bluuebunny/crossref_metadata_2025 huggingface dataset:
EEG-Based Driving Fatigue Detection Using a Two-Level Learning Hierarchy Radial Basis Function
Authors: Ren Ziwu , Li Rihui , Chen Bin , Zhang Hongmiao , Ma Yuliang , Wang Chushan , Lin Ying , Zhang Yingchun
Published: February 2021

Electroencephalography (EEG)-based driving fatigue detection has gained increasing attention recently due to the non-invasive, low-cost, and potable nature of the EEG technology, but it is still challenging to extract informative features from noisy EEG signals for driving fatigue detection. Radial basis function (RBF) neural network has drawn lots of attention as a promising classifier due to its linear-in-the-parameters network structure, strong non-linear approximation ability, and desired generalization property. The RBF network performance heavily relies on network parameters such as the number of the hidden nodes, number of the center vectors, width, and output weights. However, global optimization methods that directly optimize all the network parameters often result in high evaluation cost and slow convergence. To enhance the accuracy and efficiency of EEG-based driving fatigue detection model, this study aims to develop a two-level learning hierarchy RBF network (RBF-TLLH) which allows for global optimization of the key network parameters. Experimental EEG data were collected, at both fatigue and alert states, from six healthy participants in a simulated driving environment. Principal component analysis was first utilized to extract features from EEG signals, and the proposed RBF-TLLH was then employed for driving status (fatigue vs. alert) classification. The results demonstrated that the proposed RBF-TLLH approach achieved a better classification performance (mean accuracy: 92.71%; area under the receiver operating curve: 0.9199) compared to other widely used artificial neural networks. Moreover, only three core parameters need to be determined using the training datasets in the proposed RBF-TLLH classifier, which increases its reliability and applicability. The findings demonstrate that the proposed RBF-TLLH approach can be used as a promising framework for reliable EEG-based driving fatigue detection.
NGN2 mmRNA-Based Transcriptional Programming in Microfluidic Guides hiPSCs Toward Neural Fate With Multiple Identities
Authors: Tolomeo Anna Maria , Laterza Cecilia , Grespan Eleonora , Michielin Federica , Canals Isaac , Kokaia Zaal , Muraca Maurizio , Gagliano Onelia , Elvassore Nicola
Published: February 2021

Recent advancements in cell engineering have succeeded in manipulating cell identity with the targeted overexpression of specific cell fate determining transcription factors in a process named transcriptional programming. Neurogenin2 (NGN2) is sufficient to instruct pluripotent stem cells (PSCs) to acquire a neuronal identity when delivered with an integrating system, which arises some safety concerns for clinical applications. A non-integrating system based on modified messenger RNA (mmRNA) delivery method, represents a valuable alternative to lentiviral-based approaches. The ability of NGN2 mmRNA to instruct PSC fate change has not been thoroughly investigated yet. Here we aimed at understanding whether the use of an NGN2 mmRNA-based approach combined with a miniaturized system, which allows a higher transfection efficiency in a cost-effective system, is able to drive human induced PSCs (hiPSCs) toward the neuronal lineage. We show that NGN2 mRNA alone is able to induce cell fate conversion. Surprisingly, the outcome cell population accounts for multiple phenotypes along the neural development trajectory. We found that this mixed population is mainly constituted by neural stem cells (45% ± 18 PAX6 positive cells) and neurons (38% ± 8 βIIITUBULIN positive cells) only when NGN2 is delivered as mmRNA. On the other hand, when the delivery system is lentiviral-based, both providing a constant expression of NGN2 or only a transient pulse, the outcome differentiated population is formed by a clear majority of neurons (88% ± 1 βIIITUBULIN positive cells). Altogether, our data confirm the ability of NGN2 to induce neuralization in hiPSCs and opens a new point of view in respect to the delivery system method when it comes to transcriptional programming applications.
Transcranial Doppler Ultrasonographic Evaluation of Cerebrovascular Abnormalities in Children With Acute Bacterial Meningitis
Authors: Fonseca Yudy , Tshimanga Taty , Ray Stephen , Malhotra Helen , Pongo Jean , Bodi Mabiala Joseph , Gushu Montfort Bernard , Phiri Tusekile , Chikaonda Bertha Mekiseni , Ambitapio Musungufu Davin , Uchama Mananu , O'Brien Nicole Fortier
Published: February 2021

Introduction: Bacterial meningitis (BM) is a global public health concern that results in significant morbidity and mortality. Cerebral arterial narrowing contributes to stroke in BM and may be amenable to intervention. However, it is difficult to diagnose in resource-limited settings where the disease is common.

Methods: This was a prospective observational study from September 2015 to December 2019 in sub-Saharan Africa. Children 1 month−18 years of age with neutrophilic pleocytosis or a bacterial pathogen identified in the cerebrospinal fluid were enrolled. Transcranial Doppler ultrasound (TCD) of the middle cerebral arteries was performed daily with the aim to identify flow abnormalities consistent with vascular narrowing.

Results: Forty-seven patients were analyzed. The majority had Streptococcus pneumoniae (36%) or Neisseria meningitides (36%) meningitis. Admission TCD was normal in 10 (21%). High flow with a normal pulsatility index (PI) was seen in 20 (43%) and high flow with a low PI was identified in 7 (15%). Ten (21%) had low flow. All children with a normal TCD had a good outcome. Patients with a high-risk TCD flow pattern (high flow/low PI or low flow) were more likely to have a poor outcome (82 vs. 38%, p = 0.001).

Conclusions: Abnormal TCD flow patterns were common in children with BM and identified those at high risk of poor neurological outcome.
Cyclosporine-A-Induced Intracranial Thrombotic Complications: Systematic Review and Cases Report
Authors: Song Si-ying , Wang Zhong-ao , Ding Yu-chuan , Ji Xun-ming , Meng Ran
Published: February 2021

This study reported two cases of intracranial thrombotic events of aplastic anemia (AA) under therapy with cyclosporine-A (CsA) and reviewed both drug-induced cerebral venous thrombosis (CVT) and CsA-related thrombotic events systematically. We searched PubMed Central (PMC) and EMBASE up to Sep 2019 for publications on drug-induced CVT and Cs-A-induced thrombotic events. Medical subject headings and Emtree headings were used with the following keywords: “cyclosporine-A” and “cerebral venous thrombosis OR cerebral vein thrombosis” and “stroke OR Brain Ischemia OR Brain Infarction OR cerebral infarction OR intracerebral hemorrhage OR intracranial hemorrhage.” We found that CsA might be a significant risk factor in inducing not only CVT but also cerebral arterial thrombosis in patients with AA.
Abnormal Default-Mode Network Homogeneity in Patients With Mild Cognitive Impairment in Chinese Communities
Authors: Cao Yuping , Yang Huan , Zhou Zhenhe , Cheng Zaohuo , Zhao Xingfu
Published: February 2021

Background and Objective: Current evidence suggests that abnormalities within the default-mode network (DMN) play a key role in the broad-scale cognitive problems that characterize mild cognitive impairment (MCI). However, little is known about the alterations of DMN network homogeneity (NH) in MCI.

Methods: Resting-state functional magnetic resonance imaging scans (rs-fMRI) were collected from 38 MCI patients and 69 healthy controls matched for age, gender, and education. NH approach was employed to analyze the imaging dataset. Cognitive performance was measured with the Chinese version of Alzheimer's disease assessment scale-Cognitive subscale (ADAS-Cog).

Results: Two groups have no significant differences between demographic factors. And mean ADAS-Cog score in MCI was 12.02. MCI patients had significantly lower NH values than controls in the right anterior cingulate cortex and significantly higher NH values in the ventral medial prefrontal cortex(vmPFC) than those in healthy controls. No significant correlations were found between abnormal NH values and ADAS-Cog in the patients.

Conclusions: These findings provide further evidence that abnormal NH of the DMN exists in MCI, and highlight the significance of DMN in the pathophysiology of cognitive problems occurring in MCI.
Distinct Vestibular Evoked Myogenic Potentials in Patients With Parkinson Disease and Progressive Supranuclear Palsy
Authors: Carpinelli Sandra , Valko Philipp O. , Waldvogel Daniel , Buffone Elena , Baumann Christian R. , Straumann Dominik , Werth Esther , Bockisch Christopher J. , Weber Konrad P. , Valko Yulia
Published: February 2021

Background: Early brainstem neurodegeneration is common in Parkinson's disease (PD) and progressive supranuclear palsy (PSP). While previous work showed abnormalities in vestibular evoked myogenic potentials (VEMPs) in patients with either disorder as compared to healthy humans, it remains unclear whether ocular and cervical VEMPs differ between PD and PSP patients.

Methods: We prospectively included 12 PD and 11 PSP patients, performed ocular and cervical VEMPs, and calculated specific VEMP scores (0 = normal, 12 = most pathological) based on latencies, amplitude, and absent responses. In addition, we assessed disease duration, presence of imbalance, motor asymmetry, and motor disability using the Movement Disorder Society Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III). Moreover, we ascertained various sleep parameters by video-polysomnography.

Results: PSP and PD patients had similar oVEMP scores (6 [3–6] vs. 3 [1.3–6], p = 0.06), but PSP patients had higher cVEMP scores (3 [0–6] vs. 0 [0–2.8], p = 0.03) and total VEMP scores (9 [5–12] vs. 4 [2–7.5], p = 0.01). Moreover, total VEMP scores >10 were only observed in PSP patients (45%, p = 0.01). MDS-UPDRS III correlated with cVEMP scores (rho = 0.77, p = 0.01) in PSP, but not in PD. In PD, but not in PSP, polysomnographic markers of disturbed sleep, including decreased rapid eye movement sleep, showed significant correlations with VEMP scores.

Conclusions: Our findings suggest that central vestibular pathways are more severely damaged in PSP than in PD, as indicated by higher cervical and total VEMP scores in PSP than PD in a between-groups analysis. Meaningful correlations between VEMPs and motor and non-motor symptoms further encourage its use in neurodegenerative Parkinsonian syndromes.
Association of Genetic Variants With Migraine Subclassified by Clinical Symptoms in Adult Females
Authors: Kossowsky Joe , Schuler Megan S. , Giulianini Franco , Berde Charles B. , Reis Ben , Ridker Paul M , Buring Julie E. , Kurth Tobias , Chasman Daniel I.
Published: February 2021

Migraine is heritable and formally diagnosed by structured criteria that require presence of some but not all possible migraine symptoms which include aura, several distinct manifestations of pain, nausea/vomiting, and sensitivity to light or sound. The most recent genome-wide genetic association study (GWAS) for migraine identified 38 loci. We investigated whether 46 single-nucleotide polymorphisms (SNPs), i.e., genetic variants, at these loci may have especially pronounced, i.e., selective, association with migraine presenting with individual symptoms compared to absence of migraine. Selective genetic associations of SNPs were evaluated through a likelihood framework in the Women's Genome Health Study (WGHS), a population-based cohort of middle-aged women including 3,003 experiencing migraine and 18,108 not experiencing migraine, all with genetic information. SNPs at 12 loci displayed significant selective association for migraine subclassified by specific symptoms, among which six selective associations are novel. Symptoms showing selective association include aura, nausea/vomiting, photophobia, and phonophobia. The selective associations were consistent whether the women met all formal criteria for diagnostic for migraine or lacked one of the diagnostic criteria, formally termed probable migraine. Subsequently, we performed latent class analysis of migraine diagnostic symptoms among 69,861 women experiencing migraine from the WGHS recruitment sample to assess whether there were clusters of specific symptoms that might also have a genetic basis. However, no globally robust latent migraine substructures of diagnostic symptoms were observed nor were there selective genetic associations with specific combinations of symptoms revealed among weakly supported latent classes. The findings extend previously reported selective genetic associations with migraine diagnostic symptoms while supporting models for shared genetic susceptibility across all qualifying migraine at many loci.
Early Axonal Dysfunction of the Peripheral Nervous System Influences Disease Progression of ALS: Evidence From Clinical Neuroelectrophysiology
Authors: Yu Huiyan , Chen Lu , Zhang Shuo , He Jing , Fan Dongsheng
Published: February 2021

Objective: To assess the prognostic value of the decrement in compound muscle action potential amplitude within 12 months of symptom onset (CMAP-12 amplitude) for the survival of patients with amyotrophic lateral sclerosis (ALS).

Methods: Patients were stratified into 4 groups according to the decrement of the CMAP-12 amplitudes: normal (≥the lower limit of normal, LLN), mild (<LLN but ≥50% of LLN), moderate (<50% but ≥30% of LLN) and severe (<30% of LLN). All patients were followed up every 3 months. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazards regression.

Results: A total of 149 patients were included in the analysis [90 males (60.4%); mean age at onset, 50.7 years]. The decrement of CMAP-12 amplitudes was normal in 24.2% of patients, mild in 22.1%, moderate in 15.4% and severe in 38.3%. Kaplan–Meier analysis showed there was a significant difference in the overall survival across the 4 groups (p < 0.05). Further pairwise comparisons identified significant differences in survival between the normal vs. the moderate group (p < 0.05) and the normal vs. the severe group (p < 0.01). There was a significant inverse correlation between the CMAP-12 amplitude and overall survival. Compared to that in the normal group, survival in the moderately and severely decreased groups was significantly shorter (HR 3.394, 95% CI 1.292–8.917, p = 0.013; and HR 4.732, 95% CI 2.032–11.017; p = 0.000, respectively).

Conclusions: Our results suggest that CMAP-12 amplitude could be a prognostic indicator of disease progression in ALS. More importantly, our findings provide clinical evidence for the viewpoint that early axonal dysfunction of the peripheral nervous system accelerates disease progression of ALS.
Association of Static Posturography With Severity of White Matter Hyperintensities
Authors: Liu Bin , Zhao Guifeng , Jin Ling , Shi Jingping
Published: February 2021

Background: Impaired gait and balance are associated with severity of leukoaraiosis. Evaluation of balance is based on neurological examination using Romberg's test with bipedal standing, assessment scale, and posturographic parameters. The goal of this study was to determine the relationship between static equilibrium and grades of white matter hyperintensities (WMHs) using static posturography as a quantitative technical method.

Method: One hundred and eighteen (118) patients with lacunar infarct were recruited and assessed on MRI with Fazekas's grading scale into four groups. On admission, age, gender, height, weight, Berg Balance Scale (BBS), mini-mental state examination (MMSE), and static posturography parameters were recorded, and their correlations with WMHs were determined.

Results: Age was significantly and positively correlated with severity of WMHs (r = 0.39, p < 0.05). WMH score was negatively correlated with BBS score (r = −0.65, p < 0.05) and MMSE score (r = −0.79, p < 0.05). There was a significant positive correlation between track length anteroposterior (AP, with eyes closed) and severity of WMHs (r = 0.70, p < 0.05). Partial correlation analysis and multiple logistic regression analysis indicated that track length AP with eyes closed, was a predictor for the severity of WMHs (p< 0.05).

Conclusion: The severity of WHMs is associated with age, cognitive decline, and impairment in balance. Posturography parameter in track length in AP direction with eyes closed in relation to cognition and balance, may be a potential marker for disease progression in WMHs.
Facilitative Effects of Transcranial Direct Current Stimulation on Semantic Memory Examined by Text-Mining Analysis in Patients With Schizophrenia
Authors: Sumiyoshi Chika , Narita Zui , Inagawa Takuma , Yamada Yuji , Sueyoshi Kazuki , Hasegawa Yumi , Shirama Aya , Hashimoto Ryota , Sumiyoshi Tomiki
Published: February 2021

Background: Beneficial effects of transcranial direct current stimulation (tDCS) are relevant to cognition and functional capacity, in addition to psychiatric symptoms in patients with schizophrenia. However, whether tDCS would improve higher-order cognition, e.g., semantic memory organization, has remained unclear. Recently, text-mining analyses have been shown to reveal semantic memory. The purpose of the current study was to determine whether tDCS would improve semantic memory, as evaluated by text-mining analyses of category fluency data, in patients with schizophrenia.

Methods: Twenty-eight patients entered the study. Cognitive assessment including the category fluency task was conducted at baseline (before tDCS treatment) and 1 month after t administration of tDCS (2 mA × 20 min, twice per day) for 5 days, according to our previous study. The category fluency data were also obtained from 335 healthy control subjects. The verbal outputs (i.e., animal names) from the category fluency task were submitted to singular valued decomposition (SVD) analysis. Semantic memory structures were estimated by calculating inter-item cosines (i.e., similarities) among animal names frequently produced in the category fluency task. Data were analyzed longitudinally and cross-sectionally to compare the semantic structure within the patient group (i.e., baseline vs. follow-up) and between groups (patients vs. healthy controls). In the former, semantic associations for frequent items were compared in the form of cosine profiles, while in the latter, the difference in the magnitude of the correlations for inter-item cosines between healthy controls and patients (baseline, follow-up) was examined.

Results: Cosine profiles in the patient group became more cluster-based (i.e., pet, carnivores, and herbivores) at follow-up compared to those at baseline, yielding higher cosines within subcategories. The correlational coefficient of inter-item cosines between healthy controls and patients was significantly greater at follow-up compared to baseline; semantic associations in patients approached the normality status after multi-session tDCS.

Conclusions: To our knowledge, this is the first study to demonstrate the facilitative effect of tDCS on semantic memory organization in patients with schizophrenia. Text-mining analysis was indicated to effectively evaluate semantic memory structures in patients with psychiatric disorders.
The Effect on the Kidney in Patients With Anti-N-methyl D-aspartate Receptor Antibody Encephalitis
Authors: Liu Lizhi , Gu Meifeng , Liu Jia , Liu Qing , Xu Xiaofeng , Fan Rong , Peng Fuhua , Jiang Ying
Published: February 2021

Objectives: The function of the N-methyl-D-aspartate receptor (NMDAR) in the kidney has been studied. However, the effect on the kidney from anti-NAMDAR antibody encephalitis has not been investigated thus far.

Methods: Case data were collected from 82 patients with anti-NMDAR antibody encephalitis and 166 age- and sex-matched healthy controls (HCs). Clinical characteristics, urinalysis [including urine pH and urine specific gravity (SG)], serum creatinine (Scr), and estimated glomerular filtration rate (eGFR) based on Cr levels were evaluated.

Results: At initial admission, urine pH levels and urine SG levels in anti-NMDAR antibody encephalitis patients were significantly higher and lower, respectively, than HCs (both p < 0.001). There were no significant differences in Scr and eGFR between anti-NMDAR antibody encephalitis patients and HCs. Urine pH levels in patients with anti-NMDAR antibody <1:32 were significantly lower than those in patients with anti-NMDAR antibody ≥1:32 (p = 0.029). Urine pH levels were significantly lower (p = 0.004) and urine SG levels were significantly higher (p = 0.027) in a follow-up evaluation 3 months after treatment.

Conclusions: The changes in urinalysis occur in patients with anti-NMDAR antibody encephalitis. The pathophysiological changes in anti-NMDAR antibody encephalitis were not limited to the CNS.
Effects of Low-Frequency Repetitive Transcranial Magnetic Stimulation of the Bilateral Parietal Cortex in Patients With Tourette Syndrome
Authors: Fu Mengmeng , Wei Hua , Meng Xianghong , Chen Hai , Shang Baoxiang , Chen Fuyong , Huang Zhaoyang , Sun Ying , Wang Yuping
Published: February 2021

Background: Traditional medical treatments are not effective for some patients with Tourette syndrome (TS). According to the literature, repetitive transcranial magnetic stimulation (rTMS) may be effective for the treatment of TS; however, different targets show different results.

Objective: To assess the efficacy and safety of low-frequency rTMS in patients with TS, with the bilateral parietal cortex as the target.

Methods: Thirty patients with TS were divided into two groups: active and sham groups. The active group was subjected to 0.5-Hz rTMS at 90% of resting motor threshold (RMT) with 1,200 stimuli/day/side, whereas the sham group was subjected to 0.5-Hz rTMS at 10% of RMT with 1,200 stimuli/day/side with changes in the coil direction. Both groups were bilaterally stimulated over the parietal cortex (P3 and P4 electrode sites) for 10 consecutive days. The symptoms of tics and premonitory urges were evaluated using the Yale Global Tic Severity Scale (YGTSS), Modified Scoring Method for the Rush Video-based Tic Rating Scale (MRVBTS), and Premonitory Urge for Tics Scale (PUTS) scores at baseline, the end of the 10-day treatment, 1 week after treatment, and 1 month after treatment.

Results: At the end of the 10-day treatment, the YGTSS total, YGTSS motor tic, YGTSS phonic tic, MRVBTS, and PUTS scores in the active group significantly improved and improvements were maintained for at least 1 month.

Conclusions: Low-frequency bilateral rTMS of the parietal cortex can markedly alleviate motor tics, phonic tics, and premonitory urges in patients with TS.
Patterns and Predictors of Cognitive Function Among Virally Suppressed Women With HIV
Authors: Dastgheyb Raha M. , Buchholz Alison S. , Fitzgerald Kathryn C. , Xu Yanxun , Williams Dionna W. , Springer Gayle , Anastos Kathryn , Gustafson Deborah R. , Spence Amanda B. , Adimora Adaora A. , Waldrop Drenna , Vance David E. , Milam Joel , Bolivar Hector , Weber Kathleen M. , Haughey Norman J. , Maki Pauline M. , Rubin Leah H.
Published: February 2021

Cognitive impairment remains frequent and heterogeneous in presentation and severity among virally suppressed (VS) women with HIV (WWH). We identified cognitive profiles among 929 VS-WWH and 717 HIV-uninfected women from 11 Women's Interagency HIV Study sites at their first neuropsychological (NP) test battery completion comprised of: Hopkins Verbal Learning Test-Revised, Trail Making, Symbol Digit Modalities, Grooved Pegboard, Stroop, Letter/Animal Fluency, and Letter-Number Sequencing. Using 17 NP performance metrics (T-scores), we used Kohonen self-organizing maps to identify patterns of high-dimensional data by mapping participants to similar nodes based on T-scores and clustering those nodes. Among VS-WWH, nine clusters were identified (entropy = 0.990) with four having average T-scores ≥45 for all metrics and thus combined into an “unimpaired” profile (n = 311). Impaired profiles consisted of weaknesses in: (1) sequencing (Profile-1; n = 129), (2) speed (Profile-2; n = 144), (3) learning + recognition (Profile-3; n = 137), (4) learning + memory (Profile-4; n = 86), and (5) learning + processing speed + attention + executive function (Profile-5; n = 122). Sociodemographic, behavioral, and clinical variables differentiated profile membership using Random Forest models. The top 10 variables distinguishing the combined impaired vs. unimpaired profiles were: clinic site, age, education, race, illicit substance use, current and nadir CD4 count, duration of effective antiretrovirals, and protease inhibitor use. Additional variables differentiating each impaired from unimpaired profile included: depression, stress-symptoms, income (Profile-1); depression, employment (Profile 2); depression, integrase inhibitor (INSTI) use (Profile-3); employment, INSTI use, income, atazanavir use, non-ART medications with anticholinergic properties (Profile-4); and marijuana use (Profile-5). Findings highlight consideration of NP profile heterogeneity and potential modifiable factors contributing to impaired profiles.
Myocardial Iron Overload in an Experimental Model of Sudden Unexpected Death in Epilepsy
Authors: Akyuz Enes , Doganyigit Zuleyha , Eroglu Ece , Moscovicz Franco , Merelli Amalia , Lazarowski Alberto , Auzmendi Jerónimo
Published: February 2021

Uncontrolled repetitive generalized tonic-clonic seizures (GTCS) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). GTCS can be observed in models such as Pentylenetetrazole kindling (PTZ-K) or pilocarpine-induced Status Epilepticus (SE-P), which share similar alterations in cardiac function, with a high risk of SUDEP. Terminal cardiac arrhythmia in SUDEP can develop as a result of a high rate of hypoxic stress-induced by convulsions with excessive sympathetic overstimulation that triggers a neurocardiogenic injury, recently defined as “Epileptic Heart” and characterized by heart rhythm disturbances, such as bradycardia and lengthening of the QT interval. Recently, an iron overload-dependent form of non-apoptotic cell death called ferroptosis was described at the brain level in both the PTZ-K and SE-P experimental models. However, seizure-related cardiac ferroptosis has not yet been reported. Iron overload cardiomyopathy (IOC) results from the accumulation of iron in the myocardium, with high production of reactive oxygen species (ROS), lipid peroxidation, and accumulation of hemosiderin as the final biomarker related to cardiomyocyte ferroptosis. Iron overload cardiomyopathy is the leading cause of death in patients with iron overload secondary to chronic blood transfusion therapy; it is also described in hereditary hemochromatosis. GTCS, through repeated hypoxic stress, can increase ROS production in the heart and cause cardiomyocyte ferroptosis. We hypothesized that iron accumulation in the “Epileptic Heart” could be associated with a terminal cardiac arrhythmia described in the IOC and the development of state-potentially in the development of SUDEP. Using the aforementioned PTZ-K and SE-P experimental models, after SUDEP-related repetitive GTCS, we observed an increase in the cardiac expression of hypoxic inducible factor 1α, indicating hypoxic-ischemic damage, and both necrotic cells and hemorrhagic areas were related to the possible hemosiderin production in the PTZ-K model. Furthermore, we demonstrated for the first time an accumulation of hemosiderin in the heart in the SE-P model. These results suggest that uncontrolled recurrent seizures, as described in refractory epilepsy, can give rise to high hypoxic stress in the heart, thus inducing hemosiderin accumulation as in IOC, and can act as an underlying hidden mechanism contributing to the development of a terminal cardiac arrhythmia in SUDEP. Because iron accumulation in tissues can be detected by non-invasive imaging methods, cardiac iron overload in refractory epilepsy patients could be treated with chelation therapy to reduce the risk of SUDEP.
A Virtual, Randomized, Control Trial of a Digital Therapeutic for Speech, Language, and Cognitive Intervention in Post-stroke Persons With Aphasia
Authors: Braley Michelle , Pierce Jordyn Sims , Saxena Sadhvi , De Oliveira Emily , Taraboanta Laura , Anantha Veera , Lakhan Shaheen E. , Kiran Swathi
Published: February 2021

Background: Post-stroke aphasia is a chronic condition that impacts people's daily functioning and communication for many years after a stroke. Even though these individuals require sustained rehabilitation, they face extra burdens to access care due to shortages in qualified clinicians, insurance limitations and geographic access. There is a need to research alternative means to access intervention remotely, such as in the case of this study using a digital therapeutic.

Objective: To assess the feasibility and clinical efficacy of a virtual speech, language, and cognitive digital therapeutic for individuals with post-stroke aphasia relative to standard of care.

Methods: Thirty two participants completed the study (experimental: average age 59.8 years, 7 female, 10 male, average education: 15.8 years, time post-stroke: 53 months, 15 right handed, 2 left handed; control: average age 64.2 years, 7 female, 8 male, average education: 15.3 years, time post-stroke: 36.1 months, 14 right handed, 1 left handed). Patients in the experimental group received 10 weeks of treatment using a digital therapeutic, Constant Therapy-Research (CT-R), for speech, language, and cognitive therapy, which provides evidence-based, targeted therapy with immediate feedback for users that adjusts therapy difficulty based on their performance. Patients in the control group completed standard of care (SOC) speech-language pathology workbook pages.

Results: This study provides Class II evidence that with the starting baseline WAB-AQ score, adjusted by −0.69 for every year of age, and by 0.122 for every month since stroke, participants in the CT-R group had WAB-AQ scores 6.43 higher than the workbook group at the end of treatment. Additionally, secondary outcome measures included the WAB-Language Quotient, WAB-Cognitive Quotient, Brief Test of Adult Cognition by Telephone (BTACT), and Stroke and Aphasia Quality of Life Scale 39 (SAQOL-39), with significant changes in BTACT verbal fluency subtest and the SAQOL-39 communication and energy scores for both groups.

Conclusions: Overall, this study demonstrates the feasibility of a fully virtual trial for patients with post-stroke aphasia, especially given the ongoing COVID19 pandemic, as well as a safe, tolerable, and efficacious digital therapeutic for language/cognitive rehabilitation.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT04488029.
An Interview-Based Assessment of the Experience of Cognitive Impairment in Multiple Sclerosis: The Cognitive Assessment Interview (CAI)
Authors: Eilam-Stock Tehila , Best Pamela , Sherman Kathleen , Shaw Michael T. , Ventura Joseph , Krupp Lauren B. , Charvet Leigh E.
Published: February 2021

Background: Cognitive impairment is a common feature of multiple sclerosis (MS). A semi-structured interview, including informant input, can characterize the experience of individuals living with MS and cognitive involvement.

Objective: We administered the Cognitive Assessment Interview (CAI), a patient- and informant-based semi-structured interview, to characterize the experience of cognitive impairments in those living with MS.

Methods: Trained raters administered the CAI to a sample of MS participants and their informants enrolled for a trial of cognitive remediation. Cognitive impairments on the CAI were characterized and compared to those captured by neuropsychological and self-report measures.

Results: A total of n = 109 MS participants (mean age = 50.3 ± 12.2) and their available informants (n = 71) were interviewed. Participants reported experiencing processing speed (90/106, 85%), working memory (87/109, 80%), and learning and memory (79/109, 72%) problems most commonly. CAI-based ratings were moderately correlated with a self-report measure (Multiple Sclerosis Neuropsychological Screening Questionnaire, rs = 0.52, p < 0.001) and only mildly correlated with objective neuropsychological measures specific to executive functions (rs = 0.21, p = 0.029). For those with informant interviews, ratings were overall consistent, suggesting that the CAI is valid even in cases in which an informant is unavailable and the interview is conducted with the patient alone (as is often the case in clinical and research settings).

Conclusions: The CAI provides a semi-structured interview to characterize the experience of cognitive impairment in MS, with findings representing real-world functioning, adding valuable information to both self-report measures and neuropsychological assessment.
The Putative Role of mTOR Inhibitors in Non-tuberous Sclerosis Complex-Related Epilepsy
Authors: Goldstein Hannah E. , Hauptman Jason S.
Published: February 2021

Epilepsy affects ~5 out of every 10,000 children per year. Up to one-third of these children have medically refractory epilepsy, with limited to no options for improved seizure control. mTOR, a ubiquitous 289 kDa serine/threonine kinase in the phosphatidylinositol 3-kinase (PI3K)-related kinases (PIKK) family, is dysregulated in a number of human diseases, including tuberous sclerosis complex (TSC) and epilepsy. In cell models of epilepsy and TSC, rapamycin, an mTOR inhibitor, has been shown to decrease seizure frequency and duration, and positively affect cell growth and morphology. Rapamycin has also been shown to prevent or improve epilepsy and prolong survival in animal models of TSC. To date, clinical studies looking at the effects of mTOR inhibitors on the reduction of seizures have mainly focused on patients with TSC. Everolimus (Novartis Pharmaceuticals), a chemically modified rapamycin derivative, has been shown to reduce seizure frequency with reasonable safety and tolerability. Mutations in mTOR or the mTOR pathway have been found in hemimegalencephaly (HME) and focal cortical dysplasias (FCDs), both of which are highly correlated with medically refractory epilepsy. Given the evidence to date, a logical next step is to investigate the role of mTOR inhibitors in the treatment of children with medically refractory non-TSC epilepsy, particularly those children who have also failed resective surgery.
Clear and Consistent Imaging of Hippocampal Internal Architecture With High Resolution Multiple Image Co-registration and Averaging (HR-MICRA)
Authors: Ver Hoef Lawrence , Deshpande Hrishikesh , Cure Joel , Selladurai Goutham , Beattie Julia , Kennedy Richard E. , Knowlton Robert C. , Szaflarski Jerzy P.
Published: February 2021

Magnetic resonance imaging of hippocampal internal architecture (HIA) at 3T is challenging. HIA is defined by layers of gray and white matter that are less than 1 mm thick in the coronal plane. To visualize HIA, conventional MRI approaches have relied on sequences with high in-plane resolution (≤0.5 mm) but comparatively thick slices (2–5 mm). However, thicker slices are prone to volume averaging effects that result in loss of HIA clarity and blurring of the borders of the hippocampal subfields in up to 61% of slices as has been reported. In this work we describe an approach to hippocampal imaging that provides consistently high HIA clarity using a commonly available sequence and post-processing techniques that is flexible and may be applicable to any MRI platform. We refer to this approach as High Resolution Multiple Image Co-registration and Averaging (HR-MICRA). This approach uses a variable flip angle turbo spin echo sequence to repeatedly acquire a whole brain T2w image volume with high resolution in three dimensions in a relatively short amount of time, and then co-register the volumes to correct for movement and average the repeated scans to improve SNR. We compared the averages of 4, 9, and 16 individual scans in 20 healthy controls using a published HIA clarity rating scale. In the body of the hippocampus, the proportion of slices with good or excellent HIA clarity was 90%, 83%, and 67% for the 16x, 9x, and 4x HR-MICRA images, respectively. Using the 4x HR-MICRA images as a baseline, the 9x HR-MICRA images were 2.6 times and 16x HR-MICRA images were 3.2 times more likely to have high HIA ratings (p < 0.001) across all hippocampal segments (head, body, and tail). The thin slices of the HR-MICRA images allow reformatting in any plane with clear visualization of hippocampal dentation in the sagittal plane. Clear and consistent visualization of HIA will allow application of this technique to future hippocampal structure research, as well as more precise manual or automated segmentation.
Quantifying Signal Quality From Unimodal and Multimodal Sources: Application to EEG With Ocular and Motion Artifacts
Authors: Nahmias David O. , Kontson Kimberly L.
Published: February 2021

With prevalence of electrophysiological data collected outside of the laboratory from portable, non-invasive modalities growing at a rapid rate, the quality of these recorded data, if not adequate, could affect the effectiveness of medical devices that depend of them. In this work, we propose novel methods to evaluate electrophysiological signal quality to determine how much of the data represents the physiological source of interest. Data driven models are investigated through Bayesian decision and deep learning-based methods to score unimodal (signal and noise recorded on same device) and multimodal (signal and noise each recorded from different devices) data, respectively. We validate these methods and models on three electroencephalography (EEG) data sets (N = 60 subjects) to score EEG quality based on the presence of ocular artifacts with our unimodal method and motion artifacts with our multimodal method. Further, we apply our unimodal source method to compare the performance of two different artifact removal algorithms. Our results show we are able to effectively score EEG data using both methods and apply our method to evaluate the performance of other artifact removal algorithms that target ocular artifacts. Methods developed and validated here can be used to assess data quality and evaluate the effectiveness of certain noise-reduction algorithms.
24 h-Heart Rate Variability as a Communication Tool for a Personalized Psychosomatic Consultation in Occupational Health
Authors: Jarczok Marc N. , Buckley Thomas , Guendel Harald O. , Boeckelmann Irina , Mauss Daniel , Thayer Julian F. , Balint Elisabeth M.
Published: February 2021

New tools for non-specific primary prevention strategies covering somatic and mental health in occupational medicine are urgently needed. Heart rate variability (HRV) reflects the capacity of the body to adapt to environmental challenges and of the mind to regulate emotions. Hence, a 24 h-measurement of HRV offers a unique possibility to quantify the interaction between situation-specific emotional regulation within a specific psychosocial environment and physiological state, thereby increasing self-perception and inducing motivation to change behavior. The focus of the present study represents such a 24 h-measurement of HRV and its presentation as a comprehensive graph including protocol situations of the client. A special training program for occupational health physicians and questionnaires for clients were developed and administered. The article reports the first data of the study “healthy leadership and work – body signals for managers and employees”, an investigator-initiated, interventional, single-arm, open (non-blinded), multicenter, national trial with 168 participants. They reported a significantly improved perception of their bodily needs after the consultation (from Median = 7, interquartile range 5–8 to Median = 8, interquartile range 7–9; scale range from 1 to 10; p < 0.001, Wilcoxon rank test; effect size 0.49). The 16 occupational health physicians stated that the measurement of HRV was very well suited to enter into dialog with the managers and was feasible to show interactions between situations, thoughts, feelings, and bodily reactions. Taken together, we show that a 24 h-HRV-measurement can be a feasible and effective approach for holistic, psychosomatic primary prevention in occupational medicine. We discuss possible mechanisms for improving the individual health via the consultation, containing mindset and improved ANS activity.
Interplay of Good Bacteria and Central Nervous System: Cognitive Aspects and Mechanistic Considerations
Authors: Salami Mahmoud
Published: February 2021

The human gastrointestinal tract hosts trillions of microorganisms that is called “gut microbiota.” The gut microbiota is involved in a wide variety of physiological features and functions of the body. Thus, it is not surprising that any damage to the gut microbiota is associated with disorders in different body systems. Probiotics, defined as living microorganisms with health benefits for the host, can support or restore the composition of the gut microbiota. Numerous investigations have proved a relationship between the gut microbiota with normal brain function as well as many brain diseases, in which cognitive dysfunction is a common clinical problem. On the other hand, increasing evidence suggests that the existence of a healthy gut microbiota is crucial for normal cognitive processing. In this regard, interplay of the gut microbiota and cognition has been under focus of recent researches. In the present paper, I review findings of the studies considering beneficial effects of either gut microbiota or probiotic bacteria on the brain cognitive function in the healthy and disease statuses.
A New Apparatus for Recording Evoked Responses to Painful and Non-painful Sensory Stimulation in Freely Moving Mice
Authors: Zhang Jiaojiao , Embray Lee , Yanovsky Yevgenij , Brankačk Jurij , Draguhn Andreas
Published: February 2021

Experiments on pain processing in animals face several methodological challenges including the reproducible application of painful stimuli. Ideally, behavioral and physiological correlates of pain should be assessed in freely behaving mice, avoiding stress, fear or behavioral restriction as confounding factors. Moreover, the time of pain-evoked brain activity should be precisely related to the time of stimulation, such that pain-specific neuronal activity can be unambiguously identified. This can be achieved with laser-evoked heat stimuli which are also well established for human pain research. However, laser-evoked neuronal potentials are rarely investigated in awake unrestrained rodents, partially due to the practical difficulties in precisely and reliably targeting and triggering stimulation. In order to facilitate such studies we have developed a versatile stimulation and recording system for freely moving mice. The custom-made apparatus can provide both laser- and mechanical stimuli with simultaneous recording of evoked potentials and behavioral responses. Evoked potentials can be recorded from superficial and deep brain areas showing graded pain responses which correlate with pain-specific behavioral reactions. Non-painful mechanical stimuli can be applied as a control, yielding clearly different electrophysiological and behavioral responses. The apparatus is suited for simultaneous acquisition of precisely timed electrophysiological and behavioral evoked responses in freely moving mice. Besides its application in pain research it may be also useful in other fields of sensory physiology.
Decreased Plasma Levels of Angiotensin-Converting Enzyme Among Patients With Bipolar Disorder
Authors: Sanches Marsal , Colpo Gabriela D. , Cuellar Valeria A. , Bockmann Taya , Rogith Deevakar , Soares Jair C. , Teixeira Antonio L.
Published: February 2021

Background

Dysfunctions in the renin-angiotensin system (RAS) seem to be involved in the pathophysiology of several mental illness, including schizophrenia and mood disorders. We carried out a cross-sectional study assessing the levels of RAS-related molecules among bipolar disorder (BD) patients compared to healthy controls.

Methods

our sample consisted of 30 outpatients with BD type 1 (10 males, 20 females, age = 35.53 ± 10.59 years, 14 euthymic, 16 experiencing mood episodes) and 30 healthy controls (10 males, 20 females, age = 34.83 ± 11.49 years). Plasma levels of angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin-II (Ang II), and angiotensin (1–7) [Ang-(1–7)] were determined by ELISA.

Results

BD patients experiencing ongoing mood episodes had significantly lower ACE levels compared to controls (median: 459.00 vs. 514.10, p < 0.05). There was no association between the levels of these biomarkers and clinical parameters.

Conclusion

Our findings support the involvement of RAS dysfunction in the pathophysiology of BD. Considering the potential therapeutic implications linked to a better understanding of the role of RAS dysfunction in BD, studies allowing a better characterization of RAS-related molecules level and activity across different mood states are of high interest.
Coupled VO2 Oscillators Circuit as Analog First Layer Filter in Convolutional Neural Networks
Authors: Corti Elisabetta , Cornejo Jimenez Joaquin Antonio , Niang Kham M. , Robertson John , Moselund Kirsten E. , Gotsmann Bernd , Ionescu Adrian M. , Karg Siegfried
Published: February 2021

In this work we present an in-memory computing platform based on coupled VO2 oscillators fabricated in a crossbar configuration on silicon. Compared to existing platforms, the crossbar configuration promises significant improvements in terms of area density and oscillation frequency. Further, the crossbar devices exhibit low variability and extended reliability, hence, enabling experiments on 4-coupled oscillator. We demonstrate the neuromorphic computing capabilities using the phase relation of the oscillators. As an application, we propose to replace digital filtering operation in a convolutional neural network with oscillating circuits. The concept is tested with a VGG13 architecture on the MNIST dataset, achieving performances of 95% in the recognition task.
Isoliquiritigenin Confers Neuroprotection and Alleviates Amyloid-β42-Induced Neuroinflammation in Microglia by Regulating the Nrf2/NF-κB Signaling
Authors: Fu Yue , Jia Jianping
Published: February 2021

Background

Neuroinflammation and oxidative stress are two major pathological characteristics of Alzheimer’s disease (AD). Amyloid-β oligomers (AβO), a toxic form of Aβ, promote the neuroinflammation and oxidative stress in the development of AD. Isoliquiritigenin (ISL), a natural flavonoid isolated from the root of liquorice, has been shown to exert inhibitory effects on inflammatory response and oxidative stress.

Objectives

The main purpose of this study is to assess the influence of ISL on inflammatory response and oxidative stress in BV2 cells stimulated with AβO, and to explore the underlying molecular mechanisms.

Methods

3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H- tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) cytotoxicity assays were used to assess the toxic or protective effects of ISL. The expression levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assays. Morphological changes in BV2 cells were assessed by immunofluorescence method. Nitric oxide (NO) assay kit was used to determinate the NO production. Western blot, qRT-PCR and immunofluorescence were used to explore the underlying molecular mechanisms.

Results

ISL treatment reduced the production of inflammatory cytokines and NO, and alleviated the morphological changes in BV2 cells induced by AβO. ISL treatment further protected N2a cells from the toxic medium of AβO-stimulated BV2 cells. ISL activated nuclear factor erythroid-2 related factor 2 (Nrf2) signaling and suppressed nuclear factor-κB (NF-κB) signaling in BV2 cells.

Conclusion

ISL suppresses AβO-induced inflammation and oxidative stress in BV2 cells via the regulation of Nrf2/NF-κB signaling. Therefore, ISL indirectly protects neurons from the damage of toxic conditioned media.