuse extracellular matrix (ECM) between cells and are a major component of perineuronal nets (PNNs), the condensed ECM present around some neurons. HSPGs are more associated with the surface of neurons and glia, with synapses and in the PNNs. Both CSPGs and HSPGs consist of a protein core to which are attached repeating disaccharide chains modified by sulphation at various positions. The sequence of sulphation gives the chains a unique structure and local charge density. These sulphation codes govern the binding properties and biological effects of the proteoglycans. CSPGs are sulphated along their length, the main forms being 6- and 4-sulphated. In general, the chondroitin 4-sulphates are inhibitory to cell attachment and migration, while chondroitin 6-sulphates are more permissive. HSPGs tend to be sulphated in isolated motifs with un-sulphated regions in between. The sulphation patterns of HS motifs and of CS glycan chains govern their binding to the PTPsigma receptor and binding of many effector molecules to the proteoglycans, such as growth factors, morphogens, and molecules involved in neurodegenerative disease. Sulphation patterns change as a result of injury, inflammation and ageing. For CSPGs, attention has focussed on PNNs and their role in the control of plasticity and memory, and on the soluble CSPGs upregulated in glial scar tissue that can inhibit axon regeneration. HSPGs have key roles in development, regulating cell migration and axon growth. In the adult CNS, they have been associated with tau aggregation and amyloid-beta processing, synaptogenesis, growth factor signalling and as a component of the stem cell niche. These functions of CSPGs and HSPGs are strongly influenced by the pattern of sulphation of the glycan chains, the sulphation code. This review focuses on these sulphation patterns and their effects on the function of the mature CNS.
Functional Characterization of CLCN4 Variants Associated With X-Linked Intellectual Disability and Epilepsy
Authors: Guzman Raul E. , Sierra-Marquez Juan , Bungert-Plümke Stefanie , Franzen Arne , Fahlke Christoph
Published: June 2022

Early/late endosomes, recycling endosomes, and lysosomes together form the endo-lysosomal recycling pathway. This system plays a crucial role in cell differentiation and survival, and dysregulation of the endo-lysosomal system appears to be important in the pathogenesis of neurodevelopmental and neurodegenerative diseases. Each endo-lysosomal compartment fulfils a specific function, which is supported by ion transporters and channels that modify ion concentrations and electrical gradients across endo-lysosomal membranes. CLC-type Cl–/H+ exchangers are a group of endo-lysosomal transporters that are assumed to regulate luminal acidification and chloride concentration in multiple endosomal compartments. Heterodimers of ClC-3 and ClC-4 localize to various internal membranes, from the endoplasmic reticulum and Golgi to recycling endosomes and late endosomes/lysosomes. The importance of ClC-4-mediated ion transport is illustrated by the association of naturally occurring CLCN4 mutations with epileptic encephalopathy, intellectual disability, and behavioral disorders in human patients. However, how these mutations affect the expression, subcellular localization, and function of ClC-4 is insufficiently understood. We here studied 12 CLCN4 variants that were identified in patients with X-linked intellectual disability and epilepsy and were already characterized to some extent in earlier work. We analyzed the consequences of these mutations on ClC-4 ion transport, subcellular trafficking, and heterodimerization with ClC-3 using heterologous expression in mammalian cells, biochemistry, confocal imaging, and whole-cell patch-clamp recordings. The mutations led to a variety of changes in ClC-4 function, ranging from gain/loss of function and impaired heterodimerization with ClC-3 to subtle impairments in transport functions. Our results suggest that even slight functional changes to the endosomal Cl–/H+ exchangers can cause serious neurological symptoms.
Transcriptomic Profiling of Intracranial Arteries in Adult Patients With Moyamoya Disease Reveals Novel Insights Into Its Pathogenesis
Authors: Xu Shuangxiang , Wei Wei , Zhang Feiyang , Chen Tongyu , Dong Lixin , Shi Jichun , Wu Xiaolin , Zhang Tingbao , Li Zhengwei , Zhang Jianjian , Li Xiang , Chen Jincao
Published: June 2022

Moyamoya disease (MMD) is a rare, progressively steno-occlusive cerebrovascular disorder of unknown etiology. Here, we revealed the gene expression profile of the intracranial arteries in MMD via the RNA-sequencing (RNA-seq). We identified 556 differentially expressed genes (DEGs) for MMD, including 449 and 107 significantly upregulated or downregulated genes. Compared with atherosclerosis-associated intracranial artery stenosis/occlusion (AS-ICASO) controls, upregulated genes were mainly involved in extracellular matrix (ECM) organization, whereas downregulated genes were primarily associated with mitochondrial function and oxidative phosphorylation in MMD. Moreover, we found that a separate sex analysis uncovers more DEGs (n = 1.022) compared to an combined sex analysis in MMD. We identified 133 and 439 sex-specific DEGs for men and women in MMD, respectively. About 95.6% of sex-specific DEGs were protein-coding genes and 3% of the genes belonged to long non-coding RNAs (lncRNA). Sex-specific DEGs were observed on all chromosomes, of which 95.49 and 96.59% were autosomal genes in men and women, respectively. These sex-specific DEGs, such as aquaporin-4 (AQP4), superoxide dismutase 3 (SOD3), and nuclear receptor subfamily 4 group A member 1 (NR4A1), may contribute to sex differences in MMD. This transcriptomic study highlighted that ECM and mitochondrial function are the central molecular mechanisms underlying MMD, and revealed sex differences in the gene expression in the intracranial arteries, thereby providing new insights into the pathogenesis of MMD.
Brain Activity Characteristics of Patients With Disorders of Consciousness in the EEG Resting State Paradigm: A Review
Authors: Duszyk-Bogorodzka Anna , Zieleniewska Magdalena , Jankowiak-Siuda Kamila
Published: June 2022

The assessment of the level of consciousness in disorders of consciousness (DoC) is still one of the most challenging problems in contemporary medicine. Nevertheless, based on the multitude of studies conducted over the last 20 years on resting states based on electroencephalography (EEG) in DoC, it is possible to outline the brain activity profiles related to both patients without preserved consciousness and minimally conscious ones. In the case of patients without preserved consciousness, the dominance of low, mostly delta, frequency, and the marginalization of the higher frequencies were observed, both in terms of the global power of brain activity and in functional connectivity patterns. In turn, the minimally conscious patients revealed the opposite brain activity pattern—the characteristics of higher frequency bands were preserved both in global power and in functional long-distance connections. In this short review, we summarize the state of the art of EEG-based research in the resting state paradigm, in the context of providing potential support to the traditional clinical assessment of the level of consciousness.
Modeling Human Visual Search in Natural Scenes: A Combined Bayesian Searcher and Saliency Map Approach
Authors: Bujia Gaston , Sclar Melanie , Vita Sebastian , Solovey Guillermo , Kamienkowski Juan Esteban
Published: June 2022

Finding objects is essential for almost any daily-life visual task. Saliency models have been useful to predict fixation locations in natural images during a free-exploring task. However, it is still challenging to predict the sequence of fixations during visual search. Bayesian observer models are particularly suited for this task because they represent visual search as an active sampling process. Nevertheless, how they adapt to natural images remains largely unexplored. Here, we propose a unified Bayesian model for visual search guided by saliency maps as prior information. We validated our model with a visual search experiment in natural scenes. We showed that, although state-of-the-art saliency models performed well in predicting the first two fixations in a visual search task ( 90% of the performance achieved by humans), their performance degraded to chance afterward. Therefore, saliency maps alone could model bottom-up first impressions but they were not enough to explain scanpaths when top-down task information was critical. In contrast, our model led to human-like performance and scanpaths as revealed by: first, the agreement between targets found by the model and the humans on a trial-by-trial basis; and second, the scanpath similarity between the model and the humans, that makes the behavior of the model indistinguishable from that of humans. Altogether, the combination of deep neural networks based saliency models for image processing and a Bayesian framework for scanpath integration probes to be a powerful and flexible approach to model human behavior in natural scenarios.
Two, Six, and Twelve-Month Dropout Rate and Predictor Factors After a Multidisciplinary Residential Program for Obesity Treatment. A Prospective Cohort Study
Authors: Perna Simone , Salman Majeda , Gasparri Clara , Cavioni Alessandro , Faliva Milena Anna , Mansueto Francesca , Naso Maurizio , Patelli Zaira , Peroni Gabriella , Tartara Alice , Riva Antonella , Petrangolini Giovanna , Rondanelli Mariangela
Published: June 2022

Introduction

The aim of the present study was to assess the dropout rate at 2, 6, and 12 months after an inpatient multidisciplinary residential program (MRP) for the treatment of obesity. Furthermore, this study assessed anthropometric and biochemical predictors associated with the dropout.

Methods

Adult and elderly patients (age 59 ± 14 years) with obesity had undergone an MRP, were followed up from 2 to 12 months. Biochemical and anthropometric markers have been assessed at the beginning of the follow-up period after the MRP.

Results

The study enrolled 178 subjects, 117 women and 61 men. The overall dropout rate at 2 months was 21.3%, after 6 months was 44.4%, and after 1 year was 68.5%. There was no difference by gender recorded. Furthermore, patients under medical treatment with psychiatric disorders did not show an association with the dropout rate. Patients with a higher level of body mass index (BMI) at the discharge of MRP showed +48% of dropout at 6 months. After the MRP, the baseline values of uricemia and white blood cells (WBCs) resulted as predictors of dropout at 2 months (p > 0.05). Furthermore, the excess percentage of fat mass lost during the MRP was associated with the risk of dropout at 2, 6, and 12 months (p > 0.05).

Conclusion

The MRP for obesity is an opportunity for losing weight for patients with established criteria. The future challenge will be addressing the best strategic plans in order to reduce the dropout rate after this intervention. Investigating deeply the main predictors could be an opportunity to improve the long-term efficacy of MRP.
circDNMT1 Promotes Malignant Progression of Gastric Cancer Through Targeting miR-576-3p/Hypoxia Inducible Factor-1 Alpha Axis
Authors: Li Hanghang , Cao Bo , Zhao Ruiyang , Li Tian , Xu Xingming , Cui Hao , Deng Huan , Gao Jingwang , Wei Bo
Published: June 2022

Background

Circular RNAs (circRNAs) regulate multiple malignant behaviors of various types of cancer. The role of circDNMT1, a newly identified circRNA, remains unknown in gastric cancer (GC). This study aimed to elucidate the underlying mechanisms of circDNMT1 in regulating GC progression.

Methods

microRNA (miRNA) and circRNA expression was detected by quantitative real-time PCR. Western blotting was performed to measure hypoxia inducible factor-1 alpha (HIF-1α) protein expression. Sanger sequencing, gel electrophoresis and fluorescence in situ hybridization were performed to identify the presence of circDNMT1. The clinicopathological features and overall survival of patients were analyzed based on circDNMT1 expression. The proliferation, migration and invasion of GC cells were determined by cell counting kit-8, 5-ethynyl-2’-deoxyuridine, wound healing and transwell assays. Glycolysis of GC cells was detected based on the levels of glucose uptake, the lactate acid, ATP and pyruvic acid production and the extracellular acidification and oxygen consumption rates. The binding sites between miR-576-3p and circDNMT1 or HIF-1α were predicted by online bioinformatic tools and were validated using RNA pull-down and luciferase reporter assays. Xenograft models were established to determine the effects of the circDNMT1/miR-576-3p/HIF-1α axis on GC growth and metastasis in vivo.

Results

circDNMT1 was successfully identified and shown to be overexpressed in GC tissues and cell lines. The expression levels of circDNMT1 were correlated with pathological T stage, pathological TNM stage and shorter survival time of GC patients. circDNMT1 knockdown inhibited the proliferation, migration, invasion and glycolysis of GC cells. circDNMT1 functioned as an oncogenic factor by sponging miR-576-3p. HIF-1α was negatively regulated by miR-576-3p via binding its mRNA 3’ untranslated region. circDNMT1 promoted malignant behaviors and metabolic reprogramming of GC by targeting the miR-576-3p/HIF-1α axis both in vitro and in vivo.

Conclusion

These findings demonstrated that circDNMT1 knockdown inhibited GC proliferation, migration, invasion and glycolysis through sponging miR-576-3p/HIF-1α axis. circDNMT1 may be a novel target for GC treatment.
Associations Between Serum Reproductive Hormone Concentrations and Hormonal Receptor Status Among Postmenopausal Chinese Women With Breast Cancer: An Observational Study
Authors: Jiang Chuner , Wu Peng , He Xiangming , Ni Jianfen , Ding Xiaowen , Xu Xiaohong , Wang Fangzheng , Zou Dehong
Published: June 2022

Background and Objectives

Reproductive hormones and receptors play crucial roles in breast cancer development and progression. The association between preoperative serum reproductive hormone levels and receptor status in postmenopausal women with breast cancer remains unclear. Therefore, this study investigated the relationship between serum reproductive hormone concentrations and patient characteristics and hormone receptor status among postmenopausal Chinese women with breast cancer.

Materials and Methods

The medical records of 352 postmenopausal breast cancer patients who underwent an operation between October 2007 and October 2010 at the Department of Breast Tumor Surgery of Zhejiang Cancer Hospital were retrospectively evaluated. Serum levels of reproductive hormones were measured before surgery by liquid-chromatography tandem mass spectrometry. Hormone receptor levels were measured by an immunohistochemical assay using a mouse monoclonal antibody. The associations between serum hormone concentrations and hormone receptors were investigated by analysis of covariance.

Results

In this patient cohort, the serum level of luteinizing hormone (LH) declined with PMP duration. The median LH concentration was significantly higher in patients within 5 years of PMP than that in patients with PMP duration exceeding 5 years (23 vs. 18.32 mIU/ml,P<.0001). Significantly more patients with strong estrogen receptor (ER) or progesterone receptor (PR) expression had postmenopausal durations of less than 5 years compared to those with postmenopausal durations greater than 5 years (103 vs. 61 cases,P= .019; 93 vs. 46 cases,P= .0005). While most patients either lacked (97.1%) or co-expressed (84.3%) ER and PR, some patients expressed either ER or PR alone. ER and PR expression were negatively associated with receptor-tyrosine kinase erbB-2 (HER2) expression in postmenopausal patients with breast cancer. Meanwhile, increased ER and PR expression were associated with decreased serum levels of LH or follicle-stimulating hormone (FSH).

Conclusion

Decreased serum LH and FSH levels were associated with increased ER and PR expressions and decreased HER2 expression in postmenopausal patients with breast cancer.
Risk of CVD Following Radiotherapy for Head and Neck Cancer: An Updated Systematic Review and Meta-Analysis
Authors: Lin Ping-Yi , Cheng Ping-Chia , Hsu Wan-Lun , Lo Wu-Chia , Hsieh Chen-Hsi , Shueng Pei-Wei , Liao Li-Jen
Published: June 2022

Background

The relative risk for cerebrovascular disease (CVD) is increased in patients with head and neck cancer (HNC) treated with radiotherapy (RT). However, the current relative risk for CVD following RT has not been well clarified. The purpose of this study was to analyze the effect of RT and update the risk of CVD following RT in HNC patients through a systematic review and meta-analysis.

Material and Methods

We conducted an online database search and systematic review of observational studies that reported on CVD and extracranial carotid stenosis in patients with HNC who had undergone RT. Articles published in Medline and PubMed from 1980 to 2021 were identified and collected.

Results

Of the forty-seven articles identified from PubMed and forty-four articles identified from 3 systematic reviews, twenty-two studies were included. We found that neck RT was a significant risk factor for CVD (HR 3.97, 95% CI: 2.89-5.45). Patients with HNC treated by RT had an increased OR (7.36, 95% CI: 4.13-13.11) for CVD, and approximately 26% (95% CI: 22%-31%) of HNC patients treated with RT were at risk for CVD with more than 50% reduction in carotid diameter.

Conclusion

The risk of CVD is increased in patients with HNC treated by RT, and recent improvements in RT techniques may have contributed to the decreased risk of CVD. These results suggest that regular follow-up and appropriate screening for CVD should be required for patients with HNC.