bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatable Hyperkinetic Movement Disorders Not to Be Missed
Authors: Méneret Aurélie , Garcin Béatrice , Frismand Solène , Lannuzel Annie , Mariani Louise-Laure , Roze Emmanuel
Published: December 2021

Hyperkinetic movement disorders are characterized by the presence of abnormal involuntary movements, comprising most notably dystonia, chorea, myoclonus, and tremor. Possible causes are numerous, including autoimmune disorders, infections of the central nervous system, metabolic disturbances, genetic diseases, drug-related causes and functional disorders, making the diagnostic process difficult for clinicians. Some diagnoses may be delayed without serious consequences, but diagnosis delays may prove detrimental in treatable disorders, ranging from functional disabilities, as in dopa-responsive dystonia, to death, as in Whipple's disease. In this review, we focus on treatable disorders that may present with prominent hyperkinetic movement disorders.
The Effect of Adding Transcranial Direct Current Stimulation to Hyperbaric Oxygen Therapy in Patients With Delayed Encephalopathy After Carbon Monoxide Poisoning: A Randomised Controlled Trial
Authors: Cao Huifang , Tan Xiaona , Liu Zibo , Zhao Long , Chi Lin , Li Manyu , Liu Chunhui , Li Hongling
Published: December 2021

Objective: To investigate the effect of transcranial direct current stimulation (tDCS) combined with hyperbaric oxygen therapy (HBOT) in patients with delayed encephalopathy after carbon monoxide poisoning (DEACMP).

Design: A parallel-group, open-label randomised controlled study.

Setting: Hyperbaric Oxygen Therapy Room of the Second Hospital of Hebei Medical University.

Subjects: A total of 40 patients were recruited for the current study. Patients were randomly divided into a treatment group and a control group (20 cases/group).

Interventions: Control group: conventional, individualised rehabilitation therapy. Treatment group: conventional, individualised rehabilitation therapy and tDCS.

Main Measures: cognitive function of patients, the Barthel Index (BI).

Results: After treatment, significantly higher MMSE and BI scores, as well as a greater reduction in P300 latency and an increase in P300 amplitude, were observed in the treatment group compared to the control group (MMSE: 13 ± 7 vs. 9 ± 5; P300 latency: 342 ± 29 vs. 363 ± 17 ms; P300 amplitude: 7.0 ± 3.3 vs. 5.1 ± 2.7 μV; all P < 0.05). In both groups, however, MMSE and BI scores, in addition to P300 amplitude, were significantly improved; in contrast, there was a decrease in P300 latency in both groups after treatment compared to before treatment (all P < 0.05).

Conclusion: Combined with HBOT, tDCS can help improve cognitive function and ADL in patients with DEACMP. This combination therapy might be a helpful method to enhance the recovery of patients with DEACMP.
Automated Machine Learning Model Development for Intracranial Aneurysm Treatment Outcome Prediction: A Feasibility Study
Authors: Ou Chubin , Liu Jiahui , Qian Yi , Chong Winston , Liu Dangqi , He Xuying , Zhang Xin , Duan Chuan-Zhi
Published: December 2021

Background: The prediction of aneurysm treatment outcomes can help to optimize the treatment strategies. Machine learning (ML) has shown positive results in many clinical areas. However, the development of such models requires expertise in ML, which is not an easy task for surgeons.

Objectives: The recently emerged automated machine learning (AutoML) has shown promise in making ML more accessible to non-computer experts. We aimed to evaluate the feasibility of applying AutoML to develop the ML models for treatment outcome prediction.

Methods: The patients with aneurysms treated by endovascular treatment were prospectively recruited from 2016 to 2020. Treatment was considered successful if angiographic complete occlusion was achieved at follow-up. A statistical prediction model was developed using multivariate logistic regression. In addition, two ML models were developed. One was developed manually and the other was developed by AutoML. Three models were compared based on their area under the precision-recall curve (AUPRC) and area under the receiver operating characteristic curve (AUROC).

Results: The aneurysm size, stent-assisted coiling (SAC), and posterior circulation were the three significant and independent variables associated with treatment outcome. The statistical model showed an AUPRC of 0.432 and AUROC of 0.745. The conventional manually trained ML model showed an improved AUPRC of 0.545 and AUROC of 0.781. The AutoML derived ML model showed the best performance with AUPRC of 0.632 and AUROC of 0.832, significantly better than the other two models.

Conclusions: This study demonstrated the feasibility of using AutoML to develop a high-quality ML model, which may outperform the statistical model and manually derived ML models. AutoML could be a useful tool that makes ML more accessible to the clinical researchers.
Association Between Types of Posterior Staphyloma and Refractive Error After Cataract Surgery for High Myopia
Authors: Wu Jing , Wang Ruochen , Liu Can , Zhou Yu , Jiang Ziyuan , Liu Fang
Published: December 2021

Purpose: To investigate the association between different types of posterior staphyloma (PS) and refractive error (RE) after cataract surgery in patients with high myopia.

Methods: This retrospective study included 113 eyes of 113 highly myopic patients with PS. PS was detected using a wide-field fundus imaging system. PS was classified into wide macular, narrow macular, and other types. RE equaled the actual spherical equivalent (SE) minus the targeted SE values 3 months after cataract surgery.

Results: The rates of wide macular, narrow macular, and other types of PS were 46.02, 39.82, and 14.16%, respectively. There were no significant differences in best corrected distance visual acuity (BCDVA) or SE among the three classifications of PS before cataract surgery (P > 0.05). However, postoperative BCDVA and SE were significantly different among the three types of PS patients (P < 0.05). The average RE values were 0.98 ± 1.00 D, 0.19 ± 0.87 D, 0.13 ± 0.59 D, respectively; the statistical differences of RE were <0.01, <0.01, and 0.81 (wide macular vs. narrow macular, wide macular vs. other types, narrow macular vs. other types), respectively. Multivariate linear regression analysis revealed that higher hyperopia RE after surgery was associated with wide macular staphyloma (P < 0.001), more myopic SE (P = 0.003), and increased BCDVA (P = 0.002) before surgery.

Conclusions: Wide macular PS may be associated with more hyperopic RE; it may serve as a critical biomarker of hyperopic RE after cataract surgery in highly myopic patients.
Change in Cav3.2 T-Type Calcium Channel Induced by Varicella-Zoster Virus Participates in the Maintenance of Herpetic Neuralgia
Authors: Li Rongzhen , Ou Mingxi , Yang Shaomin , Huang Jiabin , Chen Jiamin , Xiong Donglin , Xiao Lizu , Wu Songbin
Published: December 2021

Pain, as the most prevalent neurological complication of herpes zoster (HZ), may occur before or during the rash onset or even after the rash has recovered. Particularly, postherpetic neuralgia (PHN) is a refractory chronic condition, usually defined as pain persisting for 3 months or longer from the onset of HZ. Pain evoked by HZ impairs the normal physical and emotional functions of the patients, severely reducing their quality of life. However, how zoster-associated pain occurs and develops into PHN are elusive, making PHN difficult to predict. Uncovering the pathogenesis of zoster-associated pain (or HN) helps us to better understand the onset of PHN and supports developing more effective treatments. In this study, we successfully constructed a model for zoster-associated pain through varicella-zoster virus (VZV) infections of mouse footpads and pain behavior assessments. Next, we used the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Gene Ontology (GO) to analyze PHN rodent dorsal root ganglion (DRG) gene microarray data and found that calcium signal disorder might be involved in the onset of PHN. By using reverse transcription real-time fluorescent quantitative PCR (RT-qPCR) and Western blotting, we confirmed that VZV infection could significantly upregulate the expression of T-type calcium channel Cav3.2 in DRG and spinal dorsal horn (SDH). Intrathecal administration of Cav3.2 blocker (2R/S)-6-prenylnaringenin (6-PNG) relieved mechanical and thermal hyperalgesia induced by VZV. Taken together, our data indicated that VZV might participate in the occurrence and development of HN by upregulating the expression of Cav3.2 in DRG and SDH. These findings will help to reveal the underlying mechanisms on long-lasting pain and PHN formation, providing a new insight that Cav3.2 can be the promising drug target for remitting PHN.
Electrophysiological Signature and the Prediction of Deep Brain Stimulation Withdrawal and Insertion Effects
Authors: Trenado Carlos , Cif Laura , Pedroarena-Leal Nicole , Ruge Diane
Published: December 2021

Deep brain stimulation (DBS) serves as a treatment for neurological and psychiatric disorders, such as Parkinson's disease (PD), essential tremor, dystonia, Tourette Syndrome (GTS), Huntington's disease, and obsessive-compulsive disorder (OCD). There is broad experience with the short-term effects of DBS in individual diseases and their signs/symptoms. However, even in acute treatment and for the same disorder or a given disorder, a prediction of effect is not perfect. Even further, the factors that influence the long-term effect of DBS and its withdrawal are hardly characterized. In this work, we aim to shed light on an important topic, the question of “DBS dependency.” To address this, we make use of the Kuramoto model of phase synchronization (oscillation feature) endowed with neuroplasticity to study the effects of DBS under successive withdrawals and renewals of neuromodulation as well as influence of treatment duration in de novo DBS “patients.” The results of our simulation show that the characteristics of neuroplasticity have a profound effect on the stability and mutability of oscillation synchronization patterns across successive withdrawal and renewal of DBS in chronic “patients” and also in de novo DBS “patients” with varying duration of treatment (here referred to as the “number of iterations”). Importantly, the results demonstrate the strong effect of the individual neuroplasticity makeup on the behavior of synchrony of oscillatory activity that promotes certain disorder/disease states or symptoms. The effect of DBS-mediated neuromodulation and withdrawal is highly dependent on the makeup of the neuroplastic signature of a disorder or an individual.
Intravenous Thrombolysis by Telestroke in the 3- to 4.5-h Time Window
Authors: Simon Erik , Forghani Matin , Abramyuk Andrij , Winzer Simon , Wojciechowski Claudia , Pallesen Lars-Peder , Siepmann Timo , Reichmann Heinz , Puetz Volker , Barlinn Kristian , Barlinn Jessica
Published: December 2021

Background: While intravenous thrombolysis (IVT) in ischemic stroke can be safely applied in telestroke networks within 3 h from symptom onset, there is a lack of evidence for safety in the expanded 3- to 4. 5-h time window. We assessed the safety and short-term efficacy of IVT in acute ischemic stroke (AIS) in the expanded time window delivered through a hub-and-spoke telestroke network.

Methods: Observational study of patients with AIS who received IVT at the Stroke Eastern Saxony Telemedical Network between 01/2014 and 12/2015. We compared safety data including symptomatic intracerebral hemorrhage (sICH; according to European Cooperative Acute Stroke Study II definition) and any intracerebral hemorrhage (ICH) between patients admitted to telestroke spoke sites and patients directly admitted to a tertiary stroke center representing the hub of the network. We also assessed short-term efficacy data including favorable functional outcome (i.e., modified Rankin Scale ≤ 2) and National Institutes of Health Stroke Scale (NIHSS) at discharge, hospital discharge disposition, and in-hospital mortality.

Results: In total, 152 patients with AIS were treated with IVT in the expanded time window [spoke sites, n = 104 (26.9%); hub site, n = 48 (25.9%)]. Patients treated at spoke sites had less frequently a large vessel occlusion [8/104 (7.7) vs. 20/48 (41.7%); p < 0.0001], a determined stroke etiology (p < 0.0001) and had slightly shorter onset-to-treatment times [210 (45) vs. 228 (58) min; p = 0.02] than patients who presented to the hub site. Both cohorts did not display any further differences in demographics, vascular risk factors, median baseline NIHSS scores, or median baseline Alberta stroke program early CT score (p > 0.05). There was no difference in the frequency of sICH (4.9 vs. 6.3%; p = 0.71) or any ICH (8.7 vs. 16.7%; p = 0.15). Neither there was a difference regarding favorable functional outcome (44.1 vs. 39.6%; p = 0.6) nor median NIHSS [3 (5.5) vs. 2.5 (5.75); p = 0.92] at discharge, hospital discharge disposition (p = 0.28), or in-hospital mortality (9.6 vs. 8.3%; p = 1.0). Multivariable modeling did not reveal an association between telestroke and sICH or favorable functional outcome (p > 0.05).

Conclusions: Delivery of IVT in the expanded 3- to 4.5-h time window through a telestroke network appears to be safe with equivalent short-term functional outcomes for spoke-and-hub center admissions.
Case Report: Behavioral Disorder Following Hemispherotomy: A Valproate Effect?
Authors: Makridis Konstantin L. , Triller Sebastian , Atalay Deniz A. , Prager Christine , Elger Christian E. , Kaindl Angela M.
Published: December 2021

Background: Hemispherotomy is an epilepsy surgery procedure applied to cure particularly pharmacorefractory lesional epilepsy due to unihemispheric pathologies. Such a disconnection of an entire hemisphere is followed by reorganizational processes.

Methods: We describe an acute aggravation of behavioral problems following a hemispherotomy in a patient treated with valproic acid, which subsided once valproate was discontinued.

Results: A 9-year-old boy with drug-resistant epilepsy caused by the residua of a perinatal stroke treated for several years with valproic acid and lamotrigine underwent hemispherotomy. Shortly after surgery, minimal preoperative behavioral problems intensified dramatically, and aggression occurred as a new symptom. Assuming a correlation between valproate treatment and the postoperative altered neuronal network, we tapered off valproate. The behavioral problems decreased in intensity with the reduction of valproate dose and disappeared after drug discontinuation.

Conclusion: We describe severe behavioral problems after hemispherotomy that subsided when valproate was tapered off. While we cannot rule out a spontaneous correction of a post-hemispherotomy network dysregulation, our report raises awareness to possible altered effects of the anticonvulsant valproic acid parallel to reorganizational processes after hemispherotomy.
Seizure Semiology, EEG, and Imaging Findings in Epilepsy Secondary to Mitochondrial Disease
Authors: Fine Anthony L. , Liebo Greta , Gavrilova Ralitza H. , Britton Jeffrey W.
Published: December 2021

Background: Identification of an underlying mitochondrial disorder can be challenging due to the significant phenotypic variability between and within specific disorders. Epilepsy can be a presenting symptom with several mitochondrial disorders. In this study, we evaluated clinical, electrophysiologic, and imaging features in patients with epilepsy and mitochondrial disorders to identify common features, which could aid in earlier identification of a mitochondrial etiology.

Methods: This is a retrospective case series from January 2011 to December 2019 at a tertiary referral center of patients with epilepsy and a genetically confirmed diagnosis of a mitochondrial disorder. A total of 164 patients were reviewed with 20 patients fulfilling inclusion criteria.

Results: A total of 20 patients (14 females, 6 males) aged 0.5–61 years with epilepsy and genetically confirmed mitochondrial disorders were identified. Status epilepticus occurred in 15 patients, with focal status epilepticus in 13 patients, including 9 patients with visual features. Abnormalities over the posterior cerebral regions were seen in 66% of ictal recordings and 44% of imaging studies. All the patients were on nutraceutical supplementation with no significant change in disease progression seen. At last follow-up, eight patients were deceased and the remainder had moderate-to-severe disability.

Discussion: In this series of patients with epilepsy and mitochondrial disorders, we found increased propensity for seizures arising from the posterior cerebral regions. Over time, electroencephalogram (EEG) and imaging abnormalities increasingly occurred over the posterior cerebral regions. Focal seizures and focal status epilepticus with visual symptoms were common. Additional study is needed on nutraceutical supplementation in mitochondrial disorders.
Phenotypic and Genotypic Characterization of NPRL2-Related Epilepsy: Two Case Reports and Literature Review
Authors: Sun Yulin , Wan Lin , Yan Huimin , Li Zhichao , Yang Guang
Published: December 2021

The phenotype of nitrogen permease regulator-like 2 (NPRL2) gene-related epilepsy clinically manifests as a range of epilepsy syndromes, including familial focal epilepsy with variable foci (FFEVF), sleep-related hypermotor epilepsy (SHE), temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), and infantile spasms (IS). The association between phenotype and genotype of NPRL2 variants has not been widely explored. This study aimed to explore the phenotype and genotype spectrum of NPRL2-related epilepsy. Here, we presented two clinical cases with NPRL2-related epilepsy, and discussed the characteristics, diagnosis, and treatment processes in the context of existing literature. Two novel NPRL2 likely pathogenic variants were identified by next-generation sequencing, including one splicing mutation (c.933-1G>A), and one frameshift mutation (c.257delG). The results of literature review showed that there were a total of 20 patients with NPRL2-related epilepsy whose mutations were mostly missense and hereditary. These findings indicate that the possibility of NPRL2 gene mutations in focal epilepsy should be considered for patients with family history, and that patients carrying different NPRL2 variants have different clinical manifestations. Our study expanded the genotype spectrum of NPRL2 and suggested that the type of NPRL2 variants might provide important information for the prognosis evaluation.
When Right Goes Left: Phantom Touch Induced by Mirror Box Procedure in Healthy Individuals
Authors: Ricci Raffaella , Caldano Michela , Sabatelli Ilaria , Cirillo Emanuele , Gammeri Roberto , Cesim Ezgi , Salatino Adriana , Berti Anna
Published: December 2021

In the present article, we investigated the possibility of inducing phantom tactile sensations in healthy individuals similar to those that we observed in patients after stroke. On the basis of previous research, we assumed that manipulating visual feedbacks may guide and influence, under certain conditions, the phenomenal experience of touch. To this aim, we used the Tactile Quadrant Stimulation (TQS) test in which subjects, in the crucial condition, must indicate whether and where they perceive a double tactile stimulation applied simultaneously in different quadrants of the two hands (asymmetrical Double Simultaneous Stimulation trial, Asym-DSS). The task was performed with the left-hand out of sight and the right-hand reflected in a mirror so that the right-hand reflected in the mirror looks like the own left-hand. We found that in the Asym-DSS trial, the vision of the right-hand reflected in the mirror and stimulated by a tactile stimulus elicited on the left-hand the sensation of having been touched in the same quadrant as the right-hand. In other words, we found in healthy subjects the same phantom touch effect that we previously found in patients. We interpreted these results as modulation of tactile representation by bottom-up (multisensory integration of stimuli coming from the right real and the right reflected hand) and possibly top-down (body ownership distortion) processing triggered by our experimental setup, unveiling bilateral representation of touch.
Deep Brain Stimulation Treating Dystonia: A Systematic Review of Targets, Body Distributions and Etiology Classifications
Authors: Fan Houyou , Zheng Zijian , Yin Zixiao , Zhang Jianguo , Lu Guohui
Published: December 2021

Background: Deep brain stimulation (DBS) is a typical intervention treating drug-refractory dystonia. Currently, the selection of the better target, the GPi or STN, is debatable. The outcomes of DBS treating dystonia classified by body distribution and etiology is also a popular question.

Objective: To comprehensively compare the efficacy, quality of life, mood, and adverse effects (AEs) of GPi-DBS vs. STN-DBS in dystonia as well as in specific types of dystonia classified by body distribution and etiology.

Methods: PubMed, Embase, the Cochrane Library, and Google Scholar were searched to identify studies of GPi-DBS and STN-DBS in populations with dystonia. The efficacy, quality of life, mood, and adverse effects were quantitatively compared. Meta-regression analyses were also performed. This analysis has been registered in PROSPERO under the number CRD42020146145.

Results: Thirty five studies were included in the main analysis, in which 319 patients underwent GPI-DBS and 113 patients underwent STN-DBS. The average follow-up duration was 12.48 months (range, 3–49 months). The GPI and STN groups were equivalent in terms of efficacy, quality of life, mood, and occurrence of AEs. The focal group demonstrated significantly better disability symptom improvement (P = 0.012) than the segmental and generalized groups but showed less SF-36 enhancement than the segmental group (P < 0.001). The primary groups exhibited significantly better movement and disability symptom improvements than the secondary non-hereditary group (P < 0.005), which demonstrated only disability symptom improvement compared with the secondary hereditary group (P < 0.005). The primary hereditary and idiopathic groups had a significantly lower frequency of AEs than the secondary non-hereditary group (P < 0.005). The correlation between disability symptom improvement and movement symptom improvement was also significant (P < 0.05).

Conclusion: GPi-DBS and STN-DBS were both safe and resulted in excellent improvement in efficacy and quality of life in patients with dystonia. Compared with patients with segmental dystonia, patients with focal dystonia demonstrated better improvement in dystonia symptoms but less enhancement of quality of life. Those with primary dystonia had a better response to DBS in terms of efficacy than those with secondary dystonia. Patients who exhibit a significant improvement in movement symptoms might also exhibit excellent improvement in disability symptoms.
AS3MT Polymorphism: A Risk Factor for Epilepsy Susceptibility and Adverse Drug Reactions to Valproic Acid and Oxcarbazepine Treatment in Children From South China
Authors: Fan Xiaomei , Chen Yuna , Lu Jieluan , Li Wenzhou , Li Xi , Guo Huijuan , Chen Qing , Yang Yanxia , Xia Hanbing
Published: December 2021

Epilepsy is a common neurologic disorder characterized by intractable seizures, involving genetic factors. There is a need to develop reliable genetic markers to predict the risk of epilepsy and design effective therapies. Arsenite methyltransferase (AS3MT) catalyzes the biomethylation of arsenic and hence regulates arsenic metabolism. AS3MT variation has been linked to the progression of various diseases including schizophrenia and attention deficit or hyperactivity disorder. Whether genetic polymorphism of AS3MT contributes to epilepsy remains unclear. In this study, we investigated the association of AS3MT gene polymorphism with susceptibility to epilepsy in children from south China. We also explored the effect of AS3MT variation on the safety of antiepileptic drugs. Genotypic analysis for AS3MT rs7085104 was performed using samples from a Chinese cohort of 200 epileptic children and 244 healthy individuals. The results revealed a genetic association of AS3MT rs7085104 with susceptibility to pediatric epilepsy. Mutant homozygous GG genotype exhibited a lower susceptibility to childhood epilepsy than AA genotype. Carriers of AS3MT rs7085104 AA genotype exhibited a higher risk of digestive adverse drug reactions (dADRs) in children when treated with valproic acid (VPA) or oxcarbazepine (OXC). Additionally, bioinformatics analysis identified eight AS3MT target genes related to epilepsy and three AS3MT-associated genes in VPA-related dADRs. The effects of AS3MT on epilepsy might involve multiple targets including CNNM2, CACNB2, TRIM26, MTHFR, GSTM1, CYP17A1, NT5C2, and YBX3. This study reveals that AS3MT may be a new gene contributing to epileptogenesis. Hence, analysis of AS3MT polymorphisms will help to evaluate susceptibility to pediatric epilepsy and drug safety.
Comparison of Different Metrics for the Identification of Vascular Changes in Diabetic Retinopathy Using OCTA
Authors: Mendes Luis , Marques Inês P. , Cunha-Vaz José
Published: December 2021

Retinal vessel metrics identifying microvascular changes such as vessel closure (VC) have shown potential clinical value by identifying eyes with diabetic retinopathy (DR) at different severity levels and at increased risk for disease progression to more severe stages. We compare the performance of 11 different metrics, which include 2 metrics supplied by the manufacturer, based on OCTA for identification of VC in different Early Treatment for Diabetic Retinopathy Study (ETDRS) severity groups. OCTA en-face slabs from 84 healthy eyes (70 ± 4.8 years) and 78 eyes of diabetic individuals (67 ± 7.5 years) were processed using different methods that include abnormal intercapillary spaces (AIS), vessel density (VD), and nine metrics extracted from the en-face slab. The best separation between the eyes with DR and the control group was obtained in the superficial capillary plexus (SCP), with the full retina (FR) also performing well. In the SCP, the metrics that show better performance were the AIS and the VD with a value of area under curve (AUC) equal to 0.89 [95% CI 0.84–0.94] and 0.85 [95% CI 0.79–0.91], respectively, indicating that the VD metric supported by the manufacturer is satisfactory. The values of these metrics on the different ETDRS groups show a progressive increase in VC, which is correlated with disease severity.
Extracranial 125I Seed Implantation Allows Non-invasive Stereotactic Radioablation of Hippocampal Adult Neurogenesis in Guinea Pigs
Authors: Wan Lily , Huang Rou-Jie , Yang Chen , Ai Jia-Qi , Zhou Qian , Gong Jiao-E , Li Jian , Zhang Yun , Luo Zhao-Hui , Tu Ewen , Pan Aihua , Xiao Bo , Yan Xiao-Xin
Published: December 2021

Adult hippocampal neurogenesis (AHN) is important for multiple cognitive functions. We sort to establish a minimal or non-invasive radiation approach to ablate AHN using guinea pigs as an animal model. 125I seeds with different radiation dosages (1.0, 0.8, 0.6, 0.3 mCi) were implanted unilaterally between the scalp and skull above the temporal lobe for 30 and 60 days, with the radiation effect on proliferating cells, immature neurons, and mature neurons in the hippocampal formation determined by assessment of immunolabeled (+) cells for Ki67, doublecortin (DCX), and neuron-specific nuclear antigen (NeuN), as well as Nissl stain cells. Spatially, the ablation effect of radiation occurred across the entire rostrocaudal and largely the dorsoventral dimensions of the hippocampus, evidenced by a loss of DCX+ cells in the subgranular zone (SGZ) of dentate gyrus (DG) in the ipsilateral relative to contralateral hemispheres in reference to the 125I seed implant. Quantitatively, Ki67+ and DCX+ cells at the SGZ in the dorsal hippocampus were reduced in all dosage groups at the two surviving time points, more significant in the ipsilateral than contralateral sides, relative to sham controls. NeuN+ neurons and Nissl-stained cells were reduced in the granule cell layer of DG and the stratum pyramidale of CA1 in the groups with 0.6-mCi radiation for 60 days and 1.0 mCi for 30 and 60 days. Minimal cranial trauma was observed in the groups with 0.3– 1.0-mCi radiation at 60 days. These results suggest that extracranial radiation with 125I seed implantation can be used to deplete HAN in a radioactivity-, duration-, and space-controllable manner, with a “non-invasive” stereotactic ablation achievable by using 125I seeds with relatively low radioactivity dosages.
The Effect of Dehydroepiandrosterone Treatment on Neurogenesis, Astrogliosis and Long-Term Cocaine-Seeking Behavior in a Cocaine Self-Administration Model in Rats
Authors: Ahdoot-Levi Hadas , Croitoru Ofri , Bareli Tzofnat , Sudai Einav , Peér-Nissan Hilla , Jacob Avi , Gispan Iris , Maayan Rachel , Weizman Abraham , Yadid Gal
Published: December 2021

Cocaine addiction is an acquired behavioral state developed in vulnerable individuals after cocaine exposure. It is characterized by compulsive drug-seeking and high vulnerability to relapse even after prolonged abstinence, associated with decreased neurogenesis in the hippocampus. This addictive state is hypothesized to be a form of “memory disease” in which the drug exploits the physiological neuroplasticity mechanisms that mediate regular learning and memory processes. Therefore, a major focus of the field has been to identify the cocaine-induced neuroadaptations occurring in the usurped brain’s reward circuit. The neurosteroid dehydroepiandrosterone (DHEA) affects brain cell morphology, differentiation, neurotransmission, and memory. It also reduces drug-seeking behavior in an animal model of cocaine self-administration. Here, we examined the long-lasting effects of DHEA treatment on the attenuation of cocaine-seeking behavior. We also examined its short- and long-term influence on hippocampal cells architecture (neurons and astrocytes). Using a behavioral examination, immunohistochemical staining, and diffusion tensor imaging, we found an immediate effect on tissue density and activation of astrocytes, which has a continuous beneficial effect on neurogenesis and tissue organization. This research emphasizes the requites concert between astrocytes and neurons in the rehabilitation from addiction behavior. Thus, DHEA may serve as a treatment that corrects brain damage following exposure to and abstinence from cocaine.
Home-Based Speech Perception Monitoring for Clinical Use With Cochlear Implant Users
Authors: van Wieringen Astrid , Magits Sara , Francart Tom , Wouters Jan
Published: December 2021

Speech-perception testing is essential for monitoring outcomes with a hearing aid or cochlear implant (CI). However, clinical care is time-consuming and often challenging with an increasing number of clients. A potential approach to alleviating some clinical care and possibly making room for other outcome measures is to employ technologies that assess performance in the home environment. In this study, we investigate 3 different speech perception indices in the same 40 CI users: phoneme identification (vowels and consonants), digits in noise (DiN) and sentence recognition in noise (SiN). The first two tasks were implemented on a tablet and performed multiple times by each client in their home environment, while the sentence task was administered at the clinic. Speech perception outcomes in the same forty CI users showed that DiN assessed at home can serve as an alternative to SiN assessed at the clinic. DiN scores are in line with the SiN ones by 3–4 dB improvement and are useful to monitor performance at regular intervals and to detect changes in auditory performance. Phoneme identification in quiet also explains a significant part of speech perception in noise, and provides additional information on the detectability and discriminability of speech cues. The added benefit of the phoneme identification task, which also proved to be easy to administer at home, is the information transmission analysis in addition to the summary score. Performance changes for the different indices can be interpreted by comparing against measurement error and help to target personalized rehabilitation. Altogether, home-based speech testing is reliable and proves powerful to complement care in the clinic for CI users.
A Noradrenergic Lesion Attenuates Surgery-Induced Cognitive Impairment in Rats by Suppressing Neuroinflammation
Authors: Wang Jiayu , Zhou Ying , Li Ke , Li Xiaofeng , Guo Meimei , Peng Mian
Published: December 2021

Postoperative cognitive dysfunction (POCD) is a common postoperative neurocognitive complication in elderly patients. However, the specific pathogenesis is unknown, and it has been demonstrated that neuroinflammation plays a key role in POCD. Recently, increasing evidence has proven that the locus coeruleus noradrenergic (LCNE) system participates in regulating neuroinflammation in some neurodegenerative disorders. We hypothesize that LCNE plays an important role in the neuroinflammation of POCD. In this study, 400 μg of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) was injected intracerebroventricularly into each rat 7 days before anesthesia/surgery to deplete the locus coeruleus (LC) noradrenaline (NE). We applied a simple laparotomy and brief upper mesenteric artery clamping surgery as the rat POCD model. The open field test, novel objection and novel location (NL) recognition, and Morris water maze (MWM) were performed to assess postoperative cognition. High-performance liquid chromatography (HPLC) was used to measure the level of NE in plasma and brain tissues, and immunofluorescence staining was applied to evaluate the activation of microglia and astrocytes. We also used enzyme-linked immune-sorbent assay (ELISA) to assess the levels of inflammatory cytokines and brain-derived neurotrophic factor (BDNF). Pretreatment with DSP-4 decreased the levels of systemic and central NE, increased the level of interleukin-6 (IL-6) in the plasma at 6 h after the surgery, decreased the concentration of IL-6 in the prefrontal cortex and hippocampus, and decreased the level of interleukin-1β (IL-1β) in the plasma, prefrontal cortex, and hippocampus at 1 week postoperatively. In addition, DSP-4 treatment attenuated hippocampal-dependent learning and memory impairment in rats with POCD, with a downregulation of the activation of microglia and astrocytes in the prefrontal cortex and hippocampus. In conclusion, these findings provide evidence of the effects of LCNE in modulating neuroinflammation in rats with POCD and provide a new perspective in the prevention and treatment of POCD.
The Fine Art of Writing a Message: RNA Metabolism in the Shaping and Remodeling of the Nervous System
Authors: Landínez-Macías María , Urwyler Olivier
Published: December 2021

Neuronal morphogenesis, integration into circuits, and remodeling of synaptic connections occur in temporally and spatially defined steps. Accordingly, the expression of proteins and specific protein isoforms that contribute to these processes must be controlled quantitatively in time and space. A wide variety of post-transcriptional regulatory mechanisms, which act on pre-mRNA and mRNA molecules contribute to this control. They are thereby critically involved in physiological and pathophysiological nervous system development, function, and maintenance. Here, we review recent findings on how mRNA metabolism contributes to neuronal development, from neural stem cell maintenance to synapse specification, with a particular focus on axon growth, guidance, branching, and synapse formation. We emphasize the role of RNA-binding proteins, and highlight their emerging roles in the poorly understood molecular processes of RNA editing, alternative polyadenylation, and temporal control of splicing, while also discussing alternative splicing, RNA localization, and local translation. We illustrate with the example of the evolutionary conserved Musashi protein family how individual RNA-binding proteins are, on the one hand, acting in different processes of RNA metabolism, and, on the other hand, impacting multiple steps in neuronal development and circuit formation. Finally, we provide links to diseases that have been associated with the malfunction of RNA-binding proteins and disrupted post-transcriptional regulation.
The Impacts of Short-Term NMN Supplementation on Serum Metabolism, Fecal Microbiota, and Telomere Length in Pre-Aging Phase
Authors: Niu Kai-Min , Bao Tongtong , Gao Lumin , Ru Meng , Li Yumeng , Jiang Liang , Ye Changming , Wang Shujin , Wu Xin
Published: December 2021

Aging is a natural process with concomitant changes in the gut microbiota and associate metabolomes. Beta-nicotinamide mononucleotide, an important NAD+ intermediate, has drawn increasing attention to retard the aging process. We probed the changes in the fecal microbiota and metabolomes of pre-aging male mice (C57BL/6, age: 16 months) following the oral short-term administration of nicotinamide mononucleotide (NMN). Considering the telomere length as a molecular gauge for aging, we measured this in the peripheral blood mononuclear cells (PBMC) of pre-aging mice and human volunteers (age: 45–60 years old). Notably, the NMN administration did not influence the body weight and feed intake significantly during the 40 days in pre-aging mice. Metabolomics suggested 266 upregulated and 58 downregulated serum metabolites. We identified 34 potential biomarkers linked with the nicotinamide, purine, and proline metabolism pathways. Nicotinamide mononucleotide significantly reduced the fecal bacterial diversity (p < 0.05) with the increased abundance of Helicobacter, Mucispirillum, and Faecalibacterium, and lowered Akkermansia abundance associated with nicotinamide metabolism. We propose that this reshaped microbiota considerably lowered the predicated functions of aging with improved immune and cofactors/vitamin metabolism. Most notably, the telomere length of PBMC was significantly elongated in the NMN-administered mice and humans. Taken together, these findings suggest that oral NMN supplementation in the pre-aging stage might be an effective strategy to retard aging. We recommend further studies to unravel the underlying molecular mechanisms and comprehensive clinical trials to validate the effects of NMN on aging.
Acute Effects of Salvia Supplementation on Cognitive Function in Athletes During a Fatiguing Cycling Exercise: A Randomized Cross-Over, Placebo-Controlled, and Double-Blind Study
Authors: Babault Nicolas , Noureddine Ahmad , Amiez Nicolas , Guillemet Damien , Cometti Carole
Published: December 2021

Background:Salvia (sage) supplementation has been shown to improve the cognition function in healthy individuals or patients (e.g., attention, memory). To date, no study has explored its relevancy in the context of sporting performance. The aim of this study was to explore the acute effects of a combination of Salvia officinalis and Salvia lavandulaefolia on cognitive function in athletes performing a fatiguing cycling task.

Methods: Twenty-six volunteers were included in this cross-over, randomized, double-bind vs. placebo trial. Two hours before the two experimental sessions (here called SAGE and PLACEBO), volunteers randomly received a supplementation of sage or placebo. During each experimental session, participants were tested at four occasions while cycling during a warm-up, in the middle and at the end of a fatiguing task and after a short 5-min recovery. Tests included a Stroop task, a simple reaction time task, and a backward digit span memory task. Heart rate and rating of perceived exertion (RPE) were also measured at the beginning of the four test sessions.

Results: Heart rate was significantly greater during the fatiguing exercise than during warm-up and recovery (P < 0.001) without any supplementation effect. RPE was greater during the fatiguing exercise than during warm-up and recovery (P < 0.001). Moreover, RPE was significantly lower during the SAGE session as compared to PLACEBO (P = 0.002). Reaction time was not altered during the exercise but was significantly shorter with SAGE as compared to PLACEBO (P = 0.023). The Stroop task only revealed significantly longer reaction time during warm-up as compared to recovery (P = 0.02) independently of the supplementation. The digit span memory test revealed a significant greater span score with SAGE as compared to PLACEBO (P = 0.044).

Conclusion: The combination of Salvia improved the cognitive functions (perceived exertion, working memory, and reaction time). The positive effects were obtained in fresh condition and were maintained with fatigue.
Circular RNA Circ_0000098 Elevates ALX4 Expression via Adsorbing miR-1204 to Inhibit the Progression of Hepatocellular Carcinoma
Authors: Li Ming , Yue Wenjing , Li Qiankun , Yu Wenyu , Li Yao , Cao Xiaoling
Published: December 2021

Background

Circular RNAs (CircRNAs) feature prominently in the progression of various cancers. However, the biological functions of many circRNAs in hepatocellular carcinoma (HCC) are far from fully clarified. This work is performed to decipher the function of circ_0000098 (circSLC30A7) in modulating the progression of HCC and its molecular mechanism.

Methods

Microarray data (GSE97332) were available from the Gene Expression Omnibus (GEO) database, and circRNA differentially expressed in HCC tissues was screened out by GEO2R tool. Circ_0000098, microRNA-1204 (miR-1204), and aristaless-like homeobox-4 (ALX4) mRNA expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8), scratch wound healing, and Transwell assays were adopted to determine proliferation, migration, and invasion of HCC cells. ALX4 protein, E-cadherin, N-cadherin, and Vimentin expressions were evaluated by Western blot. In addition, the targeting relationship between miR-1204 and circ_0000098 or ALX4 was studied with dual-luciferase reporter assay and RIP assay.

Results

Circ_0000098 expression level was markedly declined in HCC tissues and cells, and its underexpression was associated with larger tumor size of HCC patients. Knocking down circ_0000098 observably promoted the multiplication, migration, invasion, and epithelial-mesenchymal transition (EMT) of Huh7 and SMMC-7721 cells. Additionally, circ_0000098 was mainly distributed in the cytoplasm of HCC cells, and up-regulated ALX4 expression through competitively decoying miR-1204.

Conclusion

Circ_0000098, as a competitive endogenous RNA (ceRNA) of miR-1204, upregulates ALX4 expression and suppresses the growth, migration, invasion, and EMT of HCC cells.
Early Assessment of Response to Radiofrequency Ablation With CT Perfusion Imaging in Rabbit VX2 Liver Tumor Model
Authors: Yue Xiaofei , Dong Xiangjun , Huang Mengting , Yang Hongli , Qian Kun , Yi Changhong , Alwalid Osamah , Ren Yanqiao , Han Ping , Li Qian
Published: December 2021

Objectives

To discriminate viable tumors from benign periablational enhancement (BPE) in early stage after radiofrequency ablation (RFA) is a major confounding problem. The goal of this study is to evaluate quantitative assessment and diagnostic value of CT perfusion between viable tumors and BPE after RFA in the rabbit liver VX2 tumor model, with pathological results as the standard.

Methods

Twenty-eight VX2 liver tumors were treated with RFA, on days 1, 3, 7, and 14, seven rabbits were randomly chosen for CT perfusion and performed pathology examinations immediately. The perfusion parameters along with the profile of time-density curves (TDCs) and pseudo-color images of the parameters were observed in both BPE and viable tumors, then compared with the pathology results. The perfusion parameters included blood flow (BF), blood volume (BV), time to peak (TTP), permeability (P), arterial liver perfusion (ALP), portal venous perfusion (PVP) and hepatic perfusion index (HPI).

Results

A total of 26/28 rabbits successfully underwent CT perfusion, while 6/26 lesions were confirmed to be viable tumors. The TDCs of BPE were mainly speed-up platform curves (15/26), while the viable tumors showed mainly speed-up speed-down (3/6) and speed-up platform (2/6) curves. The PVP values were significantly higher, and the HPI values were significantly lower for BPE at all time points than viable tumors (P < 0.05). Both of PVP value and HPI value have high efficiency for the differential diagnosis of the viable tumors and BPE at each time point. These characteristics of CT perfusion parameters were consistent with pathological changes.

Conclusions

The TDCs, PVP and HPI have the potential to indicate BPE and viable tumors effectively early after RFA treatment, the results were highly consistent with pathology. CT perfusion has advantages with great efficacy in monitoring the therapeutic effect early after RFA treatment.
Single-Cell RNA Sequencing Reveals Multiple Pathways and the Tumor Microenvironment Could Lead to Chemotherapy Resistance in Cervical Cancer
Authors: Gu Meijia , He Ti , Yuan Yuncong , Duan Suling , Li Xin , Shen Chao
Published: December 2021

Background

Cervical cancer is one of the most common gynecological cancers worldwide. The tumor microenvironment significantly influences the therapeutic response and clinical outcome. However, the complex tumor microenvironment of cervical cancer and the molecular mechanisms underlying chemotherapy resistance are not well studied. This study aimed to comprehensively analyze cells from pretreated and chemoresistant cervical cancer tissues to generate a molecular census of cell populations.

Methods

Biopsy tissues collected from patients with cervical squamous cell carcinoma, cervical adenocarcinoma, and chronic cervicitis were subjected to single-cell RNA sequencing using the 10× Genomics platform. Unsupervised clustering analysis of cells was performed to identify the main cell types, and important cell clusters were reclustered into subpopulations. Gene expression profiles and functional enrichment analysis were used to explore gene expression and functional differences between cell subpopulations in cervicitis and cervical cancer samples and between chemoresistant and chemosensitive samples.

Results

A total of 24,371 cells were clustered into nine separate cell types, including immune and non-immune cells. Differentially expressed genes between chemoresistant and chemosensitive patients enriched in the phosphoinositide 3-kinase (PI3K)/AKT pathway were involved in tumor development, progression, and apoptosis, which might lead to chemotherapy resistance.

Conclusions

Our study provides a comprehensive overview of the cancer microenvironment landscape and characterizes its gene expression and functional difference in chemotherapy resistance. Consequently, our study deepens the insights into cervical cancer biology through the identification of gene markers for diagnosis, prognosis, and therapy.