
Editorial
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Alzheimer's disease (AD) so far did not have promising treatment. The accurate and early diagnosis is still the important issue. For these purpose, biomarkers related to diagnosis, clinical course, and other aims have been proposed and reported. Meanwhile, along with the ongoing researches for AD, biomarkers with their own aims are also on the way.
Recent years have witnessed the fascinating development of imaging approaches to studying neural activities; this progress has been based on an influx of ideas and methods from molecular biology and optical engineering. Here we review the design and application of genetically encoded indicators for calcium ions, membrane potential and neurotransmitters. We also summarize common strategies for the design and optimization of genetically encoded neural activity indicators.
The Hippo pathway, a highly conserved kinase cascade, regulates cell proliferation, apoptosis, organ size, and tissue homeostasis. Dysregulation of this pathway reportedly plays an important role in the progression of various human cancers. Yes-association protein (YAP), the Hippo pathway’s core effector, is considered a marker for cancer therapy and patient prognosis. In addition, studies have indicated that YAP is involved in promoting anticancer drug resistance. This review summarizes current knowledge on YAP’s role in cancer progression, anticancer drug resistance, and advances in the development of YAP-targeting drugs. A thorough understanding of the complex interactions among molecular, cellular, and environmental factors concerning YAP function in cancer progression may provide new insight into the underlying mechanism of anticancer drug resistance. It might lead to improved prognosis through novel combined therapies.


Microvascular decompression (MVD) surgery has been popularized as an etiological treatment around the world for more than half a century. However, as a functional operation in the cerebellopontine angle, this process should be refined to enhance cure and minimize complication. After accomplishing more than 10,000 MVDs, we have learned the following concerning the operative technique: (1) the principle of MVD is to separate the neurovascular confliction, rather than isolate with prostheses; (2) identification of the conflict relies on good exposure; (3) a satisfactory working space can be created by the appropriate positioning, i.e., either a close-to-the-sigmoid craniectomy or caudorostral approach; (4) a sharp dissection of arachnoids leads to a maximal visualization of the entire intracranial course of the nerve root; (5) all vessels contacting the trigeminal nerve root should be cleared off; (6) intraoperative electrophysiological monitoring may predict the prognosis of hemifacial spasm and guide the operation; and (7) the dura must be closed with watertight stitches at the end.
Alzheimer’s disease (AD) is the most common neurodegenerative disorder. However, it still has no available disease‐modifying therapies. Its pathology cascade begins decades before symptomatic presentation. For these reasons, highly sensitive and highly specific fluid biomarkers should be developed for the early diagnosis of AD. In this study, the well‐established and emerging fluid biomarkers of AD are summarized, and recent advances on their role in early diagnosis and progression monitoring as well as their correlations with AD pathology are highlighted. Future prospects and related research directions are also discussed.
The emerging field of affective computing focuses on enhancing computers’ ability to understand and appropriately respond to people’s affective states in human-computer interactions, and has revealed significant potential for a wide spectrum of applications. Recently, the electroencephalography (EEG) based affective computing has gained increasing interest for its good balance between mechanistic exploration and real-world practical application. The present work reviewed ten theoretical and operational challenges for the existing affective computing researches from an interdisciplinary perspective of information technology, psychology, and neuroscience. On the theoretical side, we suggest that researchers should be well aware of the limitations of the commonly used emotion models, and be cautious about the widely accepted assumptions on EEG-emotion relationships as well as the transferability of findings based on different research paradigms. On the practical side, we propose several operational recommendations for the challenges about data collection, feature extraction, model implementation, online system design, as well as the potential ethical issues. The present review is expected to contribute to an improved understanding of EEG-based affective computing and promote further applications.
Spastic paralysis of the limb mainly results from the central lesion, in which spastic cerebral palsy is the common cause. Due to durative muscle spasm in spastic cerebral palsy, it is often accompanied by the formation of secondary musculoskeletal deformities, resulting in limb motor disability. Based on its pathogenesis, surgical treatment is currently applied: selective posterior rhizotomy (SPR) or orthopedic surgery. The primary purpose of early orthopedic surgery was simply to correct limb deformities, which usually led to the recurrence of deformity as a result of the presence of spasticity. With the application of SPR, high muscle tone was successfully relieved, but limb deformity was still present postoperatively. Therefore, this study aimed to elaborate on the management of orthopedic surgery, common deformities of the lower limb, and orthopedic operative methods; discuss the relationship between SPR and orthopedic procedure for limb deformity; and focus on the indications, timing of intervention, and postoperative outcome of different surgical methods.
Excitatory-inhibitory (E/I) balance is essential for normal neural development, behavior and cognition. E/I imbalance leads to a variety of neurological disorders, such as autism and schizophrenia. NMDA receptors (NMDARs) regulate AMPAR-mediated excitatory and GABAAR-mediated inhibitory synaptic transmission, suggesting that NMDARs play an important role in the establishment and maintenance of the E/I balance. In this review, we briefly introduced NMDARs, AMPARs and GABAARs, summarized the current studies on E/I balance mediated by NMDARs, and discussed the current advances in NMDAR-mediated AMPAR and GABAAR development. Specifically, we analyzed the role of NMDAR subunits in the establishment and maintenance of E/I balance, which may provide new therapeutic strategies for the recovery of E/I imbalance in neurological disorders.
In this case report, we describe the design, fabrication and clinical outcomes of a novel bioresorbable, mineralized collagen burr-hole plug for the reconstruction of craniotomy burr-holes.
Mineralized collagen burr-hole plugs were fabricated via a biomimetic mineralization process. The biomimetic mineralized collagen has a similar chemical composition and microstructure to natural bone tissue, thereby possessing good biocompatibility and osteoconductivity. The mineralized collagen burr-hole plugs were implanted into three patients, and clinical outcomes were evaluated at one-year follow-ups.
All bone defects healed very well using the mineralized collagen burr-hole plugs, and there were no adverse reactions at the surgical sites.
The clinical outcomes indicated that the mineralized collagen was effective for reconstructing burr-holes in the skull after craniotomy.
This study aimed to employ time-resolved spectroscopy (TRS) to explore age-related differences in prefrontal cortex (PFC) activity while subjects performed a working memory task.
We employed TRS to measure PFC activity in ten healthy younger and ten healthy older subjects while they performed a working memory (WM) task. All subjects performed the Sternberg test (ST) in which the memory-set size varied between one and six digits. Using TRS, we recorded changes in cerebral blood oxygenation as a measure of changes in PFC activity during the task. In order to identify left/right asymmetry of PFC activity during the working memory task, we calculated the laterality score, i.e., Δoxy-Hb (right Δoxy-Hb—left Δoxy-Hb); positive values indicate greater activity in the right PFC, while negative values indicate greater activity in the left PFC.
During the ST, statistical analyses showed no significant differences between the younger and older groups in accuracy for low memory-load and high memory-load. In high memory-load tasks, however, older subjects were slower than younger subjects (P < 0.05). We found that the younger group showed right lateral responses with a stronger right than left activation in the frontal pole, whereas the older group showed bilateral responses (P < 0.05).
The present results are consistent with the hemispheric asymmetry reduction in older adults (HAROLD) model; working memory tasks cause asymmetrical PFC activation in younger adults, while older adults tend to show reduced hemispheric lateralization.
Although deep brain stimulation (DBS) and motor cortex stimulation (MCS) are effective in patients with refractory neuropathic pain, their application is still empirical; there is no consensus on which technique is better.
To enhance the success rate of trial stimulation of invasive neuromodulation techniques and identify approapriate stimulation targets in individual patients, we performed a simultaneous trial of thalamic ventralis caudalis (Vc) DBS and MCS in 11 patients with chronic neuropathic pain and assessed the results of the trial stimulation and long-term analgesia.
Of the 11 patients implanted with both DBS and MCS electrodes, nine (81.8%) had successful trials. Seven of these nine patients (77.8%) responded to MCS, and two (18.2%) responded to Vc DBS. With long-term follow-up (56 ± 27.5 months), the mean numerical rating scale decreased significantly (P < 0.05). The degree of percentage pain relief in the chronic MCS (n = 7) and chronic DBS (n = 2) groups were 34.1% ± 18.2% and 37.5%, respectively, and there was no significant difference (P = 0.807). Five out of the seven MCS patients (71%) and both DBS patients had long-term success with the treatments, defined as >30% pain relief compared with baseline.
With simultaneous trial of DBS and MCS, we could enhance the success rate of invasive trials. Considering the initial success rate and the less invasive nature of epidural MCS over DBS, we suggest that MCS may be a better, initial means of treatment in chronic intractable neuropathic pain. Further investigations including other subcortical target-associated medial pain pathways are warranted.
The frontal lobe may be involved in circuits associated with depression, apathy, aggression, and other psychiatric symptoms. Although white matter changes (WMC) are related to the severity of behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease (AD), it is unclear which part of the WMC may play the most important role in BPSD. This study was designed to investigate the relationship between the location of WMC and the severity of BPSD in AD patients.
Among patients diagnosed with Alzheimer's disease between 2009 and 2014, 387 patients were retrospectively reviewed after those with pre-existing organic brain syndrome, psychiatric diseases, or toxic-metabolic encephalopathy were excluded. Patients' demographic and laboratory data, WMC measured with brain computed tomography and scored using the age-related white matter changes (ARWMC) scale, and neuropsychological tests, including the cognitive abilities screening instrument (CASI), the Mini-Mental State Examination (MMSE), the clinical dementia rating scale with sum-box (CDR-SB), and the neuropsychiatric inventory (NPI) were analyzed.
There was no significant difference in the NPI between patients with and without a history of stroke, hypertension, and diabetes. No significant difference in the NPI was identified between different sexes or different Apolipoprotein E (APOE) alleles. The NPI score was significantly correlated with the duration of education (r = −0.4515, P = 0.0172), CASI (r = −0.2915, P < 0.0001), MMSE (r = −0.8476, P < 0.0001), and CDR-SB (r = 2.2839, P < 0.0001). WMC in the right frontal lobe showed a significant difference in NPI in comparison to those without WMC (P = 0.0255). After adjusting for age, duration of education, and CASI, WMC in the right frontal lobe remained significantly associated with the NPI score (β = 3.8934, P = 0.042).
WMC involving the right frontal lobe may play an important role in the BPSD in AD patients during their dementia diagnosis. Further studies are necessary to confirm whether controlling the risk factors of WMC can slow the progression of BPSD.
To study the effect of fetal stem cell (FSC) therapy on Grade I and II respiratory failure in patients with amyotrophic lateral sclerosis (ALS) and muscular dystrophy (MD).
A comparative study was conducted on 41 patients with Grade I or II respiratory failure (RF) resulting from ALS or MD. The patients were divided into 4 groups according to the underlying disease and the degree of RF. Patients underwent combined treatment, including the experimental application of FSC therapy, and were examined before FSC treatment, and 6 months and 12 months after treatment.
FSC treatment improved both subjective and objective breathing parameters as early as 6 months post-treatment. A significant increase in the forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) was reported by all patients with Grade I RF linked to ALS and MD compared to baseline. Patient respiratory improvement was maintained over the next 6 months. Grade II RF patients with MD reported a significant improvement in FVC 12 months after treatment.
Evidence for respiratory improvement was observed as early as 6 months in all patients after combined treatment including FSC therapy, and this was maintained for a further 6 months after therapy. In MD patients with Grade II RF, treatment resulted in a significant FVC and FEV1 increase within 6 months and downgrading to Grade I RF within a year after FSC treatment.
Large-conductance calcium- and voltage-dependent potassium (BK) channels are ubiquitously expressed in mammalian cells and participate in various physiological and pathological processes such as neurotransmission and cerebral ischemia. BK channels comprise up to four pore-forming α subunits and zero to four accessory subunits. Although microglial BK currents were initially recorded 27 years ago, their roles have long been elusive. Studies have demonstrated that BK channels modulate the activation, phagocytosis, and probably migration of microglia and have associated microglial BK channels with many neurological diseases, including neuropathic pain and stroke. This review summarizes the available information regarding the biophysical, functional, and pathological aspects of microglial BK channels and discusses future directions of research into these channels.
Rhythmicity and oscillations are common features in nature, and can be seen in phenomena such as seasons, breathing, and brain activity. Despite the fact that a single neuron transmits its activity to its neighbor through a transient pulse, rhythmic activity emerges from large population-wide activity in the brain, and such rhythms are strongly coupled with the state and cognitive functions of the brain. However, it is still debated whether the oscillations of brain activity actually carry information. Here, we briefly introduce the biological findings of brain oscillations, and summarize the recent progress in understanding how oscillations mediate brain function. Finally, we examine the possible relationship between brain cognitive function and oscillation, focusing on how oscillation is related to memory, particularly with respect to state-dependent memory formation and memory retrieval under specific brain waves. We propose that oscillatory waves in the neocortex contribute to the synchronization and activation of specific memory trace ensembles in the neocortex by promoting long-range neural communication.
Few studies have investigated the factors associated with the prognosis of children with medulloblastoma. This retrospective observational study evaluated the association of molecular subtype, clinical characteristics, and pathological types with the outcomes of children with medulloblastoma. This study included 40 patients with medulloblastoma who underwent surgical resection at the Affiliated Children's Hospital of Fudan University between January 2004 and June 2014. The primary outcome was overall survival (OS). Risk factors associated with survival, disease progression, and recurrence were analyzed by univariate Cox regression analysis; the identified significant risk factors were further analyzed by Kaplan-Meier survival curves. Immunohistochemistry analysis of Yes-associated protein 1 (YAP1) and GRB2-associated protein 1 (GAB1) was used for medulloblastoma subtype identification; 20% of tumors were the WNT subtype, and 32.5% were the SHH subtype, with the remainder being non-SHH/WNT. Factors associated with OS included M stage, calcification, cerebrospinal fluid fistula, postoperative treatment (radiotherapy, chemotherapy, or both), postoperative Karnofsky Performance Scale score, and molecular subtype (P < 0.044). Patients with the WNT subtype had better survival outcomes (hazard ratio [HR] = 0.16, 95% confidence interval [CI]: 0.05–0.58). Number of symptoms, M stage, and postoperative radiotherapy were associated with disease progression (P ≤ 0.033). The risk of recurrence increased with advanced M stage (HR = 30.71; 95% CI: 3.92—240.44, P = 0.001). Patients receiving both chemotherapy and radiotherapy were less likely to have a recurrence (P = 0.040). Molecular subtyping of medulloblastoma was more predictive of survival than histopathology in patients undergoing adjuvant therapy.
Alzheimer’s disease (AD) increasingly affects society due to aging populations. Even at pre‐clinical stages, earlier and accurate diagnoses are essential for optimal AD management and improved clinical outcomes. Biomarkers such as beta‐amyloid (Aβ) or tau protein in cerebrospinal fluid (CSF) have been used as reliable markers to distinguish AD from non‐AD, and predicting clinical outcomes, to attain these goals. However, given CSF access methods’ invasiveness, these biomarkers are not used extensively in clinical settings. Blood Aβ has been proposed as an alternative biomarker since it is less invasive than CSF; however, sampling heterogeneity has limited its clinical applicability. In this review, we investigated blood Aβ as a biomarker in AD and explored how Aβ can be facilitated as a viable biomarker for successful AD management.