bluuebunny/crossref_metadata_2025 huggingface dataset:
Ocean Aerobiology
Authors: Alsante Alyssa N. , Thornton Daniel C. O. , Brooks Sarah D.
Published: October 2021

Ocean aerobiology is defined here as the study of biological particles of marine origin, including living organisms, present in the atmosphere and their role in ecological, biogeochemical, and climate processes. Hundreds of trillions of microorganisms are exchanged between ocean and atmosphere daily. Within a few days, tropospheric transport potentially disperses microorganisms over continents and between oceans. There is a need to better identify and quantify marine aerobiota, characterize the time spans and distances of marine microorganisms’ atmospheric transport, and determine whether microorganisms acclimate to atmospheric conditions and remain viable, or even grow. Exploring the atmosphere as a microbial habitat is fundamental for understanding the consequences of dispersal and will expand our knowledge of biodiversity, biogeography, and ecosystem connectivity across different marine environments. Marine organic matter is chemically transformed in the atmosphere, including remineralization back to CO2. The magnitude of these transformations is insignificant in the context of the annual marine carbon cycle, but may be a significant sink for marine recalcitrant organic matter over long (∼104 years) timescales. In addition, organic matter in sea spray aerosol plays a significant role in the Earth’s radiative budget by scattering solar radiation, and indirectly by affecting cloud properties. Marine organic matter is generally a poor source of cloud condensation nuclei (CCN), but a significant source of ice nucleating particles (INPs), affecting the formation of mixed-phase and ice clouds. This review will show that marine biogenic aerosol plays an impactful, but poorly constrained, role in marine ecosystems, biogeochemical processes, and the Earth’s climate system. Further work is needed to characterize the connectivity and feedbacks between the atmosphere and ocean ecosystems in order to integrate this complexity into Earth System models, facilitating future climate and biogeochemical predictions.
The Evasion of Antiviral Innate Immunity by Chicken DNA Viruses
Authors: Gao Li , Zheng Shijun , Wang Yongqiang
Published: October 2021

The innate immune system constitutes the first line of host defense. Viruses have evolved multiple mechanisms to escape host immune surveillance, which has been explored extensively for human DNA viruses. There is growing evidence showing the interaction between avian DNA viruses and the host innate immune system. In this review, we will survey the present knowledge of chicken DNA viruses, then describe the functions of DNA sensors in avian innate immunity, and finally discuss recent progresses in chicken DNA virus evasion from host innate immune responses.
Evaluation of the Diagnostic Potential of Candidate Hypermethylated Genes in Epithelial Ovarian Cancer in North Indian Population
Authors: Singh Alka , Gupta Sameer , Sachan Manisha
Published: October 2021

Most ovarian cancers, despite improvement in management of cancer, are still diagnosed at an advanced stage. Early detection plays an essential role in reducing ovarian cancer mortality and, therefore, is critically needed. Liquid biopsies-based approaches hold significant promise for cancer detection. The present study investigates a panel of epigenetic biomarkers for the detection of epithelial ovarian cancer. A qPCR assay has been developed based on the assessment of DNA methylation markers in circulating cell-free DNA as a minimally invasive tool. Herein, the promoter methylation of seven ovarian cancer-specific genes (RASSF1A, DAPK1, SOX1, HOXA9, HIC1, SPARC, and SFRP1) was analyzed quantitatively in 120 tissue samples by MethyLight assay. The best-performing genes were further evaluated for their methylation status in 70 matched serum cell-free DNA of cancerous and non-cancerous samples. Additionally, DNA methylation patterns of these best-performing genes were validated by clonal bisulfite sequencing. The ROC (Receiver-operator characteristic) curves were constructed to evaluate the diagnostic performances of both individual and combined gene panels. The seven candidate genes displayed a methylation frequency of 61.0–88.0% in tissue samples. The promoter methylation frequencies for all the seven candidate genes were significantly higher in cancer samples than in normal matched controls. In tissue samples, the multiplex MethyLight assay for HOXA9, HIC1, and SOX1 were the best performing gene panels in terms of sensitivity and specificity. The three best-performing genes exhibited individual frequencies of 53.0–71.0% in serum CFDNA, and the multiplex assay for these genes were identified to discriminate serum from cancer patients and healthy individuals (area under the curve: HOXA9+HIC1 = 0.95, HIC1+SOX1 = 0.93 and HOXA9+SOX1 = 0.85). The results of MethyLight showed high concordance with clonal bisulfite sequencing results. Individual genes and combined panel exhibited better discriminatory efficiencies to identify ovarian cancer at various stages of disease when analyzed in tissue and serum cell-free DNA. We report a qPCR-based non-invasive epigenetic biomarker assay with high sensitivity and specificity for OC screening. Our findings also reveal the potential utility of methylation-based detection of circulating cell-free tumor DNA in the clinical management of ovarian cancer.
Serum miR-214 Serves as a Biomarker for Prodromal Parkinson’s Disease
Authors: Li Lanting , Ren Jingru , Pan Chenxi , Li Yuqian , Xu Jianxia , Dong Hui , Chen Yong , Liu Weiguo
Published: October 2021

Circulating microRNAs (miRNAs) have been proposed to be accessible biomarkers for Parkinson’s disease (PD). However, there is a lack of known miRNAs that can serve as biomarkers for prodromal PD (pPD). We previously identified that miR-31 and miR-214 were dysregulated in PD. The aim of this study was to explore the roles of miR-31 and miR-214 in pPD. We recruited 25 pPD patients, 20 patients with de novo PD (dnPD), 24 advanced PD (aPD) patients and 21 controls. Next, we investigated the expression of miR-31 and miR-214. Compared to controls, miR-214 was found to be significantly upregulated in pPD patients while miR-31 was significantly upregulated in aPD patients. In addition, the expression of miR-214 was lower in aPD patients compared to both dnPD or pPD patients, while the expression of miR-31 was higher in aPD patients compared to dnPD patients. In order to predict pPD via miRNA expression, the receiver operating characteristic curve was constructed and the area under curve (AUC) was calculated. For pPD prediction by miR-214, the AUC was 0.756. The optimal cut-off value of miR-214 was 0.1962, and the sensitivity and specificity were 72.0% and 76.2%, respectively. On the other hand, the AUC for aPD detection by miR-31 was 0.744. The optimal cut-off value for miR-31 was 0.0148, with a sensitivity of 87.5% and a specificity of 71.4%. In conclusion, miR-214 can distinguish pPD patients from controls and may be used as a potential biomarker for pPD diagnosis.
Anosognosia in Amnestic Mild Cognitive Impairment Is Related to Diminished Hippocampal Volume Comparable to Alzheimer’s Disease Dementia: Preliminary MRI Findings
Authors: Flores-Vázquez Juan Francisco , Ramírez-García Gabriel , Marrufo-Meléndez Oscar René , Alcalá-Lozano Ruth , Lietz Morten Peter , Rodríguez-Agudelo Yaneth , Acosta-Castillo Gilberto Isaac , Renken Remco J. , Aleman Andre , Enriquez-Geppert Stefanie , Sosa-Ortiz Ana Luisa
Published: October 2021

Although the presence of anosognosia in amnestic mild cognitive impairment (aMCI) may be predictive of conversion to Alzheimer’s disease (AD), little is known about its neural correlates in AD and aMCI. Four different groups were compared using volumetric and diffusion magnetic resonance imaging metrics in regions of interest (hippocampus and cingulum cortex gray matter, cingulum bundle white matter): aMCI subjects with anosognosia (n = 6), aMCI subjects without anosognosia (n = 12), AD subjects with anosognosia (n = 6), and AD subjects without anosognosia (n = 9). aMCI subjects with anosognosia displayed a significantly lower gray matter density (GMD) in the bilateral hippocampus than aMCI subjects without anosognosia, which was accounted for by bilateral hippocampal differences. Furthermore, we identified that the mean hippocampal gray matter density of aMCI subjects with anosognosia was not statistically different than that of AD subjects. The groups of aMCI and AD subjects with anosognosia also displayed a lower GMD in the bilateral cingulum cortex compared to subjects without anosognosia, but these differences were not statistically significant. No statistically significant differences were found in the fractional anisotropy or mean diffusivity of the hippocampus or cingulum between subjects with and without anosognosia in aMCI or AD groups. While these findings are derived from a small population of subjects and are in need of replication, they suggest that anosognosia in aMCI might be a useful clinical marker to suspect brain changes associated with AD neuropathology.
Transcranial Direct Current Stimulation for Parkinson's Disease: A Systematic Review and Meta-Analysis
Authors: Liu Xiang , Liu Huiyu , Liu Zicai , Rao Jinzhu , Wang Jing , Wang Pu , Gong Xiaoqian , Wen Youliang
Published: October 2021

Background: Parkinson's disease is a common neurodegenerative disorder with motor and non-motor symptoms. Recently, as adjuvant therapy, transcranial direct current stimulation (tDCS) has been shown to improve the motor and non-motor function of patients with Parkinson's disease (PD). This systematic review aimed to evaluate the existing evidence for the efficacy of tDCS for PD. We included English databases (PubMed, the Cochrane Library, Embase, and Web of Science) and Chinese databases [Wanfang database, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and China Biology Medicine (CBM)] without restricting the year of publication. Twenty-one tDCS studies, with a total of 736 participants, were included in the analysis. Two independent researchers extracted the data and characteristics of each study. There was a significant pooled effect size (−1.29; 95% CI = −1.60, −0.98; p < 0.00001; I2 = 0%) in the Unified PD Rating Scale (UPDRS) I and the Montreal cognitive assessment (SMD = 0.87, 95% CI = 0.50 to 1.24; p < 0.00001; I2 = 0%). The poor effect size was observed in the UPDRS III scores (SMD = −0.13; 95% CI = −0.64, 0.38; p = 0.61; I2 = 77%), and similar results were observed for the timed up and go (TUG) test, Berg balance scale, and gait assessment. The results of this meta-analysis showed that there was insufficient evidence that tDCS improves the motor function of patients with PD. However, tDCS seemed to improve their cognitive performance. Further multicenter research with a larger sample size is needed. In addition, future research should focus on determining the tDCS parameters that are most beneficial to the functional recovery of patients with PD.
The Anti-diabetic Drug Gliquidone Modulates Lipopolysaccharide-Mediated Microglial Neuroinflammatory Responses by Inhibiting the NLRP3 Inflammasome
Authors: Kim Jieun , Park Jin-Hee , Shah Keshvi , Mitchell Scott John , Cho Kwangwook , Hoe Hyang-Sook
Published: October 2021

The sulfonylurea drug gliquidone is FDA approved for the treatment of type 2 diabetes. Binding of gliquidone to ATP-sensitive potassium channels (SUR1, Kir6 subunit) in pancreatic β-cells increases insulin release to regulate blood glucose levels. Diabetes has been associated with increased levels of neuroinflammation, and therefore the potential effects of gliquidone on micro- and astroglial neuroinflammatory responses in the brain are of interest. Here, we found that gliquidone suppressed LPS-mediated microgliosis, microglial hypertrophy, and proinflammatory cytokine COX-2 and IL-6 levels in wild-type mice, with smaller effects on astrogliosis. Importantly, gliquidone downregulated the LPS-induced microglial NLRP3 inflammasome and peripheral inflammation in wild-type mice. An investigation of the molecular mechanism of the effects of gliquidone on LPS-stimulated proinflammatory responses showed that in BV2 microglial cells, gliquidone significantly decreased LPS-induced proinflammatory cytokine levels and inhibited ERK/STAT3/NF-κB phosphorylation by altering NLRP3 inflammasome activation. In primary astrocytes, gliquidone selectively affected LPS-mediated proinflammatory cytokine expression and decreased STAT3/NF-κB signaling in an NLRP3-independent manner. These results indicate that gliquidone differentially modulates LPS-induced microglial and astroglial neuroinflammation in BV2 microglial cells, primary astrocytes, and a model of neuroinflammatory disease.
Double-Coated Poly(butyl Cyanoacrylate) Nanoparticles as a Potential Carrier for Overcoming P-Gp- and BCRP-Mediated Multidrug Resistance in Cancer Cells
Authors: Kaushal Neeraj , Chen Zhe-Sheng , Lin Senshang
Published: October 2021

The present study evaluates poly (butyl cyanoacrylate) nanoparticles (PBCA-NPs), double-coated with Tween 80 and polyethylene glycol (PEG) 20,000 as a potential carrier system for overcoming P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP)-mediated multidrug resistance (MDR) in cancer cell lines. Doxorubicin-loaded PBCA-NPs were prepared by the anionic polymerization method and were successively double-coated with Tween 80 and PEG 20000 at varied concentrations. MDR reversing potential was investigated by cellular uptake in P-gp overexpressing cell line. And, the outcomes were verified by modified MTT assay in P-gp or BCRP overexpressing cell lines. The findings from the cell uptake study indicate that double-coated PBCA-NPs significantly enhanced doxorubicin accumulation within the cells. MTT assays revealed that double-coated PBCA-NPs significantly potentiated the sensitivity of doxorubicin in P-gp overexpressing cells, in comparison to free doxorubicin, single-, and un-coated PBCA-NPs, respectively. Moreover, further increase in concentration with Tween 80, double-coated PBCA-NPs significantly enhanced the sensitivity of doxorubicin in BCRP overexpressing cell line, in comparison to single- and double-coated formulations (with lower concentration of Tween 80). Hence, it could be concluded that double-coated PBCA-NPs can be used as a potential carrier for enhancing doxorubicin accumulation in MDR cancer cells.
A Novel Assay Allowing Drug Self-Administration, Extinction, and Reinstatement Testing in Head-Restrained Mice
Authors: Vollmer Kelsey M. , Doncheck Elizabeth M. , Grant Roger I. , Winston Kion T. , Romanova Elizaveta V. , Bowen Christopher W. , Siegler Preston N. , Green Lisa M. , Bobadilla Ana-Clara , Trujillo-Pisanty Ivan , Kalivas Peter W. , Otis James M.
Published: October 2021

Multiphoton microscopy is one of several new technologies providing unprecedented insight into the activity dynamics and function of neural circuits. Unfortunately, some of these technologies require experimentation in head-restrained animals, limiting the behavioral repertoire that can be integrated and studied. This issue is especially evident in drug addiction research, as no laboratories have coupled multiphoton microscopy with simultaneous intravenous drug self-administration, a behavioral paradigm that has predictive validity for treatment outcomes and abuse liability. Here, we describe a new experimental assay wherein head-restrained mice will press an active lever, but not inactive lever, for intravenous delivery of heroin or cocaine. Similar to freely moving animals, we find that lever pressing is suppressed through daily extinction training and subsequently reinstated through the presentation of relapse-provoking triggers (drug-associative cues, the drug itself, and stressors). Finally, we show that head-restrained mice will show similar patterns of behavior for oral delivery of a sucrose reward, a common control used for drug self-administration experiments. Overall, these data demonstrate the feasibility of combining drug self-administration experiments with technologies that require head-restraint, such as multiphoton imaging. The assay described could be replicated by interested labs with readily available materials to aid in identifying the neural underpinnings of substance use disorder.
Changes in Brain Matrix Glycan Sulfation Associate With Reactive Gliosis and Motor Coordination in Mice With Head Trauma
Authors: Alonge Kimberly M. , Herbert Melanie J. , Yagi Mayumi , Cook David G. , Banks William A. , Logsdon Aric F.
Published: October 2021

Perineuronal nets (PNNs) are extracellular matrix (ECM) structures that enmesh and regulate neurocircuits involved in motor and sensory function. Maladaptive changes to the composition and/or abundance of PNNs have been implicated in preclinical models of neuroinflammation and neurocircuit destabilization. The central nervous system (CNS) is limited in its capacity to repair and reorganize neural networks following traumatic brain injury (TBI) and little is known about mechanisms of ECM repair in the adult brain after TBI. In this study, adult male C57BL/6 mice were subjected to a TBI via a controlled cortical impact (CCI) to the right motor and somatosensory cortices. At 7 days following CCI, histological analysis revealed a loss of Wisteria floribunda agglutinin (WFA) positive PNN matrices in the ipsilateral cortex. PNNs are comprised of chondroitin sulfate (CS) and dermatan sulfate (DS)-glycosaminoglycans (GAGs), the composition of which are known to influence neuronal integrity and repair. Using an innovative liquid chromatography tandem mass spectrometry (LC-MS/MS) method, we analyzed the relative abundance of six specific CS/DS-GAG isomers (Δ4S-, Δ6S-, Δ4S6S-, Δ2S6S-, Δ0S-CS, and Δ2S4S-DS) from fixed-brain sections after CCI injury. We report a significant shift in CS/DS-GAG sulfation patterns within the rostro-caudal extent of the injury site from mice exposed to CCI at 7 days, but not at 1 day, post-CCI. In the ipsilateral thalamus, the appearance of WFA+ puncta occurred in tandem with gliosis at 7 days post-CCI, but weakly colocalized with markers of gliosis. Thalamic WFA+ puncta showed moderate colocalization with neuronal ubiquitin C-terminal hydrolase L1 (UCHL1), a clinical biomarker for TBI injury. A shift in CS/DS-GAG sulfation was also present in the thalamus including an increase of 6S-CS, which is a specific isomer that associates with the presence of glial scarring. Upregulation of the 6S-CS-specific sulfotransferase (CHST3) gene expression was accompanied by reactive gliosis in both the ipsilateral cortex and thalamus. Moreover, changes in 6S-CS extracted from the thalamus positively correlated with deficits in motor coordination after CCI. Collectively, these data argue that CCI alters CS/DS-GAG sulfation in association with the spatiotemporal progression of neurorepair. Therapeutic interventions targeting restoration of CS/DS-GAG sulfation patterns may improve outcomes from TBI.
DeepBhvTracking: A Novel Behavior Tracking Method for Laboratory Animals Based on Deep Learning
Authors: Sun Guanglong , Lyu Chenfei , Cai Ruolan , Yu Chencen , Sun Hao , Schriver Kenneth E. , Gao Lixia , Li Xinjian
Published: October 2021

Behavioral measurement and evaluation are broadly used to understand brain functions in neuroscience, especially for investigations of movement disorders, social deficits, and mental diseases. Numerous commercial software and open-source programs have been developed for tracking the movement of laboratory animals, allowing animal behavior to be analyzed digitally. In vivo optical imaging and electrophysiological recording in freely behaving animals are now widely used to understand neural functions in circuits. However, it is always a challenge to accurately track the movement of an animal under certain complex conditions due to uneven environment illumination, variations in animal models, and interference from recording devices and experimenters. To overcome these challenges, we have developed a strategy to track the movement of an animal by combining a deep learning technique, the You Only Look Once (YOLO) algorithm, with a background subtraction algorithm, a method we label DeepBhvTracking. In our method, we first train the detector using manually labeled images and a pretrained deep-learning neural network combined with YOLO, then generate bounding boxes of the targets using the trained detector, and finally track the center of the targets by calculating their centroid in the bounding box using background subtraction. Using DeepBhvTracking, the movement of animals can be tracked accurately in complex environments and can be used in different behavior paradigms and for different animal models. Therefore, DeepBhvTracking can be broadly used in studies of neuroscience, medicine, and machine learning algorithms.
A Multi-Information Fusion Method for Gait Phase Classification in Lower Limb Rehabilitation Exoskeleton
Authors: Zhang Yuepeng , Cao Guangzhong , Ling Ziqin , Li WenZhou , Cheng Haoran , He Binbin , Cao Shengbin , Zhu Aibin
Published: October 2021

Gait phase classification is important for rehabilitation training in patients with lower extremity motor dysfunction. Classification accuracy of the gait phase also directly affects the effect and rehabilitation training cycle. In this article, a multiple information (multi-information) fusion method for gait phase classification in lower limb rehabilitation exoskeleton is proposed to improve the classification accuracy. The advantage of this method is that a multi-information acquisition system is constructed, and a variety of information directly related to gait movement is synchronously collected. Multi-information includes the surface electromyography (sEMG) signals of the human lower limb during the gait movement, the angle information of the knee joints, and the plantar pressure information. The acquired multi-information is processed and input into a modified convolutional neural network (CNN) model to classify the gait phase. The experiment of gait phase classification with multi-information is carried out under different speed conditions, and the experiment is analyzed to obtain higher accuracy. At the same time, the gait phase classification results of multi-information and single information are compared. The experimental results verify the effectiveness of the multi-information fusion method. In addition, the delay time of each sensor and model classification time is measured, which shows that the system has tremendous real-time performance.
Dravet Variant SCN1AA1783V Impairs Interneuron Firing Predominantly by Altered Channel Activation
Authors: Layer Nikolas , Sonnenberg Lukas , Pardo González Emilio , Benda Jan , Hedrich Ulrike B. S. , Lerche Holger , Koch Henner , Wuttke Thomas V.
Published: October 2021

Dravet syndrome (DS) is a developmental epileptic encephalopathy mainly caused by functional NaV1.1 haploinsufficiency in inhibitory interneurons. Recently, a new conditional mouse model expressing the recurrent human p.(Ala1783Val) missense variant has become available. In this study, we provided an electrophysiological characterization of this variant in tsA201 cells, revealing both altered voltage-dependence of activation and slow inactivation without reduced sodium peak current density. Based on these data, simulated interneuron (IN) firing properties in a conductance-based single-compartment model suggested surprisingly similar firing deficits for NaV1.1A1783V and full haploinsufficiency as caused by heterozygous truncation variants. Impaired NaV1.1A1783V channel activation was predicted to have a significantly larger impact on channel function than altered slow inactivation and is therefore proposed as the main mechanism underlying IN dysfunction. The computational model was validated in cortical organotypic slice cultures derived from conditional Scn1aA1783V mice. Pan-neuronal activation of the p.Ala1783V in vitro confirmed a predicted IN firing deficit and revealed an accompanying reduction of interneuronal input resistance while demonstrating normal excitability of pyramidal neurons. Altered input resistance was fed back into the model for further refinement. Taken together these data demonstrate that primary loss of function (LOF) gating properties accompanied by altered membrane characteristics may match effects of full haploinsufficiency on the neuronal level despite maintaining physiological peak current density, thereby causing DS.
Propofol Inhibits Microglial Activation via miR-106b/Pi3k/Akt Axis
Authors: Liu Jianhui , Ai Pu , Sun Yiyan , Yang Xiaoyu , Li Chunhong , Liu Yihan , Xia Xiaohuan , Zheng Jialin C.
Published: October 2021

Propofol is an established intravenous anesthetic agent with potential neuroprotective effects. In this study, we investigated the roles and the underlying mechanisms of propofol in inhibiting the pro-inflammatory responses of microglia. Propofol significantly reduced the messenger RNA (mRNA) levels ofTnf,Nos2, and NF-κB pathway related genesTicam1,Myd88,Irf3, andNfkb1in lipopolysaccharide (LPS)-treated primary microglia. After screening the miRNA profiles in microglia under LPS and propofol treatment conditions, we found propofol abrogated the LPS-induced misexpression of miRNAs including miR-106b, miR-124, miR-185, and miR-9. Perturbation of function approaches suggested miR-106b as the core miRNA that mediated the anti-inflammatory effects of propofol on microglial activation. RNA sequencing (RNA-seq) analysis further identified Pi3k/Akt signaling as one of the most affected pathways after miR-106b perturbation of function. The treatment of Pi3k/Akt signaling agonist 740Y-P elevated miR-106b-reduced Akt phosphorylation and abolished the inhibitory effects of miR-106b on the pro-inflammatory responses of microglia. Our results suggest propofol inhibits microglial activationviamiR-106b/Pi3k/Akt axis, shedding light on a novel molecular mechanism of propofol-mediated immunomodulatory effects and implying propofol as potential therapeutics for treating neuroinflammation-related neurodegenerative diseases.
Muscle Selection and Dosing in a Phase 3, Pivotal Study of AbobotulinumtoxinA Injection in Upper Limb Muscles in Children With Cerebral Palsy
Authors: Oleszek Joyce , Tilton Ann , Carranza del Rio Jorge , Dursun Nigar , Bonikowski Marcin , Dabrowski Edward , Page Simon , Regnault Benjamin , Thompson Catherine , Delgado Mauricio R.
Published: October 2021

Background: Guidelines recommend botulinum toxin-A in pediatric upper limb spasticity as part of routine practice. Appropriate dosing is a prerequisite for treatment success and it is important that injectors have an understanding on how to tailor dosing within a safe and effective range. We report upper limb dosing data from a phase 3 study of abobotulinumtoxinA injections in children with cerebral palsy.

Methods: This was a double-blind, repeat-treatment study (NCT02106351). In Cycle 1, children were randomized to abobotulinumtoxinA at 2 U/kg control dose or clinically relevant 8 U/kg or 16 U/kg doses. Doses were divided between the primary target muscle group (PTMG, wrist or elbow flexors) and additional muscles tailored to clinical presentation. During Cycles 2–4, children received doses of 8 U/kg or 16 U/kg and investigators could change the PTMG and other muscles to be injected. Injection of muscles in the other upper limb and lower limbs was also permitted in cycles 2–4, with the total body dose not to exceed 30 U/kg or 1,000 U (whichever was lower) in the case of upper and lower limb treatment.

Results: 212 children were randomized, of which 210 received ≥1 abobotulinumtoxinA injection. Per protocol, the elbow and wrist flexors were the most commonly injected upper limb muscles. Across all 4 cycles, the brachialis was injected in 89.5% of children (dose range 0.8–6 U/kg), the brachioradialis in 83.8% (0.4–3 U/kg), the flexor carpi ulnaris in 82.4% (0.5–3 U/kg) and the flexor carpi radialis in 79.5% (0.5–4 U/kg). Other frequently injected upper limb muscles were the pronator teres(70.0%, 0.3–3 U/kg). adductor pollicis (54.3%, 0.3-1 U/kg), pronator quadratus (44.8%, 0.1–2 U/kg), flexor digitorum superficialis (39.0%, 0.5-4 U/kg), flexor digitorum profundus (28.6%, 0.5–2 U), flexor pollicis brevis/opponens pollicis (27.6%, 0.3-1 U/kg) and biceps (27.1%, 0.5–6 U/kg). AbobotulinumtoxinA was well-tolerated at these doses; muscular weakness was reported in 4.3% of children in the 8 U/kg group and 5.7% in the 16 U/kg group.

Conclusions: These data provide information on the pattern of injected muscles and dose ranges used in this study, which were well-tolerated. Per protocol, most children received injections into the elbow and wrist flexors. However, there was a wide variety of other upper limb muscles injected as physicians tailored injection patterns to clinical need.
The Role of GM130 in Nervous System Diseases
Authors: Huang Bei , Li Xihong , Zhu Xiaoshi
Published: October 2021

Golgi matrix protein 130 (GM130) is a Golgi-shaping protein located on the cis surface of the Golgi apparatus (GA). It is one of the most studied Golgin proteins so far. Its biological functions are involved in many aspects of life processes, including mitosis, autophagy, apoptosis, cell polarity, and directed migration at the cellular level, as well as intracellular lipid and protein transport, microtubule formation and assembly, lysosome function maintenance, and glycosylation modification. Mutation inactivation or loss of expression of GM130 has been detected in patients with different diseases. GM130 plays an important role in the development of the nervous system, but the studies on it are limited. This article reviewed the current research progress of GM130 in nervous system diseases. It summarized the physiological functions of GM130 in the occurrence and development of Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), microcephaly (MCPH), sepsis associated encephalopathy (SAE), and Ataxia, aiming to provide ideas for the further study of GM130 in nervous system disease detection and treatment.
Immediate Effect of Dry Needling at Myofascial Trigger Point on Hand Spasticity in Chronic Post-stroke Patients: A Multicenter Randomized Controlled Trial
Authors: Zhang Zengqiao , Wang Wu , Song Yongjia , Zhai Tianjun , Zhu Yan , Jiang Liming , Li Qunfeng , Jin Lei , Li Kunpeng , Feng Wei
Published: October 2021

Background: Hand spasticity after stroke influences the rehabilitation of hand function. Immediate and effective relief of spasticity potentially creates conditions for later rehabilitation training, which has far-reaching significance in the smooth transition of patients to the recovery period.

Objective: To evaluate the immediate effect of dry needling (DN) at myofascial trigger point on hand spasticity in stroke patients.

Methods: This was a prospective, evaluator blind, multicenter, randomized controlled study. A total of 210 participants were randomly divided into DN group (DN, N = 70), sham dry needling group (SDN, N = 70), and control group (N = 70). Participants in the DN group were treated with DN at myofascial trigger point five times (30 min each time) every week for 4 weeks. Subjects in the SDN group were manipulated the same way as in the DN group, except that the acupuncture site was located in the area adjacent to the myofascial trigger point, which constituted a SDN. Routine rehabilitation treatment was performed for participants in the two groups and in the control group. The primary evaluation index was the immediate effect of hand spasticity relief. Secondary evaluation indicators included the cumulative effect of hand spasticity relief from baseline to week 4, and the changes in flexion angles of the wrist, thumb, and fingers 2–5 in the rest position before, immediately after, and 4 weeks after intervention.

Results: The immediate effective rate of spasticity relief (thumb, fingers 2–5, and wrist) of patients with different degrees of spasticity in the DN group was higher than that in the control and SDN groups (thumb, χ2 = 55.833, P < 0.001; fingers 2–5, χ2 = 68.096, P < 0.001; wrist, χ2 = 49.180, P < 0.001) (P < 0.05). The effective rate of spasticity relief from baseline to 4 weeks in the DN group exceeded that in the control group and SDN groups (thumb, χ2 = 8.806, P = 0.012; fingers 2–5, χ2 = 8.087, P = 0.018; and wrist, χ2 = 8.653, P = 0.013) (P < 0.05). No difference in immediate and cumulative effect was found between the control group and SDN group. The change of joints flexion angles in resting position before and after each treatment in the DN group was higher than that in the control and SDN groups (P < 0.05), but it was not significantly different between the control group and SDN group. At 4 weeks, although the change in the DN group was higher than that in the control group and SDN group, this difference was not statistically significant (P > 0.05).

Conclusion: Dry needling can relieve varying degrees of hand spasticity instantly in post-stroke.

Trial Registration:www.chictr.org.cn, ChiCTR1900022379.
Treatment Outcome and Risk Factors of Adult Newly Diagnosed Epilepsy: A Prospective Hospital-Based Study in Northeast China
Authors: Li Nan , Li Jing , Chen Yanyan , Chu Chaojia , Lin Weihong
Published: October 2021

Objective: The study was conducted to summarize the treatment outcomes of newly diagnosed epilepsy (NDE) and analyse the risk factors for refractory epilepsy (RE) in Northeast China.

Methods: A total of 466 adult patients with NDE were consecutively enrolled in this programme. Clinical data were collected at baseline and each follow-up. Several scales concerning recognition and mood were also completed at the first visit.

Results: Seizure-free status was achieved by 52% (n = 244) of the patients; however, 15% (n = 68) manifested RE. A total of 286 (61%) patients continued with the first ASM as monotherapy, among which 186 (40%) patients became seizure-free. Fifteen (22%) patients with RE became seizure-free following ASM adjustment and 34 patients (14%) had breakthrough seizures after being classified as seizure-free. One patient developed RE after attaining seizure-free status. Breakthrough seizures during the first expected interictal interval [Odds ratio (OR) = 5.81, 95% CI: 2.70–12.50], high seizure frequency at baseline (OR = 1.24, 95% CI: 1.04–1.49), younger age of onset (OR = 1.42, 95% CI: 1.12–1.79), and male sex (OR = 2.64, 95% CI: 1.26–5.53) were risk factors for RE.

Significance: Treatment outcomes of the majority of NDE cases are good. New risk factors could help physicians more promptly and accurately identify patients who are likely to develop RE. Seizure-free state is not long enough to commence the withdrawal of ASMs. RE is not permanent and seizure-free may be achieved subsequently by appropriate drug adjustment.
Theoretical Perspective on an Ideomotor Brain-Computer Interface: Toward a Naturalistic and Non-invasive Brain-Computer Interface Paradigm Based on Action-Effect Representation
Authors: Le Bars Solène , Chokron Sylvie , Balp Rodrigo , Douibi Khalida , Waszak Florian
Published: October 2021

Recent years have been marked by the fulgurant expansion of non-invasive Brain-Computer Interface (BCI) devices and applications in various contexts (medical, industrial etc.). This technology allows agents “to directly act with thoughts,” bypassing the peripheral motor system. Interestingly, it is worth noting that typical non-invasive BCI paradigms remain distant from neuroscientific models of human voluntary action. Notably, bidirectional links between action and perception are constantly ignored in BCI experiments. In the current perspective article, we proposed an innovative BCI paradigm that is directly inspired by the ideomotor principle, which postulates that voluntary actions are driven by the anticipated representation of forthcoming perceptual effects. We believe that (1) adapting BCI paradigms could allow simple action-effect bindings and consequently action-effect predictions and (2) using neural underpinnings of those action-effect predictions as features of interest in AI methods, could lead to more accurate and naturalistic BCI-mediated actions.
The Developmental Eye Movement Test as a Diagnostic Aid in Cerebral Visual Impairment
Authors: Tanke Nouk , Barsingerhorn Annemiek D. , Goossens Jeroen , Boonstra F. Nienke
Published: October 2021

The symptoms that characterize children with cerebral visual impairments (CVI) are diverse, ranging from extensive behavioral or physical disabilities to subtle changes that can easily be missed. A correct diagnosis of CVI is therefore difficult to make, but having a wide variety of tests available can be helpful. This study aims to determine if the developmental eye movement test (DEM) can be one of those tests. In this test, a fixed set of numbers has to be read aloud, first in vertical columns and then in horizontal lines. In order to measure differences between children with CVI compared to normally sighted age-matched controls and children with a visual impairment (VI), we determined DEM times, crowding intensities and the reaction time to a large visual stimulus for all three groups. We found that children with CVI or VI need significantly more time to read the DEM numbers than age-matched controls. Additionally, children with CVI need more time than children with VI to read the horizontal DEM, but not the vertical DEM. We also found a significant difference between the children with CVI and the other two groups in the relationship between horizontal DEM performance and crowding intensity. However, for the relationship between DEM performance and visual detection time, no group-differences were found. We conclude that the DEM can be a useful addition in the diagnosis of CVI, especially in combination with information about crowding.
Influence of the Inter-Trial Interval, Movement Observation, and Hand Dominance on the Previous Trial Effect
Authors: Oda Hitoshi , Sawaguchi Yasushi , Kawasaki Taku , Fukuda Shiho , Hiraoka Koichi
Published: October 2021

Previous studies have shown that current movement is influenced by the previous movement, which is known as the previous trial effect. In this study, we investigated the influence of the inter-trial interval, movement observation, and hand dominance on the previous trial effect of the non-target discrete movement. Right-handed healthy humans abducted the index finger in response to a start cue, and this task was repeated with constant inter-trial intervals. The absolute difference in the reaction time (RT) between the previous and current trials increased as the inter-trial interval increased. The absolute difference in RT reflects the reproducibility of the time taken for the motor execution between two consecutive trials. Thus, the finding supported the view that there is a carryover of movement information from one trial to the next, and that the underlying reproducibility of the RT between the two consecutive trials decays over time. This carryover of movement information is presumably conveyed by implicit short-term memory, which also decays within a short period of time. The correlation coefficient of the RT between the previous and current trials decreased with an increase in the inter-trial interval, indicating that the common responsiveness of two consecutive trials weakens over time. The absolute difference was smaller when the response was performed while observing finger movement, indicating that a carryover of the visual information to the next trial enhances the reproducibility of the motor execution process between consecutive trials. Hand dominance did not influence the absolute difference or correlation coefficient, indicating that the central process mediating previous trial effect of hand movement is not greatly lateralized.
Psychophysiological, but Not Behavioral, Indicator of Working Memory Capacity Predicts Video Game Proficiency
Authors: Jakubowska Natalia , Dobrowolski Paweł , Binkowska Alicja Anna , Arslan Ibrahim V. , Myśliwiec Monika , Brzezicka Aneta
Published: October 2021

Visual working memory (VWM) is the ability to actively maintain visual information over short periods of time and is strongly related to global fluid intelligence and overall cognitive ability. In our study, we used two indices of visual working memory capacity: the behavioral estimate of capacity (K) and contralateral delay activity (CDA) in order to check whether training in a Real-Time Strategy (RTS) video game StarCraft II can influence the VWM capacity measured by the change detection task. We also asked a question whether individual differences in behavioral and psychophysiological indices of VWM can predict the effectiveness of video game training. Sixty-two participants (non-players) were recruited to the experiment. Participants were randomly assigned to either experimental (Variable environment), active control (Fixed environment), and passive control groups. Experimental and active control groups differed in the type of training received. Training consisted of 30 h of playing the StarCraft II game. Participants took part in two EEG sessions (pre- and post-training) during which they performed the VWM task. Our results showed that working memory capacity (K calculated according to Pashler’s formula) increases after training in both experimental groups, but not in a control group. We have also found a correlation between average visual working memory capacity (calculated as K) and mean CDA amplitude no matter which group we are looking at. And, last but not least, we have found that we can predict the amount of improvement in the RTS video game by looking at the psychophysiological indices (CDA amplitude) recorded at baseline (before training), but only in the experimental group. We think that the strength of the psychophysiological indicator of VWM capacity might be a marker of the future success in video game acquisition.
Resting-State Functional Magnetic Resonance Imaging Networks as a Quantitative Metric for Impact of Neurosurgical Interventions
Authors: Yang Peter H. , Hacker Carl D. , Patel Bhuvic , Daniel Andy G. S. , Leuthardt Eric C.
Published: October 2021

Objective: Resting-state functional MRI (rs-fMRI) has been used to evaluate brain network connectivity as a result of intracranial surgery but has not been used to compare different neurosurgical procedures. Laser interstitial thermal therapy (LITT) is an alternative to conventional craniotomy for the treatment of brain lesions such as tumors and epileptogenic foci. While LITT is thought of as minimally invasive, its effect on the functional organization of the brain is still under active investigation and its impact on network changes compared to conventional craniotomy has not yet been explored. We describe a novel computational method for quantifying and comparing the impact of two neurosurgical procedures on brain functional connectivity.

Methods: We used a previously described seed-based correlation analysis to generate resting-state network (RSN) correlation matrices, and compared changes in correlation patterns within and across RSNs between LITT and conventional craniotomy for treatment of 24 patients with singular intracranial tumors at our institution between 2014 and 2017. Specifically, we analyzed the differences in patient-specific changes in the within-hemisphere correlation patterns of the contralesional hemisphere.

Results: In a post-operative follow-up period up to 2 years within-hemisphere connectivity of the contralesional hemisphere after surgery was more highly correlated to the pre-operative state in LITT patients when compared to craniotomy patients (P = 0.0287). Moreover, 4 out of 11 individual RSNs demonstrated significantly higher degrees of correlation between pre-operative and post-operative network connectivity in patients who underwent LITT (all P < 0.05).

Conclusion: Rs-fMRI may be used as a quantitative metric to determine the impact of different neurosurgical procedures on brain functional connectivity. Global and individual network connectivity in the contralesional hemisphere may be more highly preserved after LITT when compared to craniotomy for the treatment of brain tumors.
Characterization of Generalizability of Spike Timing Dependent Plasticity Trained Spiking Neural Networks
Authors: Chakraborty Biswadeep , Mukhopadhyay Saibal
Published: October 2021

A Spiking Neural Network (SNN) is trained with Spike Timing Dependent Plasticity (STDP), which is a neuro-inspired unsupervised learning method for various machine learning applications. This paper studies the generalizability properties of the STDP learning processes using the Hausdorff dimension of the trajectories of the learning algorithm. The paper analyzes the effects of STDP learning models and associated hyper-parameters on the generalizability properties of an SNN. The analysis is used to develop a Bayesian optimization approach to optimize the hyper-parameters for an STDP model for improving the generalizability properties of an SNN.
Formant-Based Recognition of Words and Other Naturalistic Sounds in Rhesus Monkeys
Authors: Melchor Jonathan , Vergara José , Figueroa Tonatiuh , Morán Isaac , Lemus Luis
Published: October 2021

In social animals, identifying sounds is critical for communication. In humans, the acoustic parameters involved in speech recognition, such as the formant frequencies derived from the resonance of the supralaryngeal vocal tract, have been well documented. However, how formants contribute to recognizing learned sounds in non-human primates remains unclear. To determine this, we trained two rhesus monkeys to discriminate target and non-target sounds presented in sequences of 1–3 sounds. After training, we performed three experiments: (1) We tested the monkeys’ accuracy and reaction times during the discrimination of various acoustic categories; (2) their ability to discriminate morphing sounds; and (3) their ability to identify sounds consisting of formant 1 (F1), formant 2 (F2), or F1 and F2 (F1F2) pass filters. Our results indicate that macaques can learn diverse sounds and discriminate from morphs and formants F1 and F2, suggesting that information from few acoustic parameters suffice for recognizing complex sounds. We anticipate that future neurophysiological experiments in this paradigm may help elucidate how formants contribute to the recognition of sounds.
B and T Immunoregulation: A New Insight of B Regulatory Lymphocytes in Autism Spectrum Disorder
Authors: De Giacomo Andrea , Gargano Concetta Domenica , Simone Marta , Petruzzelli Maria Giuseppina , Pedaci Chiara , Giambersio Donatella , Margari Lucia , Ruggieri Maddalena
Published: October 2021

Introduction: Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by a complex pathogenesis, by impairment social communication and interaction, and may also manifest repetitive patterns of behavior. Many studies have recognized an alteration of the immune response as a major etiological component in ASDs. Despite this, it is still unclear the variation of the function of the immune response.

Aim: Our aim is to investigate the levels of immunological markers in peripheral blood of children with ASD such as: regulatory B and T cells, memory B and natural killer (NK) cells.

Materials and Methods: We assessed various subsets of immune cells in peripheral blood (regulatory B and T cells, B-cell memory and natural killer cells) by multi-parametric flow cytometric analysis in 26 ASD children compared to 16 healthy controls (HCs) who matched age and gender.

Results: No significant difference was observed between B-cell memory and NK cells in ASDs and HCs. Instead, regulatory B cells and T cells were decreased (p < 0.05) in ASD subjects when compared to HCs.

Discussion: Regulatory B and T cells have a strategic role in maintaining the immune homeostasis. Their functions have been associated with the development of multiple pathologies especially in autoimmune diseases. According to our study, the immunological imbalance of regulatory B and T cells may play a pivotal role in the evolution of the disease, as immune deficiencies could be related to the severity of the ongoing disorder.