bluuebunny/crossref_metadata_2025 huggingface dataset:
Rich-Club Organization Disturbances of the Individual Morphological Network in Subjective Cognitive Decline
Authors: Peng Liling , Feng Jing , Ma Di , Xu Xiaowen , Gao Xin
Published: February 2022

Background

Subjective cognitive decline (SCD) was considered to be the preclinical stage of Alzheimer’s disease (AD). However, less is known about the altered rich-club organizations of the morphological networks in individuals with SCD.

Methods

This study included 53 individuals with SCD and 54 well-matched healthy controls (HC) from the Alzheimer’s disease Neuroimaging Initiative (ADNI) database. Individual-level brain morphological networks were constructed by estimating the Jensen-Shannon distance-based similarity in the distribution of regional gray matter volume. Rich-club properties were then detected, followed by statistical comparison.

Results

The characteristic rich-club organization of morphological networks (normalized rich-club coefficients > 1) was observed for both the SCD and HC groups under a range of thresholds. The SCD group showed a reduced normalized rich-club coefficient compared with the HC group. The SCD group exhibited the decreased strength and degree of rich-club connections than the HC group (strength: HC = 79.93, SCD = 74.37, p = 0.028; degree: HC = 85.28, SCD = 79.34, p = 0.027). Interestingly, the SCD group showed an increased strength of local connections than the HC group (strength: HC = 1982.16, SCD = 2003.38, p = 0.036).

Conclusion

Rich-club organization disturbances of morphological networks in individuals with SCD reveal a distinct pattern between the rich-club and peripheral regions. This altered rich-club organization pattern provides novel insights into the underlying mechanism of SCD and could be used to investigate prevention strategies at the preclinical stage of AD.
X-Ray Lithography for Nanofabrication: Is There a Future?
Authors: Bharti Amardeep , Turchet Alessio , Marmiroli Benedetta
Published: February 2022

X-ray lithography has been first proposed almost 50 years ago, and the related LIGA process around 25 years ago. It is therefore a good time to make an analysis of the technique, with its pros and cons. In this perspective article, we describe X-ray lithography’s latest advancements. First, we report the improvement in the fabrication of the high aspect ratio and high-resolution micro/nanostructures. Then, we present the radiation-assisted synthesis and processing of novel materials for the next generation of functional devices. We finally draw our conclusion on the future prospects of the technique.
Acute Effects of Various Movement Noise in Differential Learning of Rope Skipping on Brain and Heart Recovery Analyzed by Means of Multiscale Fuzzy Measure Entropy
Authors: John Alexander Thomas , Barthel Anna , Wind Johanna , Rizzi Nikolas , Schöllhorn Wolfgang Immanuel
Published: February 2022

In search of more detailed explanations for body-mind interactions in physical activity, neural and physiological effects, especially regarding more strenuous sports activities, increasingly attract interest. Little is known about the underlying manifold (neuro-)physiological impacts induced by different motor learning approaches. The various influences on brain or cardiac function are usually studied separately and modeled linearly. Limitations of these models have recently led to a rapidly growing application of nonlinear models. This study aimed to investigate the acute effects of various sequences of rope skipping on irregularity of the electrocardiography (ECG) and electroencephalography (EEG) signals as well as their interaction and whether these depend on different levels of active movement noise, within the framework of differential learning theory. Thirty-two males were randomly and equally distributed to one of four rope skipping conditions with similar cardiovascular but varying coordinative demand. ECG and EEG were measured simultaneously at rest before and immediately after rope skipping for 25 mins. Signal irregularity of ECG and EEG was calculated via the multiscale fuzzy measure entropy (MSFME). Statistically significant ECG and EEG brain area specific changes in MSFME were found with different pace of occurrence depending on the level of active movement noise of the particular rope skipping condition. Interaction analysis of ECG and EEG MSFME specifically revealed an involvement of the frontal, central, and parietal lobe in the interplay with the heart. In addition, the number of interaction effects indicated an inverted U-shaped trend presenting the interaction level of ECG and EEG MSFME dependent on the level of active movement noise. In summary, conducting rope skipping with varying degrees of movement variation appears to affect the irregularity of cardiac and brain signals and their interaction during the recovery phase differently. These findings provide enough incentives to foster further constructive nonlinear research in exercise-recovery relationship and to reconsider the philosophy of classical endurance training.
A Neural Controller Model Considering the Vestibulospinal Tract in Human Postural Control
Authors: Omura Yuichiro , Kaminishi Kohei , Chiba Ryosuke , Takakusaki Kaoru , Ota Jun
Published: February 2022

Humans are able to control their posture in their daily lives. It is important to understand how this is achieved in order to understand the mechanisms that lead to impaired postural control in various diseases. The descending tracts play an important role in controlling posture, particularly the reticulospinal and the vestibulospinal tracts (VST), and there is evidence that the latter is impaired in various diseases. However, the contribution of the VST to human postural control remains unclear, despite extensive research using neuroscientific methods. One reason for this is that the neuroscientific approach limits our understanding of the relationship between an array of sensory information and the muscle outputs. This limitation can be addressed by carrying out studies using computational models, where it is possible to make and validate hypotheses about postural control. However, previous computational models have not considered the VST. In this study, we present a neural controller model that mimics the VST, which was constructed on the basis of physiological data. The computational model is composed of a musculoskeletal model and a neural controller model. The musculoskeletal model had 18 degrees of freedom and 94 muscles, including those of the neck related to the function of the VST. We used an optimization method to adjust the control parameters for different conditions of muscle tone and with/without the VST. We examined the postural sway for each condition. The validity of the neural controller model was evaluated by comparing the modeled postural control with (1) experimental results in human subjects, and (2) the results of a previous study that used a computational model. It was found that the pattern of results was similar for both. This therefore validated the neural controller model, and we could present the neural controller model that mimics the VST.
Relaxation-Compensated Chemical Exchange Saturation Transfer MRI in the Brain at 7T: Application in Relapsing-Remitting Multiple Sclerosis
Authors: O'Grady Kristin P. , Satish Sanjana , Owen Quinn R. , Box Bailey A. , Bagnato Francesca , Combes Anna J. E. , Cook Sarah R. , Westervelt Holly James , Feiler Haley R. , Lawless Richard D. , Sarma Asha , Malone Shekinah D. , Ndolo Josephine M. , Yoon Keejin , Dortch Richard D. , Rogers Baxter P. , Smith Seth A.
Published: February 2022

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) can probe tissue biochemistry in vivo with high resolution and sensitivity without requiring exogenous contrast agents. Applying CEST MRI at ultrahigh field provides advantages of increasing spectral resolution and improving sensitivity to metabolites with faster proton exchange rates such as glutamate, a critical neurotransmitter in the brain. Prior magnetic resonance spectroscopy and CEST MRI studies have revealed altered regulation of glutamate in patients with multiple sclerosis (MS). While CEST imaging facilitates new strategies for investigating the pathology underlying this complex and heterogeneous neurological disease, CEST signals are contaminated or diluted by concurrent effects (e.g., semi-solid magnetization transfer (MT) and direct water saturation) and are scaled by the T1 relaxation time of the free water pool which may also be altered in the context of disease. In this study of 20 relapsing-remitting MS patients and age- and sex-matched healthy volunteers, glutamate-weighted CEST data were acquired at 7.0 T. A Lorentzian fitting procedure was used to remove the asymmetric MT contribution from CEST z-spectra, and the apparent exchange-dependent relaxation (AREX) correction was applied using an R1 map derived from an inversion recovery sequence to further isolate glutamate-weighted CEST signals from concurrent effects. Associations between AREX and cognitive function were examined using the Minimal Assessment of Cognitive Function in MS battery. After isolating CEST effects from MT, direct water saturation, and T1 effects, glutamate-weighted AREX contrast remained higher in gray matter than in white matter, though the difference between these tissues decreased. Glutamate-weighted AREX in normal-appearing gray and white matter in MS patients did not differ from healthy gray and white matter but was significantly elevated in white matter lesions. AREX in some cortical regions and in white matter lesions correlated with disability and measures of cognitive function in MS patients. However, further studies with larger sample sizes are needed to confirm these relationships due to potential confounding effects. The application of MT and AREX corrections in this study demonstrates the importance of isolating CEST signals for more specific characterization of the contribution of metabolic changes to tissue pathology and symptoms in MS.
Temporal Progression Patterns of Brain Atrophy in Corticobasal Syndrome and Progressive Supranuclear Palsy Revealed by Subtype and Stage Inference (SuStaIn)
Authors: Saito Yuya , Kamagata Koji , Wijeratne Peter A. , Andica Christina , Uchida Wataru , Takabayashi Kaito , Fujita Shohei , Akashi Toshiaki , Wada Akihiko , Shimoji Keigo , Hori Masaaki , Masutani Yoshitaka , Alexander Daniel C. , Aoki Shigeki
Published: February 2022

Differentiating corticobasal degeneration presenting with corticobasal syndrome (CBD-CBS) from progressive supranuclear palsy with Richardson's syndrome (PSP-RS), particularly in early stages, is often challenging because the neurodegenerative conditions closely overlap in terms of clinical presentation and pathology. Although volumetry using brain magnetic resonance imaging (MRI) has been studied in patients with CBS and PSP-RS, studies assessing the progression of brain atrophy are limited. Therefore, we aimed to reveal the difference in the temporal progression patterns of brain atrophy between patients with CBS and those with PSP-RS purely based on cross-sectional data using Subtype and Stage Inference (SuStaIn)—a novel, unsupervised machine learning technique that integrates clustering and disease progression modeling. We applied SuStaIn to the cross-sectional regional brain volumes of 25 patients with CBS, 39 patients with typical PSP-RS, and 50 healthy controls to estimate the two disease subtypes and trajectories of CBS and PSP-RS, which have distinct atrophy patterns. The progression model and classification accuracy of CBS and PSP-RS were compared with those of previous studies to evaluate the performance of SuStaIn. SuStaIn identified distinct temporal progression patterns of brain atrophy for CBS and PSP-RS, which were largely consistent with previous evidence, with high reproducibility (99.7%) under cross-validation. We classified these diseases with high accuracy (0.875) and sensitivity (0.680 and 1.000, respectively) based on cross-sectional structural brain MRI data; the accuracy was higher than that reported in previous studies. Moreover, SuStaIn stage correctly reflected disease severity without the label of disease stage, such as disease duration. Furthermore, SuStaIn also showed the genialized performance of differentiation and reflection for CBS and PSP-RS. Thus, SuStaIn has potential for improving our understanding of disease mechanisms, accurately stratifying patients, and providing prognoses for patients with CBS and PSP-RS.
CSF and Serum Levels of Inflammatory Markers in PD: Sparse Correlation, Sex Differences and Association With Neurodegenerative Biomarkers
Authors: Lerche Stefanie , Zimmermann Milan , Wurster Isabel , Roeben Benjamin , Fries Franca Laura , Deuschle Christian , Waniek Katharina , Lachmann Ingolf , Gasser Thomas , Jakobi Meike , Joos Thomas O. , Schneiderhan-Marra Nicole , Brockmann Kathrin
Published: February 2022

Background

An involvement of the central-nervous and peripheral, innate and adaptive immune system in the pathogenesis of Parkinson's disease (PD) is nowadays well established.

Objectives

We face several open questions in preparation of clinical trials aiming at disease-modification by targeting the immune system: Do peripheral (blood) inflammatory profiles reflect central (CSF) inflammatory processes? Are blood/CSF inflammatory markers associated with CSF levels of neurodegenerative/PD-specific biomarkers?

Methods

Using a multiplex assay we assessed 41 inflammatory markers in CSF/serum pairs in 453 sporadic PD patients. We analyzed CSF/serum correlation as well as associations of inflammatory markers with clinical outcome measures (UPDRS-III, H&Y, MoCA) and with CSF levels of α-synuclein, Aβ1−42, t-Tau, p181-Tau and NFL. All analyses were stratified by sex as the immune system shows relevant sex-specific differences.

Results

Correlations between CSF and serum were sparse and detected in only 25% (9 out of 36) of the analysable inflammatory markers in male PD patients and in only 38% (12 out of 32) of female PD patients. The most important pro-inflammatory mediators associated with motor and cognitive decline as well as with neurodegenerative/PD-specific biomarkers were FABP, ICAM-1, IL-8, MCP-1, MIP-1-beta, and SCF. Results were more robust for CSF than for serum.

Interpretation

Levels of central-nervous and peripheral inflammatory markers might be regulated independently of each other with CSF inflammatory markers reflecting CNS pathology more accurately than peripheral markers. These findings along with sex-specific characteristics have to be considered when designing clinical trials aiming at disease-modification by targeting the immune system.
An Automated Tongue Tracker for Quantifying Bulbar Function in ALS
Authors: Northall Alicia , Mukhopadhyay Budhaditya , Weber Miriam , Petri Susanne , Prudlo Johannes , Vielhaber Stefan , Schreiber Stefanie , Kuehn Esther
Published: February 2022

Introduction

Bulbar symptoms, including difficulty swallowing and speaking, are common in amyotrophic lateral sclerosis (ALS) and other neurological disorders, such as stroke. The presence of bulbar symptoms provides important information regarding clinical outcomes, such as survival time after diagnosis. Nevertheless, there are currently no easily accessible, quantitative methods to measure bulbar function in patients.

Methods

We developed an open-source tool called Tongue Tracker (TT) to quantify bulbar function by training a neural network to track kinematic tongue features of short video clips of lateral tongue movements. We tested 16 healthy controls and ten patients with ALS, of whom two patients were clinically diagnosed with bulbar-onset type and eight patients were clinically diagnosed with limb-onset type. Of the limb-onset patients, five patients also showed symptoms of bulbar impairment.

Results

We validated TT by comparing the results with manual delineation of tongue movements in the clips. We demonstrate an early-stage bulbar-onset patient who showed fewer and slower tongue sweeps compared to healthy controls and limb-onset patients and we show that five bulbar-impaired limb-onset patients have a different tongue kinematic profile compared to healthy controls.

Discussion

TT may serve to detect quantitative markers of bulbar dysfunction in ALS and other motor disorders, such as stroke, by identifying signatures of spasticity or muscle weakness that affects tongue movement speed and/or tongue movement topography.
Clinical and Instrumental Characterization of Patients With Late-Onset Epilepsy
Authors: DiFrancesco Jacopo C. , Labate Angelo , Romoli Michele , Chipi Elena , Salvadori Nicola , Galimberti Carlo Andrea , Perani Daniela , Ferrarese Carlo , Costa Cinzia
Published: February 2022

Epilepsy is classically considered a childhood disease. However, it represents the third most frequent neurological condition in the elderly, following stroke, and dementia. With the progressive aging of the general population, the number of patients with Late-Onset Epilepsy (LOE) is constantly growing, with important economic and social consequences, in particular for the more developed countries where the percentage of elderly people is higher. The most common causes of LOE are structural, mainly secondary to cerebrovascular or infectious diseases, brain tumors, trauma, and metabolic or toxic conditions. Moreover, there is a growing body of evidence linking LOE with neurodegenerative diseases, particularly Alzheimer's disease (AD). However, despite a thorough characterization, the causes of LOE remain unknown in a considerable portion of patients, thus termed as Late-Onset Epilepsy of Unknown origin (LOEU). In order to identify the possible causes of the disease, with an important impact in terms of treatment and prognosis, LOE patients should always undergo an exhaustive phenotypic characterization. In this work, we provide a detailed review of the main clinical and instrumental techniques for the adequate characterization of LOE patients in the clinical practice. This work aims to provide an easy and effective tool that supports routine activity of the clinicians facing LOE.
Case Report: Thymidine Kinase 2 (TK2) Deficiency: A Novel Mutation Associated With Childhood-Onset Mitochondrial Myopathy and Atypical Progression
Authors: Manini Arianna , Meneri Megi , Rodolico Carmelo , Corti Stefania , Toscano Antonio , Comi Giacomo Pietro , Musumeci Olimpia , Ronchi Dario
Published: February 2022

The nuclear gene TK2 encodes the mitochondrial thymidine kinase, an enzyme involved in the phosphorylation of deoxycytidine and deoxythymidine nucleosides. Biallelic TK2 mutations are associated with a spectrum of clinical presentations mainly affecting skeletal muscle and featuring muscle mitochondrial DNA (mtDNA) instability. Current classification includes infantile- ( ≤ 1 year), childhood- (1–12 years), and late-onset (≥12 years) forms. In addition to age at onset, these forms differ for progression, life expectancy, and signs of mtDNA instability (mtDNA depletion vs. accumulation of multiple mtDNA deletions). Childhood-onset TK2 deficiency typically causes a rapidly progressive proximal myopathy, which leads to wheelchair-bound status within 10 years of disease onset, and severe respiratory impairment. Muscle biopsy usually reveals a combination of mitochondrial myopathy and dystrophic features with reduced mtDNA content. Here we report the case of an Italian patient presenting childhood-onset, slowly progressive mitochondrial myopathy, ptosis, hypoacusis, dysphonia, and dysphagia, harboring the TK2 variants c.278A>G and c.543del, the latter unreported so far. Compared to other childhood-onset TK2-patients, our case displays atypical features, including slowly progressive muscle weakness and absence of respiratory failure, which are usually observed in late-onset forms. This report extends the genetic background of TK2-related myopathy, highlighting the clinical overlap among different forms.
From Expert to Elite? — Research on Top Archer’s EEG Network Topology
Authors: Gu Feng , Gong Anmin , Qu Yi , Bao Aiyong , Wu Jin , Jiang Changhao , Fu Yunfa
Published: February 2022

It is not only difficult to be a sports expert but also difficult to grow from a sports expert to a sports elite. Professional athletes are often concerned about the differences between an expert and an elite and how to eventually become an elite athlete. To explore the differences in brain neural mechanism between experts and elites in the process of motor behavior and reveal the internal connection between motor performance and brain activity, we collected and analyzed the electroencephalography (EEG) findings of 14 national archers and 14 provincial archers during aiming and resting states and constructed the EEG brain network of the two archer groups based on weighted phase lag index; the graph theory was used to analyze and compare the network characteristics via local network and global network topologies. The results showed that compared with the expert archers, the elite archers had stronger functional coupling in beta1 and beta2 bands, and the difference was evident in the frontal and central regions; in terms of global characteristics of brain network topology, the average clustering coefficient and global efficiency of elite archers were significantly higher than that of expert archers, and the eigenvector centrality of expert archers was higher; for local characteristics, elite archers had higher local efficient; and the brain network characteristics of expert archers showed a strong correlation with archery performance. This suggests that compared with expert archers, elite archers showed stronger functional coupling, higher integration efficiency of global and local information, and more independent performance in the archery process. These findings reveal the differences in brain electrical network topologies between elite and expert archers in the archery preparation stage, which is expected to provide theoretical reference for further training and promotion of professional athletes.
Brain Atrophy and Clinical Characterization of Adults With Mild Cognitive Impairment and Different Cerebrospinal Fluid Biomarker Profiles According to the AT(N) Research Framework of Alzheimer’s Disease
Authors: Rivas-Fernández Miguel Ángel , Lindín Mónica , Zurrón Montserrat , Díaz Fernando , Aldrey-Vázquez José Manuel , Pías-Peleteiro Juan Manuel , Vázquez-Vázquez Laura , Pereiro Arturo Xosé , Lojo-Seoane Cristina , Nieto-Vieites Ana , Galdo-Álvarez Santiago
Published: February 2022

Introduction

This study aimed to evaluate, in adults with mild cognitive impairment (MCI), the brain atrophy that may distinguish between three AT(N) biomarker-based profiles, and to determine its clinical value.

Methods

Structural MRI (sMRI) was employed to evaluate the volume and cortical thickness differences in MCI patients with different AT(N) profiles, namely, A−T−(N)−: normal AD biomarkers; A+T−(N)−: AD pathologic change; and A+T+(N)+: prodromal AD. Sensitivity and specificity of these changes were also estimated.

Results

An initial atrophy in medial temporal lobe (MTL) areas was found in the A+T−(N)− and A+T+(N)+ groups, spreading toward the parietal and frontal regions in A+T+(N)+ patients. These structural changes allowed distinguishing AT(N) profiles within the AD continuum; however, the profiles and their pattern of neurodegeneration were unsuccessful to determine the current clinical status.

Conclusion

sMRI is useful in the determination of the specific brain structural changes of AT(N) profiles along the AD continuum, allowing differentiation between MCI adults with or without pathological AD biomarkers.
Effectiveness of Different Methods for Baroreflex Sensitivity Assessment in Determining the Severity of Cardiovascular Autonomic Neuropathy in Patients With Parkinson’s Disease
Authors: Huang Chih-Cheng , Lai Yun-Ru , Lien Chia-Yi , Cheng Ben-Chung , Kung Chia-Te , Chiang Yi-Fang , Lu Cheng-Hsien
Published: February 2022

Background

Autonomic disorders are an important non-motor feature of Parkinson’s disease (PD). Baroreflex sensitivity (BRS) is often used as an indicator of cardiovascular autonomic function, and it is clinically significant. Several different methods of BRS assessment have been described. We evaluated and compared the efficiency of several methods of BRS assessment for additional insight into the underlying physiology and the determination of its severity in patients with PD.

Materials and Methods

Eighty-five patients with PD underwent cardiovascular autonomic testing. The Composite Autonomic Scoring Scale (CASS) was used to grade the severity of autonomic impairment and to define the presence of cardiovascular autonomic neuropathy (CAN). BRS was assessed using the Valsalva maneuver (BRS_VM). In addition, spontaneous BRS was computed using the sequence method and the spectral method.

Results and Conclusion

There was considerable agreement between the different methods of BRS assessment. Nevertheless, BRS_VM exhibited a higher degree of correlation with cardiovascular autonomic function than spontaneous BRS indexes obtained by the sequence or spectral method. BRS_VM, rather than spontaneous BRS, also had a predictive value for the presence of CAN to the diagnostic criteria by CASS in patients with PD.
The Unfolded Protein Responses in Health, Aging, and Neurodegeneration: Recent Advances and Future Considerations
Authors: Wodrich Andrew P. K. , Scott Andrew W. , Shukla Arvind Kumar , Harris Brent T. , Giniger Edward
Published: February 2022

Aging and age-related neurodegeneration are both associated with the accumulation of unfolded and abnormally folded proteins, highlighting the importance of protein homeostasis (termed proteostasis) in maintaining organismal health. To this end, two cellular compartments with essential protein folding functions, the endoplasmic reticulum (ER) and the mitochondria, are equipped with unique protein stress responses, known as the ER unfolded protein response (UPRER) and the mitochondrial UPR (UPRmt), respectively. These organellar UPRs play roles in shaping the cellular responses to proteostatic stress that occurs in aging and age-related neurodegeneration. The loss of adaptive UPRER and UPRmt signaling potency with age contributes to a feed-forward cycle of increasing protein stress and cellular dysfunction. Likewise, UPRER and UPRmt signaling is often altered in age-related neurodegenerative diseases; however, whether these changes counteract or contribute to the disease pathology appears to be context dependent. Intriguingly, altering organellar UPR signaling in animal models can reduce the pathological consequences of aging and neurodegeneration which has prompted clinical investigations of UPR signaling modulators as therapeutics. Here, we review the physiology of both the UPRER and the UPRmt, discuss how UPRER and UPRmt signaling changes in the context of aging and neurodegeneration, and highlight therapeutic strategies targeting the UPRER and UPRmt that may improve human health.
Type I Interferon Response Is Mediated by NLRX1-cGAS-STING Signaling in Brain Injury
Authors: Fritsch Lauren E. , Ju Jing , Gudenschwager Basso Erwin Kristobal , Soliman Eman , Paul Swagatika , Chen Jiang , Kaloss Alexandra M. , Kowalski Elizabeth A. , Tuhy Taylor C. , Somaiya Rachana Deven , Wang Xia , Allen Irving Coy , Theus Michelle H. , Pickrell Alicia M.
Published: February 2022

Background

Inflammation is a significant contributor to neuronal death and dysfunction following traumatic brain injury (TBI). Recent evidence suggests that interferons may be a key regulator of this response. Our studies evaluated the role of the Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes (cGAS-STING) signaling pathway in a murine model of TBI.

Methods

Male, 8-week old wildtype, STING knockout (−/−), cGAS−/−, and NLRX1−/− mice were subjected to controlled cortical impact (CCI) or sham injury. Histopathological evaluation of tissue damage was assessed using non-biased stereology, which was complemented by analysis at the mRNA and protein level using qPCR and western blot analysis, respectively.

Results

We found that STING and Type I interferon-stimulated genes were upregulated after CCI injury in a bi-phasic manner and that loss of cGAS or STING conferred neuroprotection concomitant with a blunted inflammatory response at 24 h post-injury. cGAS−/− animals showed reduced motor deficits 4 days after injury (dpi), and amelioration of tissue damage was seen in both groups of mice up to 14 dpi. Given that cGAS requires a cytosolic damage- or pathogen-associated molecular pattern (DAMP/PAMP) to prompt downstream STING signaling, we further demonstrate that mitochondrial DNA is present in the cytosol after TBI as one possible trigger for this pathway. Recent reports suggest that the immune modulator NLR containing X1 (NLRX1) may sequester STING during viral infection. Our findings show that NLRX1 may be an additional regulator that functions upstream to regulate the cGAS-STING pathway in the brain.

Conclusions

These findings suggest that the canonical cGAS-STING-mediated Type I interferon signaling axis is a critical component of neural tissue damage following TBI and that mtDNA may be a possible trigger in this response.
Synaptic Vesicle Recycling and the Endolysosomal System: A Reappraisal of Form and Function
Authors: Ivanova Daniela , Cousin Michael A.
Published: February 2022

The endolysosomal system is present in all cell types. Within these cells, it performs a series of essential roles, such as trafficking and sorting of membrane cargo, intracellular signaling, control of metabolism and degradation. A specific compartment within central neurons, called the presynapse, mediates inter-neuronal communication via the fusion of neurotransmitter-containing synaptic vesicles (SVs). The localized recycling of SVs and their organization into functional pools is widely assumed to be a discrete mechanism, that only intersects with the endolysosomal system at specific points. However, evidence is emerging that molecules essential for endolysosomal function also have key roles within the SV life cycle, suggesting that they form a continuum rather than being isolated processes. In this review, we summarize the evidence for key endolysosomal molecules in SV recycling and propose an alternative model for membrane trafficking at the presynapse. This includes the hypotheses that endolysosomal intermediates represent specific functional SV pools, that sorting of cargo to SVs is mediated via the endolysosomal system and that manipulation of this process can result in both plastic changes to neurotransmitter release and pathophysiology via neurodegeneration.
Real-Time Detection and Feedback of Canonical Electroencephalogram Microstates: Validating a Neurofeedback System as a Function of Delay
Authors: Asai Tomohisa , Hamamoto Takamasa , Kashihara Shiho , Imamizu Hiroshi
Published: February 2022

Recent neurotechnology has developed various methods for neurofeedback (NF), in which participants observe their own neural activity to be regulated in an ideal direction. EEG-microstates (EEGms) are spatially featured states that can be regulated through NF training, given that they have recently been indicated as biomarkers for some disorders. The current study was conducted to develop an EEG-NF system for detecting “canonical 4 EEGms” in real time. There are four representative EEG states, regardless of the number of channels, preprocessing procedures, or participants. Accordingly, our 10 Hz NF system was implemented to detect them (msA, B, C, and D) and audio-visually inform participants of its detection. To validate the real-time effect of this system on participants’ performance, the NF was intentionally delayed for participants to prevent their cognitive control in learning. Our results suggest that the feedback effect was observed only under the no-delay condition. The number of Hits increased significantly from the baseline period and increased from the 1- or 20-s delay conditions. In addition, when the Hits were compared among the msABCD, each cognitive or perceptual function could be characterized, though the correspondence between each microstate and psychological ability might not be that simple. For example, msD should be generally task-positive and less affected by the inserted delay, whereas msC is more delay-sensitive. In this study, we developed and validated a new EEGms-NF system as a function of delay. Although the participants were naive to the inserted delay, the real-time NF successfully increased their Hit performance, even within a single-day experiment, although target specificity remains unclear. Future research should examine long-term training effects using this NF system.
Deficient Recurrent Cortical Processing in Congenital Deafness
Authors: Yusuf Prasandhya Astagiri , Lamuri Aly , Hubka Peter , Tillein Jochen , Vinck Martin , Kral Andrej
Published: February 2022

The influence of sensory experience on cortical feedforward and feedback interactions has rarely been studied in the auditory cortex. Previous work has documented a dystrophic effect of deafness in deep cortical layers, and a reduction of interareal couplings between primary and secondary auditory areas in congenital deafness which was particularly pronounced in the top-down direction (from the secondary to the primary area). In the present study, we directly quantified the functional interaction between superficial (supragranular, I to III) and deep (infragranular, V and VI) layers of feline’s primary auditory cortex A1, and also between superficial/deep layers of A1 and a secondary auditory cortex, namely the posterior auditory field (PAF). We compared adult hearing cats under acoustic stimulation and cochlear implant (CI) stimulation to adult congenitally deaf cats (CDC) under CI stimulation. Neuronal activity was recorded from auditory fields A1 and PAF simultaneously with two NeuroNexus electrode arrays. We quantified the spike field coherence (i.e., the statistical dependence of spike trains at one electrode with local field potentials on another electrode) using pairwise phase consistency (PPC). Both the magnitude as well as the preferred phase of synchronization was analyzed. The magnitude of PPC was significantly smaller in CDCs than in controls. Furthermore, controls showed no significant difference between the preferred phase of synchronization between supragranular and infragranular layers, both in acoustic and electric stimulation. In CDCs, however, there was a large difference in the preferred phase between supragranular and infragranular layers. These results demonstrate a loss of synchrony and for the first time directly document a functional decoupling of the interaction between supragranular and infragranular layers of the primary auditory cortex in congenital deafness. Since these are key for the influence of top-down to bottom-up computations, the results suggest a loss of recurrent cortical processing in congenital deafness and explain the outcomes of previous studies by deficits in intracolumnar microcircuitry.
Molecular Imaging in Multiple Myeloma—Novel PET Radiotracers Improve Patient Management and Guide Therapy
Authors: von Hinten Johannes , Kircher Malte , Dierks Alexander , Pfob Christian H. , Higuchi Takahiro , Pomper Martin G. , Rowe Steven P. , Buck Andreas K. , Samnick Samuel , Werner Rudolf A. , Lapa Constantin
Published: February 2022

Due to its proven value in imaging of multiple myeloma (MM), including staging, prognostication, and assessment of therapy response, 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) is utilized extensively in the clinic. However, its accuracy is hampered by imperfect sensitivity (e.g., so-called FDG-negative MM) as well as specificity (e.g., inflammatory processes), with common pitfalls including fractures and degenerative changes. Novel approaches providing a read-out of increased protein or lipid membrane syntheses, such as [11C]methionine and [11C]choline or the C-X-C motif chemokine receptor 4-targeting radiotracer [68Ga]Pentixafor, have already been shown to be suitable adjuncts or alternatives to FDG. In the present focused review, those imaging agents along with their theranostic potential in the context of MM are highlighted.
Impact of Overhydration on Left Ventricular Hypertrophy in Patients With Chronic Kidney Disease
Authors: Sun Lianqin , Li Qing , Sun Zhiying , Duan Suyan , Nie Guangyan , Dong Jiaxin , Zhang Chengning , Zeng Ming , Sun Bin , Yuan Yanggang , Wang Ningning , Mao Huijuan , Xing Changying , Zhang Bo
Published: February 2022

Objective

Volume overload is a frequent feature related to left ventricular hypertrophy (LVH) in dialysis patients, but its influence on patients with chronic kidney disease (CKD) not on dialysis has not been accurately uncovered. This article was to examine the relationship between overhydration (OH) and LVH in patients with CKD not yet on dialysis.

Methods

A total of 302 patients with CKD stages 1–4 were included. Participants were divided into different subgroups according to occurring LVH or not, and OH tertiles. Clinical and laboratory parameters were compared among groups. Spearman correlation analyses were adopted to explore the relationships of echocardiographic findings with the clinical and laboratory characteristics. Binary logistic regression models were performed to estimate the odds ratios (ORs) for the associations between OH and LVH. Restricted cubic splines were implemented to assess the possible non-linear relationship between OH and LVH. LVH was defined as left ventricular mass index (LVMI) >115 g/m2 in men and >95 g/m2 in women.

Results

Of the enrolled patients with CKD, the mean age was 45.03 ± 15.14 years old, 165 (54.6%) cases were men, and 65 (21.5%) cases had LVH. Spearman correlation analyses revealed that OH was positively correlated with LVMI (r = 0.263, P < 0.001). After adjustment for age, gender, diabetes, body mass index (BMI), systolic blood pressure (SBP), hemoglobin, serum albumin, estimated glomerular filtration rate (eGFR), and logarithmic transformation of urinary sodium and urinary protein, multivariate logistic regression analyses demonstrated that both the middle and highest tertile of OH was associated with increased odds of LVH [OR: 3.082 (1.170–8.114), P = 0.023; OR: 4.481 (1.332–15.078), P = 0.015, respectively], in comparison to the lowest tierce. Restricted cubic spline analyses were employed to investigate the relationship between OH and LVH, which unfolded a significant non-linear association (P for non-linear = 0.0363). Furthermore, patients were divided into two groups according to CKD stages. The multivariate logistic regression analyses uncovered that increased odds of LVH were observed in the middle and the highest tertile of OH [OR: 3.908 (0.975–15.670), P = 0.054; OR: 6.347 (1.257–32.054), P = 0.025, respectively] in patients with stages 1–2.

Conclusion

These findings suggest that a higher level of OH was associated with a higher occurrence of LVH in patients with CKD not on dialysis, especially in patients with CKD stages 1–2.
Are Dietitians With Obesity Perceived as Competent and Warm? Applying the Stereotype Content Model to Weight Stigma in Brazil
Authors: Cassiano Giovana Santarosa , Carvalho-Ferreira Joana Pereira , Buckland Nicola J. , Ulian Mariana Dimitrov , da Cunha Diogo Thimoteo
Published: February 2022

The aim of this study was to understand how dietitians' body size influences perceived competence and warmth, based on the Stereotype Content Model (SCM). Online data were collected from 1,039 Brazilians, who were either laypeople, registered dietitians, or nutrition students. Participants rated the competence and warmth dimensions of three dietitians who differed in sex, body weight, and age. Participants also indicated how likelythey would consult or recommend each dietitian for nutritional advice, and indicated their attitudes toward people with obesity (PWO) [using The Antifat Attitudes Test (AFAT)]. Laypeople attributed less competence and warmth to all profiles compared to dietitians and students (p < 0.001). Three clusters occupied the SCM warmth-by-competence space. However, the clusters were different among groups (laypeople, dietitians, and students). For lay participants, the woman without overweight, the older woman, and the older man were located in the high competence/medium warmth cluster. Meanwhile, the woman with obesity was located in the medium competence/high warmth cluster. The dietitians and students map found the woman with obesity and the older woman in a high competence and warmth cluster. In general, the woman with obesity, the man without obesity, and the older man can be classified as ambivalent stereotypes, the woman being perceived as more warm than competent and the men more competent than warm. Participants with high AFAT scores were less likely to consult or recommend to a family member a dietitian with obesity. This study contributes to identifying ambivalent stereotypes for dietitians. Dietitians with obesity can be seen as warm but less competent. Also, although less intense than laypeople, dietitians, and students exhibited weight stigma. These findings can foster important discussions about weight stigma and emphasize the need to increase population awareness about the causes of obesity.
Coated Zinc Oxide Improves Growth Performance of Weaned Piglets via Gut Microbiota
Authors: Sun Yiwei , Ma Ning , Qi Zengkai , Han Meng , Ma Xi
Published: February 2022

Weaned piglets stayed in transitional stages of internal organ development and external environment change. The dual stresses commonly caused intestinal disorders followed by damaged growth performance and severe diarrhea. High dose of zinc oxide could improve production efficiency and alleviate disease status whereas caused serious environmental pollution. This research investigated if coated ZnO (C_ZnO) in low dose could replace the traditional dose of ZnO to improve the growth performance, intestinal function, and gut microbiota structures in the weaned piglets. A total of 126 cross-bred piglets (7.0 ± 0.5 kg body weight) were randomly allocated into three groups and fed a basal diet or a basal diet supplemented with ZnO (2,000 mg Zn/kg) or C_ZnO (500 mg Zn/kg), respectively. The test lasted for 6 weeks. C_ZnO improved average daily gain (ADG) and feed efficiency, alleviated diarrhea, decreased the lactulose/mannitol ratio (L/M) in the urine, increased the ileal villus height, and upregulated the expression of Occludin in the ileal tissue and the effect was even better than a high concentration of ZnO. Importantly, C_ZnO also regulated the intestinal flora, enriching Streptococcus and Lactobacillus and removing Bacillus and intestinal disease-associated pathogens, including Clostridium_sensu_stricto_1 and Cronobacter in the ileal lumen. Although, colonic microbiota remained relatively stable, the marked rise of Blautia, a potential probiotic related to body health, could still be found. In addition, C_ZnO also led to a significant increase of acetate and propionate in both foregut and hindgut. Collectively, a low concentration of C_ZnO could effectively promote growth performance and reduce diarrhea through improving small intestinal morphology and permeability, enhancing the barrier function, adjusting the structure of gut microbiota, and raising the concentration of short-chain fatty acids (SCFAs) in the weaned piglets.
The Effect of Microwave Baking Conditions on the Quality of Biscuits and the Control of Thermal Processing Hazards in the Maillard Reaction
Authors: Dong Lu , Qiu Caiyi , Wei Fan , Yu Zhenting , Zhang Yan , Wang Shuo
Published: February 2022

To reduce thermal processing hazards (TPHs), microwave baking has been extensively used in food thermal processing. In this study, the influence of microwave power and microwave time on the formation of TPHs and their precursors was explored in microwave-baked biscuits. The results indicated that the content of acrylamide, 5-hydroxymethylfurfural, methylglyoxal, and 3-deoxyglucosone increased linearly with the extension of microwave time (2, 2.5, and 3 min) and microwave power (440, 480, and 520 W). There was a significant correlation between the four TPHs. 3-Deoxyglucosone may directly or indirectly participate in the formation of the other three TPHs. The relationship between TPH levels with some heat-induced sensory characteristics was analyzed. The correlation between the sensory characteristics and the content of TPHs is L* > a* > hardness > Water activity (AW). The correlation coefficients between L* value and the four TPHs are −0.950, −0.891, −0.803, and −0.985. Furthermore, the content of TPHs produced by traditional baking and microwave baking under the same texture level was compared. Compared with traditional baking (190°C, 7 min), microwave baking at 440 W for 3 min successfully decrease methylglyoxal, 3-Deoxyglucosone, acrylamide, and 5-hydroxymethylfurfural content by 60.75, 30.19, 30.87, and 61.28%, respectively. Traditionally baked biscuits, which had a more obvious color, as characterized by lower L* value, larger a* and b* values, are more susceptible to the formation of TPHs. Therefore, microwave baking can reduce the generation of TPHs.
Fabrication and Characterization of Ultra-High-Pressure (UHP)-Induced Whey Protein Isolate/κ-Carrageenan Composite Emulsion Gels for the Delivery of Curcumin
Authors: Su Jiaqi , Wang Linlin , Dong Wenxia , Wei Jiao , Liu Xi , Yan Jinxin , Ren Fazheng , Yuan Fang , Wang Pengjie
Published: February 2022

The emulsion gels have attracted extensive interests due to their unique physical characters, remarkable stability, and control release properties of flavor and functional components compared to emulsions in liquid. In the current work, whey protein isolate (WPI)/κ-carrageenan (κ-CG) composite emulsion gels were fabricated based on the ultra-high-pressure (UHP) technology, in replacement of the traditional thermal, acid, or enzyme processing. Uniform composite emulsion gels could be fabricated by UHP above 400 MPa with minimum WPI and κ-CG concentrations of 8.0 and 1.0 wt%, respectively. The formation of UHP-induced emulsion gels is mostly attributed to the hydrophobic interaction and hydrogen bonding. The emulsion gels with different textures, rheology properties, and microstructures could be fabricated through adjusting the formulations (WPI concentration, κ-CG concentration, and oil phase fraction) as well as processing under different conditions (pressure and time). Afterward, curcumin-loaded emulsion gels were fabricated and subjected to an in vitro simulated gastrointestinal digestion in order to investigate the gastrointestinal fate of curcumin. In vitro simulated digestion results demonstrated that the UHP treatment significantly retarded the release of curcumin but had little impact on the bioaccessibility of curcumin. The results in this work provide useful information for the construction of emulsion gels through a non-thermal process, which showed great potential for the delivery of heat-sensitive bioactive components.