bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparative Study of Structural and Metabolic Brain Networks in Patients With Mild Cognitive Impairment
Authors: Wei Cuibai , Gong Shuting , Zou Qi , Zhang Wei , Kang Xuechun , Lu Xinliang , Chen Yufei , Yang Yuting , Wang Wei , Jia Longfei , Lyu Jihui , Shan Baoci
Published: December 2021

Background: Changes in the metabolic and structural brain networks in mild cognitive impairment (MCI) have been widely researched. However, few studies have compared the differences in the topological properties of the metabolic and structural brain networks in patients with MCI.

Methods: We analyzedmagnetic resonance imaging (MRI) and fluoro-deoxyglucose positron emission tomography (FDG-PET) data of 137 patients with MCI and 80 healthy controls (HCs). The HC group data comes from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The permutation test was used to compare the network parameters (characteristic path length, clustering coefficient, local efficiency, and global efficiency) between the two groups. Partial Pearson’s correlation analysis was used to calculate the correlations of the changes in gray matter volume and glucose intake in the key brain regions in MCI with the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-cog) sub-item scores.

Results: Significant changes in the brain network parameters (longer characteristic path length, larger clustering coefficient, and lower local efficiency and global efficiency) were greater in the structural network than in the metabolic network (longer characteristic path length) in MCI patients than in HCs. We obtained the key brain regions (left globus pallidus, right calcarine fissure and its surrounding cortex, left lingual gyrus) by scanning the hubs. The volume of gray matter atrophy in the left globus pallidus was significantly positively correlated with comprehension of spoken language (p = 0.024) and word-finding difficulty in spontaneous speech item scores (p = 0.007) in the ADAS-cog. Glucose intake in the three key brain regions was significantly negatively correlated with remembering test instructions items in ADAS-cog (p = 0.020, p = 0.014, and p = 0.008, respectively).

Conclusion: Structural brain networks showed more changes than metabolic brain networks in patients with MCI. Some brain regions with significant changes in betweenness centrality in both structural and metabolic networks were associated with MCI.
Reunification of Object and View-Center Background Information in the Primate Medial Temporal Lobe
Authors: Chen He , Naya Yuji
Published: December 2021

Recent work has shown that the medial temporal lobe (MTL), including the hippocampus (HPC) and its surrounding limbic cortices, plays a role in scene perception in addition to episodic memory. The two basic factors of scene perception are the object (“what”) and location (“where”). In this review, we first summarize the anatomical knowledge related to visual inputs to the MTL and physiological studies examining object-related information processed along the ventral pathway briefly. Thereafter, we discuss the space-related information, the processing of which was unclear, presumably because of its multiple aspects and a lack of appropriate task paradigm in contrast to object-related information. Based on recent electrophysiological studies using non-human primates and the existing literature, we proposed the “reunification theory,” which explains brain mechanisms which construct object-location signals at each gaze. In this reunification theory, the ventral pathway signals a large-scale background image of the retina at each gaze position. This view-center background signal reflects the first person’s perspective and specifies the allocentric location in the environment by similarity matching between images. The spatially invariant object signal and view-center background signal, both of which are derived from the same retinal image, are integrated again (i.e., reunification) along the ventral pathway-MTL stream, particularly in the perirhinal cortex. The conjunctive signal, which represents a particular object at a particular location, may play a role in scene perception in the HPC as a key constituent element of an entire scene.
Early Tranexamic Acid in Intracerebral Hemorrhage: A Meta-Analysis of Randomized Controlled Trials
Authors: Jiao Xu , Li Mingfei , Li Lulu , Hu Xinyu , Guo Xiaohui , Lu Yun
Published: December 2021

Objective: Intracranial hemorrhage (ICH) is a common complication of traumatic brain, in which tranexamic acid has been recommended as an additional therapy to prevent a second bleeding. However, the effect of early administration of tranexamic acid for ICH patients remains controversial.

Methods: A systematic search was performed in Cochrane Library, Medline, Embase, and Web of Science. Poor outcome refers to significant hemorrhage growth, new intracranial hemorrhage, new focal cerebral ischaemic lesions, the need for neurosurgery, or death. Study heterogeneity and publication bias were estimated.

Results: Seven randomized controlled trials involving 3,192 participants were included in our meta-analysis. Tranexamic acid administration in ICH patients was associated with better outcomes of hematoma expansion (odd ratios [OR] 0.79; 95% confidence interval (CI) CI, 0.67–0.93; I2 = 0%; P = 0.006) and growth of hemorrhagic lesions (weighted mean difference [WMD], −1.97 ml; 95% CI, −2.94 to −1.00; I2 = 14%; P < 0.001) than the placebo. No difference was found between the mortality, poor outcome, neurosurgical intervention, new bleeding, and the duration of hospital stay. Moreover, no publication bias was found.

Conclusion: Our analysis reveals that the early treatment with tranexamic acid can significantly reduce the incidence of hematoma expansion and the volume of hemorrhagic lesion, but does not exert considerable effects on mortality, poor outcome, neurosurgery, rebleeding, and the duration of stay.
Machine Learning in Action: Stroke Diagnosis and Outcome Prediction
Authors: Mainali Shraddha , Darsie Marin E. , Smetana Keaton S.
Published: December 2021

The application of machine learning has rapidly evolved in medicine over the past decade. In stroke, commercially available machine learning algorithms have already been incorporated into clinical application for rapid diagnosis. The creation and advancement of deep learning techniques have greatly improved clinical utilization of machine learning tools and new algorithms continue to emerge with improved accuracy in stroke diagnosis and outcome prediction. Although imaging-based feature recognition and segmentation have significantly facilitated rapid stroke diagnosis and triaging, stroke prognostication is dependent on a multitude of patient specific as well as clinical factors and hence accurate outcome prediction remains challenging. Despite its vital role in stroke diagnosis and prognostication, it is important to recognize that machine learning output is only as good as the input data and the appropriateness of algorithm applied to any specific data set. Additionally, many studies on machine learning tend to be limited by small sample size and hence concerted efforts to collate data could improve evaluation of future machine learning tools in stroke. In the present state, machine learning technology serves as a helpful and efficient tool for rapid clinical decision making while oversight from clinical experts is still required to address specific aspects not accounted for in an automated algorithm. This article provides an overview of machine learning technology and a tabulated review of pertinent machine learning studies related to stroke diagnosis and outcome prediction.
Altered Default Mode Network Is Associated With Cognitive Impairment in CADASIL as Revealed by Multimodal Neuroimaging
Authors: Li Panlong , Huang Qi , Ban Shiyu , Qiao Yuan , Wu Jing , Zhai Yu , Du Xiaoxia , Hua Fengchun , Su Jingjing
Published: December 2021

Background and Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy caused by mutations in the NOTCH3 gene is a hereditary cerebral small vessel disease, manifesting with stroke, cognitive impairment, and mood disturbances. Functional or structural changes in the default mode network (DMN), which plays important role in cognitive and mental maintenance, have been found in several neurological and mental diseases. However, it remains unclear whether DMN is altered in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Methods: Multimodal imaging methods, including MRI and positron emission tomography (PET), were applied to evaluate the functional, structural, and metabolic characteristics of DMN in 25 patients with CADASIL and 42 healthy controls.

Results: Compared with controls, patients with CADASIL had decreased nodal efficiency and degree centrality of the dorsal medial pre-frontal cortex and hippocampal formation within DMN. Structural MRI and diffusion tensor imaging (DTI) showed decreased gray matter volume and fiber tracks presented in the bilateral hippocampal formation. Meanwhile, PET imaging showed decreased metabolism within the whole DMN in CADASIL. Furthermore, correlation analyses showed that these nodal characteristics, gray matter volume, and metabolic signals of DMN were related to cognitive scores in CADASIL.

Conclusions: Our results suggested that altered network characteristics of DMN might play important roles in cognitive deficits of CADASIL.
Combined Application of Sodium Fluorescein and Neuronavigation Techniques in the Resection of Brain Gliomas
Authors: Xue Zhan , Kong Lu , Hao Shuyu , Wang Yu , Jia Guijun , Wu Zhen , Jia Wang , Zhang Junting , Zhang Liwei
Published: December 2021

Objectives: To explore the effectiveness and safety of the combined application of sodium fluorescein and neuronavigation techniques in the resection of brain gliomas in different locations and patients of different ages.

Methods: Fifty clinical cases of brain gliomas treated at the Department of Neurosurgery of Beijing Tiantan Hospital were collected from March 2014 to March 2019. These cases were divided into a supratentorial group (24 cases) and a brainstem group (26 cases) based on location and an adult group (28 cases) and a pediatric group (22 cases) based on age. Fluorescein-guided surgery was performed: the adult group received 5 mg/kg sodium fluorescein before opening the dura, while the pediatric group received 2.5 mg/kg during resection. Tumor visualization was evaluated by the enhancement of yellow fluorescein and considered “satisfactory” if the illumination demarcated the tumor boundary. Additionally, the consistency between fluorescein and neuronavigation was analyzed. The Karnofsky performance score (KPS) of all patients was recorded and assessed at admission, discharge, and the 6-month follow-up.

Results: In the 28 adult cases, 4 were unsatisfactory, while in the 22 pediatric cases, 2 were unsatisfactory; in 7 cases, there was an inconsistency between yellow fluorescein enhancement and neuronavigation, 6 were in the supratentorial group, and 1 was in the brainstem group. Statistical analysis showed no significant differences in the satisfactory rate between the adult and pediatric groups (P = 0.575), whereas there were significant differences inconsistency between the supratentorial group and brainstem group (P = 0.031). The mean KPS at admission was between 70 and 100, which was not significantly different from that at discharge (P = 0.839), but the KPS at the 6-month follow-up was significantly higher than that at admission (P = 0.041).

Conclusions: The consistency between sodium fluorescein and the neuronavigation system was higher in the brainstem group than in the supratentorial group; a half dose of sodium fluorescein (2.5 mg/kg) was sufficient for pediatric patients. The combined utilization of sodium fluorescein and neuronavigation techniques may confer glioma patients the opportunity to obtain better clinical outcomes after surgery.
Improving Diagnosis and Prognosis in Acute Severe Brain Injury: A Multimodal Imaging Protocol
Authors: Kazazian Karnig , Norton Loretta , Laforge Geoffrey , Abdalmalak Androu , Gofton Teneille E. , Debicki Derek , Slessarev Marat , Hollywood Sarah , Lawrence Keith St. , Owen Adrian M.
Published: December 2021

Multi-modal neuroimaging techniques have the potential to dramatically improve the diagnosis of the level consciousness and prognostication of neurological outcome for patients with severe brain injury in the intensive care unit (ICU). This protocol describes a study that will utilize functional Magnetic Resonance Imaging (fMRI), electroencephalography (EEG), and functional Near Infrared Spectroscopy (fNIRS) to measure and map the brain activity of acute critically ill patients. Our goal is to investigate whether these modalities can provide objective and quantifiable indicators of good neurological outcome and reliably detect conscious awareness. To this end, we will conduct a prospective longitudinal cohort study to validate the prognostic and diagnostic utility of neuroimaging techniques in the ICU. We will recruit 350 individuals from two ICUs over the course of 7 years. Participants will undergo fMRI, EEG, and fNIRS testing several times over the first 10 days of care to assess for residual cognitive function and evidence of covert awareness. Patients who regain behavioral awareness will be asked to complete web-based neurocognitive tests for 1 year, as well as return for follow up neuroimaging to determine which acute imaging features are most predictive of cognitive and functional recovery. Ultimately, multi-modal neuroimaging techniques may improve the clinical assessments of patients' level of consciousness, aid in the prediction of outcome, and facilitate efforts to find interventional methods that improve recovery and quality of life.
Postural Asymmetries and Assistive Devices Used by Adults With Cerebral Palsy in Lying, Sitting, and Standing
Authors: Rodby-Bousquet Elisabet , Agustsson Atli
Published: December 2021

Purpose: To describe the use of assistive devices and postural asymmetries in lying, sitting and standing positions in adults with cerebral palsy, and to analyze postural asymmetries and any associations with their ability to maintain or change position and time in these positions.

Methods: A cross-sectional study based on data from the Swedish Cerebral Palsy follow-up program of 1,547 adults aged 16–76 years, at Gross Motor Function Classification System (GMFCS) levels I (n = 330), II (n = 323), III (n = 235), IV (n = 298), and V (n = 361). Assistive devices such as wheelchairs, seating systems, adjustable beds, standing equipment and time in each position were reported. The Posture and Postural Ability Scale was used to identify asymmetries and rate the ability to maintain or change position. Binary logistic regression models were used to estimate odds ratios (OR) for postural asymmetries in supine, sitting and standing.

Results: Assistive devices were used by 63% in sitting (range 5–100% GMFCS levels I–V), 42% in lying (4–92% levels I-V), and 32% in standing (2–70% levels II–V). Wheelchairs were used as seating systems by 57%. Most adults had postural asymmetries in supine (75%; range 35–100% levels I–V), sitting (81%; 50–99% levels I–V) and standing (88%; 65–100% levels I–V). Men were more likely than women to have postural asymmetries, and the likelihood of postural asymmetries increased with age, GMFCS levels and inability to change position. Inability to maintain position increased the probability of postural asymmetries in all positions from OR 2.6 in standing to OR 8.2 in lying and OR 13.1 in sitting.

Conclusions: Almost twice as many adults used assistive devices in sitting than in lying or standing. Two thirds of the adults who used standing devices used it for <1 h per day, indicating that they might spend the remaining 23 out of 24 h per day either sitting or lying. Asymmetric postures were frequent across all ages and were highly associated with inability to change or maintain position.
Case Report: Functional Investigation of an Undescribed Missense Variant Affecting Splicing in a Patient With Dravet Syndrome
Authors: Sparber Peter , Mikhaylova Svetlana , Galkina Varvara , Itkis Yulia , Skoblov Mikhail
Published: December 2021

Pathogenic variants in the SCN1A gene are associated with a spectrum of epileptic disorders ranging in severity from familial febrile seizures to Dravet syndrome. Large proportions of reported pathogenic variants in SCN1A are annotated as missense variants and are often classified as variants of uncertain significance when no functional data are available. Although loss-of-function variants are associated with a more severe phenotype in SCN1A, the molecular mechanism of single nucleotide variants is often not clear, and genotype-phenotype correlations in SCN1A-related epilepsy remain uncertain. Coding variants can affect splicing by creating novel cryptic splicing sites in exons or by disrupting exonic cis-regulation elements crucial for proper pre-mRNA splicing. Here, we report a novel case of Dravet syndrome caused by an undescribed missense variant, c.4852G>A (p.(Gly1618Ser)). By midigene splicing assay, we demonstrated that the identified variant is in fact splice-affecting. To our knowledge, this is the first report on the functional investigation of a missense variant affecting splicing in Dravet syndrome.
TNFα in MS and Its Animal Models: Implications for Chronic Pain in the Disease
Authors: Maguire Aislinn D. , Bethea John R. , Kerr Bradley J.
Published: December 2021

Multiple Sclerosis (MS) is a debilitating autoimmune disease often accompanied by severe chronic pain. The most common type of pain in MS, called neuropathic pain, arises from disease processes affecting the peripheral and central nervous systems. It is incredibly difficult to study these processes in patients, so animal models such as experimental autoimmune encephalomyelitis (EAE) mice are used to dissect the complex mechanisms of neuropathic pain in MS. The pleiotropic cytokine tumor necrosis factor α (TNFα) is a critical factor mediating neuropathic pain identified by these animal studies. The TNF signaling pathway is complex, and can lead to cell death, inflammation, or survival. In complex diseases such as MS, signaling through the TNFR1 receptor tends to be pro-inflammation and death, whereas signaling through the TNFR2 receptor is pro-homeostatic. However, most TNFα-targeted therapies indiscriminately block both arms of the pathway, and thus are not therapeutic in MS. This review explores pain in MS, inflammatory TNF signaling, the link between the two, and how it could be exploited to develop more effective TNFα-targeting pain therapies.
The Safety and Efficacy of Stem Cell Therapy as an Emerging Therapy for ALS: A Systematic Review of Controlled Clinical Trials
Authors: Aljabri Ammar , Halawani Alhussain , Bin Lajdam Ghassan , Labban Suhail , Alshehri Samah , Felemban Razaz
Published: December 2021

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a heterogeneous course that ultimately leads to death. Currently, there is no cure, and new treatments that can slow the progression of the disease are needed. Stem cell (SC) transplantation is an emerging therapy that has shown a lot of potential in recent clinical trials. This review is aimed to examine the results of various clinical trials on this topic, thus assessing the safety and efficacy of SC transplantation as a potential treatment for ALS. We identified 748 studies in our search, of which 134 full-text studies were assessed for eligibility. Six studies met the inclusion criteria and were included in this review. Although some of the included studies showed the positive effect of SC transplantation, other studies found that there was no significant difference compared to the control group. We observed more positive effects with bone marrow mesenchymal stem cells (BM-MSC) treatments than Granulocyte colony-stimulating factor (G-CSF) ones. However, other factors, such as route of administration, number of doses, and number of cells per dose, could also play a role in this discrepancy. Based on this information, we conclude that more properly conducted clinical trials are needed to appreciate the benefit of this treatment.
Trauma Communications Center Coordinated Severity-Based Stroke Triage: Protocol of a Hybrid Type 1 Effectiveness-Implementation Study
Authors: Gropen Toby I. , Ivankova Nataliya V. , Beasley Mark , Hess Erik P. , Mittman Brian , Gazi Melissa , Minor Michael , Crawford William , Floyd Alice B. , Varner Gary L. , Lyerly Michael J. , Shoemaker Camella C. , Owens Jackie , Wilson Kent , Gray Jamie , Kamal Shaila
Published: December 2021

Background:Mechanical thrombectomy (MT) can improve the outcomes of patients with large vessel occlusion (LVO), but a minority of patients with LVO are treated and there are disparities in timely access to MT. In part, this is because in most regions, including Alabama, the emergency medical service (EMS) transports all patients with suspected stroke, regardless of severity, to the nearest stroke center. Consequently, patients with LVO may experience delayed arrival at stroke centers with MT capability and worse outcomes. Alabama's trauma communications center (TCC) coordinates EMS transport of trauma patients by trauma severity and regional hospital capability. Our aims are to develop a severity-based stroke triage (SBST) care model based on Alabama's trauma system, compare the effectiveness of this care pathway to current stroke triage in Alabama for improving broad, equitable, and timely access to MT, and explore stakeholder perceptions of the intervention's feasibility, appropriateness, and acceptability.

Methods:This is a hybrid type 1 effectiveness-implementation study with a multi-phase mixed methods sequential design and an embedded observational stepped wedge cluster trial. We will extend TCC guided stroke severity assessment to all EMS regions in Alabama; conduct stakeholder interviews and focus groups to aid in development of region and hospital specific prehospital and inter-facility stroke triage plans for patients with suspected LVO; implement a phased rollout of TCC Coordinated SBST across Alabama's six EMS regions; and conduct stakeholder surveys and interviews to assess context-specific perceptions of the intervention. The primary outcome is the change in proportion of prehospital stroke system patients with suspected LVO who are treated with MT before and after implementation of TCC Coordinated SBST. Secondary outcomes include change in broad public health impact before and after implementation and stakeholder perceptions of the intervention's feasibility, appropriateness, and acceptability using a mixed methods approach. With 1200 to 1300 total observations over 36 months, we have 80% power to detect a 15% improvement in the primary endpoint.

Discussion:This project, if successful, can demonstrate how the trauma system infrastructure can serve as the basis for a more integrated and effective system of emergency stroke care.
Plasma Uric Acid Helps Predict Cognitive Impairment in Patients With Amyotrophic Lateral Sclerosis
Authors: Tang Jiahui , Yang Yuan , Gong Zhenxiang , Li Zehui , Huang Lifang , Ding Fengfei , Liu Mao , Zhang Min
Published: December 2021

Objective: Uric acid as an antioxidant plays an important role in neurodegenerative disease. Our objective is to investigate the relationship between plasma uric acid and cognitive impairment in patients with amyotrophic lateral sclerosis (ALS).

Methods: In this cross-sectional study, 124 ALS patients were screened by the Edinburgh Cognitive and Behavioral Screen (ECAS) and classified according to the revised Strong's criteria. Additionally, based on total ECAS cut-off score patients were categorized into those with cognitive impairment (ALS-cie) and those without cognitive impairment (ALS-ncie), and clinical data and uric acid level were compared between the two groups. Parameters with significant differences were further included in a multivariate linear regression analysis with ECAS score as a dependent variable. Hold-out validation was performed to evaluate the fitness of regression model.

Results: Up to 60% of ALS patients showed cognitive or/and behavioral impairment. The ALS-cie group had lower education level (p < 0.001), older age at symptom onset (p = 0.001), older age at testing (p = 0.001), and lower plasma uric acid (p = 0.01). Multivariate analysis showed increased uric acid (β = 0.214, p = 0.01), lower age at testing (β = −0.378, p < 0.001), and higher education level (β = 0.424, p < 0.001) could predict higher ECAS score (F = 19.104, R2 = 0.381, p < 0.0001). Validation analysis showed that predicted ECAS score was significantly correlated with raw ECAS score in both the training set (rs = 0.621, p < 0.001) and the testing set (rs = 0.666, p < 0.001).

Conclusions: Cognitive impairment was a common feature in our Chinese ALS patients. Plasma uric acid might help evaluate the risk of cognitive impairment in ALS patients when combined with education level and age at testing.
Different Patterns of Attention Modulation in Early N140 and Late P300 sERPs Following Ipsilateral vs. Contralateral Stimulation at the Fingers and Cheeks
Authors: Lindenbaum Laura , Zehe Sebastian , Anlauff Jan , Hermann Thomas , Kissler Johanna Maria
Published: December 2021

Intra-hemispheric interference has been often observed when body parts with neighboring representations within the same hemisphere are stimulated. However, patterns of interference in early and late somatosensory processing stages due to the stimulation of different body parts have not been explored. Here, we explore functional similarities and differences between attention modulation of the somatosensory N140 and P300 elicited at the fingers vs. cheeks. In an active oddball paradigm, 22 participants received vibrotactile intensity deviant stimulation either ipsilateral (within-hemisphere) or contralateral (between-hemisphere) at the fingers or cheeks. The ipsilateral deviant always covered a larger area of skin than the contralateral deviant. Overall, both N140 and P300 amplitudes were higher following stimulation at the cheek and N140 topographies differed between fingers and cheek stimulation. For the N140, results showed higher deviant ERP amplitudes following contralateral than ipsilateral stimulation, regardless of the stimulated body part. N140 peak latency differed between stimulated body parts with shorter latencies for the stimulation at the fingers. Regarding P300 amplitudes, contralateral deviant stimulation at the fingers replicated the N140 pattern, showing higher responses and shorter latencies than ipsilateral stimulation at the fingers. For the stimulation at the cheeks, ipsilateral deviants elicited higher P300 amplitudes and longer latencies than contralateral ones. These findings indicate that at the fingers ipsilateral deviant stimulation leads to intra-hemispheric interference, with significantly smaller ERP amplitudes than in contralateral stimulation, both at early and late processing stages. By contrast, at the cheeks, intra-hemispheric interference is selective for early processing stages. Therefore, the mechanisms of intra-hemispheric processing differ from inter-hemispheric ones and the pattern of intra-hemispheric interference in early and late processing stages is body-part specific.
Segmental Abnormalities of White Matter Microstructure in End-Stage Renal Disease Patients: An Automated Fiber Quantification Tractography Study
Authors: Jiang Yuhan , Liu Yangyingqiu , Gao Bingbing , Che Yiwei , Lin Liangjie , Jiang Jian , Chang Peipei , Song Qingwei , Wang Nan , Wang Weiwei , Miao Yanwei
Published: December 2021

Background and Purpose: End-stage renal disease (ESRD) results in extensive white matter abnormalities, but the specific damage segment cannot be identified. This study aimed to determine the segmental abnormalities of white matter microstructure in ESRD and its relationship with cognitive and renal function indicators.

Methods: Eighteen ESRD patients and 19 healthy controls (HCs) were prospectively recruited. All participants underwent DTI and clinical assessments. Automatic fiber quantification (AFQ) was applied to generate bundle profiles along 16 main white matter tracts. We compared the DTI parameters between groups. Besides, we used partial correlation and multiple linear regression analyses to explore the associations between white matter integrity and cognitive performance as well as renal function indicators.

Results: In the global tract level, compared to HCs, ESRD patients had greater MD, AD, and RD values and lower FA value in several fibers (P < 0.05, FDR correction). In the point-wise level, extensive damage existed in specific locations of different fiber tracts, particularly in the left hemisphere (P < 0.05, FDR correction). Among these tracts, the mean AD values of the left cingulum cingulate correlated negatively with MoCA score. Urea and UA level were independent predictors of the AD value of superior component of the left corticospinal. Besides, urea level was the independent predictors of mean MD value of left anterior thalamic radiation (ATR).

Conclusion: White matter fiber tract damage in ESRD patients may be characterized by abnormalities in its specific location, especially in the left hemisphere. Aberrational specific located fibers were related to cognitive impairment and renal dysfunction.
Auditory Sensory Gating in Children With Cochlear Implants: A P50-N100-P200 Study
Authors: Chen Yan-Xin , Xu Xin-Ran , Huang Shuo , Guan Rui-Rui , Hou Xiao-Yan , Sun Jia-Qiang , Sun Jing-Wu , Guo Xiao-Tao
Published: December 2021

Background: While a cochlear implant (CI) can restore access to audibility in deaf children, implanted children may still have difficulty in concentrating. Previous studies have revealed a close relationship between sensory gating and attention. However, whether CI children have deficient auditory sensory gating remains unclear.

Methods: To address this issue, we measured the event-related potentials (ERPs), including P50, N100, and P200, evoked by paired tone bursts (S1 and S2) in CI children and normal-hearing (NH) controls. Suppressed amplitudes for S2 compared with S1 in these three ERPs reflected sensory gating during early and later phases, respectively. A Swanson, Nolan, and Pelham IV (SNAP-IV) scale was performed to assess the attentional performance.

Results: Significant amplitude differences between S1 and S2 in N100 and P200 were observed in both NH and CI children, indicating the presence of sensory gating in the two groups. However, the P50 suppression was only found in NH children and not in CI children. Furthermore, the duration of deafness was significantly positively correlated with the score of inattention in CI children.

Conclusion: Auditory sensory gating can develop but is deficient during the early phase in CI children. Long-term auditory deprivation has a negative effect on sensory gating and attentional performance.
Effects of Nrf1 in Hypothalamic Paraventricular Nucleus on Regulating the Blood Pressure During Hypertension
Authors: Yu Xiao-Jing , Xiao Tong , Liu Xiao-Jing , Li Ying , Qi Jie , Zhang Nianping , Fu Li-Yan , Liu Kai-Li , Li Yanjun , Kang Yu-Ming
Published: December 2021

The incidence rate and mortality of hypertension increase every year. Hypothalamic paraventricular nucleus (PVN) plays a critical role on the pathophysiology of hypertension. It has been demonstrated that the imbalance of neurotransmitters including norepinephrine (NE), glutamate (Glu) and γ-aminobutyric acid (GABA) are closely related to sympathetic overactivity and pathogenesis of hypertension. N-methyl-D-aspartate receptor (NMDAR), consisting of GluN1 and GluN2 subunits, is considered to be a glutamate-gated ion channel, which binds to Glu, and activates neuronal activity. Studies have found that the synthesis of respiratory chain enzyme complex was affected and mitochondrial function was impaired in spontaneously hypertensive rats (SHR), further indicating that mitochondria is associated with hypertension. Nuclear respiratory factor 1 (Nrf1) is a transcription factor that modulates mitochondrial respiratory chain and is related to GluN1, GluN2A, and GluN2B promoters. However, the brain mechanisms underlying PVN Nrf1 modulating sympathoexcitation and blood pressure during the development of hypertension remains unclear. In this study, an adeno-associated virus (AAV) vector carrying the shRNA targeting rat Nrf1 gene (shNrf1) was injected into bilateral PVN of male rats underwent two kidneys and one clip to explore the role of Nrf1 in mediating the development of hypertension and sympathoexcitation. Administration of shNrf1 knocked down the expression of Nrf1 and reduced the expression of excitatory neurotransmitters, increased the expression of inhibitory neurotransmitters, and reduced the production of reactive oxygen species (ROS), and attenuated sympathoexcitation and hypertension. The results indicate that knocking down Nrf1 suppresses sympathoexcitation in hypertension by reducing PVN transcription of NMDAR subunits (GluN1, GluN2A, and GluN2B), rebalancing PVN excitatory and inhibitory neurotransmitters, inhibiting PVN neuronal activity and oxidative stress, and attenuating sympathetic activity.
Comprehensive DNA Methylation Analysis of Human Neuroblastoma Cells Treated With Haloperidol and Risperidone
Authors: Du Jianbin , Nakachi Yutaka , Kiyono Tomoki , Fujii Shinya , Kasai Kiyoto , Bundo Miki , Iwamoto Kazuya
Published: December 2021

Accumulating evidence suggests that the epigenetic alterations induced by antipsychotics contribute to the therapeutic efficacy. However, global and site-specific epigenetic changes by antipsychotics and those shared by different classes of antipsychotics remain poorly understood. We conducted a comprehensive DNA methylation analysis of human neuroblastoma cells cultured with antipsychotics. The cells were cultured with low and high concentrations of haloperidol or risperidone for 8 days. DNA methylation assay was performed with the Illumina HumanMethylation450 BeadChip. We found that both haloperidol and risperidone tended to cause hypermethylation changes and showed similar DNA methylation changes closely related to neuronal functions. A total of 294 differentially methylated probes (DMPs), including 197 hypermethylated and 97 hypomethylated DMPs, were identified with both haloperidol and risperidone treatment. Gene ontology analysis of the hypermethylated probe-associated genes showed enrichment of genes related to the regulation of neurotransmitter receptor activity and lipoprotein lipase activity. Pathway analysis identified that among the DMP-associated genes, SHANK1 and SHANK2 were the major genes in the neuropsychiatric disorder-related pathways. Our data would be valuable for understanding the mechanisms of action of antipsychotics from an epigenetic viewpoint.
Impact of Maternal Intake of Artificial Sweetener, Acesulfame-K, on Metabolic and Reproductive Health Outcomes in Male and Female Mouse Offspring
Authors: Bridge-Comer Pania E. , Vickers Mark H. , Morton-Jones Jacob , Spada Ana , Rong Jing , Reynolds Clare M.
Published: December 2021

Guidelines advising pregnant women to avoid food and beverages with high fat and sugar have led to an increase in the consumption of “diet” options sweetened by artificial sweeteners (AS). Yet, there is limited information regarding the impact of AS intake during pregnancy on the long-term risk of cardiometabolic and reproductive complications in adult offspring. This study examined the influence of maternal acesulfame-K (Ace-K) and fructose consumption on metabolic and reproductive outcomes in offspring. Pregnant C57BL/6 mice received standard chow ad-libitum with either water (CD), fructose (Fr; 20% kcal intake), or AS (AS; 12.5 mM Ace-K) throughout pregnancy and lactation (n = 8/group). Postweaning offspring were maintained on a CD diet for the remainder of the experiment. Body weight, food intake, and water intake were measured weekly. Oral glucose tolerance tests (OGTT) were undertaken at 12 weeks, and the offspring were culled at week 14. Female, but not male, AS groups exhibited decreased glucose tolerance compared to Fr. There was an increase in gonadal fat adipocyte size in male offspring from AS and Fr groups compared to CD groups. In female offspring, adipocyte size was increased in the Fr group compared to the CD group. In female, but not male offspring, there was a trend toward increase in Fasn gene expression in AS group compared to the CD group. Maternal AS and Fr also negatively impacted upon female offspring estrus cycles and induced alterations to markers associated with ovulation. In summary, exposure to Ace-k via the maternal diet leads to impaired glucose tolerance and impacts adipocyte size in a sex-specific manner as well as significantly affecting estrus cycles and related gene markers in female offspring. This has implications in terms of providing tailored dietary advice for pregnant women and highlights the potential negative influence of artificial sweetener intake in the context of intergenerational impacts.
Processed Food and Atopic Dermatitis: A Pooled Analysis of Three Cross-Sectional Studies in Chinese Adults
Authors: Li Yajia , Su Juan , Luo Dan , Duan Yanying , Huang Zhijun , He Meian , Tao Juan , Xiao Shuiyuan , Xiao Yi , Chen Xiang , Shen Minxue
Published: December 2021

Objective: The effect of processed foods on atopic dermatitis (AD) in adults is unclear. This study was to evaluate the association between processed foods and AD in the Chinese adult population.

Design: This study included three population-based cross-sectional studies using cluster sampling by villages, institutions, or factories. Participants underwent dermatological examinations by certificated dermatologists and a food frequency questionnaire survey. A spot urine sample was collected to estimate the daily sodium intake. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were presented as the effect size.

Setting: Shiyan city of Hubei province, and Huayuan, Shimen, Hengyang, Zhuzhou, and Changsha of Hunan province.

Participants: Automobile manufacture workers from Shiyan of Hubei province, and rural residents and civil servants from Hunan.

Results: A total of 15,062 participants, including 3,781 rural residents, 5,111 civil servants, and 6,170 workers, completed all evaluations. Compared to those hardly consumed pickles, consumption of pickles 1–3 times per week was significantly associated with AD (aOR: 1.35; 95% CI: 1.06–1.70). The intake of processed meats 1–3 times per month (aOR: 1.29; 95% CI: 1.05–1.58) and 1–3 times per week (aOR: 1.44; 95% CI: 1.11–1.87) were associated with AD dose-dependently when compared with those who rarely ate processed meats. Compared with non-consumers, the consumption of any processed foods 1–3 times per week (aOR: 1.39; 95% CI: 1.08–1.80) and ≥4 times per week (aOR: 1.41; 95% CI: 1.05–1.89) showed increased risks of AD. A positive association of estimated sodium intake with AD was also observed.

Conclusion: Intake of processed foods is associated with AD in Chinese adults.
Meta-analysis of Glutamine on Immune Function and Post-Operative Complications of Patients With Colorectal Cancer
Authors: Yang Tao , Yan Xuhong , Cao Yibo , Bao Tiantian , Li Guangsong , Gu Shengliang , Xiong Kai , Xiao Tianbao
Published: December 2021

The aim of this meta-analysis was to evaluate the clinical significance of glutamine in the management of patients with colorectal cancer (CRC) after radical operation. Electronic databases, including PubMed, EMBASE, MEDLINE, Cochrane Library, Chinese Biomedical Database (CBM), China National Knowledge Infrastructure (CNKI), VIP medicine information system (VIP), and Wanfang electronic databases were comprehensively searched from inception to 30, July 2021. Prospective randomized trials with glutamine vs. routine nutrition or blank therapy were selected. The immune function related indicators (including IgA, IgG, IgM, CD4+, CD8+, and the ratio of CD4+/CD8+), post-operative complications [including surgical site infection (SSI), anastomotic leakage, and length of hospital stay (LOS)], and corresponding 95% confidence intervals (CIs) were assessed in the pooled analysis. Subsequently, the heterogeneity between studies, sensitivity, publication bias, and meta-regression analysis were performed. Consequently, 31 studies which contained 2,201 patients (1,108 in the glutamine group and 1,093 in the control group) were included. Results of pooled analysis indicated that glutamine significantly improved the humoral immune function indicators [including IgA (SMD = 1.15, 95% CI: 0.72–1.58), IgM (SMD = 0.68, 95% CI: 0.48–0.89), and IgG (SMD = 1.10, 95% CI: 0.70–1.50)], and the T cell immune function indicators [including CD4+ (SMD = 0.76, 95% CI: 0.53–0.99) and the ratio of CD4+/CD8+ (SMD = 0.92, 95% CI: 0.57–1.28)]. Meanwhile, the content of CD8+ was decreased significantly (SMD = −0.50, 95% CI: −0.91 to −0.10) followed by glutamine intervention. Pooled analysis of SSI (RR = 0.48, 95% CI: 0.30–0.75), anastomotic leakage (RR = 0.23, 95% CI: 0.09–0.61), and LOS (SMD = −1.13, 95% CI: −1.68 to −0.58) were decreased significantly in glutamine group compared with control group. Metaregression analysis revealed that the covariate of small-sample effects influenced the robustness and reliability of IgG outcome potentially. Findings of the present work demonstrated that glutamine ought to be applied as an effective immunenutrition therapy in the treatment of patients with CRC after radical surgery. The present meta-analysis has been registered in PROSPERO (no. CRD42021243327).

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO, Identifier: CRD42021243327.
Development and Characterization of Crackers Substitution of Wheat Flour With Jellyfish
Authors: Maisont Suchada , Samutsri Wisutthana , Phae-ngam Wuttichai , Limsuwan Pichet
Published: December 2021

The objective of this study was to investigate the possibility of using jellyfish (Lobonema smithii) for the production of nutritionally improved crackers. In this study, ground jellyfish were incorporated into different levels (20, 30, and 40%) to replace wheat flour in cracker formula. Physicochemical characteristics (linear expansion, hardness, and color) and sensory quality of the developed crackers were examined and compared with control crackers. The crackers with jellyfish were found significantly darker, with more brittleness, and less consumer accepted than the control samples (p < 0.05). Moisture content, aw, and thiobarbituric acid reactive substances (TBARS)-values of jellyfish crackers increased while the hardness of the jellyfish crackers decreased with increasing the storage time for both crackers stored at 35 and 45°C. The substitution of wheat flour with jellyfish led to high protein content in the crackers. The cracker with 30% of jellyfish gained characteristics of cracker, liking scores, as well as the subjective quality of the final product and had good physical and chemical conditions, being able to be consumed for 12 weeks stored at 35°C.
Metabolic Pathways and Targets in Chondrosarcoma
Authors: Micaily Ida , Roche Megan , Ibrahim Mohammad Y. , Martinez-Outschoorn Ubaldo , Mallick Atrayee Basu
Published: December 2021

Chondrosarcomas are the second most common primary bone malignancy. Chondrosarcomas are characterized by the production of cartilaginous matrix and are generally resistant to radiation and chemotherapy and the outcomes are overall poor. Hence, there is strong interest in determining mechanisms of cancer aggressiveness and therapeutic resistance in chondrosarcomas. There are metabolic alterations in chondrosarcoma that are linked to the epigenetic state and tumor microenvironment that drive treatment resistance. This review focuses on metabolic changes in chondrosarcoma, and the relationship between signaling via isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), hedgehog, PI3K-mTOR-AKT, and SRC, as well as histone acetylation and angiogenesis. Also, potential treatment strategies targeting metabolism will be discussed including potential synergy with immunotherapies.
Determination of Current Flow Induced by Transcutaneous Electrical Nerve Stimulation for the Treatment of Migraine: Potential for Optimization
Authors: Thomas Chris , Truong Dennis Q. , Lee Kiwon , Deblieck Choi , Androulakis Xiao Michelle , Datta Abhishek
Published: December 2021

Introduction: Transcutaneous electrical nerve stimulation (TENS) for migraine involves the application of pulsatile stimulation through electrodes placed on the forehead to target the underlying trigeminal nerves. It is a simple, safe modality and has secured clinical approval in several markets including the European Union and the United States. Despite nearing almost 7 years of use (postclinical approval), the exact mechanism of action is not fully known. Guided by the need to stimulate the trigeminal nerves bilaterally, electrode dimensions are simply required to extend enough to cover the underlying nerves. The goal of this study is to examine induced current flow [magnitude and spatial distribution of electric field (EF)] and another driver of stimulation [activating function (AF)] due to TENS therapy for migraine for the first time. We further consider the effect of changing the electrode dimension and shape and propose a design modification to deliver optimal flow.

Methods: We developed the first ultra-high-resolution finite element (FE) model of TENS for migraine incorporating the target supratrochlear (ST) and the supraorbital (SO) nerves. We first simulated the clinically approved V-shaped geometry. We then considered three additional designs: extended V-shaped, idealized pill-shaped, and finally an extended V-shaped but with greater contact spacing (extended V-shaped +CS).

Results: Our findings revealed that the clinically approved electrode design delivered substantially higher mean current flow to the ST nerve in comparison with the SO nerves (Medial: 53% and Lateral: 194%). Consideration of an extended design (~10 mm longer and ~ 4 mm shorter) and a pill-like design had negligible impact on the induced current flow pattern. The extended V-shaped +CS montage delivered relatively comparable current flow to each of the three target nerves. The EF induced in the ST nerve was 49 and 141% higher in the Medial and Lateral SO nerve, respectively. When considering maximum induced values, the delivery of comparable stimulation was further apparent. Given the existing electrode design's established efficacy, our results imply that preferential targeting of the ST nerve is related to the mechanism of action. Additionally, if comparable targeting of all three nerves continues to hold promise, the extended V-shaped +CS montage presents an optimized configuration to explore in clinical studies.