bluuebunny/crossref_metadata_2025 huggingface dataset:
ANTXR1 Is a Prognostic Biomarker and Correlates With Stromal and Immune Cell Infiltration in Gastric Cancer
Authors: Huang Xiaodong , Zhang Jie , Zheng Yongbin
Published: January 2021

Gastric cancer (GC) is a complex and heterogeneous disease, making it difficult to ascertain the optimal therapeutic approach for individual GC patients. Stromal and immune cell infiltration in GC has a strong correlation with clinical outcomes; however, the underlying mechanisms that drive immunosuppression remain vastly undiscovered. Recent studies validated that anthrax toxin receptor 1 (ANTXR1) is aberrantly expressed in several cancers and holds promise as a new therapeutic target for cancer. However, its immunological roles in GC are still unclear. Here, we show that we identify the distinct stromal and immune cell infiltration in GC between the high and low ANTXR1 expression group by analyzing genomic data. Clinically, ANTXR1 is highly expressed in GC and correlates with adverse clinicopathological characteristics. Additionally, high ANTXR1 expression is linked to markedly poor clinical outcomes and resistance to chemotherapy, whereas the low ANTXR1 expression group is correlated with better outcomes and response to chemotherapy in GC patients. We further revealed the differential landscape of somatic tumor mutation burden (TMB) between the two groups and observed that patients with high ANTXR1 expression suffered from a lower TMB, potentially leading to less sensitivity to checkpoint therapy. Molecularly, results displayed that ANTXR1 is an immunosuppressive element, which may perform its function via promoting the secretion of immunosuppressive factors that play a significant role in modulating tumor-associated fibroblast transformation, M2 macrophage polarization, and T cell exhaustion. Gene set enrichment analysis revealed that cancer-related pathways including epithelial-to-mesenchymal transition, focal adhesion, and transforming growth factor-β (TGF-β) signaling pathways were enriched in high ANTXR1 expression tumors. Our work suggests that ANTXR1 could not only serve as a valuable prognostic biomarker in GC but also be deemed as a potential immunotherapeutic target and useful biomarker of sensitivity to chemotherapy.
Development and Testing of Force Field Parameters for Phenylalanine and Tyrosine Derivatives
Authors: Wang Xiaowen , Li Wenjin
Published: January 2021

Theoretical analyses are valuable for the exploration of the effects of unnatural amino acids on enzyme functions; however, many necessary parameters for unnatural amino acids remain lacking. In this study, we developed and tested force field parameters compatible with Amber ff14SB for 18 phenylalanine and tyrosine derivatives. The charge parameters were derived from ab initio calculations using the RESP fitting approach and then adjusted to reproduce the benchmark relative energies (at the MP2/TZ level) of the α- and β-backbones for each unnatural amino acid dipeptide. The structures optimized under the proposed force field parameters for the 18 unnatural amino acid dipeptides in both the α- and β-backbone forms were in good agreement with their QM structures, as the average RMSD was as small as 0.1 Å. The force field parameters were then tested in their application to seven proteins containing unnatural amino acids. The RMSDs of the simulated configurations of these unnatural amino acids were approximately 1.0 Å compared with those of the crystal structures. The vital interactions between proteins and unnatural amino acids in five protein–ligand complexes were also predicted using MM/PBSA analysis, and they were largely consistent with experimental observations. This work will provide theoretical aid for drug design involving unnatural amino acids.
Systematic Comparisons for Composition Profiles, Taxonomic Levels, and Machine Learning Methods for Microbiome-Based Disease Prediction
Authors: Song Kuncheng , Wright Fred A. , Zhou Yi-Hui
Published: January 2021

Microbiome composition profiles generated from 16S rRNA sequencing have been extensively studied for their usefulness in phenotype trait prediction, including for complex diseases such as diabetes and obesity. These microbiome compositions have typically been quantified in the form of Operational Taxonomic Unit (OTU) count matrices. However, alternate approaches such as Amplicon Sequence Variants (ASV) have been used, as well as the direct use of k-mer sequence counts. The overall effect of these different types of predictors when used in concert with various machine learning methods has been difficult to assess, due to varied combinations described in the literature. Here we provide an in-depth investigation of more than 1,000 combinations of these three clustering/counting methods, in combination with varied choices for normalization and filtering, grouping at various taxonomic levels, and the use of more than ten commonly used machine learning methods for phenotype prediction. The use of short k-mers, which have computational advantages and conceptual simplicity, is shown to be effective as a source for microbiome-based prediction. Among machine-learning approaches, tree-based methods show consistent, though modest, advantages in prediction accuracy. We describe the various advantages and disadvantages of combinations in analysis approaches, and provide general observations to serve as a useful guide for future trait-prediction explorations using microbiome data.
Systematic and Comprehensive Automated Ventricle Segmentation on Ventricle Images of the Elderly Patients: A Retrospective Study
Authors: Zhou Xi , Ye Qinghao , Jiang Yinghui , Wang Minhao , Niu Zhangming , Menpes-Smith Wade , Fang Evandro Fei , Liu Zhi , Xia Jun , Yang Guang
Published: January 2021

Background and Objective: Ventricle volume is closely related to hydrocephalus, brain atrophy, Alzheimer's, Parkinson's syndrome, and other diseases. To accurately measure the volume of the ventricles for elderly patients, we use deep learning to establish a systematic and comprehensive automated ventricle segmentation framework.

Methods: The study participation included 20 normal elderly people, 20 patients with cerebral atrophy, 64 patients with normal pressure hydrocephalus, and 51 patients with acquired hydrocephalus. Second, get their imaging data through the picture archiving and communication systems (PACS) system. Then use ITK software to manually label participants' ventricular structures. Finally, extract imaging features through machine learning.

Results: This automated ventricle segmentation method can be applied not only to CT and MRI images but also to images with different scan slice thicknesses. More importantly, it produces excellent segmentation results (Dice > 0.9).

Conclusion: This automated ventricle segmentation method has wide applicability and clinical practicability. It can help clinicians find early disease, diagnose disease, understand the patient's disease progression, and evaluate the patient's treatment effect.
Role of Nanomedicine in Management and Prevention of COVID-19
Authors: Wankar Jitendra N. , Chaturvedi Vivek K. , Bohara Chandrashekhar , Singh Mohan P. , Bohara Raghvendra A.
Published: January 2021

COVID-19, or the Coronavirus disease 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic. At the time of writing this (July 28, 2020), more than 17 million people have become affected and 0.7 million people have died across the world. Remdesivir has shown glimpses of insight into how to fight the virus, but as of yet remain far from victory. Nanotechnology has proven its role in medicine to deliver the drug at the target site with minimal side effects, particularly in the anticancer domain. Most specifically, a range of nanotechnology-based products, such as nanosilver, are currently on the market because they have demonstrated the potential to combat viruses. This article provides an overview of the role of nanomedicine, including polymeric and inorganic materials, and its future capabilities in the management of the disease outbreak. Taking all this into account, an attempt has been made to educate readers in the simplest way of the role of nanomedicine, which can play a pivotal role in the management of diseases.
Cannabidiol Acts at 5-HT1A Receptors in the Human Brain: Relevance for Treating Temporal Lobe Epilepsy
Authors: Martínez-Aguirre Christopher , Carmona-Cruz Francia , Velasco Ana Luisa , Velasco Francisco , Aguado-Carrillo Gustavo , Cuéllar-Herrera Manola , Rocha Luisa
Published: January 2021

Experimental evidence indicates that cannabidiol (CBD) induces anxiolytic and antiepileptic effects through the activation of 5-HT1A receptors. These receptors are coupled to Gi/o proteins and induce inhibitory effects. At present, the interaction of CBD with 5-HT1A receptors in the human brain is unknown. The aim of this study focused on evaluating the interaction between CBD and 5-HT1A receptors in cell membranes obtained from the hippocampus and temporal neocortex of autopsies and patients with drug-resistant mesial temporal lobe epilepsy (DR-MTLE). Cell membranes were isolated from the hippocampus and temporal neocortex of a group of patients with DR-MTLE who were submitted to epilepsy surgery (n = 11) and from a group of autopsies (n = 11). The [3H]-8-OH-DPAT binding assay was used to determine the pharmacological interaction of CBD with 5-HT1A receptors. The [35S]-GTPγS assay was used to investigate the CBD-induced activation of Gi/o proteins through its action on 5-HT1A receptors.The CBD affinity (pKi) for 5-HT1A receptors was similar for autopsies and patients with DR-MTLE (hippocampus: 4.29 and 4.47, respectively; temporal neocortex: 4.67 and 4.74, respectively). Concerning the [35S]-GTPγS assay, no statistically significant changes were observed for both hippocampal and neocortical tissue (p > 0.05) at low CBD concentrations (1 pM to 10 μM). In contrast, at high concentrations (100 μM), CBD reduced the constitutive activity of Gi/o proteins of autopsies and DR-MTLE patients (hippocampus: 39.2% and 39.6%, respectively; temporal neocortex: 35.2% and 24.4%, respectively). These changes were partially reversed in the presence of WAY-100635, an antagonist of 5-HT1A receptors, in the autopsy group (hippocampus, 59.8%, p < 0.0001; temporal neocortex, 71.5%, p < 0.0001) and the group of patients with DR-MTLE (hippocampus, 53.7%, p < 0.0001; temporal neocortex, 68.5%, p < 0.001). Our results show that CBD interacts with human 5-HT1A receptors of the hippocampus and temporal neocortex. At low concentrations, the effect of CBD upon Gi/o protein activation is limited. However, at high concentrations, CBD acts as an inverse agonist of 5-HT1A receptors. This effect could modify neuronal excitation and epileptic seizures in patients with DR-MTLE.
The PEDtracker: An Automatic Staging Approach for Drosophila melanogaster Larvae
Authors: Schumann Isabell , Triphan Tilman
Published: January 2021

The post-embryonal development of arthropod species, including crustaceans and insects, is characterized by ecdysis or molting. This process defines growth stages and is controlled by a conserved neuroendocrine system. Each molting event is divided in several critical time points, such as pre-molt, molt, and post-molt, and leaves the animals in a temporarily highly vulnerable state while their cuticle is re-hardening. The molting events occur in an immediate ecdysis sequence within a specific time window during the development. Each sub-stage takes only a short amount of time, which is generally in the order of minutes. To find these relatively short behavioral events, one needs to follow the entire post-embryonal development over several days. As the manual detection of the ecdysis sequence is time consuming and error prone, we designed a monitoring system to facilitate the continuous observation of the post-embryonal development of the fruit flyDrosophila melanogaster. Under constant environmental conditions we are able to observe the life cycle from the embryonic state to the adult, which takes about 10 days in this species. Specific processing algorithms developed and implemented in Fiji and R allow us to determine unique behavioral events on an individual level—including egg hatching, ecdysis and pupation. In addition, we measured growth rates and activity patterns for individual larvae. Our newly created RPackage PEDtracker can predict critical developmental events and thus offers the possibility to perform automated screens that identify changes in various aspects of larval development. In conclusion, the PEDtracker system presented in this study represents the basis for automated real-time staging and analysis not only for the arthropod development.
Resting-State Functional Connectivity of the Punishment Network Associated With Conformity
Authors: Du Yin , Wang Yinan , Yu Mengxia , Tian Xue , Liu Jia
Published: January 2021

Fear of punishment prompts individuals to conform. However, why some people are more inclined than others to conform despite being unaware of any obvious punishment remains unclear, which means the dispositional determinants of individual differences in conformity propensity are poorly understood. Here, we explored whether such individual differences might be explained by individuals’ stable neural markers to potential punishment. To do this, we first defined the punishment network (PN) by combining all potential brain regions involved in punishment processing. We subsequently used a voxel-based global brain connectivity (GBC) method based on resting-state functional connectivity (FC) to characterize the hubs in the PN, which reflected an ongoing readiness state (i.e., sensitivity) for potential punishment. Then, we used the within-network connectivity (WNC) of each voxel in the PN of 264 participants to explain their tendency to conform by using a conformity scale. We found that a stronger WNC in the right thalamus, left insula, postcentral gyrus, and dACC was associated with a stronger tendency to conform. Furthermore, the FC among the four hubs seemed to form a three-phase ascending pathway, contributing to conformity propensity at every phase. Thus, our results suggest that task-independent spontaneous connectivity in the PN could predispose individuals to conform.
Depression Is Associated With Constipation in Patients With Parkinson's Disease
Authors: Xiao-ling Qin , Gang Chen , Bo Lu , Zai-li Li , Xue-kui Liu , Xue Li , Ming-yu Shi , Yin-zhen Du , Xu Chen , Dian-shuai Gao
Published: January 2021

Objective:Constipation is one of the most frequent non-motor symptoms (NMS) in Parkinson's disease (PD), causing great disturbance to patients. The present study investigated the prevalence and the clinical features of constipation in patients with PD and explored the difference between prodromal and clinical constipation of PD.

Methods:A total of 186 patients with PD were recruited into this study. Subjective constipation was defined by ROME III criteria. Demographic and PD-related clinical information of the participants were collected. The PD patients were objectively assessed by a spectrum of rating scales of motor symptoms, non-motor symptoms, and quality of life.

Results:In total, 51.61% (96/186) of PD patients suffer from constipation. Compared with patients without constipation, the patients with constipation were prone to have restless leg syndrome, depression, and anxiety and have higher scores of the non-motor symptoms scale. Among patients with constipation, 21.88% (21/96) patients had constipation in prodromal stage. Compared with patients with constipation in clinical stage, patients with prodromal constipation had a lower age of constipation onset (56.48 ± 9.63 and 65.26 ± 8.42, χ2= 4.091,P< 0.001), longer timespan from constipation onset to motor symptom onset (6.62 ± 3.91 and 3.18 ± 2.13, χ2= −3.877,P= 0.001). Patients with prodromal constipation were predominantly tremor onset (χ2= 4.405,P= 0.044) and usually had a better quality of life [28 (14.50–37.5) and 40 (25.0–55.0), χ2= 2.011,P= 0.046]. Depression was the only risk factor of constipation in PD patients. Body mass index, depression, and anxiety were factors that affected the life quality in patients with constipation.

Conclusions:Our results supported the high incidence of constipation in patients with PD and that, in some patients, constipation occurred before the onset of motor symptoms. The specific clinical characteristics of patients with constipation and with prodromal constipation help to make early diagnosis, to discover the relationship between constipation and PD, and to further explore the pathogenesis of this degenerative disease.
Phase Lag Analyses on Ictal Scalp Electroencephalography May Predict Outcomes of Corpus Callosotomy for Epileptic Spasms
Authors: Oguri Masayoshi , Okanishi Tohru , Kanai Sotaro , Baba Shimpei , Nishimura Mitsuyo , Ogo Kaoru , Himoto Takashi , Okanari Kazuo , Maegaki Yoshihiro , Enoki Hideo , Fujimoto Ayataka
Published: January 2021

Objective: We aimed to clarify the patterns of ictal power and phase lag among bilateral hemispheres on scalp electroencephalography (EEG) recorded pre-operatively during epileptic spasms (ESs) and the correlation with the outcomes following corpus callosotomy.

Methods: We enrolled 17 patients who underwent corpus callosotomy for ESs before 20 years of age. After corpus callosotomy, seven patients did not experience further ESs (favorable outcome group), and the remaining 10 patients had ongoing ESs (unfavorable outcome group). We used pre-operative scalp EEG data from monopolar montages using the average reference. The relative power spectrum (PS), ictal power laterality (IPL) among the hemispheres, and phase lag, calculated by the cross-power spectrum (CPS) among symmetrical electrodes (i.e., F3 and F4), were analyzed in the EEG data of ESs from 143 pre-operative scalp video-EEG records. Analyses were conducted separately in each frequency band from the delta, theta, alpha, beta, and gamma range. We compared the means of those data in each patient between favorable and unfavorable outcome groups.

Results: Among all frequency bands, no significant differences were seen in the individual mean relative PSs in the favorable and unfavorable outcome group. Although the mean IPLs in each patient tended to be high in the unfavorable outcome group, no significant differences were found. The mean CPSs in the delta, theta, and gamma frequency bands were significantly higher in the unfavorable than in the favorable outcome group. Using the Youden index, the optimal cutoff points of those mean CPS values for unfavorable outcomes were 64.00 in the delta band (sensitivity: 100%, specificity: 80%), 74.20 in the theta band (100, 80%), and 82.05 in the gamma band (100, 80%). Subanalyses indicated that those CPS differences originated from pairs of symmetrical electrodes in the bilateral frontal and temporal areas.

Significance: Ictal power and laterality of the ictal power in each frequency band were not associated with the outcomes of CC; however, the phase lags seen in the delta, theta, and gamma frequency bands were larger in the unfavorable than in the favorable outcome group. The phase lags may predict outcomes of CC for ESs on pre-surgical scalp-ictal EEGs.
Acupuncture vs. Pharmacological Prophylaxis of Migraine: A Systematic Review of Randomized Controlled Trials
Authors: Giovanardi Carlo Maria , Cinquini Michela , Aguggia Marco , Allais Gianni , Campesato Manuela , Cevoli Sabina , Gentili Fabio , Matrà Annunzio , Minozzi Silvia
Published: January 2021

Introduction: Migraine is a chronic paroxymal neurological disorder characterized by attacks of moderate to severe headache and reversible neurological and systemic symptoms. Treatment of migraine includes acute therapies, that aim to reduce the intensity of pain of each attack, and preventive therapies that should decrease the frequency of headache recurrence. The objective of this systematic review was to assess the efficacy and safety of acupuncture for the prophylaxis of episodic or chronic migraine in adult patients compared to pharmacological treatment.

Methods: We included randomized-controlled trials published in western languages that compared any treatment involving needle insertion (with or without manual or electrical stimulation) at acupuncture points, pain points or trigger points, with any pharmacological prophylaxis in adult (≥18 years) with chronic or episodic migraine with or without aura according to the criteria of the International Headache Society.

Results: Nine randomized trials were included encompassing 1,484 patients. At the end of intervention we found a small reduction in favor of acupuncture for the number of days with migraine per month: (SMD: −0.37; 95% CI −1.64 to −0.11), and for response rate (RR: 1.46; 95% CI 1.16–1.84). We found a moderate effect in the reduction of pain intensity in favor of acupuncture (SMD: −0.36; 95% CI −0.60 to −0.13), and a large reduction in favor of acupuncture in both the dropout rate due to any reason (RR 0.39; 95% CI 0.18 to 0.84) and the dropout rate due to adverse event (RR 0.26; 95% CI 0.09 to 0.74). Quality of evidence was moderate for all these primary outcomes. Results at longest follow-up confirmed these effects.

Conclusions: Based on moderate certainty of evidence, we conclude that acupuncture is mildly more effective and much safer than medication for the prophylaxis of migraine.
Altered Prefrontal–Basal Ganglia Effective Connectivity in Patients With Poststroke Cognitive Impairment
Authors: Zhang Jing , Li Zixiao , Cao Xingxing , Zuo Lijun , Wen Wei , Zhu Wanlin , Jiang Jiyang , Cheng Jian , Sachdev Perminder , Liu Tao , Wang Yongjun
Published: January 2021

We investigated the association between poststroke cognitive impairment and a specific effective network connectivity in the prefrontal–basal ganglia circuit. The resting-state effective connectivity of this circuit was modeled by employing spectral dynamic causal modeling in 11 poststroke patients with cognitive impairment (PSCI), 8 poststroke patients without cognitive impairment (non-PSCI) at baseline and 3-month follow-up, and 28 healthy controls. Our results showed that different neuronal models of effective connectivity in the prefrontal–basal ganglia circuit were observed among healthy controls, non-PSCI, and PSCI patients. Additional connected paths (extra paths) appeared in the neuronal models of stroke patients compared with healthy controls. Moreover, changes were detected in the extra paths of non-PSCI between baseline and 3-month follow-up poststroke, indicating reorganization in the ipsilesional hemisphere and suggesting potential compensatory changes in the contralesional hemisphere. Furthermore, the connectivity strengths of the extra paths from the contralesional ventral anterior nucleus of thalamus to caudate correlated significantly with cognitive scores in non-PSCI and PSCI patients. These suggest that the neuronal model of effective connectivity of the prefrontal–basal ganglia circuit may be sensitive to stroke-induced cognitive decline, and it could be a biomarker for poststroke cognitive impairment 3 months poststroke. Importantly, contralesional brain regions may play an important role in functional compensation of cognitive decline.
Outcome Predictors of Stroke Mortality in the Neurocritical Care Unit
Authors: Viderman Dmitriy , Issanov Alpamys , Temirov Talgat , Goligher Ewan , la Fleur Philip
Published: January 2021

Background: Risk factors for medium to long-term mortality after stroke are well-established but predictors of in-hospital stroke mortality are less clearly characterized. Kazakhstan has the highest age-standardized mortality rate from ischemic stroke in the world.

Methods: We performed a retrospective analysis of patients with stroke who were admitted over a 3.5-years period to the neurocritical care unit of a tertiary care hospital in Nur-Sultan, Kazakhstan.

Results: In total, 148 critically ill patients were included in the analysis (84 ischemic stroke, 64 hemorrhagic stroke). The mean age was 63 years, 45% were male and the mean Glasgow Coma Score (±SD) at baseline was 10.3 (±3.4). The in-hospital mortality rate was similar in patients with ischemic (36%) and hemorrhagic (39%) stroke (HR 0.88, 95%CI 0.48–1.60). Median survival was 38 days (range: 1–89 days) in patients with ischemic stroke and 39 days (range: 1–63 days) in patients with hemorrhagic stroke. Univariable analysis found that patients who had a lower Glasgow Coma Scale, were in coma and who had cerebral edema were more likely to die in-hospital (P = 0.04, 0.02, <0.01, respectively).

Conclusions: Our analysis showed that mortality risk in critically ill patients with hemorrhagic stroke was closer to mortality risk in patients with ischemic stroke than has been reported in other analyses. Hypertension, chronic heart failure, ischemic heart disease and atrial fibrillation were the most frequent comorbidities in patients who developed severe (life-threatening) stroke. Coma and cerebral edema on admission appear to be associated with poor outcome. This is the first publication of in-hospital stroke mortality from a Central Asian population and could form the basis for future research including development of risk scores and identifying modifiable risk factors.
Hearing Loss and Irritability Reporting Without Vestibular Differences in Explosive Breaching Professionals
Authors: Modica Claire M. , Johnson Brian R. , Zalewski Christopher , King Kelly , Brewer Carmen , King John E. , Yarnell Angela M. , LoPresti Matthew L. , Walker Peter B. , Dell Kristine C. , Polejaeva Elena , Quick Alycia , Arnold Bobby , Wassermann Eric M. , Stone James R. , Ahlers Stephen T. , Carr Walter
Published: January 2021

Background: Blast exposure is a potential hazard in modern military operations and training, especially for some military occupations. Helmets, peripheral armor, hearing protection, and eye protection worn by military personnel provide some acute protection from blast effects but may not fully protect personnel against cumulative effects of repeated blast overpressure waves experienced over a career. The current study aimed to characterize the long-term outcomes of repeated exposure to primary blast overpressure in experienced career operators with an emphasis on the assessment of hearing and vestibular outcomes.

Methods: Participants included experienced “breachers” (military and law enforcement explosives professionals who gain entry into structures through controlled detonation of charges) and similarly aged and experienced “non-breachers” (non-breaching military and law enforcement personnel). Responses to a clinical interview and performance on audiological and vestibular testing were compared.

Results: Hearing loss, ringing in the ears, irritability, and sensitivity to light or noise were more common among breachers than non-breachers. Breachers reported more combat exposure than non-breachers, and subsequently, memory loss and difficulty concentrating were associated with both breaching and combat exposure. Vestibular and ocular motor outcomes were not different between breachers and non-breachers.

Conclusion: Hearing-related, irritability, and sensitivity outcomes are associated with a career in breaching. Future studies examining long-term effects of blast exposure should take measures to control for combat exposure.
New Insights Into Vertigo Attack Frequency as a Predictor of Ischemic Stroke
Authors: Qiu Dongxu , Zhang Lei , Deng Jun , Xia Zhiwei , Duan Jingfeng , Wang Juan , Zhang Rongsen
Published: January 2021

Background: Recurrent attacks of vertigo account for 2.6 million emergency department visits per year in the USA, of which more than 4% are attributable to ischemic infarction. However, few studies have investigated the frequency of attacks of vertigo before an ischemic stroke.

Methods: We conducted this retrospective analysis and manually screened the medical records of 231 patients who experienced recurrent attacks of vertigo prior to an ischemic stroke. Patients were divided into four different groups based on the frequency of vertigo attacks as well as the region of ischemic infarction. Those with ≤2 attacks of vertigo preceding the ischemic stroke were defined as the low-frequency group. Those with ≥3 attacks were defined as the high-frequency group. Clinical parameters, including vascular risk factors, average National Institutes of Health Stroke Scale (NIHSS) score, and infarction volume, were compared between the groups.

Results: On analysis, we found that patients with posterior infarction in the high-frequency group exhibited a higher prevalence of vertebral artery stenosis. However, the incidence of diabetes mellitus (DM) was higher in the low-frequency group. In addition, patients with posterior infarction in the low-frequency group were more active in seeking medical intervention after an attack of vertigo. Notably, the brain stem, especially the lateral medullary region, had a higher probability of being involved in posterior infarction in the high-frequency group. However, the cerebellum was more commonly involved in posterior infarction in the low-frequency group.

Conclusions: Our findings indicate that the clinical parameters, including arterial stenosis, DM, and magnetic resonance imaging (MRI) findings, differed between the low- and high-frequency groups. We also found that patients in the low-frequency group were more willing to seek medical intervention after the attacks of vertigo. These findings could be valuable for clinicians to focus on specific examination of the patients according to the frequency of vertigo attacks.
Severity and Its Contributing Factors in Patients With Vestibular Migraine: A Cohort Study
Authors: Liu Wei , Dong Hongli , Yang Le , Zhao Hongru , Dong Wanli , Yang Yi
Published: January 2021

Objective: As a recently defined disease entity, vestibular migraine (VM) is a variant of migraine with broad spectrum of manifestations. We evaluated a prospective cohort of patients with VM in two centers to assess severity of VM attacks and investigate its contributing factors in patients with VM.

Methods: Adult participants with the diagnosis of VM or probable VM were enrolled according to the 2012 International Headache Society-Bárány Society Criteria. Every outpatient was followed up for 6 months to record the occurrence of VM attacks. Clinical data such as age, sex, number of VM attacks, severity on the visual analog scale, and lipid intake were collected and analyzed. Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Horne and Ostberg Morningness-Eveningness Questionnaires, and Pittsburgh Sleep Quality Index were also administered to find contributing factors.

Results: During a 6-month clinical follow-up, 313 VM attack were reported. According to the Visual Analog Scale, the patients were divided into two groups. Then univariate and multivariable analyses were conducted. Among the risk factors, duration of illness (adjusted OR, 1.041; 95% CI, 1.010–1.073; P = 0.009), time of onset: 00:00:00–12:00:00 (adjusted OR, 3.961; 95% CI, 1.966–7.979; P < 0.001) and PSQI scores (adjusted OR, 1.086; 95% CI, 1.002–1.178; P = 0.046) were significantly associated with the severity of VM attack assessed by VAS.

Conclusion: The data suggest that patients tended to experienced more severe VM attacks in early hours of a day, especially for those sufferers with longer duration of illness or poor sleep quality. Targeted management of such factors is required to reduce the severity of attacks.
Clinical and Radiological Features of Adult Onset Bilateral Medial Frontal Cerebral Cortical Encephalitis With Anti-myelin Oligodendrocyte Glycoprotein Antibody
Authors: Fujimori Juichi , Nakamura Masashi , Yagihashi Takahito , Nakashima Ichiro
Published: January 2021

Objective: To clarify the clinical and radiological features of adult onset anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated bilateral medial frontal cerebral cortical encephalitis (BFCCE).

Methods: We systematically reviewed the literature for patients with anti-MOG antibody-associated BFCCE. Patients who were also positive for other encephalitis-related autoantibodies were excluded from the study. The frequency of several characteristic neurological symptoms and lesion distributions were analyzed.

Results: We identified six patients with anti-MOG antibody-associated BFCCE. Among them, 6/6 had headache, 4/6 had fever, 3/6 had seizure, 2/6 had paraparesis, 2/6 had lethargy, and 2/6 had memory disturbance. CSF pleocytosis was observed in 5/6 patients, while CSF myelin basic protein was not elevated in any of the six patients. On brain MRI, 6/6 had bilateral medial frontal cortical lesions, 3/6 had corpus callosum lesions, and 3/6 had leptomeningeal enhancements. Most of the lesions were distributed in the territory of the anterior cerebral artery (ACA).

Conclusion: Our results indicate that anti-MOG antibody-associated BFCCE presents with characteristic clinical symptoms and MRI findings, which might reflect lesion formation in the ACA territory.
Adult Sellar Region Atypical Teratoid/Rhabdoid Tumor: A Retrospective Study and Literature Review
Authors: Liu Fujun , Fan Shucai , Tang Xin , Fan Shuangmin , Zhou Liangxue
Published: January 2021

Background: Adult sellar region atypical teratoid/rhabdoid tumor (AT/RT) is a rare lesion. We aimed to elucidate clinical, radiologic, and pathological characteristics, treatment strategies, and outcomes of this disease.

Methods: Five adult sellar AT/RT patients were retrospectively analyzed between January 2015 and December 2018. In addition, we performed a review of the reported data on adult sellar AT/RT.

Results: Patients (n = 5) were female with a median age of 50 years. The mean duration of symptoms, of which headache was the most frequent, was 1.6 months (range, 2 weeks−8 months). The average tumor size was 2.82 cm (range, 1.9–4.5 cm). All lesions were irregularly shaped. MRI showed heterogeneous enhancement in three of five lesions. Four of five patients underwent subtotal resection (STR) and one gross total resection (GTR). Whereas, one patient received post-operative adjuvant radiotherapy, one patient received post-operative combination of radio- and chemotherapy. The review of the reported data showed that 39 cases of adult sellar AT/RT had been reported. The estimated median overall survival (OS) was 23 months with a 1-year survival estimate of 59.7%. The median OS for patients with GTR was 28 months and 17 months for patients with STR. Kaplan–Meier analysis showed that patients with high (≥35%) MIB-1/Ki67 index value had a significantly shorter OS compared with those with low (<35%) index value (p = 0.033), and that patients who received post-operative combination radio- and chemotherapy had longer OS than that of those who did not (p < 0.001).

Conclusion: Adult sellar region AT/RT is a rapidly growing tumor with a poor prognosis. High levels of MIB1/Ki-67 on histology may indicate aggressive feature of the tumor. Maximal safe resection followed by adjuvant radiotherapy combined with chemotherapy may be the optimal therapeutic strategy for adult sellar region AT/RT.
Antibodies Against Lysophosphatidic Acid Protect Against Blast-Induced Ocular Injuries
Authors: Arun Peethambaran , Rossetti Franco , DeMar James C. , Wang Ying , Batuure Andrew B. , Wilder Donna M. , Gist Irene D. , Morris Andrew J. , Sabbadini Roger A. , Long Joseph B.
Published: January 2021

Exposure to blast overpressure waves is implicated as the major cause of ocular injuries and resultant visual dysfunction in veterans involved in recent combat operations. No effective therapeutic strategies have been developed so far for blast-induced ocular dysfunction. Lysophosphatidic acid (LPA) is a bioactive phospholipid generated by activated platelets, astrocytes, choroidal plexus cells, and microglia and is reported to play major roles in stimulating inflammatory processes. The levels of LPA in the cerebrospinal fluid have been reported to increase acutely in patients with traumatic brain injury (TBI) as well as in a controlled cortical impact (CCI) TBI model in mice. In the present study, we have evaluated the efficacy of a single intravenous administration of a monoclonal LPA antibody (25 mg/kg) given at 1 h post-blast for protection against injuries to the retina and associated ocular dysfunctions. Our results show that a single 19 psi blast exposure significantly increased the levels of several species of LPA in blood plasma at 1 and 4 h post-blast. The anti-LPA antibody treatment significantly decreased glial cell activation and preserved neuronal cell morphology in the retina on day 8 after blast exposure. Optokinetic measurements indicated that anti-LPA antibody treatment significantly improved visual acuity in both eyes on days 2 and 6 post-blast exposure. Anti-LPA antibody treatment significantly increased rod photoreceptor and bipolar neuronal cell signaling in both eyes on day 7 post-blast exposure. These results suggest that blast exposure triggers release of LPAs, which play a major role promoting blast-induced ocular injuries, and that a single early administration of anti-LPA antibodies provides significant protection.
Optical Coherence Tomography and Optical Coherence Tomography Angiography Findings After Optic Neuritis in Multiple Sclerosis
Authors: Murphy Olwen C. , Kalaitzidis Grigorios , Vasileiou Eleni , Filippatou Angeliki G. , Lambe Jeffrey , Ehrhardt Henrik , Pellegrini Nicole , Sotirchos Elias S. , Luciano Nicholas J. , Liu Yihao , Fitzgerald Kathryn C. , Prince Jerry L. , Calabresi Peter A. , Saidha Shiv
Published: January 2021

Background: In people with multiple sclerosis (MS), optic neuritis (ON) results in inner retinal layer thinning, and reduced density of the retinal microvasculature.

Objective: To compare inter-eye differences (IEDs) in macular optical coherence tomography (OCT) and OCT angiography (OCTA) measures in MS patients with a history of unilateral ON (MS ON) vs. MS patients with no history of ON (MS non-ON), and to assess how these measures correlate with visual function outcomes after ON.

Methods: In this cross-sectional study, people with MS underwent OCT and OCTA. Superficial vascular plexus (SVP) density of each eye was quantified using a deep neural network. IEDs were calculated with respect to the ON eye in MS ON patients, and with respect to the right eye in MS non-ON patients. Statistical analyses used mixed-effect regression models accounting for intra-subject correlations.

Results: We included 43 MS ON patients (with 92 discrete OCT/OCTA visits) and 14 MS non-ON patients (with 24 OCT/OCTA visits). Across the cohorts, mean IED in SVP density was −2.69% (SD 3.23) in MS ON patients, as compared to 0.17% (SD 2.39) in MS non-ON patients (p = 0.002). When the MS ON patients were further stratified according to time from ON and compared to MS non-ON patients with multiple cross-sectional analyses, we identified that IED in SVP density was significantly increased in MS ON patients at 1–3 years (p = < 0.001) and >3 years post-ON (p < 0.001), but not at <3 months (p = 0.21) or 3–12 months post-ON (p = 0.07), while IED in ganglion cell + inner plexiform layer (GCIPL) thickness was significantly increased in MS ON patients at all time points post-ON (p ≦ 0.01 for all). IED in SVP density and IED in GCIPL thickness demonstrated significant relationships with IEDs in 100% contrast, 2.5% contrast, and 1.25% contrast letter acuity in MS ON patients (p < 0.001 for all).

Conclusions: Our findings suggest that increased IED in SVP density can be detected after ON in MS using OCTA, and detectable changes in SVP density after ON may occur after changes in GCIPL thickness. IED in SVP density and IED in GCIPL thickness correlate well with visual function outcomes in MS ON patients.
Electroencephalogram Access for Emotion Recognition Based on a Deep Hybrid Network
Authors: Zhong Qinghua , Zhu Yongsheng , Cai Dongli , Xiao Luwei , Zhang Han
Published: January 2021

In the human-computer interaction (HCI), electroencephalogram (EEG) access for automatic emotion recognition is an effective way for robot brains to perceive human behavior. In order to improve the accuracy of the emotion recognition, a method of EEG access for emotion recognition based on a deep hybrid network was proposed in this paper. Firstly, the collected EEG was decomposed into four frequency band signals, and the multiscale sample entropy (MSE) features of each frequency band were extracted. Secondly, the constructed 3D MSE feature matrices were fed into a deep hybrid network for autonomous learning. The deep hybrid network was composed of a continuous convolutional neural network (CNN) and hidden Markov models (HMMs). Lastly, HMMs trained with multiple observation sequences were used to replace the artificial neural network classifier in the CNN, and the emotion recognition task was completed by HMM classifiers. The proposed method was applied to the DEAP dataset for emotion recognition experiments, and the average accuracy could achieve 79.77% on arousal, 83.09% on valence, and 81.83% on dominance. Compared with the latest related methods, the accuracy was improved by 0.99% on valence and 14.58% on dominance, which verified the effectiveness of the proposed method.
Emotional Reactivity and Regulation in Preschool-Age Children Who Do and Do Not Stutter: Evidence From Autonomic Nervous System Measures
Authors: Tumanova Victoria , Wilder Blair , Gregoire Julia , Baratta Michaela , Razza Rachel
Published: January 2021

Purpose:This experimental cross-sectional research study examined the emotional reactivity and emotion regulation in preschool-age children who do (CWS) and do not stutter (CWNS) by assessing their psychophysiological response during rest and while viewing pictures from the International Affective Picture System (Lang et al.,2008).

Method:Participants were 18 CWS (16 boys and two girls; mean age 4 years, 5 months) and 18 age- and gender-matched CWNS. Participants' psychophysiological responses were measured during two baselines and two picture viewing conditions. Skin conductance level (SCL) and heart rate were measured to assess emotional reactivity. Respiratory sinus arrhythmia (RSA) was measured to assess emotional regulation. Participants' shyness and executive function were assessed via parent report and considered for their effects on participants' psychophysiological responses.

Results:First, CWNS and CWS did not differ in their initial baseline SCL, heart rate, or RSA, but all participants had higher SCL and lower RSA in the second baseline, subsequent to the first challenge condition, compared to the first baseline. Second, during the challenge conditions, CWS did not differ from CWNS in their SCL, but showed a significantly higher heart rate than CWNS. Third, CWS exhibited a significantly lower RSA during the challenge conditions compared to CWNS. Lastly, the temperamental quality of shyness was associated with preschool-age children's SCL, such that participants who were rated higher in shyness had a higher SCL during the challenge conditions. Participants' executive function had a marginally significant effect on the RSA, such that the participants who had higher executive function composite scores exhibited lower RSA during the challenge conditions.

Conclusions:Our findings suggest that CWS and CWNS did not differ in their emotional reactivity and emotional regulation abilities at rest. During challenge conditions, however, CWS tended to be more emotionally reactive, as indicated by a higher heart rate, and also employed more emotional regulation, indexed by a greater decrease in RSA, compared to CWNS. Preschool-age children's behavior is largely dominated by reactivity, but there is the emergence of regulation, which can help children adjust to various contextual demands. For CWS who are more emotionally reactive, regulatory skills may be particularly critical to their prognosis and treatment.
Unraveling Early Signs of Navigational Impairment in APPswe/PS1dE9 Mice Using Morris Water Maze
Authors: Karunakaran Smitha
Published: January 2021

Mild behavioral deficits, which are part of normal aging, can be early indicators of an impending Alzheimer's disease. Using the APPswe/PS1dE9 (APP/PS1) mouse model of Alzheimer's disease, we utilized the Morris water maze spatial learning paradigm to systematically evaluate mild behavioral deficits that occur during the early stages of disease pathogenesis. Conventional behavioral analysis using this model indicates that spatial memory is intact at 2 months of age. In this study, we used an alternative method to analyze the behavior of mice, aiming to gain a better understanding of the nature of cognitive deficits by focusing on the unsuccessful trials during water maze learning rather than on the successful ones. APP/PS1 mice displayed a higher number of unsuccessful trials during the initial days of training, unlike their wild-type counterparts. However, with repeated trial and error, learning in APP/PS1 reached levels comparable to that of the wild-type mice during the later days of training. Individual APP/PS1 mice preferred a non-cognitive search strategy called circling, which led to abrupt learning transitions and an increased number of unsuccessful trials. These findings indicate the significance of subtle intermediate readouts as early indicators of conditions such as Alzheimer's disease.
Accumulation of Cerebrospinal Fluid Glycerophospholipids and Sphingolipids in Cognitively Healthy Participants With Alzheimer’s Biomarkers Precedes Lipolysis in the Dementia Stage
Authors: Fonteh Alfred N. , Chiang Abby J. , Arakaki Xianghong , Edminster Sarah P. , Harrington Michael G
Published: January 2021

Insight into lipids’ roles in Alzheimer’s disease (AD) pathophysiology is limited because brain membrane lipids have not been characterized in cognitively healthy (CH) individuals. Since age is a significant risk factor of AD, we hypothesize that aging renders the amyloid precursor protein (APP) more susceptible to abnormal processing because of deteriorating membrane lipids. To reflect brain membranes, we studied their lipid components in cerebrospinal fluid (CSF) and brain-derived CSF nanoparticle membranes. Based on CSF Aβ42/Tau levels established biomarkers of AD, we define a subset of CH participants with normal Aβ42/Tau (CH-NAT) and another group with abnormal or pathological Aβ42/Tau (CH-PAT). We report that glycerophospholipids are differentially metabolized in the CSF supernatant fluid and nanoparticle membrane fractions from CH-NAT, CH-PAT, and AD participants. Phosphatidylcholine molecular species from the supernatant fraction of CH-PAT were higher than in the CH-NAT and AD participants. Sphingomyelin levels in the supernatant fraction were lower in the CH-PAT and AD than in the CH-NAT group. The decrease in sphingomyelin corresponded with an increase in ceramide and dihydroceramide and an increase in the ceramide to sphingomyelin ratio in AD. In contrast to the supernatant fraction, sphingomyelin is higher in the nanoparticle fraction from the CH-PAT group, accompanied by lower ceramide and dihydroceramide and a decrease in the ratio of ceramide to sphingomyelin in CH-PAT compared with CH-NAT. On investigating the mechanism for the lipid changes in AD, we observed that phospholipase A2 (PLA2) activity was higher in the AD group than the CH groups. Paradoxically, acid and neutral sphingomyelinase (SMase) activities were lower in AD compared to the CH groups. Considering external influences on lipids, the clinical groups did not differ in their fasting blood lipids or dietary lipids, consistent with the CSF lipid changes originating from brain pathophysiology. The lipid accumulation in a prodromal AD biomarker positive stage identifies perturbation of lipid metabolism and disturbances in APP/Amyloid beta (Aβ) as early events in AD pathophysiology. Our results identify increased lipid turnover in CH participants with AD biomarkers, switching to a predominantly lipolytic state in dementia. This knowledge may be useful for targeting and testing new AD treatments.