bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Fatty Infiltration of Paraspinal Muscles in Patients With Lumbar Spinal Stenosis: Goutallier Classification and Quantitative MRI Measurements
Authors: Mandelli Filippo , Nüesch Corina , Zhang Yuancheng , Halbeisen Florian , Schären Stefan , Mündermann Annegret , Netzer Cordula
Published: September 2021

Objective: Fatty infiltration of paraspinal muscle is associated with spinal disorders. It can be assessed qualitatively (i.e., Goutallier classification) and quantitatively using image processing software. The aims of this study were to compare paraspinal muscle fatty infiltration as assessed using the Goutallier classification vs. quantitative magnetic resonance images (MRI) measurements and to investigate the association between anthropometric parameters and paraspinal muscle morphology and fatty infiltration in patients with symptomatic lumbar spinal stenosis (LSS).

Methods: Patients affected by symptomatic LSS scheduled for surgery with available MRI of the lumbar spine were included in this retrospective cross-sectional study. Fatty infiltration at each lumbar level was rated qualitatively according to the Goutallier classification and quantified based on the cross-sectional area (CSA) of the paraspinal muscle, of its lean fraction (LeanCSA), and the ratio between LeanCSA and CSA and the CSA relative to the CSA of vertebral body (RCSA). Considering the muscle as a single unit, overall fatty infiltration according to Goutallier, overall CSA, LeanCSA, LeanCSA/CSA, and RCSA were computed as averages (aGoutallier, aCSA, aLeanCSA, aLeanCSA/aCSA, and aRCSA). Associations among parameters were assessed using Spearman's respective Pearson's correlation coefficients.

Results: Eighteen patients, with a mean age of 71.3 years, were included. aGoutallier correlated strongly with aLeanCSA and aLeanCSA/aCSA (R = −0.673 and R = −0.754, both P < 0.001). There was a very strong correlation between values of the left and right sides for CSA (R = 0.956, P < 0.001), LeanCSA (R = 0.900, P < 0.001), and LeanCSA/CSA (R = 0.827, P < 0.001) at all levels. Among all anthropometric measurements, paraspinal muscle CSA correlated the most with height (left: R = 0.737, P < 0.001; right: R = 0.700, P < 0.001), while there was a moderate correlation between vertebral body CSA and paraspinal muscle CSA (left: R = 0.448, P < 0.001; right: R = 0.454, P < 0.001). Paraspinal muscle CSA correlated moderately with body mass index (BMI; left: R = 0.423, P < 0.001; right: R = 0.436, P < 0.001), and there was no significant correlation between aLeanCSA or aLeanCSA/CSA and BMI.

Conclusions: The Goutallier classification is a reliable yet efficient tool for assessing fatty infiltration of paraspinal muscles in patients with symptomatic LSS. We suggest taking body height as a reference for normalization in future studies assessing paraspinal muscle atrophy and fatty infiltration.
Smoking Status and Functional Outcomes in Young Stroke
Authors: Liang Cheng-Loong , Chen Han-Jung , Lee Yi-Che , Wu Cheng-Chun , Tsai Chon-Haw , Chen Po-Lin , Chang Wei-Lun , Yeh Po-Yen , Wei Cheng-Yu , Tsai Ming-Jun , Sun Yu , Lin Chih-Hao , Lee Jiunn-Tay , Lai Ta-Chang , Lien Li-Ming , Lin Mei-Chen , Lin Cheng-Li , Wang Hao-Kuang , Hsu Chung Y.
Published: September 2021

Objective: Stroke in young adults is uncommon, and the etiologies and risk factors of stroke in young adults differ from those in older populations. Smoker's paradox is an unexpected favorable outcome, and age difference is used to explain the association between smoking and the favorable functional outcome. This study aimed to investigate the existence of this phenomenon in young stroke patients.

Methods: We analyzed a total of 9,087 young stroke cases registered in the nationwide stroke registry system of Taiwan between 2006 and 2016. Smoking criteria included having a current history of smoking more than one cigarette per day for more than 6 months. After matching for sex and age, a Cox model was used to compare mortality and function outcomes between smokers and non-smokers.

Results: Compared with the non-smoker group, smoking was associated with older age, higher comorbidities, and higher alcohol consumption. Patients who report smoking with National Institutes of Health Stroke Scale scores of 11–15 had a worse functional outcome (adjusted odds ratio, 0.81; 95% confidence interval, 0.76 – 0.87).

Conclusion: Smokers had a higher risk of unfavorable functional outcomes at 3 months after stroke, and therefore, we continue to strongly advocate the importance of smoking cessation.
Pathophysiology of Vascular Stenosis and Remodeling in Moyamoya Disease
Authors: Fox Brandon M. , Dorschel Kirsten B. , Lawton Michael T. , Wanebo John E.
Published: September 2021

Moyamoya disease (MMD) and moyamoya syndrome (MMS) are progressive vascular pathologies unique to the cerebrovasculature that are important causes of stroke in both children and adults. The natural history of MMD is characterized by primary progressive stenosis of the supraclinoid internal carotid artery, followed by the formation of fragile collateral vascular networks. In MMS, stenosis and collateralization occur in patients with an associated disease or condition. The pathological features of the stenosis associated with MMD include neointimal hyperplasia, disruption of the internal elastic lamina, and medial attenuation, which ultimately lead to progressive decreases in both luminal and external arterial diameter. Several molecular pathways have been implicated in the pathophysiology of stenosis in MMD with functions in cellular proliferation and migration, extracellular matrix remodeling, apoptosis, and vascular inflammation. Importantly, several of these molecular pathways overlap with those known to contribute to diseases of systemic arterial stenosis, such as atherosclerosis and fibromuscular dysplasia (FMD). Despite these possible shared mechanisms of stenosis, the contrast of MMD with other stenotic pathologies highlights the central questions underlying its pathogenesis. These questions include why the stenosis that is associated with MMD occurs in such a specific and limited anatomic location and what process initiates this stenosis. Further investigation of these questions is critical to developing an understanding of MMD that may lead to disease-modifying medical therapies. This review may be of interest to scientists, neurosurgeons, and neurologists involved in both moyamoya research and treatment and provides a review of pathophysiologic processes relevant to diseases of arterial stenosis on a broader scale.
Case Report: Double Micro-Guidewire Technique for Emergent Rescue of Proximal Stent Collapse During Recanalization of Nonacute Occlusion of Vertebral Artery
Authors: Zhang Kun , Xia Jin-Chao , Gao Hui-Li , Gao Bu-Lang , Wang Yong-Feng , Li Zhao-Shuo , Li Tian-Xiao , Wang Zi-Liang
Published: September 2021

Cerebral arteries are usually tortuous, and in the treatment of cerebrovascular diseases with stenting, a stent deployed may be collapsed at one end, leading to reduced blood flow and subsequent stent occlusion. Immediate rescuing measures should be implemented to prevent severe ischemic events. In this case report, we present a case with V4 segment occlusion of the right vertebral artery treated with endovascular stent angioplasty. An Enterprise stent deployed at the occlusion segment was collapsed at the proximal end after withdrawal of the delivery system. Immediate rescuing measures were taken by navigating a micro-guidewire through the lateral stent mesh at the proximal end into the stent lumen followed by advancing a second micro-guidewire right through the reopened proximal stent end into the stent lumen for deployment of a supporting balloon-expandable Apollo stent to prevent stent collapse. Follow-up digital subtraction angiography 6 months later demonstrated patent stents and unobstructed blood flow.
Intraplaque Enhancement Is Associated With Artery-to-Artery Embolism in Symptomatic Vertebrobasilar Atherosclerotic Diseases
Authors: Hou Zhikai , Li Mingyao , Lyu Jinhao , Xu Ziqi , Liu Yifan , He Jianfeng , Jing Jing , Wang Rong , Wang Yongjun , Lou Xin , Miao Zhongrong , Ma Ning
Published: September 2021

Objective: There are limited data regarding the characteristics of intracranial plaques according to stroke mechanism in the posterior circulation. This study aims to compare whether the plaque characteristics and baseline features are different in patients with artery-to-artery (A-to-A) embolism and those with parent artery disease in the intracranial vertebrobasilar atherosclerotic disease.

Methods: From September 2014 to January 2017, patients with recent posterior circulation stroke due to intracranial vertebrobasilar atherosclerotic disease were retrospectively analyzed. Patients with the following eligibility criteria were included: (1) age ≥18 years old, (2) ischemic stroke in the vertebrobasilar territory, (3) 70–99% stenosis of the intracranial vertebral artery or basilar artery, and (4) two or more atherosclerotic risk factors. Patients with concomitant ipsilateral or bilateral extracranial vertebral artery >50% stenosis, cardio-embolism, or non-atherosclerotic stenosis were excluded. The plaque characteristics, including intraplaque compositions (intraplaque hemorrhage and intraplaque calcification), intraplaque enhancement, and remodeling index, were evaluated by using 3T high-resolution magnetic resonance imaging (HRMRI). The baseline features including vascular risk factors and the involved artery were collected. Patients were divided into A-to-A embolism and parent artery disease groups based on the diffusion-weighted images, T2-weighted images, or computed tomography. The plaque characteristics and baseline features were compared between the two groups.

Results: Among consecutive 298 patients, 51 patients were included. Twenty-nine patients had A-to-A embolism and 22 patients had parent artery disease. Compared with parent artery disease, the occurrence rates of intraplaque enhancement and intracranial vertebral involvement were higher in the A-to-A embolism group (79.3 vs. 36.4%; p = 0.002 and 62.1 vs. 18.2%; p = 0.002, respectively). Multivariable logistic regression analysis showed that intraplaque enhancement and intracranial vertebral artery plaques were also associated with A-to-A embolism (adjusted OR, 7.31; 95% CI 1.58–33.77; p = 0.011 and adjusted OR, 9.42; 95% CI 1.91–46.50; p = 0.006, respectively).

Conclusion: Intraplaque enhancement and intracranial vertebral artery plaques seem to be more closely associated with A-to-A embolism than parent artery disease in patients with symptomatic intracranial vertebrobasilar disease.

Clinical Trial Registration:http://www.clinicaltrials.gov, identifier: NCT02705599.
Efficacy of Melatonin in Animal Models of Subarachnoid Hemorrhage: A Systematic Review and Stratified Meta-Analysis
Authors: Hu Xiangyu , Zhu Yuwei , Zhou Fangfang , Peng Cuiying , Hu Zhiping , Chen Chunli
Published: September 2021

Background and Purpose: Subarachnoid hemorrhage (SAH) is a severe disease characterized by sudden headache, loss of consciousness, or focal neurological deficits. Melatonin has been reported as a potential neuroprotective agent of SAH. It provides protective effects through the anti-inflammatory effects or the autophagy pathway. Our systematic review aims to evaluate the efficacy of melatonin administration on experimental SAH animals and offer support for the future clinical trial design of the melatonin treatment following SAH.

Methods: The following online databases were searched for experimentally controlled studies of the effect of melatonin on SAH models: PubMed, Web of Knowledge, Embase, and China National Knowledge Infrastructure (all until March 2021). The melatonin effect on the brain water content (BWC) and neurological score (NS) were compared between the treatment and control groups using the standardized mean difference (SMD).

Results: Our literature identified 160 possible articles, and most of them were excluded due to duplication (n = 69) and failure to meet the inclusion criteria (n = 56). After screening the remaining 35 articles in detail, we excluded half of them because of no relevant outcome measures (n = 16), no relevant interventions (n = 3), review articles (n = 1), duplicated publications (n = 1), and studies on humans or cells (n = 2). Finally, this systematic review contained 12 studies between 2008 and 2018. All studies were written in English except for one study in Chinese, and all of them showed the effect of melatonin on BWC and NS in SAH models.

Conclusion: Our research shows that melatonin can significantly improve the behavior and pathological results of SAH animal models. However, due to the small number of studies included in this meta-analysis, the experimental design and experimental method limitations should be considered when interpreting the results. Significant clinical and animal studies are still required to evaluate whether melatonin can be used in the adjuvant treatment of clinical SAH patients.
Long-Term Retrospective Analysis of Re-do Microvascular Decompression in Patients With Hemifacial Spasm
Authors: Liu Jiayu , Li Fang , Wu Guangyong , Liu Bo , Zhou Jingru , Fan Cungang , Jiao Feng , Wang Dongliang , Wu Gang , Song Haidong , Liu Ruen
Published: September 2021

Objective: To explore the clinical characteristics of patients with persistent or recurrent hemifacial spasm (HFS) and the experience of microvascular decompression (MVD) in the treatment of such patients to accumulate additional clinical evidence for optimal treatment protocols.

Methods: We retrospectively analyzed the clinical data, surgical methods and treatment efficacies of 176 patients with persistent or recurrent HFS from January 2009 to January 2018.

Results: Missing compression zones was the main reason for symptom persistence (87.50%) or recurrence (71.50%) after MVD treatment of HFS. We divided the surgical area into three zones. Most persistent or recurrent cases had decompression only in the root exit zone (REZ) (Zone 1) but missed the ventrolateral pons-involved area (Zone 2) or the bulbopontine sulcus-involved area (Zone 3) in the first MVD. Too much use of Teflon (12.50%), arachnoid adhesions (5.60%) and Teflon granulomas (10.40%) can also cause a recurrence. The difference between preoperative and postoperative Cohen scores was statistically significant in persistent or recurrent HFS patients (p<0.05). The postoperative follow-up time ranged from 36 to 108 months (71.75 ± 22.77).

Conclusions: MVD should be performed in the compression site, which is mostly located at the brainstem/facial REZ. Intraoperative exploration should be conducted in accordance with the abovementioned zones to effectively avoid missing offending vessels. Re-do MVD is effective in patients with persistent or recurrent HFS.
Correlation Between Tumor Molecular Markers and Perioperative Epilepsy in Patients With Glioma: A Systematic Review and Meta-Analysis
Authors: Song Li , Quan Xingyun , Chen Chaoyi , Chen Ligang , Zhou Jie
Published: September 2021

Purpose: Tumors derived from the neuroepithelium are collectively termed gliomas and are the most common malignant primary brain tumor. Epilepsy is a common clinical symptom in patients with glioma, which can impair neurocognitive function and quality of life. Currently, the pathogenesis of glioma-related epilepsy is not fully described. Therefore, it is necessary to further understand the mechanism of seizures in patients with glioma. In this study, a comprehensive meta-analysis was conducted to investigate the relationship between five commonly used tumor molecular markers and the incidence of perioperative epilepsy in patients with glioma.

Methods: PubMed, EMBASE, and Cochrane Library databases were searched for related research studies. Odds ratio and the corresponding 95% confidence interval were used as the main indicators to evaluate the correlation between tumor molecular markers and the incidence of perioperative epilepsy in patients with glioma.

Results: A total of 12 studies were included in this meta-analysis. The results showed that isocitrate dehydrogenase 1 (IDH1) mutation was significantly correlated with the incidence of perioperative epilepsy. A subgroup analysis showed that IDH1 was significantly correlated with the incidence of preoperative epilepsy, but not with intraoperative and postoperative epilepsy. There was no correlation between O6-methylguanine-DNA methyltransferase methylation and 1p/19q deletion and the incidence of perioperative epilepsy. Tumor protein p53 and epidermal growth factor receptor could not be analyzed because of the limited availability of relevant literature. There was no significant heterogeneity or publication bias observed among the included studies.

Conclusion: The present meta-analysis confirms the relationship between tumor molecular markers and the incidence of perioperative epilepsy in patients with glioma. The present results provide more comprehensive evidence for the study of the pathogenesis of glioma-related epilepsy. Our research may offer a new method for the treatment of perioperative seizures in patients with glioma.
Establishing the Minimal Clinically Important Differences for Sagittal Hip Range of Motion in Chronic Stroke Patients
Authors: Guzik Agnieszka , Drużbicki Mariusz , Perenc Lidia , Wolan-Nieroda Andżelina , Turolla Andrea , Kiper Paweł
Published: September 2021

Many researchers have pointed out that decreased sagittal range of motion (ROM) in the affected hip joint is a common consequence of stroke, and it adversely affects walking performance and walking speed. Nevertheless, the minimal clinically important differences (MCID) in hip-related kinematic gait parameters post-stroke have not yet been determined. The present study aimed to define MCID values for hip ROM in the sagittal plane i.e., flexion–extension (FE), for the affected and unaffected sides at a chronic stage post-stroke. Fifty participants with hemiparesis due to stroke were enrolled for the study. Four statistical methods were used to calculate MCID. According to the anchor-based approach, the mean change in hip FE ROM achieved by the MCID group on the affected/unaffected side amounted to 5.81°/2.86° (the first MCID estimate). The distribution-based analyses established that the standard error of measurement in the no-change group amounted to 1.56°/1.04° (the second MCID estimate). Measurements based on the third method established that a change of 4.09°/0.61° in the hip ROM corresponded to a 1.85-point change in the Barthel Index. The optimum cutoff value, based on ROC curve analysis, corresponded to 2.9/2.6° of change in the hip sagittal ROM for the affected/unaffected side (the fourth MCID estimate). To our knowledge, this is the first study to use a comprehensive set of statistical methods to determine the MCID for hip sagittal ROM for the affected and unaffected sides at a chronic stage post-stroke. According to our findings, the MCID of the hip FE ROM for the affected side amounts to 5.81° and for the unaffected side to 2.86°, in patients with chronic stroke. This indicator is extremely important because it allows clinical practitioners to assess the effects of interventions administered to patients, and to interpret the significance of improvements in sagittal kinematic parameters of the hip; ultimately, it may facilitate the process of designing effective gait reeducation programs.
Correlation Between Maximal Tongue Pressure and Swallowing Function in Spinal and Bulbar Muscular Atrophy
Authors: Gwak Dae-Won , Jung Seung-Hwan , Min Yu-Sun , Park Jin-Sung , Cho Hee-Jin , Park Donghwi , Hong Min Woo , Kang Min-Gu
Published: September 2021

Background: Spinal and bulbar muscular atrophy (SBMA) is an X-lined motor neuron disease characterized by progressive muscle weakness, bulbar palsy, and dysphagia. Dysphagia is associated with tongue weakness, which is a common manifestation of SBMA. This study aimed to investigate the correlations between tongue pressure and dysphagia in patients with SBMA.

Materials and Methods: Thirty-nine genetically confirmed SBMA patients underwent a videofluoroscopic swallowing study (VFSS) and tongue pressure assessment. Then, we analyzed the maximal tongue pressure (MTP), oral transit time, penetration-aspiration scale (PAS), videofluoroscopic dysphagia scale (VDS), amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R), and 6-min walk test (6MWT). Pearson and Spearman correlation coefficients were calculated to analyze the association of the MTP with clinical, swallowing, and functional parameters.

Results: In the correlation analysis, MTP was negatively correlated with disease duration (r = −0.396, p = 0.013) and VDS (r = −0.426, p = 0.007), and positively correlated with ALSFRS-R (r = 0.483, p = 0.002) and 6MWT (r = 0.396, p = 0.013). The bulbar (r = 0.367, p = 0.022) and gross motor (r = 0.486, p = 0.002) domains of the ALSFRS-R were correlated with MTP.

Conclusion: Tongue pressure assessment can be used as a safe and easy tool to assess swallowing function in SBMA patients. Moreover, MTP reflects functional states, including activities of daily living and gait performance, showing it to be a potential biomarker for physical performance in SBMA.
Prevalence of Hyperacusis in the General and Special Populations: A Scoping Review
Authors: Ren Jing , Xu Tao , Xiang Tao , Pu Jun-mei , Liu Lu , Xiao Yan , Lai Dan
Published: September 2021

Objectives: To study the prevalence of hyperacusis in the general population and the special population, and to determine the effect of population differences on hyperacusis.

Methods: The two authors followed a scoping review methodology and screened nearly 30 years of English literature in Pubmed, Web of Science, OVID, and EBSCO. Then, the extracted results of each study were discussed in groups and subgroups.

Results: The authors selected 42 pieces of scientific literature that met the requirements, studying a total of 34,796 subjects, including the general population (28,425 subjects), the special occupation population (2,746 subjects), and the patients with concomitant diseases (5,093 subjects). The prevalence was 0.2–17.2% in the general population, 3.8–67% in the special occupation population, and 4.7–95% in the patients with special diseases. It was found that in the general population, the high prevalence occurs in adolescents and older adults. The prevalence of hyperacusis in women is significantly higher than in men. In people with hearing disorders, the prevalence of hyperacusis is significantly higher than in people with normal hearing. Various diseases (such as Williams syndrome, tinnitus, and autism), as well as various occupations (musicians, music students, teachers, and others), have been found to be high risk factors for hyperacusis.

Conclusion: The high prevalence of hyperacusis and the large differences between reported prevalence in different studies deserves our great attention. Additionally, in order to increase the comparability of the studies, a standardized set of criteria are needed to study the prevalence of hyperacusis.
Exploring Signatures of Neurodegeneration in Early-Onset Older-Age Bipolar Disorder and Behavioral Variant Frontotemporal Dementia
Authors: Cruz-Sanabria Francy , Reyes Pablo Alexander , Triviño-Martínez Cristian , García-García Milena , Carmassi Claudia , Pardo Rodrigo , Matallana Diana L.
Published: September 2021

Introduction:Older-age bipolar disorder (OABD) may involve neurocognitive decline and behavioral disturbances that could share features with the behavioral variant of frontotemporal dementia (bvFTD), making the differential diagnosis difficult in cases of suspected dementia.

Objective:To compare the neuropsychological profile, brain morphometry, and structural connectivity patterns between patients diagnosed with bvFTD, patients classified as OABD with an early onset of the disease (EO-OABD), and healthy controls (HC).

Methods:bvFTD patients (n= 25, age: 66 ± 7, female: 64%, disease duration: 6 ± 4 years), EO-OABD patients (n= 17, age: 65 ± 9, female: 71%, disease duration: 38 ± 8 years), and HC (n= 28, age: 62 ± 7, female: 64%) were evaluated through neuropsychological tests concerning attention, memory, executive function, praxis, and language. Brain morphometry was analyzed through surface-based morphometry (SBM), while structural brain connectivity was assessed through diffusion tensor imaging (DTI).

Results:Both bvFTD and EO-OABD patients showed lower performance in neuropsychological tests of attention, verbal fluency, working memory, verbal memory, and praxis than HC. Comparisons between EO-OABD and bvFTD showed differences limited to cognitive flexibility delayed recall and intrusion errors in the memory test. SBM analysis demonstrated that several frontal, temporal, and parietal regions were altered in both bvFTD and EO-OABD compared to HC. In contrast, comparisons between bvFTD and EO-OABD evidenced differences exclusively in the right temporal pole and the left entorhinal cortex. DTI analysis showed alterations in association and projection fibers in both EO-OABD and bvFTD patients compared to HC. Commissural fibers were found to be particularly affected in EO-OABD. The middle cerebellar peduncle and the pontine crossing tract were exclusively altered in bvFTD. There were no significant differences in DTI analysis between EO-OABD and bvFTD.

Discussion:EO-OABD and bvFTD may share an overlap in cognitive, brain morphometry, and structural connectivity profiles that could reflect common underlying mechanisms, even though the etiology of each disease can be different and multifactorial.
Effects of Galvanic Vestibular Stimulation on Vestibular Compensation in Unilaterally Labyrinthectomized Mice
Authors: Nam Gi-Sung , Nguyen Thanh Tin , Kang Jin-Ju , Han Gyu Cheol , Oh Sun-Young
Published: September 2021

Objectives: To investigate the ameliorating effects of sinusoidal galvanic vestibular stimulation (GVS) on vestibular compensation from unilateral vestibular deafferentation (UVD) using a mouse model of unilateral labyrinthectomy (UL).

Methods: Sixteen male C57BL/6 mice were allocated into two groups that comprise UL groups with GVS (GVS group, n = 9) and without GVS intervention (non-GVS group, n = 7). In the experimental groups, we assessed vestibulo-ocular reflex (VOR) recovery before (baseline) and at 3, 7, and 14 days after surgical unilateral labyrinthectomy. In the GVS group, stimulation was applied for 30 min daily from postoperative days (PODs) 0–4 via electrodes inserted subcutaneously next to both bony labyrinths.

Results: Locomotion and VOR were significantly impaired in the non-GVS group compared to baseline. The mean VOR gain of the non-GVS group was attenuated to 0.23 at POD 3 and recovered continuously to the value of 0.54 at POD 14, but did not reach the baseline values at any frequency. GVS intervention significantly accelerated recovery of locomotion, as assessed by the amount of circling and total path length in the open field tasks compared to the non-GVS groups on PODs 3 (p < 0.001 in both amount of circling and total path length) and 7 (p < 0.01 in amount of circling and p < 0.001 in total path length, Mann–Whitney U-test). GVS also significantly improved VOR gain compared to the non-GVS groups at PODs 3 (p < 0.001), 7 (p < 0.001), and 14 (p < 0.001, independent t-tests) during sinusoidal rotations. In addition, the recovery of the phase responses and asymmetry of the VOR was significantly better in the GVS group than in the non-GVS group until 2 weeks after UVD (phase, p = 0.001; symmetry, p < 0.001 at POD 14).

Conclusion: Recoveries for UVD-induced locomotion and VOR deficits were accelerated by an early intervention with GVS, which implies that GVS has the potential to improve vestibular compensation in patients with acute unilateral vestibular failure.
The Effect of Repetitive Transcranial Magnetic Stimulation on Lower-Limb Motor Ability in Stroke Patients: A Systematic Review
Authors: Fan Huiliu , Song Yang , Cen Xuanzhen , Yu Peimin , Bíró István , Gu Yaodong
Published: September 2021

Repetitive transcranial magnetic stimulation (rTMS) is fundamental in inducing neuroplastic changes and promoting brain function restoration. Nevertheless, evidence based on the systematic assessment of the implication of rTMS in stroke patients is inadequate. This study aimed to evaluate the value of rTMS in the treatment of lower-limb motor dysfunction in stroke patients via gait characteristics. The electronic literature search was performed in ScienceDirect, Google Scholar, and PubMed databases using “repetitive transcranial magnetic stimulation,” “gait,” and “stroke” between 2000 and 2020. By screening all the identified studies, a total of 10 studies covering 257 stroke patients were included by matching the inclusion criteria, involving both rTMS with high (≥5 Hz) and low frequency (<5 Hz). Despite the limited study number and relatively high risk of bias, the results of this review primarily confirmed the enhancing effects of rTMS on the lower-limb motor ability (e.g., gait and balance) of stroke patients. In addition, 15- to 20-min course of rTMS for 2 to 3 weeks was found to be the most common setting, and 1 Hz and 10 Hz were the most commonly used low and high frequencies, respectively. These results might have significant clinical applications for patients with weakened lower-limb mobility after a stroke. Nevertheless, more rigorous studies in this field are much warranted.

Systematic Review Registration:https://inplasy.com/, identifier INPLASY202180079.
Medical Image Interpolation Using Recurrent Type-2 Fuzzy Neural Network
Authors: Tavoosi Jafar , Zhang Chunwei , Mohammadzadeh Ardashir , Mobayen Saleh , Mosavi Amir H.
Published: September 2021

Image interpolation is an essential process for image processing and computer graphics in wide applications to medical imaging. For image interpolation used in medical diagnosis, the two-dimensional (2D) to three-dimensional (3D) transformation can significantly reduce human error, leading to better decisions. This research proposes the type-2 fuzzy neural networks method which is a hybrid of the fuzzy logic and neural networks as well as recurrent type-2 fuzzy neural networks (RT2FNNs) for advancing a novel 2D to 3D strategy. The ability of the proposed methods in the approximation of the function for image interpolation is investigated. The results report that both proposed methods are reliable for medical diagnosis. However, the RT2FNN model outperforms the type-2 fuzzy neural networks model. The average squares error for the recurrent network and the typical network reported 0.016 and 0.025, respectively. On the other hand, the number of fuzzy rules for the recurrent network and the typical network reported 16 and 22, respectively.
Fiber Clustering Acceleration With a Modified Kmeans++ Algorithm Using Data Parallelism
Authors: Goicovich Isaac , Olivares Paulo , Román Claudio , Vázquez Andrea , Poupon Cyril , Mangin Jean-François , Guevara Pamela , Hernández Cecilia
Published: September 2021

Fiber clustering methods are typically used in brain research to study the organization of white matter bundles from large diffusion MRI tractography datasets. These methods enable exploratory bundle inspection using visualization and other methods that require identifying brain white matter structures in individuals or a population. Some applications, such as real-time visualization and inter-subject clustering, need fast and high-quality intra-subject clustering algorithms. This work proposes a parallel algorithm using a General Purpose Graphics Processing Unit (GPGPU) for fiber clustering based on the FFClust algorithm. The proposed GPGPU implementation exploits data parallelism using both multicore and GPU fine-grained parallelism present in commodity architectures, including current laptops and desktop computers. Our approach implements all FFClust steps in parallel, improving execution times in all of them. In addition, our parallel approach includes a parallel Kmeans++ algorithm implementation and defines a new variant of Kmeans++ to reduce the impact of choosing outliers as initial centroids. The results show that our approach provides clustering quality results very similar to FFClust, and it requires an execution time of 3.5 s for processing about a million fibers, achieving a speedup of 11.5 times compared to FFClust.
Age-Related Changes in the Cochlea and Vestibule: Shared Patterns and Processes
Authors: Paplou Vasiliki , Schubert Nick M. A. , Pyott Sonja J.
Published: September 2021

Both age-related hearing loss (ARHL) and age-related loss in vestibular function (ARVL) are prevalent conditions with deleterious consequences on the health and quality of life. Age-related changes in the inner ear are key contributors to both conditions. The auditory and vestibular systems rely on a shared sensory organ – the inner ear – and, like other sensory organs, the inner ear is susceptible to the effects of aging. Despite involvement of the same sensory structure, ARHL and ARVL are often considered separately. Insight essential for the development of improved diagnostics and treatments for both ARHL and ARVL can be gained by careful examination of their shared and unique pathophysiology in the auditory and vestibular end organs of the inner ear. To this end, this review begins by comparing the prevalence patterns of ARHL and ARVL. Next, the normal and age-related changes in the structure and function of the auditory and vestibular end organs are compared. Then, the contributions of various molecular mechanisms, notably inflammaging, oxidative stress, and genetic factors, are evaluated as possible common culprits that interrelate pathophysiology in the cochlea and vestibular end organs as part of ARHL and ARVL. A careful comparison of these changes reveals that the patterns of pathophysiology show similarities but also differences both between the cochlea and vestibular end organs and among the vestibular end organs. Future progress will depend on the development and application of new research strategies and the integrated investigation of ARHL and ARVL using both clinical and animal models.
Neurofilament Light Chain and Intermediate HTT Alleles as Combined Biomarkers in Italian ALS Patients
Authors: Ingannato Assunta , Bagnoli Silvia , Mazzeo Salvatore , Bessi Valentina , Matà Sabrina , Del Mastio Monica , Lombardi Gemma , Ferrari Camilla , Sorbi Sandro , Nacmias Benedetta
Published: September 2021

Objective

To study the possible implication of the two biomarkers, intermediate alleles (IAs) of the Huntingtin (HTT) gene and neurofilament light chain (NfL) levels in plasma, in amyotrophic lateral sclerosis (ALS) patients.

Methods

We analyzed IAs in a cohort of 106 Italian ALS patients and measured the plasma NfL levels in 20% of the patients of the cohort. We correlated the two biomarkers with clinical phenotypes.

Results

Intermediate alleles were present in 7.5% of the patients of our cohort, a frequency higher than that reported in general population. Plasma NfL levels increased with age at onset (p < 0.05). Patients with bulbar onset (BO) had higher plasma NfL concentration (CI −0.61 to −0.06, p = 0.02) and a later age at onset of the disease (CI −24.78 to −4.93, p = 0.006) with respect to the spinal onset (SO) form. Additionally, two of the patients, with IAs and plasma NfL concentration lower with respect to normal alleles’ carriers, presented an age at onset higher than the mean of the entire cohort.

Conclusion

According to our findings, plasma NfL and IAs of HTT gene may represent potential biomarkers in ALS, providing evidence of a possible implication in clinical phenotype.
Curcumin Exerts Antinociceptive Effects in Cancer-Induced Bone Pain via an Endogenous Opioid Mechanism
Authors: Zhao Guanghai , Shi Yongqiang , Gong Chaoyang , Liu Taicong , Nan Wei , Ma Lin , Wu Zuolong , Da Chaoming , Zhou Kaisheng , Zhang Haihong
Published: September 2021

Cancer pain is one of the main complications in advanced cancer patients, and its management is still challenging. Therefore, there is an urgent need to develop novel pharmacotherapy for cancer pain. Several natural products have attracted the interest of researchers. In previous studies, curcumin has proved to exhibit antitumor, antiviral, antioxidant, anti-inflammatory, and analgesic effects. However, the analgesic mechanism of curcumin has not been elucidated. Thus, in this study, we aimed to elucidate the antinociceptive potency and analgesic mechanism of curcumin in cancer-induced bone pain. Our results showed that consecutive curcumin treatment (30, 60, 120 mg/kg, i.p., twice daily for 11 days) produced significant analgesic activity, but had no effect on the progress of the bone cancer pain. Notably, pretreatment with naloxone, a non-selective opioid receptor antagonist, markedly reversed the antinociceptive effect induced by curcumin. Moreover, in primary cultured rat dorsal root ganglion (DRG) neurons, curcumin significantly up-regulated the expression of proopiomelanocortin (Pomc) and promoted the release of β-endorphin and enkephalin. Furthermore, pretreatment with the antiserum of β-endorphin or enkephalin markedly attenuated curcumin-induced analgesia in cancer-induced bone pain. Our present study, for the first time, showed that curcumin attenuates cancer-induced bone pain. The results also suggested that stimulation of expression of DRG neurons β-endorphin and enkephalin mediates the antinociceptive effect of curcumin in pain hypersensitivity conditions.
Early Life Adversity and Polygenic Risk for High Fasting Insulin Are Associated With Childhood Impulsivity
Authors: Batra Aashita , Chen Lawrence M. , Wang Zihan , Parent Carine , Pokhvisneva Irina , Patel Sachin , Levitan Robert D. , Meaney Michael J. , Silveira Patricia Pelufo
Published: September 2021

While the co-morbidity between metabolic and psychiatric behaviors is well-established, the mechanisms are poorly understood, and exposure to early life adversity (ELA) is a common developmental risk factor. ELA is associated with altered insulin sensitivity and poor behavioral inhibition throughout life, which seems to contribute to the development of metabolic and psychiatric disturbances in the long term. We hypothesize that a genetic background associated with higher fasting insulin interacts with ELA to influence the development of executive functions (e.g., impulsivity in young children). We calculated the polygenic risk scores (PRSs) from the genome-wide association study (GWAS) of fasting insulin at different thresholds and identified the subset of single nucleotide polymorphisms (SNPs) that best predicted peripheral insulin levels in children from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort [N = 467; pt– initial = 0.24 (10,296 SNPs), pt– refined = 0.05 (57 SNPs)]. We then calculated the refined PRS (rPRS) for fasting insulin at this specific threshold in the children from the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) cohort and investigated its interaction effect with adversity on an impulsivity task applied at 36 months. We found a significant effect of interaction between fasting insulin rPRS and adversity exposure predicting impulsivity measured by the Snack Delay Task at 36 months [β = −0.329, p = 0.024], such that higher PRS [β = −0.551, p = 0.009] was linked to more impulsivity in individuals exposed to more adversity. Enrichment analysis (MetaCoreTM) of the SNPs that compose the fasting insulin rPRS at this threshold was significant for certain nervous system development processes including dopamine D2 receptor signaling. Additional enrichment analysis (FUMA) of the genes mapped from the SNPs in the fasting insulin rPRS showed enrichment with the accelerated cognitive decline GWAS. Therefore, the genetic background associated with risk for adult higher fasting insulin moderates the impact of early adversity on childhood impulsivity.
Aberrant Intraregional Brain Activity and Functional Connectivity in Patients With Diarrhea-Predominant Irritable Bowel Syndrome
Authors: Chen Xiao-Fei , Guo Yun , Lu Xing-Qi , Qi Le , Xu Kuang-Hui , Chen Yong , Li Guo-Xiong , Ding Jian-Ping , Li Jie
Published: September 2021

Background and Purpose

The appearance and aggravation of diarrhea-predominant irritable bowel syndrome (IBS-D) have proven to be closely related to psychosocial factors. We aimed to measure altered spontaneous brain activity and functional connectivity (FC) in patients with IBS-D using resting-state functional magnetic resonance imaging (RS-fMRI) and to analyze the relationship between these parameters and emotional symptoms.

Methods

Thirty-six adult IBS-D patients and thirty-six demographic-matched healthy controls (HCs) underwent RS-fMRI scans. After processing RS-fMRI data, the values of the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) of the two groups were compared. The abnormal regions were selected as the regions of interest to compare whole-brain seed-based FC between the groups. The relationships between RS-fMRI data and mood and gastrointestinal symptoms were analyzed using correlation and mediation analyses.

Results

Compared with HCs, IBS-D patients showed increased ALFF in the right cerebellum posterior lobe, the right lingual gyrus/calcarine, the right postcentral gyrus, the right superior frontal gyrus (SFG), and middle frontal gyrus (MFG), with decreased ALFF in the right inferior parietal lobule, the right striatum, the right anterior cingulated cortex, the right insula, the right hippocampus, the right thalamus, the right midbrain, and the left precuneus. IBS-D patients showed increased ReHo in the bilateral lingual gyrus/calcarine, the bilateral SFG, the right MFG, and the right postcentral gyrus, with decreased ReHo in the orbital part of the left inferior frontal gyrus and the right supplementary motor area. Patients showed enhanced FC between the left precuneus and the bilateral orbitofrontal cortex (OFC). There was a positive correlation between increased ALFF values in the right midbrain and anxiety-depression symptoms in IBS-D patients, and the mediating effect of gastrointestinal symptoms indirectly caused this correlation.

Conclusion

IBS-D patients had dysregulated spontaneous activity and FC in regions related to pain regulation and emotional arousal involved in prefrontal–limbic–midbrain circuit and somatosensory processing. The development of mood disorders in IBS-D patients may be partly related to the dysfunction of components in the dopamine pathway (especially the midbrain, OFC) due to visceral pain.
Amyloid-β and α-Synuclein Immunotherapy: From Experimental Studies to Clinical Trials
Authors: Nimmo Jacqui Taryn , Kelly Louise , Verma Ajay , Carare Roxana O. , Nicoll James A. R. , Dodart Jean-Cosme
Published: September 2021

Alzheimer’s disease and Lewy body diseases are the most common causes of neurodegeneration and dementia. Amyloid-beta (Aβ) and alpha-synuclein (αSyn) are two key proteins involved in the pathogenesis of these neurodegenerative diseases. Immunotherapy aims to reduce the harmful effects of protein accumulation by neutralising toxic species and facilitating their removal. The results of the first immunisation trial against Aβ led to a small percentage of meningoencephalitis cases which revolutionised vaccine design, causing a shift in the field of immunotherapy from active to passive immunisation. While the vast majority of immunotherapies have been developed for Aβ and tested in Alzheimer’s disease, the field has progressed to targeting other proteins including αSyn. Despite showing some remarkable results in animal models, immunotherapies have largely failed final stages of clinical trials to date, with the exception of Aducanumab recently licenced in the US by the FDA. Neuropathological findings translate quite effectively from animal models to human trials, however, cognitive and functional outcome measures do not. The apparent lack of translation of experimental studies to clinical trials suggests that we are not obtaining a full representation of the effects of immunotherapies from animal studies. Here we provide a background understanding to the key concepts and challenges involved in therapeutic design. This review further provides a comprehensive comparison between experimental and clinical studies in Aβ and αSyn immunotherapy and aims to determine the possible reasons for the disconnection in their outcomes.
Dysregulation of Principal Circulating miRNAs in Non-human Primates Following Ischemic Stroke
Authors: Chen Jian , Zhao Haiping , Huang Yuyou , Li Yuqian , Fan Junfen , Wang Rongliang , Han Ziping , Yang Zhenhong , Wu Longfei , Wu Di , Luo Yumin , Ji Xunming
Published: September 2021

Despite the recent interest in plasma microRNA (miRNA) biomarkers in acute ischemic stroke patients, there is limited knowledge about the miRNAs directly related to stroke itself due to the multiple complications in patients, which has hindered the research progress of biomarkers and therapeutic targets of ischemic stroke. Therefore, in this study, we compared the differentially expressed miRNA profiles in the plasma of three rhesus monkeys pre- and post-cerebral ischemia. After cerebral ischemia, Rfam sequence category revealed increased ribosomic RNA (rRNA) and decreased transfer RNAs (tRNAs) in plasma. Of the 2049 miRNAs detected after cerebral ischemia, 36 were upregulated, and 76 were downregulated (fold change ≥2.0, P < 0.05). For example, mml-miR-191-5p, miR-421, miR-409-5p, and let-7g-5p were found to be significantly overexpressed, whereas mml-miR-128a-5p_R − 2, miR-431_R − 1, and let-7g-3p_1ss22CT were significantly downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these differentially expressed miRNAs were implicated in the regulation of ubiquitin-mediated proteolysis and signaling pathways in cancer, glioma, chronic myeloid leukemia, and chemokine signaling. miRNA clustering analysis showed that mml-let-7g-5p and let-7g-3p_1ss22CT, which share three target genes [RB1-inducible coiled-coil 1 (RB1CC1), G-protein subunit γ 5 (GNG5), and chemokine (C-X-C motif) receptor 4 (CXCR4)], belong to one cluster, were altered in opposite directions following ischemia. These data suggest that circulating mml-let-7g may serve as a therapeutic target for ischemic stroke.
Weak Vestibular Response in Persistent Developmental Stuttering
Authors: Gattie Max , Lieven Elena V. M. , Kluk Karolina
Published: September 2021

Vibrational energy created at the larynx during speech will deflect vestibular mechanoreceptors in humans (Todd et al., 2008; Curthoys, 2017; Curthoys et al., 2019). Vestibular-evoked myogenic potential (VEMP), an indirect measure of vestibular function, was assessed in 15 participants who stutter, with a non-stutter control group of 15 participants paired on age and sex. VEMP amplitude was 8.5 dB smaller in the stutter group than the non-stutter group (p = 0.035, 95% CI [−0.9, −16.1], t = −2.1, d = −0.8, conditional R2 = 0.88). The finding is subclinical as regards gravitoinertial function, and is interpreted with regard to speech-motor function in stuttering. There is overlap between brain areas receiving vestibular innervation, and brain areas identified as important in studies of persistent developmental stuttering. These include the auditory brainstem, cerebellar vermis, and the temporo-parietal junction. The finding supports the disruptive rhythm hypothesis (Howell et al., 1983; Howell, 2004) in which sensory inputs additional to own speech audition are fluency-enhancing when they coordinate with ongoing speech.