bluuebunny/crossref_metadata_2025 huggingface dataset:
Prescribing or co-designing exercise in healthy adults? Effects on mental health and interoceptive awareness
Authors: Almarcha Maricarmen , González Ignacio , Balagué Natàlia , Javierre Casimiro
Published: July 2022

Universal exercise recommendations for adults neglect individual preferences, changing constraints, and their potential impact on associated health benefits. A recent proposal suggests replacing the standardized World Health Organisation (WHO) exercise recommendations for healthy adults by co-designed interventions where individuals participate actively in the decisions about the selected physical activities and the effort regulation. This study contrasts the effects on mental health and interoceptive awareness of a co-designed and co-adapted exercise intervention with an exercise program based on the WHO recommendations for healthy adults. Twenty healthy adults (10 men and 10 women, 40–55 y.o.) participated voluntarily in the research. They were randomly assigned to a co-designed exercise intervention (CoD group) and a prescribed exercise program (WHO group). Supervised online by specialized personal trainers, both programs lasted 9 weeks and were equivalent in volume and intensity. The effects of the exercise intervention were tested through personal interviews, questionnaires (DASS-21 and MAIA) and a cardiorespiratory exercise test. Intragroup differences (pre-post) were assessed using the Mann-Whitney Wilcoxon test and intergroup differences through Student’s t-tests. Effect sizes were calculated through Cohen’s d. Interviews were analyzed through thematic analysis. Eleven participants completed the intervention (CoD = 8, WHO = 5). Both groups improved, but non significantly, their cardiorespiratory testing results, and no differences were found between them post-intervention. Mental health was only enhanced in the CoD group (p < 0.001), and interoceptive awareness improved in seven of the eight scales in the CoD group (p < 0.001) and only in 3 scales in the WHO group (p < 0.01). In conclusion, the co-designed intervention was more effective for developing mental health, interoceptive awareness, autonomy, and exercise self-regulation than the WHO-based exercise program.
Spatial relation learning in complementary scenarios with deep neural networks
Authors: Lee Jae Hee , Yao Yuan , Özdemir Ozan , Li Mengdi , Weber Cornelius , Liu Zhiyuan , Wermter Stefan
Published: July 2022

A cognitive agent performing in the real world needs to learn relevant concepts about its environment (e.g., objects, color, and shapes) and react accordingly. In addition to learning the concepts, it needs to learnrelationsbetween the concepts, in particular spatial relations between objects. In this paper, we propose three approaches that allow a cognitive agent to learn spatial relations. First, using an embodied model, the agent learns to reach toward an object based on simple instructions involving left-right relations. Since the level of realism and its complexity does not permit large-scale and diverse experiences in this approach, we devise as a second approach a simple visual dataset for geometric feature learning and show that recent reasoning models can learn directional relations in different frames of reference. Yet, embodied and simple simulation approaches together still do not provide sufficient experiences. To close this gap, we thirdly propose utilizing knowledge bases for disembodied spatial relation reasoning. Since the three approaches (i.e., embodied learning, learning from simple visual data, and use of knowledge bases) are complementary, we conceptualize a cognitive architecture that combines these approaches in the context of spatial relation learning.
Reclaiming saliency: Rhythmic precision-modulated action and perception
Authors: Anil Meera Ajith , Novicky Filip , Parr Thomas , Friston Karl , Lanillos Pablo , Sajid Noor
Published: July 2022

Computational models of visual attention in artificial intelligence and robotics have been inspired by the concept of a saliency map. These models account for the mutual information between the (current) visual information and its estimated causes. However, they fail to consider the circular causality between perception and action. In other words, they do not consider where to sample next, given current beliefs. Here, we reclaim salience as an active inference process that relies on two basic principles: uncertainty minimization and rhythmic scheduling. For this, we make a distinction between attention and salience. Briefly, we associate attention with precision control, i.e., the confidence with which beliefs can be updated given sampled sensory data, and salience with uncertainty minimization that underwrites the selection of future sensory data. Using this, we propose a new account of attention based on rhythmic precision-modulation and discuss its potential in robotics, providing numerical experiments that showcase its advantages for state and noise estimation, system identification and action selection for informative path planning.
Homeostatic regulation of extracellular signal-regulated kinase 1/2 activity and axonal Kv7.3 expression by prolonged blockade of hippocampal neuronal activity
Authors: Baculis Brian C. , Kesavan Harish , Weiss Amanda C. , Kim Edward H. , Tracy Gregory C. , Ouyang Wenhao , Tsai Nien-Pei , Chung Hee Jung
Published: July 2022

Homeostatic plasticity encompasses the mechanisms by which neurons stabilize their synaptic strength and excitability in response to prolonged and destabilizing changes in their network activity. Prolonged activity blockade leads to homeostatic scaling of action potential (AP) firing rate in hippocampal neurons in part by decreased activity of N-Methyl-D-Aspartate receptors and subsequent transcriptional down-regulation of potassium channel genes including KCNQ3 which encodes Kv7.3. Neuronal Kv7 channels are mostly heterotetramers of Kv7.2 and Kv7.3 subunits and are highly enriched at the axon initial segment (AIS) where their current potently inhibits repetitive and burst firing of APs. However, whether a decrease in Kv7.3 expression occurs at the AIS during homeostatic scaling of intrinsic excitability and what signaling pathway reduces KCNQ3 transcript upon prolonged activity blockade remain unknown. Here, we report that prolonged activity blockade in cultured hippocampal neurons reduces the activity of extracellular signal-regulated kinase 1/2 (ERK1/2) followed by a decrease in the activation of brain-derived neurotrophic factor (BDNF) receptor, Tropomyosin receptor kinase B (TrkB). Furthermore, both prolonged activity blockade and prolonged pharmacological inhibition of ERK1/2 decrease KCNQ3 and BDNF transcripts as well as the density of Kv7.3 and ankyrin-G at the AIS. Collectively, our findings suggest that a reduction in the ERK1/2 activity and subsequent transcriptional down-regulation may serve as a potential signaling pathway that links prolonged activity blockade to homeostatic control of BDNF-TrkB signaling and Kv7.3 density at the AIS during homeostatic scaling of AP firing rate.
Decoding Neuropathic Pain: Can We Predict Fluctuations of Propagation Speed in Stimulated Peripheral Nerve?
Authors: Kutafina Ekaterina , Troglio Alina , de Col Roberto , Röhrig Rainer , Rossmanith Peter , Namer Barbara
Published: July 2022

To understand neural encoding of neuropathic pain, evoked and resting activity of peripheral human C-fibers are studied via microneurography experiments. Before different spiking patterns can be analyzed, spike sorting is necessary to distinguish the activity of particular fibers of a recorded bundle. Due to single-electrode measurements and high noise contamination, standard methods based on spike shapes are insufficient and need to be enhanced with additional information. Such information can be derived from the activity-dependent slowing of the fiber propagation speed, which in turn can be assessed by introducing continuous “background” 0.125–0.25 Hz electrical stimulation and recording the corresponding responses from the fibers. Each fiber's speed propagation remains almost constant in the absence of spontaneous firing or additional stimulation. This way, the responses to the “background stimulation” can be sorted by fiber. In this article, we model the changes in the propagation speed resulting from the history of fiber activity with polynomial regression. This is done to assess the feasibility of using the developed models to enhance the spike shape-based sorting. In addition to human microneurography data, we use animal in-vitro recordings with a similar stimulation protocol as higher signal-to-noise ratio data example for the models.
Construction and validation of a glioblastoma prognostic model based on immune-related genes
Authors: Huang Kate , Rao Changjun , Li Qun , Lu Jianglong , Zhu Zhangzhang , Wang Chengde , Tu Ming , Shen Chaodong , Zheng Shuizhi , Chen Xiaofang , Lv Fangfang
Published: July 2022

Background

Glioblastoma multiforme (GBM) is a common malignant brain tumor with high mortality. It is urgently necessary to develop a new treatment because traditional approaches have plateaued.

Purpose

Here, we identified an immune-related gene (IRG)-based prognostic signature to comprehensively define the prognosis of GBM.

Methods

Glioblastoma samples were selected from the Chinese Glioma Genome Atlas (CGGA). We retrieved IRGs from the ImmPort data resource. Univariate Cox regression and LASSO Cox regression analyses were used to develop our predictive model. In addition, we constructed a predictive nomogram integrating the independent predictive factors to determine the one-, two-, and 3-year overall survival (OS) probabilities of individuals with GBM. Additionally, the molecular and immune characteristics and benefits of ICI therapy were analyzed in subgroups defined based on our prognostic model. Finally, the proteins encoded by the selected genes were identified with liquid chromatography-tandem mass spectrometry and western blotting (WB).

Results

Six IRGs were used to construct the predictive model. The GBM patients were categorized into a high-risk group and a low-risk group. High-risk group patients had worse survival than low-risk group patients, and stronger positive associations with multiple tumor-related pathways, such as angiogenesis and hypoxia pathways, were found in the high-risk group. The high-risk group also had a low IDH1 mutation rate, high PTEN mutation rate, low 1p19q co-deletion rate and low MGMT promoter methylation rate. In addition, patients in the high-risk group showed increased immune cell infiltration, more aggressive immune activity, higher expression of immune checkpoint genes, and less benefit from immunotherapy than those in the low-risk group. Finally, the expression levels of TNC and SSTR2 were confirmed to be significantly associated with patient prognosis by protein mass spectrometry and WB.

Conclusion

Herein, a robust predictive model based on IRGs was developed to predict the OS of GBM patients and to aid future clinical research.
Analysis of the genotype–phenotype correlation in isovaleric acidaemia: A case report of long-term follow-up of a chinese patient and literature review
Authors: Liu Xingmiao , Liu Xinquan , Fan Wenxuan , Zhang Zhongbin , Zhang Peiyuan , Liu Xiaojun , Lei Meifang , Li Qing , Yu Xiaoli , Li Dong
Published: July 2022

Background

Isovaleric acidaemia (IVA), characterized by an acute metabolic crisis and psychomotor delay, is a rare inherited metabolic disease caused by a deficiency in isovaleryl-CoA dehydrogenase (IVD).

Methods

We report the case of a Chinese patient with IVA who was admitted to Tianjin Children's Hospital and followed up for 8 years. Genetic analysis of the patient and his parents was conducted using the whole-exome sequencing and Sanger sequencing. We searched for similar reported cases in the PubMed and Wanfang databases using the term “isovaleric acidaemia,” reviewed the related literature to obtain a summary of the clinical and genetic characteristics, and analyzed the genotype–phenotype correlations.

Results

The patient presented with encephalopathic symptoms, such as vomiting, lethargy, and somnolence. We identified compound heterozygous variants of the IVD gene, including the unreported variant c.224A>G (p.Asn75Ser) and the reported variant c.1195G>C (p.Asp399His). The child was prescribed a low-protein diet supplemented with L-carnitine. During the 8-year follow-up, no metabolic disorder or encephalopathic symptoms recurred. At present, the child is 11 years of age and has normal mental and motor performance. Another 154 cases identified in 25 relevant references were combined with this case, resulting in a sample of 155 patients, including 52 asymptomatic patients, 64 with neonatal onset, and 39 with the chronic intermittent disease with onset from ages of 1 month to 10 years (median age, 2 years). Among articles that reported sex, the male-to-female ratio was 1:1.06. The cardinal symptoms included vomiting, lethargy, “sweaty foot” odor, poor feeding, developmental delay, and epilepsy. The proportion of variants in regions 123–159 and 356–403 of the IVD protein was greater in symptomatic patients than in asymptomatic patients. Conversely, in asymptomatic patients, the proportion of variants in the 282–318 region was greater than in symptomatic patients.

Conclusion

This case report describes an unreported variant c.224A>G (p.Asn75Ser) of the IVD gene, and summarizes previously reported cases. Furthermore, the correlation between the genotype and clinical phenotype of IVA is analyzed to improve the understanding of this disease.
Consensus on early detection of disease progression in patients with multiple sclerosis
Authors: Meca-Lallana José E. , Casanova Bonaventura , Rodríguez-Antigüedad Alfredo , Eichau Sara , Izquierdo Guillermo , Durán Carmen , Río Jordi , Hernández Miguel Ángel , Calles Carmen , Prieto-González José M. , Ara José Ramón , Uría Dionisio F. , Costa-Frossard Lucienne , García-Merino Antonio , Oreja-Guevara Celia
Published: July 2022

Background

Early identification of the transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS) can be challenging for clinicians, as diagnostic criteria for SPMS are primarily based on physical disability and a holistic interpretation.

Objective

To establish a consensus on patient monitoring to identify promptly disease progression and the most useful clinical and paraclinical variables for early identification of disease progression in MS.

Methods

A RAND/UCLA Appropriateness Method was used to establish the level of agreement among a panel of 15 medical experts in MS. Eighty-three items were circulated to the experts for confidential rating of the grade of agreement and recommendation. Consensus was defined when ≥66% agreement or disagreement was achieved.

Results

Consensus was reached in 72 out of 83 items (86.7%). The items addressed frequency of follow-up visits, definition of progression, identification of clinical, cognitive, and radiological assessments as variables of suspected or confirmed SPMS diagnosis, the need for more accurate assessment tools, and the use of promising molecular and imaging biomarkers to predict disease progression and/or diagnose SPMS.

Conclusion

Consensus achieved on these topics could guide neurologists to identify earlier disease progression and to plan targeted clinical and therapeutic interventions during the earliest stages of SPMS.
Predictors of ischemic events in patients with unilateral extracranial vertebral artery dissection: A single-center exploratory study
Authors: Yan Yanhong , Lu Ziwei , Ding Yafang , Pu Jianhong , Hu Chunhong , Teng Zhongzhao , Hui Pinjing
Published: July 2022

Objective

Extracranial vertebral artery dissection (EVAD) is one of the main causes of stroke in young and middle-aged patients. However, the diagnosis is challenging. This study aimed to identify the characteristics of EVAD on color duplex ultrasonography (CDU) and high-resolution magnetic resonance imaging (hrMRI), hoping to improve the accuracy and determine the relative contribution of vessel findings and clinical factors to acute ischemic events.

Methods

Patients with unilateral EVAD were recruited and divided into ischemia and non-ischemia groups. Clinical features of patients and the lesion location; a variety of signs which indicate dissection, including the presence of an intimal flap, double lumen, intramural hematoma, dissecting aneurysm, intraluminal thrombus, and irregular lumen; and other quantitative parameters of each dissected segment on CDU and hrMRI were reviewed, respectively. Multiple logistic regression was performed to explore the association between clinical, imaging characteristics, and ischemic events in patients with unilateral EVAD.

Results

Ninety-six patients with unilateral EVAD who met the inclusion criteria were enrolled during a six-year period. Overall, 41 cases (42.7%) were confirmed as ischemic stroke (n = 40) or transient ischemic attack (n = 1) during the 48 h after the onset of symptoms. Men, infections during the last week, and smoking were more common in the ischemia group. Intraluminal thrombus and occlusion on CDU were more prevalent in patients with cerebral ischemia than in those without (36.6 vs. 5.5%; p < 0.001, and 39.0 vs. 9.1%; p = 0.001, respectively). On hrMRI, intraluminal thrombus and occlusion were also more frequent in the ischemia group than in the non-ischemia group (34.1 vs. 5.5%; p < 0.001, and 34.1 vs. 9.1%; p = 0.003, respectively). In addition, lesion length on hrMRI was significantly longer for patients with ischemia (81.5 ± 41.7 vs. 64.7 ± 30.8 mm; p = 0.025). In multivariable logistic regression analysis, male gender, infections during the last week, and the presence of intraluminal thrombus on CDU and hrMRI were independently associated with acute ischemic events.

Conclusion

Male sex, infections during the last week, and the presence of intraluminal thrombus due to dissection are associated with an increased risk of ischemic events in patients with unilateral EVAD.
Botulinum toxin injection combined with traditional swallowing rehabilitation improved cricopharyngeal dysfunction in neuromyelitis optica spectrum disorder: A case report
Authors: He Zitong , Zhao Fei , Shan Yilong , Dou Zulin , Wen Hongmei
Published: July 2022

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune diseases of the central nervous system, and often influence optic nerve and medulla oblongata. Previous studies found out that brain abnormalities were not rare in these patients. Medulla oblongata (MO) was commonly involved and usually located at dorsal part. Patients who diagnosed NMOSD with MO lesions were more likely to have dysphagia. Previous reports indicated that the symptoms and signs of NMOSD patients could be controlled after immunosuppressive therapy. This patient was a 49-year-old Asian woman presented with recurrent vomiting and diagnosed NMOSD with MO involvement. However, after immunotherapy in other hospital, she still suffered from dysphagia. She then came to our department and completed videofluoroscopic swallowing study (VFSS) and high-resolution pharyngeal manometry (HRPM). Her UES was not opening with aspiration and the UES residue pressure was higher than normal range, we figured that she had cricopharyngeal (CP) dysfunction. Then the SLP gave her traditional treatment, including catheter balloon dilation. But she failed improvement after treatment for 2 weeks. Then the clinicians decided to inject botulinum toxin (BTX) into her CP muscles, which needed specific location and appropriate dosage. Her UES residue pressure decreased after three times BTX injection. During this time, her SLP adjusted the treatment strategies based on her VFSS and HRM results. Combined BTX injection with traditional treatment, she can now eat food orally without restrictions. This case report we presented can provide treatment strategies for similar patients with dysphagia.
Vessel wall MR imaging of aortic arch, cervical carotid and intracranial arteries in patients with embolic stroke of undetermined source: A narrative review
Authors: Sakai Yu , Lehman Vance T. , Eisenmenger Laura B. , Obusez Emmanuel C. , Kharal G. Abbas , Xiao Jiayu , Wang Grace J. , Fan Zhaoyang , Cucchiara Brett L. , Song Jae W.
Published: July 2022

Despite advancements in multi-modal imaging techniques, a substantial portion of ischemic stroke patients today remain without a diagnosed etiology after conventional workup. Based on existing diagnostic criteria, these ischemic stroke patients are subcategorized into having cryptogenic stroke (CS) or embolic stroke of undetermined source (ESUS). There is growing evidence that in these patients, non-cardiogenic embolic sources, in particular non-stenosing atherosclerotic plaque, may have significant contributory roles in their ischemic strokes. Recent advancements in vessel wall MRI (VW-MRI) have enabled imaging of vessel walls beyond the degree of luminal stenosis, and allows further characterization of atherosclerotic plaque components. Using this imaging technique, we are able to identify potential imaging biomarkers of vulnerable atherosclerotic plaques such as intraplaque hemorrhage, lipid rich necrotic core, and thin or ruptured fibrous caps. This review focuses on the existing evidence on the advantages of utilizing VW-MRI in ischemic stroke patients to identify culprit plaques in key anatomical areas, namely the cervical carotid arteries, intracranial arteries, and the aortic arch. For each anatomical area, the literature on potential imaging biomarkers of vulnerable plaques on VW-MRI as well as the VW-MRI literature in ESUS and CS patients are reviewed. Future directions on further elucidating ESUS and CS by the use of VW-MRI as well as exciting emerging techniques are reviewed.
Cerebellar and brainstem differences in children with developmental coordination disorder: A voxel-based morphometry study
Authors: Gill Kamaldeep K. , Lang Donna , Zwicker Jill G.
Published: July 2022

Developmental coordination disorder (DCD) is a neurodevelopmental disorder that significantly impairs a child’s ability to learn motor skills and to perform everyday activities. The cause of DCD is unknown; however, evidence suggests that children with DCD have altered brain structure and function. While the cerebellum has been hypothesised to be involved in developmental coordination disorder, no studies have specifically examined cerebellar structure in this population. The purpose of our study was to examine cerebellar differences in children with DCD compared to typically-developing children. Using voxel-based morphometry, we assessed cerebellar morphology in children 8–12 years of age. Forty-six children (12 typically-developing and 34 with DCD) were investigated using high resolution T1-weighted images, which were then processed using the spatially unbiased atlas template of the cerebellum and brainstem (SUIT) toolbox for a region of interest-based examination of the cerebellum. Results revealed that children with DCD had reduced grey matter volume in several regions, namely: the brainstem, right/left crus I, right crus II, left VI, right VIIb, and right VIIIa lobules. Further, Pearson correlations revealed significant positive associations between the total motor percentile score on the Movement Assessment Battery for Children-2 and regions that had reduced grey matter volume in our cohort (brainstem, left crus I, right VIIb, and right VIIIa). These findings indicate that reductions in cerebellar grey matter volume are associated with poorer motor skills. Given the cerebellum’s involvement in internal models of movement, results of this study may help to explain why children with DCD struggle to learn motor skills.
Exploring how healthcare teams balance the neurodynamics of autonomous and collaborative behaviors: a proof of concept
Authors: Stevens Ronald , Galloway Trysha L.
Published: July 2022

Team members co-regulate their activities and move together at the collective level of behavior while coordinating their actions toward shared goals. In parallel with team processes, team members need to resolve uncertainties arising from the changing task and environment. In this exploratory study we have measured the differential neurodynamics of seven two-person healthcare teams across time and brain regions during autonomous (taskwork) and collaborative (teamwork) segments of simulation training. The questions posed were: (1) whether these abstract and mostly integrated constructs could be separated neurodynamically; and, (2) what could be learned about taskwork and teamwork by trying to do so? The taskwork and teamwork frameworks used were Neurodynamic Information (NI), an electroencephalography (EEG) derived measure shown to be a neurodynamic proxy for the pauses and hesitations associated with individual uncertainty, and inter-brain EEG coherence (IBC) which is a required component of social interactions. No interdependency was observed between NI and IBC, and second-by-second dynamic comparisons suggested mutual exclusivity. These studies show that proxies for fundamental properties of teamwork and taskwork can be separated neurodynamically during team performances of ecologically valid tasks. The persistent expression of NI and IBC were not simultaneous suggesting that it may be difficult for team members to maintain inter-brain coherence while simultaneously reducing their individual uncertainties. Lastly, these separate dynamics occur over time frames of 15–30 s providing time for real-time detection and mitigation of individual and collaborative complications during training or live patient encounters.
Non-adherence to psychiatric medication in adults experiencing homelessness is associated with incurred concussions
Authors: Rangu Neal , Frank-Pearce Sumer G. , Alexander Adam C. , Hébert Emily T. , Ra Chaelin , Kendzor Darla E. , Businelle Michael S.
Published: July 2022

This study investigated the relationship between concussions and medication adherence among 247 adults experiencing homelessness in Oklahoma City, Oklahoma, who were prescribed medication for a psychiatric disorder. Participants were asked whether they had “ever experienced a blow to the head that caused a concussion,” and medication adherence was measured by asking participants whether they had taken their psychiatric medication yesterday. The data were analyzed using univariate and multivariable logistic regressions. Results showed that more than half of the sample had a concussion history (61.9%), and homeless adults with a concussion history had higher odds of non-adherence to psychiatric medications compared with those who reported no concussion history [OR = 2.13 (95% CI = 1.08, 4.18)]. Findings suggest that medication non-adherence is associated with incurred concussions. Raising awareness among service providers of the relationship between traumatic brain injury and medication adherence may increase efforts to improve adherence in this underserved population.
Source localized infraslow neurofeedback training in people with chronic painful knee osteoarthritis: A randomized, double-blind, sham-controlled feasibility clinical trial
Authors: Mathew Jerin , Adhia Divya Bharatkumar , Smith Mark Llewellyn , De Ridder Dirk , Mani Ramakrishnan
Published: July 2022

Persistent pain is a key symptom in people living with knee osteoarthritis (KOA). Infra-slow Neurofeedback (ISF-NF) training is a recent development focusing on modulating cortical slow-wave activity to improve pain outcomes. A parallel, two-armed double-blinded, randomized sham-controlled, feasibility clinical trial aimed to determine the feasibility and safety of a novel electroencephalography-based infraslow fluctuation neurofeedback (EEG ISF-NF) training in people with KOA and determine the variability of clinical outcomes and EEG changes following NF training. Eligible participants attended nine 30-min ISF-NF training sessions involving three cortical regions linked to pain. Feasibility measures were monitored during the trial period. Pain and functional outcomes were measured at baseline, post-intervention, and follow-up after 2 weeks. Resting-state EEG was recorded at baseline and immediate post-intervention. Participants were middle-aged (61.7 ± 7.6 years), New Zealand European (90.5%), and mostly females (62%) with an average knee pain duration of 4 ± 3.4 years. The study achieved a retention rate of 91%, with 20/22 participants completing all the sessions. Participants rated high levels of acceptance and “moderate to high levels of perceived effectiveness of the training.” No serious adverse events were reported during the trial. Mean difference (95% CI) for clinical pain and function measures are as follows for pain severity [active: 0.89 ± 1.7 (−0.27 to 2.0); sham: 0.98 ± 1.1 (0.22–1.7)], pain interference [active: 0.75 ± 2.3 (−0.82 to 2.3); Sham: 0.89 ± 2.1 (−0.60 to 2.4)], pain unpleasantness [active: 2.6 ± 3.7 (0.17–5.1); sham: 2.8 ± 3 (0.62–5.0)] and physical function [active: 6.2 ± 13 (−2.6 to 15); sham: 1.6 ± 12 (−6.8 to 10)]. EEG sources demonstrated frequency-specific neuronal activity, functional connectivity, and ISF ratio changes following NF training. The findings of the study indicated that the ISF-NF training is a feasible, safe, and acceptable intervention for pain management in people with KOA, with high levels of perceived effectiveness. The study also reports the variability in clinical, brain activity, and connectivity changes following training.
The effect of photobiomodulation on the brain during wakefulness and sleep
Authors: Moro Cecile , Valverde Audrey , Dole Marjorie , Hoh Kam Jaimie , Hamilton Catherine , Liebert Ann , Bicknell Brian , Benabid Alim-Louis , Magistretti Pierre , Mitrofanis John
Published: July 2022

Over the last seventy years or so, many previous studies have shown that photobiomodulation, the use of red to near infrared light on body tissues, can improve central and peripheral neuronal function and survival in both health and in disease. These improvements are thought to arise principally from an impact of photobiomodulation on mitochondrial and non-mitochondrial mechanisms in a range of different cell types, including neurones. This impact has downstream effects on many stimulatory and protective genes. An often-neglected feature of nearly all of these improvements is that they have been induced during the state of wakefulness. Recent studies have shown that when applied during the state of sleep, photobiomodulation can also be of benefit, but in a different way, by improving the flow of cerebrospinal fluid and the clearance of toxic waste-products from the brain. In this review, we consider the potential differential effects of photobiomodulation dependent on the state of arousal. We speculate that the effects of photobiomodulation is on different cells and systems depending on whether it is applied during wakefulness or sleep, that it may follow a circadian rhythm. We speculate further that the arousal-dependent photobiomodulation effects are mediated principally through a biophoton – ultra-weak light emission – network of communication and repair across the brain.
FGF22 deletion causes hidden hearing loss by affecting the function of inner hair cell ribbon synapses
Authors: Hou Shule , Zhang Jifang , Wu Yan , Junmin Chen , Yuyu Huang , He Baihui , Yang Yan , Hong Yuren , Chen Jiarui , Yang Jun , Li Shuna
Published: July 2022

Ribbon synapses are important structures in transmitting auditory signals from the inner hair cells (IHCs) to their corresponding spiral ganglion neurons (SGNs). Over the last few decades, deafness has been primarily attributed to the deterioration of cochlear hair cells rather than ribbon synapses. Hearing dysfunction that cannot be detected by the hearing threshold is defined as hidden hearing loss (HHL). The relationship between ribbon synapses and FGF22 deletion remains unknown. In this study, we used a 6-week-old FGF22 knockout mice model (Fgf22–/–) and mainly focused on alteration in ribbon synapses by applying the auditory brainstem response (ABR) test, the immunofluorescence staining, the patch-clamp recording, and quantitative real-time PCR. In Fgf22–/– mice, we found the decreased amplitude of ABR wave I, the reduced vesicles of ribbon synapses, and the decreased efficiency of exocytosis, which was suggested by a decrease in the capacitance change. Quantitative real-time PCR revealed that Fgf22–/– led to dysfunction in ribbon synapses by downregulating SNAP-25 and Gipc3 and upregulating MEF2D expression, which was important for the maintenance of ribbon synapses’ function. Our research concluded that FGF22 deletion caused HHL by affecting the function of IHC ribbon synapses and may offer a novel therapeutic target to meet an ever-growing demand for deafness treatment.
Immunological and prognostic analysis of PSENEN in low-grade gliomas: An immune infiltration-related prognostic biomarker
Authors: Chen Kaijie , Liang Beibei , Ma Wenhao , Wan Guoqing , Chen Bing , Lu Changlian , Luo Yuzhou , Gu Xuefeng
Published: July 2022

Metformin is widely used in the treatment of type 2 diabetes (T2D) and plays a role in antitumor and antiobesity processes. A recent study identified its direct molecular target, PEN2 (PSENEN). PSENEN is the minimal subunit of the multiprotein complex γ-secretase, which promotes the differentiation of oligodendrocyte progenitors into astrocytes in the central nervous system. This study was mainly based on gene expression data and clinical data from the TCGA and CGGA databases. Analysis of differential expression of PSENEN between tissues from 31 cancers and paracancerous tissues revealed that it had high expression levels in most cancers except 2 cancers. Using univariate Cox regression analysis and Kaplan-Meier survival analysis, a high expression level of PSENEN was shown to be a risk factor in low-grade gliomas (LGG). Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses indicated that PSENEN is widely involved in immune-related signaling pathways in LGG. PSENEN expression level was significantly associated with TMB, MSI, tumor stemness index, and the expression levels of immunomodulatory genes in LGG. Finally, immune infiltration analysis revealed that PSENEN level was associated with the presence of various immune infiltrating cells, among which PSENEN was strongly associated with the presence of M2 macrophages and played a synergistic pro-cancer role. In conclusion, PSENEN may partially influence prognosis by modulating immune infiltration in patients with LGG, and PSENEN may be a candidate prognostic biomarker for determining prognosis associated with immune infiltration in LGG.
A Deficiency of the Psychiatric Risk Gene DLG2/PSD-93 Causes Excitatory Synaptic Deficits in the Dorsolateral Striatum
Authors: Yoo Taesun , Joshi Shambhu , Prajapati Sanjaya , Cho Yi Sul , Kim Jinkyeong , Park Pil-Hoon , Bae Yong Chul , Kim Eunjoon , Kim Soo Young
Published: July 2022

Genetic variations resulting in the loss of function of the discs large homologs (DLG2)/postsynaptic density protein-93 (PSD-93) gene have been implicated in the increased risk for schizophrenia, intellectual disability, and autism spectrum disorders (ASDs). Previously, we have reported that mice lacking exon 14 of the Dlg2 gene (Dlg2–/– mice) display autistic-like behaviors, including social deficits and increased repetitive behaviors, as well as suppressed spontaneous excitatory postsynaptic currents in the striatum. However, the neural substrate underpinning such aberrant synaptic network activity remains unclear. Here, we found that the corticostriatal synaptic transmission was significantly impaired in Dlg2–/– mice, which did not seem attributed to defects in presynaptic releases of cortical neurons, but to the reduced number of functional synapses in the striatum, as manifested in the suppressed frequency of miniature excitatory postsynaptic currents in spiny projection neurons (SPNs). Using transmission electron microscopy, we found that both the density of postsynaptic densities and the fraction of perforated synapses were significantly decreased in the Dlg2–/– dorsolateral striatum. The density of dendritic spines was significantly reduced in striatal SPNs, but notably, not in the cortical pyramidal neurons of Dlg2–/– mice. Furthermore, a DLG2/PSD-93 deficiency resulted in the compensatory increases of DLG4/PSD-95 and decreases in the expression of TrkA in the striatum, but not particularly in the cortex. These results suggest that striatal dysfunction might play a role in the pathology of psychiatric disorders that are associated with a disruption of the Dlg2 gene.
Regulation of NMDA Receptor Signaling at Single Synapses by Human Anti-NMDA Receptor Antibodies
Authors: Dean Charles A. , Metzbower Sarah R. , Dessain Scott K. , Blanpied Thomas A. , Benavides David R.
Published: July 2022

The NMDA receptor (NMDAR) subunit GluN1 is critical for receptor function and plays a pivotal role in synaptic plasticity. Mounting evidence has shown that pathogenic autoantibody targeting of the GluN1 subunit of NMDARs, as in anti-NMDAR encephalitis, leads to altered NMDAR trafficking and synaptic localization. However, the underlying signaling pathways affected by antibodies targeting the NMDAR remain to be fully delineated. It remains unclear whether patient antibodies influence synaptic transmission via direct effects on NMDAR channel function. Here, we show using short-term incubation that GluN1 antibodies derived from patients with anti-NMDAR encephalitis label synapses in mature hippocampal primary neuron culture. Miniature spontaneous calcium transients (mSCaTs) mediated via NMDARs at synaptic spines are not altered in pathogenic GluN1 antibody exposed conditions. Unexpectedly, spine-based and cell-based analyses yielded distinct results. In addition, we show that calcium does not accumulate in neuronal spines following brief exposure to pathogenic GluN1 antibodies. Together, these findings show that pathogenic antibodies targeting NMDARs, under these specific conditions, do not alter synaptic calcium influx following neurotransmitter release. This represents a novel investigation of the molecular effects of anti-NMDAR antibodies associated with autoimmune encephalitis.
Chinese expert consensus on minimally invasive interventional treatment of trigeminal neuralgia
Authors: Fan Xiaochong , Fu Zhijian , Ma Ke , Tao Wei , Huang Bing , Guo Gang , Huang Dong , Liu Guangzhao , Song Wenge , Song Tao , Xiao Lizu , Xia Lingjie , Liu Yanqing
Published: July 2022

Background and purpose

Trigeminal neuralgia is a common condition that is associated with severe pain, which seriously affects the quality of life of patients. When the efficacy of drugs is not satisfactory or adverse drug reactions cannot be tolerated, minimally invasive interventional therapy has become an important treatment because of its simple operation, low risk, high repeatability and low cost. In recent years, minimally invasive interventional treatments, such as radiofrequency thermocoagulation (RF) of the trigeminal nerve and percutaneous microcompression (PMC), have been widely used in the clinic to relieve severe pain in many patients, however, some related problems remain to be addressed. The Pain Association of the Chinese Medical Association organizes and compiles the consensus of Chinese experts to standardize the development of minimally invasive interventional treatment of trigeminal neuralgia to provide a basis for its clinical promotion and application.

Materials and methods

The Pain Association of the Chinese Medical Association organizes the Chinese experts to compile a consensus. With reference to the evidence-based medicine (OCEBM) system and the actual situation of the profession, the Consensus Development Committee adopts the nominal group method to adjust the recommended level.

Results

Precise imaging positioning and guidance are the keys to ensuring the efficacy and safety of the procedures. RF and PMC are the most widely performed and effective treatments among minimally invasive interventional treatments for trigeminal neuralgia.

Conclusions

The pain degree of trigeminal neuralgia is severe, and a variety of minimally invasive intervention methods can effectively improve symptoms. Radiofrequency and percutaneous microcompression may be the first choice for minimally invasive interventional therapy.
Comparing Discounting of Potentially Real Rewards and Losses by Means of Functional Magnetic Resonance Imaging
Authors: Pinger Mathieu , Thome Janine , Halli Patrick , Sommer Wolfgang H. , Koppe Georgia , Kirsch Peter
Published: July 2022

Aim

Delay discounting (DD) has often been investigated in the context of decision making whereby individuals attribute decreasing value to rewards in the distant future. Less is known about DD in the context of negative consequences. The aim of this pilot study was to identify commonalities and differences between reward and loss discounting on the behavioral as well as the neural level by means of computational modeling and functional Magnetic Resonance Imaging (fMRI). We furthermore compared the neural activation between anticipation of rewards and losses.

Method

We conducted a study combining an intertemporal choice task for potentially real rewards and losses (decision-making) with a monetary incentive/loss delay task (reward/loss anticipation). Thirty healthy participants (age 18-35, 14 female) completed the study. In each trial, participants had to choose between a smaller immediate loss/win and a larger loss/win at a fixed delay of two weeks. Task-related brain activation was measured with fMRI.

Results

Hyperbolic discounting parameters of loss and reward conditions were correlated (r = 0.56). During decision-making, BOLD activation was observed in the parietal and prefrontal cortex, with no differences between reward and loss conditions. During reward and loss anticipation, dissociable activation was observed in the striatum, the anterior insula and the anterior cingulate cortex.

Conclusion

We observed behavior concurrent with DD in both the reward and loss condition, with evidence for similar behavioral and neural patterns in the two conditions. Intertemporal decision-making recruited the fronto-parietal network, whilst reward and loss anticipation were related to activation in the salience network. The interpretation of these findings may be limited to short delays and small monetary outcomes.
Cerebello-Thalamo-Cortical Network Dynamics in the Harmaline Rodent Model of Essential Tremor
Authors: Woodward Kathryn , Apps Richard , Goodfellow Marc , Cerminara Nadia L.
Published: July 2022

Essential Tremor (ET) is a common movement disorder, characterised by a posture or movement-related tremor of the upper limbs. Abnormalities within cerebellar circuits are thought to underlie the pathogenesis of ET, resulting in aberrant synchronous oscillatory activity within the thalamo-cortical network leading to tremors. Harmaline produces pathological oscillations within the cerebellum, and a tremor that phenotypically resembles ET. However, the neural network dynamics in cerebellar-thalamo-cortical circuits in harmaline-induced tremor remains unclear, including the way circuit interactions may be influenced by behavioural state. Here, we examined the effect of harmaline on cerebello-thalamo-cortical oscillations during rest and movement. EEG recordings from the sensorimotor cortex and local field potentials (LFP) from thalamic and medial cerebellar nuclei were simultaneously recorded in awake behaving rats, alongside measures of tremor using EMG and accelerometery. Analyses compared neural oscillations before and after systemic administration of harmaline (10 mg/kg, I.P), and coherence across periods when rats were resting vs. moving. During movement, harmaline increased the 9–15 Hz behavioural tremor amplitude and increased thalamic LFP coherence with tremor. Medial cerebellar nuclei and cerebellar vermis LFP coherence with tremor however remained unchanged from rest. These findings suggest harmaline-induced cerebellar oscillations are independent of behavioural state and associated changes in tremor amplitude. By contrast, thalamic oscillations are dependent on behavioural state and related changes in tremor amplitude. This study provides new insights into the role of cerebello-thalamo-cortical network interactions in tremor, whereby neural oscillations in thalamocortical, but not cerebellar circuits can be influenced by movement and/or behavioural tremor amplitude in the harmaline model.
Association between malnutrition and leucopenia in patients with osteosarcoma
Authors: Wu Haixiao , Li Shu , Lin Yile , Wang Jun , Chekhonin Vladimir P. , Peltzer Karl , Baklaushev Vladimir P. , Abbas Kirellos Said , Zhang Jin , Li Huiyang , Zhang Chao
Published: July 2022

Background and aim

Leucopenia (LP) greatly limits the efficacy of chemotherapy in osteosarcoma patients. This study aimed to evaluate the nutritional status of osteosarcoma patients before chemotherapy, assess the risk of LP during the perichemotherapy period, and explore the association between malnutrition and LP.

Materials and methods

This study retrospectively analyzed osteosarcoma patients treated in the Tianjin Medical University Cancer Institute and Hospital, China, between January 2009 and December 2020 according to the inclusion and exclusion criteria. Malnutrition in adolescents (5 to 19 years old) and adults (≥20 years old) was diagnosed using WHO AnthroPlus software (version 1.0.4) and Global Leadership initiative on Malnutrition (GLIM), respectively. According to the diagnostic criteria of LP in CTCAE 5.0, patients were divided into the LP group and the non-LP group.

Results

A total of 245 osteosarcoma patients were included. The incidence of malnutrition was 49.0%, and the incidence of LP was 51.8%. The incidence of malnutrition in adolescent patients was 53.1%, and their incidence of LP was 55.2%; the incidence of malnutrition in adult patients was 43.1%, and their incidence of LP was 47.1%. Logistic regression analysis showed that malnutrition before chemotherapy was an independent risk factor for the occurrence of LP after chemotherapy (OR = 6.85, 95% CI = 2.16-25.43; and OR = 35.03, 95% CI = 6.98-238.46 in mildly and severely malnourished young patients; OR = 6.06; 95% CI = 1.43-30.16; and OR = 38.09, 95% CI = 7.23-285.78 in mildly and severely malnourished adult patients, respectively). The results showed that age and nutritional status had a joint effect on the occurrence of LP.

Conclusion

The nutrition status of osteosarcoma patients before chemotherapy is significantly correlated with the occurrence and severity of LP during peri-chemotherapy period. During osteosarcoma chemotherapy, necessary nutritional support should be given to patients of different ages to correct their malnutrition status in a timely manner, ultimately improving the efficacy of chemotherapy and the prognosis of patients.