bluuebunny/crossref_metadata_2025 huggingface dataset:
HOTAIR Up-Regulation Activates NF-κB to Induce Immunoescape in Gliomas
Authors: Wang Yunfei , Yi Kaikai , Liu Xing , Tan Yanli , Jin Weili , Li Yansheng , Zhou Junhu , Wang Hongjun , Kang Chunsheng
Published: November 2021

Background

Checkpoint blockade therapies targeting programmed death ligand 1 (PD-L1) and its receptor programmed cell death 1 promote T cell-mediated immune surveillance against tumors and have been associated with significant clinical benefit in cancer patients. The long-stranded non-coding RNA HOTAIR is highly expressed and associated with metastasis in a variety of cancer types and promotes tumor metastasis at least in part through association with the PRC2 complex that induces redirection to hundreds of genes involved in tumor metastasis. Here, we report that HOTAIR is an activator lncRNA of the NF-κB pathway and demonstrate that its apparent upregulation promotes inflammatory signaling and immune escape in glioma cells.

Methods

Bioinformatics analysis was used to elucidate the relationship between HOTAIR and NF-κB pathway in HOTAIR knockdown glioma cells. At the cytological level, protein hybridization and immunofluorescence were used to detect the response of proteins in the NF-κB signaling pathway to HOTAIR regulation. ChIP and ChIRP experiments identified HOTAIR target genes. Animal experiments verified alterations in inflammation and immune escape following HOTAIR knockdown and activity inhibition.

Results

HOTAIR activated the expression of proteins involved in NF-κB, TNFα, MAPK and other inflammatory signaling pathways. In addition, HOTAIR induced various proteins containing protein kinase structural domains and promoted the enrichment of proteins and complexes of important inflammatory signaling pathways, such as the TNFα/NF-κB signaling protein complex, the IκB kinase complex, and the IKKA-IKKB complex. In addition, HOTAIR aberrantly activated biological processes involved in glioma immune responses, T-cell co-stimulation and transcription initiation by RNA polymerase II. HOTAIR facilitated the induction of IκBα phosphorylation by suppressing the expression of the NF-κB upstream protein UBXN1, promoting NF-κB phosphorylation and nuclear translocation. In vivo, reduction of HOTAIR decreased PD-L1 protein expression, indicating that cells are more likely to be targeted by immune T cells.

Conclusion

In conclusion, our results provide convincing evidence that lncRNA HOTAIR drives aberrant gene transcription and immune escape from tumor cells through the NF-κB pathway.
Roles of LncRNAs in Regulating Mitochondrial Dysfunction in Septic Cardiomyopathy
Authors: Liu Shuang , Chong Wei
Published: November 2021

Sepsis is an abnormal systemic inflammatory response of the host immune system to infection and can lead to fatal multiorgan dysfunction syndrome. Epidemiological studies have shown that approximately 10-70% of sepsis cases can lead to septic cardiomyopathy. Since the pathogenesis of septic cardiomyopathy is not clear, it is difficult for medical doctors to treat the disease. Therefore, finding effective interventions to prevent and reduce myocardial damage in septic cardiomyopathy is clinically significant. Epigenetics is the study of stable genetic phenotype inheritance that does not involve changing gene sequences. Epigenetic inheritance is affected by both gene and environmental regulation. Epigenetic studies focus on the modification and influence of chromatin structure, mainly including chromatin remodelling, DNA methylation, histone modification and noncoding RNA (ncRNA)-related mechanisms. Recently, long ncRNA (lncRNA)-related mechanisms have been the focus of epigenetic studies. LncRNAs are expected to become important targets to prevent, diagnose and treat human diseases. As the energy metabolism centre of cells, mitochondria are important targets in septic cardiomyopathy. Intervention measures to prevent and treat mitochondrial damage are of great significance for improving the prognosis of septic cardiomyopathy. LncRNAs play important roles in life activities. Recently, studies have focused on the involvement of lncRNAs in regulating mitochondrial dysfunction. However, few studies have revealed the involvement of lncRNAs in regulating mitochondrial dysfunction in septic cardiomyopathy. In this article, we briefly review recent research in this area.
High-Resolution Spatiotemporal Dynamics of Harmful Algae in the Indian River Lagoon (Florida)—A Case Study of Aureoumbra lagunensis, Pyrodinium bahamense, and Pseudo-nitzschia
Authors: Lopez Cary B. , Tilney Charles L. , Muhlbach Eric , Bouchard Josée N. , Villac Maria Célia , Henschen Karen L. , Markley Laura R. , Abbe Stephanie Keller , Shankar Sugandha , Shea Colin P. , Flewelling Leanne , Garrett Matthew , Badylak Susan , Phlips Edward J. , Hall Lauren M. , Lasi Margaret A. , Parks Ashley A. , Paperno Richard , Adams Douglas H. , Edwards Dwayne D. , Schneider Jacob E. , Wald Kyle B. , Biddle Autumn R. , Landers Shawna L. , Hubbard Katherine A.
Published: November 2021

The Indian River Lagoon (IRL), located on the east coast of Florida, is a complex estuarine ecosystem that is negatively affected by recurring harmful algal blooms (HABs) from distinct taxonomic/functional groups. Enhanced monitoring was established to facilitate rapid quantification of three recurrent bloom taxa, Aureoumbra lagunensis, Pyrodinium bahamense, and Pseudo-nitzschia spp., and included corroborating techniques to improve the identification of small-celled nanoplankton (<10 μm in diameter). Identification and enumeration of these target taxa were conducted during 2015–2020 using a combination of light microscopy and species-specific approaches, specifically immunofluorescence flow cytometry as well as a newly developed qPCR assay for A. lagunensis presented here for the first time. An annual bloom index (ABI) was established for each taxon based on occurrence and abundance data. Blooms of A. lagunensis (>2 × 108 cells L–1) were observed in all 6 years sampled and across multiple seasons. In contrast, abundance of P. bahamense, largely driven by the annual temperature cycle that moderates life cycle transitions and growth, displayed a strong seasonal pattern with blooms (105–107 cells L–1) generally developing in early summer and subsiding in autumn. However, P. bahamense bloom development was delayed and abundance was significantly lower in years and locations with sustained A. lagunensis blooms. Pseudo-nitzschia spp. were broadly distributed with sporadic bloom concentrations (reaching 107 cells L–1), but with minimal concentrations of the toxin domoic acid detected (<0.02 μg L–1). In summer 2020, multiple monitoring tools characterized a novel nano-cyanobacterium bloom (reaching 109 cells L–1) that coincided with a decline in A. lagunensis and persisted into autumn. Statistical and time-series analyses of this spatiotemporally intensive dataset highlight prominent patterns in variability for some taxa, but also identify challenges of characterizing mechanisms underlying more episodic yet persistent events. Nevertheless, the intersect of temperature and salinity as environmental proxies proved to be informative in delineating niche partitioning, not only in the case of taxa with long-standing data sets but also for seemingly unprecedented blooms of novel nanoplanktonic taxa.
Effect of Dilute Magnetism in a Topological Insulator
Authors: Kabir Firoza , Hosen M. Mofazzel , Ding Xiaxin , Lane Christopher , Dhakal Gyanendra , Liu Yangyang , Dimitri Klauss , Sims Christopher , Regmi Sabin , Sakhya Anup Pradhan , Persaud Luis , Beetar John E. , Liu Yong , Chini Michael , Pathak Arjun K. , Zhu Jian-Xin , Gofryk Krzysztof , Neupane Madhab
Published: November 2021

Three-dimensional (3D) topological insulator (TI) has emerged as a unique state of quantum matter and generated enormous interests in condensed matter physics. The surfaces of a 3D TI consist of a massless Dirac cone, which is characterized by the Z2topological invariant. Introduction of magnetism on the surface of a TI is essential to realize the quantum anomalous Hall effect and other novel magneto-electric phenomena. Here, by using a combination of first-principles calculations, magneto-transport and angle-resolved photoemission spectroscopy (ARPES), we study the electronic properties of gadolinium (Gd)-doped Sb2Te3. Our study shows that Gd doped Sb2Te3is a spin-orbit-induced bulk band-gap material, whose surface is characterized by a single topological surface state. Our results provide a new platform to investigate the interactions between dilute magnetism and topology in magnetic doped topological materials.
Material Preparation and Geotechnical Properties of Transparent Cemented Soil for Physical Modeling
Authors: Leng Xianlun , Wang Chuan , Pang Rong , Sheng Qian , Chen Jian
Published: November 2021

The preparation of transparent materials suitable for simulating different rock and soil masses is the foundation for image-based physical modeling tests in studying deformation and failure mechanisms in geotechnical media. A transparent cemented soil (TCS) with similar geotechnical properties of natural soil and soft rock was prepared using fused quartz as the skeleton, hydrophobic fumed silica powder as the cement and mixed mineral oil of 15# white oil and n-dodecane as the pore fluid. Eleven groups of TCS samples with different shear strengths were synthesized by adjusting the content or mass ratio of the cement and particle size or gradation of the skeleton. Contrasting tests of unconsolidated-undrained triaxial compression were carried out and the mechanical characteristics of TCS were analyzed, showing that the stress-strain relationship, shear strength and failure mode of TCS are similar to those of natural soil. The mechanical parameters of TCS undergo complex variation with the factors, and the mesoscopic mechanism of the changes therein was revealed with the help of optical microscope photos. The similarity ratio of TCS to soft rock was derived according to geometries and stress conditions of laboratory model tests, demonstrating the feasibility of using TCS as similar materials to soft rock. Moreover, empirical formulas for the change of shear strength parameters with the factors were fitted to facilitate the preparation of TCS with target shear strength in the future. The findings can provide a basis for preparing transparent similar materials to natural soil and soft rock in physical modeling tests.
Transfer Learning-Based Algorithms for the Detection of Fatigue Crack Initiation Sites: A Comparative Study
Authors: Wang S.Y. , Guo T.
Published: November 2021

The identification of fatigue crack initiation sites (FCISs) is routinely performed in the field of engineering failure analyses; this process is not only time-consuming but also knowledge-intensive. The emergence of convolutional neural networks (CNNs) has inspired numerous innovative solutions for image analysis problems in interdisciplinary fields. As an explorative study, we trained models based on the principle of transfer learning using three state-of-the-art CNNs, namely VGG-16, ResNet-101, and feature pyramid network (FPN), as feature extractors, and a faster R-CNN as the backbone to establish models for FCISs detection. The models showed application-level detection performance, with the highest precision reaching up to 95.9% at a confidence threshold of 0.6. Among the three models, the ResNet model exhibited the highest accuracy and lowest training cost. The performance of the FPN model closely followed that of the ResNet model with an advantage in terms of the recall.
Relationship Between Deceleration Morphology and Phase Rectified Signal Averaging-Based Parameters During Labor
Authors: Rivolta Massimo W. , Barbieri Moira , Stampalija Tamara , Sassi Roberto , Frasch Martin G.
Published: November 2021

During labor, uterine contractions trigger the response of the autonomic nervous system (ANS) of the fetus, producing sawtooth-like decelerations in the fetal heart rate (FHR) series. Under chronic hypoxia, ANS is known to regulate FHR differently with respect to healthy fetuses. In this study, we hypothesized that such different ANS regulation might also lead to a change in the FHR deceleration morphology. The hypothesis was tested in an animal model comprising nine normoxic and five chronically hypoxic fetuses that underwent a protocol of umbilical cord occlusions (UCOs). Deceleration morphologies in the fetal inter-beat time interval (FRR) series were modeled using a trapezoid with four parameters, i.e., baselineb, deceleration deptha, UCO response time τuand recovery time τr. Comparing normoxic and hypoxic sheep, we found a clear difference for τu(24.8±9.4 vs. 39.8±9.7 s;p< 0.05),a(268.1±109.5 vs. 373.0±46.0 ms;p< 0.1) and Δτ = τu− τr(13.2±6.9 vs. 23.9±7.5 s;p< 0.05). Therefore, the animal model supported the hypothesis that hypoxic fetuses have a longer response time τuand larger asymmetry Δτ as a response to UCOs. Assessing these morphological parameters during labor is challenging due to non-stationarity, phase desynchronization and noise. For this reason, in the second part of the study, we quantified whether acceleration capacity (AC), deceleration capacity (DC), and deceleration reserve (DR), computed through Phase-Rectified Signal Averaging (PRSA, known to be robust to noise), were correlated with the morphological parameters. DC, AC and DR were correlated with τu, τrand Δτ for a wide range of the PRSA parameterT(Pearson's correlation ρ > 0.8,p< 0.05). In conclusion, deceleration morphologies have been found to differ between normoxic and hypoxic sheep fetuses during UCOs. The same difference can be assessed through PRSA based parameters, further motivating future investigations on the translational potential of this methodology on human data.
Simultaneous Production of Multiple Antimicrobial Compounds by Bacillus velezensis ML122-2 Isolated From Assam Tea Leaf [Camellia sinensis var. assamica (J.W.Mast.) Kitam.]
Authors: Rungsirivanich Patthanasak , Parlindungan Elvina , O’Connor Paula M. , Field Des , Mahony Jennifer , Thongwai Narumol , van Sinderen Douwe
Published: November 2021

Bacillus velezensis ML122-2 is an antimicrobial-producing strain isolated from the leaf of Assam tea or Miang [Camellia sinensis var. assamica (J.W.Mast.) Kitam.]. The cell-free supernatant (CFS) of strain ML122-2 exhibits a broad-spectrum antimicrobial activity against various Gram-positive and Gram-negative bacteria as well as the mold Penicillium expansum. The genome of B. velezensis ML122-2 was sequenced and in silico analysis identified three potential bacteriocin-associated gene clusters, that is, those involved in the production of mersacidin, amylocyclicin, and LCI. Furthermore, six gene clusters exhibiting homology (75–100% DNA sequence identity) to those associated with the secondary metabolites bacilysin, bacillibactin, surfactin, macrolactin H, bacillaene, and plipastatin were identified. Individual antimicrobial activities produced by B. velezensis ML122-2 were purified and characterized by Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry analysis, revealing three antimicrobial peptides with molecular masses corresponding to surfactin, plipastatin, and amylocyclicin. Transcriptional analysis of specific genes associated with mersacidin (mrsA), amylocyclicin (acnA), plipastatin (ppsA), and surfactin (srfAA) production by B. velezensis ML122-2 showed that the first was not transcribed under the conditions tested, while the latter three were consistent with the presence of the associated peptides as determined by mass spectrometry analysis. These findings demonstrate that B. velezensis ML122-2 has the genetic capacity to produce a wide range of antimicrobial activities that may support a specific community structure and highlight the biotechnological properties of Assam tea.
Differences in Diffusion Tensor Imaging White Matter Integrity Related to Verbal Fluency Between Young and Old Adults
Authors: Yeske Benjamin , Hou Jiancheng , Adluru Nagesh , Nair Veena A. , Prabhakaran Vivek
Published: November 2021

Throughout adulthood, the brain undergoes an array of structural and functional changes during the typical aging process. These changes involve decreased brain volume, reduced synaptic density, and alterations in white matter (WM). Although there have been some previous neuroimaging studies that have measured the ability of adult language production and its correlations to brain function, structural gray matter volume, and functional differences between young and old adults, the structural role of WM in adult language production in individuals across the life span remains to be thoroughly elucidated. This study selected 38 young adults and 35 old adults for diffusion tensor imaging (DTI) and performed the Controlled Oral Word Association Test to assess verbal fluency (VF). Tract-Based Spatial Statistics were employed to evaluate the voxel-based group differences of diffusion metrics for the values of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and local diffusion homogeneity (LDH) in 12 WM regions of interest associated with language production. To investigate group differences on each DTI metric, an analysis of covariance (ANCOVA) controlling for sex and education level was performed, and the statistical threshold was considered at p < 0.00083 (0.05/60 labels) after Bonferroni correction for multiple comparisons. Significant differences in DTI metrics identified in the ANCOVA were used to perform correlation analyses with VF scores. Compared to the old adults, the young adults had significantly (1) increased FA values on the bilateral anterior corona radiata (ACR); (2) decreased MD values on the right ACR, but increased MD on the left uncinate fasciculus (UF); and (3) decreased RD on the bilateral ACR. There were no significant differences between the groups for AD or LDH. Moreover, the old adults had only a significant correlation between the VF score and the MD on the left UF. There were no significant correlations between VF score and DTI metrics in the young adults. This study adds to the growing body of research that WM areas involved in language production are sensitive to aging.
Comparison of Time Taken to Assess Cognitive Function Using a Fully Immersive and Automated Virtual Reality System vs. the Montreal Cognitive Assessment
Authors: Wong Wei Teen , Tan Ngiap Chuan , Lim Jie En , Allen John Carson , Lee Wan Sian , Quah Joanne Hui Min , Paulpandi Muthulakshmi , Teh Tuan Ann , Lim Soon Huat , Malhotra Rahul
Published: November 2021

Introduction: Dementia is increasingly prevalent globally. Existing questionnaire-based cognitive assessment tools may not comprehensively assess cognitive function and real-time task-performance across all cognitive domains. CAVIRE (Cognitive Assessment by VIrtual REality), a fully immersive virtual reality system incorporating automated audio-visual instructions and a scoring matrix was developed to assess the six cognitive domains, with potential to maintain consistency in execution of the testing environment and possibly time-saving in busy primary care practice.

Aims: This is a feasibility study to compare the completion times of the questionnaire-based Montreal Cognitive Assessment (MoCA) and the CAVIRE in cognitively-healthy Asian adults aged between 35 and 74 years, overall, and in and across each 10-year age group (35–44; 45–54; 55–64; 65–74).

Methods: A total of 100 participants with a MoCA score of 26 or more were recruited equally into the four 10-year age groups at a primary care clinic in Singapore. Completion time for the MoCA assessment for each participant was recorded. They were assessed using the CAVIRE, comprising 13 segments featuring common everyday activities assessing all six cognitive domains, and the completion time was also recorded through the embedded automated scoring and timing framework.

Results: Completion time for CAVIRE as compared to MoCA was significantly (p < 0.01) shorter, overall (mean difference: 74.9 (SD) seconds) and in each age group. Younger, vs. older, participants completed both the MoCA and CAVIRE tasks in a shorter time. There was a greater variability in the completion time for the MoCA, most markedly in the oldest group, whereas completion time was less variable for the CAVIRE tasks in all age groups, with most consistency in the 45–54 year-age group.

Conclusion: We demonstrate almost equivalent completion times for a VR and a questionnaire-based cognition assessment, with inter-age group variation in VR completion time synonymous to that in conventional screening methods. The CAVIRE has the potential to be an alternative screening modality for cognition in the primary care setting.
A Biological Inspired Cognitive Framework for Memory-Based Multi-Sensory Joint Attention in Human-Robot Interactive Tasks
Authors: Eldardeer Omar , Gonzalez-Billandon Jonas , Grasse Lukas , Tata Matthew , Rea Francesco
Published: November 2021

One of the fundamental prerequisites for effective collaborations between interactive partners is the mutual sharing of the attentional focus on the same perceptual events. This is referred to as joint attention. In psychological, cognitive, and social sciences, its defining elements have been widely pinpointed. Also the field of human-robot interaction has extensively exploited joint attention which has been identified as a fundamental prerequisite for proficient human-robot collaborations. However, joint attention between robots and human partners is often encoded in prefixed robot behaviours that do not fully address the dynamics of interactive scenarios. We provide autonomous attentional behaviour for robotics based on a multi-sensory perception that robustly relocates the focus of attention on the same targets the human partner attends. Further, we investigated how such joint attention between a human and a robot partner improved with a new biologically-inspired memory-based attention component. We assessed the model with the humanoid robot iCub involved in performing a joint task with a human partner in a real-world unstructured scenario. The model showed a robust performance on capturing the stimulation, making a localisation decision in the right time frame, and then executing the right action. We then compared the attention performance of the robot against the human performance when stimulated from the same source across different modalities (audio-visual and audio only). The comparison showed that the model is behaving with temporal dynamics compatible with those of humans. This provides an effective solution for memory-based joint attention in real-world unstructured environments. Further, we analyzed the localisation performances (reaction time and accuracy), the results showed that the robot performed better in an audio-visual condition than an audio only condition. The performance of the robot in the audio-visual condition was relatively comparable with the behaviour of the human participants whereas it was less efficient in audio-only localisation. After a detailed analysis of the internal components of the architecture, we conclude that the differences in performance are due to egonoise which significantly affects the audio-only localisation performance.
Spatial Neglect Subtypes, Definitions and Assessment Tools: A Scoping Review
Authors: Williams Lindy J. , Kernot Jocelyn , Hillier Susan L. , Loetscher Tobias
Published: November 2021

Objective: The objective of this scoping review was to capture the reported definitions for the subtypes of neglect post stroke and map the range of assessment tools employed for each neglect subtype.

Methods: EMBASE, Emcare, Medline, and psychINFO were searched from database inception. Searching included all allied terms and mesh headings for stroke, spatial neglect, measurement, screening tools, psychometric properties. Two reviewers independently screened studies for inclusion. Primary studies with documented protocols of a spatial neglect tool for adults post stroke, with some aspect of validity or reliability were included. Two reviewers independently reviewed the documented protocols of each tool to determine the underlying subtypes and disagreements were resolved through discussion.

Results: There were 371 articles included with 292 tools used for the screening or diagnosis of neglect. The majority of studies (67%) included a tool that did not specify the neglect subtype being assessed, therefore an analysis of the underlying subtypes for each tool is presented.

Conclusions: There is no consistency with the terms used to refer to the syndrome of spatial neglect with over 200 different terms used within the included studies to refer to the syndrome as a whole or one of its subtypes. It is essential to unify the terminology and definition for each neglect subtype. There are hundreds of neglect tools available, however many are not able to differentiate presenting subtypes. It is important for clinicians and researchers to critically evaluate the neglect tools being used for the screening and diagnosis of neglect.
Effect of Obesity on Retinal Integrity in African Americans and Caucasian Americans With Relapsing Multiple Sclerosis
Authors: Rube Jacob , Bross Madeline , Bernitsas Christopher , Hackett Melody , Bao Fen , Bernitsas Evanthia
Published: November 2021

Objective: To study the effect of obesity on retinal structures in African Americans (AAs) and Caucasian Americans (CAs) with relapsing-remitting multiple sclerosis (RRMS).

Methodology: About 136 patients with RRMS without history of optic neuritis were divided into two groups, based on body mass index (BMI): 67 obese (40 AA, 27 CA, mean BMI ± SD: 36.7 ± 5.8), and 69 non-obese (23 AA, 46 CA, mean BMI ± SD: 24.0 ± 3.1). The peripapillary retinal nerve fiber layer (pRNFL) thickness was quantified by optical coherence tomography (OCT) and was segmented into quadrant thickness: superior (S), inferior (I), temporal (T), and nasal (N). Papillomacular bundle (PMB) thickness, retinal nerve fiber layer (RNFL), ganglion cell + inner plexiform layer (GCIPL), inner nuclear (INL), outer plexiform (OPL), outer nuclear (ONL), and total macular (TMV) volumes were obtained.

Results: Obesity was associated with lower T thickness (58.54 ± 15.2 vs. 61.9 12.4, p = 0.044), higher INL (0.98 ± 0.07 vs. 0.96 ± 0.06, p = 0.034), and lower RNFL (0.77 ± 0.14 vs. 0.82 ± 0.12, p = 0.009) volumes. Obese AA had significantly thinner T (58.54 ± 15.19 vs. 61.91 ± 12.39, p = 0.033), N (68.94 ± 2.7 vs. 77.94 ± 3.3, p = 0.044), and TMV (8.15 ± 0.07 vs. 8.52 ± 0.09, p = 0.003), RNFL (0.74 ± 0.02 vs. 0.82 ± 0.02, p = 0.013), OPL (0.76 ± 0.01 vs. 0.79 ± 0.1, p = 0.050), ONL (1.68 ± 0.031 vs. 1.79 ± 0.038, p = 0.026), and GCIPL (1.78 ± 0.04 vs. 1.9 ± 0.05, p = 0.038) compared to obese CA. Among patients with non-obesity, the ONL was significantly lower in AA (1.78 ± 0.04 vs. 1.9 ± 0.05, p < 0.001).

Conclusions: Obesity is associated with retinal structure abnormalities in patients with RRMS. Its impact might be more prominent in AA than CA. Large longitudinal studies are needed to validate our findings.
Dorsal and Ventral Stream Function in Children With Developmental Coordination Disorder
Authors: Micheletti Serena , Corbett Fleur , Atkinson Janette , Braddick Oliver , Mattei Paola , Galli Jessica , Calza Stefano , Fazzi Elisa
Published: November 2021

Dorsal stream cortical networks underpin a cluster of visuomotor, visuospatial, and visual attention functions. Sensitivity to global coherence of motion and static form is considered a signature of visual cortical processing in the dorsal stream (motion) relative to the ventral stream (form). Poorer sensitivity to global motion compared to global static form has been found across a diverse range of neurodevelopmental disorders, suggesting a “dorsal stream vulnerability.” However, previous studies of global coherence sensitivity in Developmental Coordination Disorder (DCD) have shown conflicting findings. We examined two groups totalling 102 children with DCD (age 5–12 years), using the “Ball in the Grass” psychophysical test to compare sensitivity to global motion and global static form. Motor impairment was measured using the Movement-ABC (M-ABC). Global coherence sensitivity was compared with a typically developing control group (N = 69) in the same age range. Children with DCD showed impaired sensitivity to global motion (p = 0.002), but not global form (p = 0.695), compared to controls. Within the DCD group, motor impairment showed a significant linear relationship with global form sensitivity (p < 0.001). There was also a significant quadratic relationship between motor impairment and global motion sensitivity (p = 0.046), where poorer global motion sensitivity was only apparent with greater motor impairment. We suggest that two distinct visually related components, associated with global form and global motion sensitivity, contribute to DCD differentially over the range of severity of the disorder. Possible neural circuitry underlying these relationships is discussed.
Neural Infection by Oropouche Virus in Adult Human Brain Slices Induces an Inflammatory and Toxic Response
Authors: Almeida Glaucia M. , Souza Juliano P. , Mendes Niele D. , Pontelli Marjorie C. , Pinheiro Nathalia R. , Nogueira Giovanna O. , Cardoso Ricardo S. , Paiva Isadora M. , Ferrari Gustavo D. , Veras Flávio P. , Cunha Fernando Q. , Horta-Junior Jose A. C. , Alberici Luciane C. , Cunha Thiago M. , Podolsky-Gondim Guilherme G. , Neder Luciano , Arruda Eurico , Sebollela Adriano
Published: November 2021

Oropouche virus (OROV) is an emerging arbovirus in South and Central Americas with high spreading potential. OROV infection has been associated with neurological complications and OROV genomic RNA has been detected in cerebrospinal fluid from patients, suggesting its neuroinvasive potential. Motivated by these findings, neurotropism and neuropathogenesis of OROV have been investigated in vivo in murine models, which do not fully recapitulate the complexity of the human brain. Here we have used slice cultures from adult human brains to investigate whether OROV is capable of infecting mature human neural cells in a context of preserved neural connections and brain cytoarchitecture. Our results demonstrate that human neural cells can be infected ex vivo by OROV and support the production of infectious viral particles. Moreover, OROV infection led to the release of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and diminished cell viability 48 h post-infection, indicating that OROV triggers an inflammatory response and tissue damage. Although OROV-positive neurons were observed, microglia were the most abundant central nervous system (CNS) cell type infected by OROV, suggesting that they play an important role in the response to CNS infection by OROV in the adult human brain. Importantly, we found no OROV-infected astrocytes. To the best of our knowledge, this is the first direct demonstration of OROV infection in human brain cells. Combined with previous data from murine models and case reports of OROV genome detection in cerebrospinal fluid from patients, our data shed light on OROV neuropathogenesis and help raising awareness about acute and possibly chronic consequences of OROV infection in the human brain.
Neuroprotection by Transcranial Direct Current Stimulation in Rodent Models of Focal Ischemic Stroke: A Meta-Analysis
Authors: Huang Jiapeng , Zhao Kehong , Zhao Ziqi , Qu Yun
Published: November 2021

Infarct size is associated with stroke severity in clinical studies, so reducing it has become an important target and research hotspot in the treatment of ischemic stroke. Some preclinical studies have shown transcranial direct current stimulation (tDCS) reduced infarct size and improved neurological deficit, but others have not found beneficial effects. Besides, the optimal pattern of tDCS for ischemic stroke remains largely unknown. To shed light on the current circumstance and future research directions, the systematic review evaluated the effect of different tDCS paradigms in reducing infarct size and improving neurological deficit in rodent models of ischemic stroke and assessed the methodological quality of current literature. We searched the MEDLINE (via PubMed), EMBASE, Web of Science, and Scopus from their inception to August 18, 2021, to identify studies evaluating the effects of tDCS in rodent models of ischemic stroke. Eight studies were included, of which seven studies were included in the meta-analysis. The results showed cathodal tDCS, rather than anodal tDCS, reduced infarct size mainly measured by tetrazolium chloride and magnetic resonance imaging (standardized mean difference: −1.13; 95% CI: −1.72, −0.53; p = 0.0002) and improved neurological deficit assessed by a modified neurological severity score (standardized mean difference: −2.10; 95% CI: −3.78, −0.42; p = 0.01) in an early stage of focal ischemic stroke in rodent models. Subgroup analyses showed effects of cathodal tDCS on infarct size were not varied by ischemia duration (ischemia for 1, 1.5, and 2 h or permanent ischemia) and anesthesia (involving isoflurane and ketamine). The overall quality of studies included was low, thus the results must be interpreted cautiously. Published studies suggest that cathodal tDCS may be a promising avenue to explore for augmenting rehabilitation from focal ischemic stroke. Considering the methodological limitations, it is unreliable to blindly extrapolate the animal data to the clinical practice. Future research is needed to investigate the mechanism of tDCS in a randomized and blinded fashion in clinically relevant stroke models, such as elderly animals, female animals, and animals with comorbidities, to find an optimal treatment protocol.
Noise Robustness Low-Rank Learning Algorithm for Electroencephalogram Signal Classification
Authors: Gao Ming , Liu Runmin , Mao Jie
Published: November 2021

Electroencephalogram (EEG) is often used in clinical epilepsy treatment to monitor electrical signal changes in the brain of patients with epilepsy. With the development of signal processing and artificial intelligence technology, artificial intelligence classification method plays an important role in the automatic recognition of epilepsy EEG signals. However, traditional classifiers are easily affected by impurities and noise in epileptic EEG signals. To solve this problem, this paper develops a noise robustness low-rank learning (NRLRL) algorithm for EEG signal classification. NRLRL establishes a low-rank subspace to connect the original data space and label space. Making full use of supervision information, it considers the local information preservation of samples to ensure the low-rank representation of within-class compactness and between-classes dispersion. The asymmetric least squares support vector machine (aLS-SVM) is embedded into the objective function of NRLRL. The aLS-SVM finds the maximum quantile distance between the two classes of samples based on the pinball loss function, which further improves the noise robustness of the model. Several classification experiments with different noise intensity are designed on the Bonn data set, and the experiment results verify the effectiveness of the NRLRL algorithm.
PrPC as a Transducer of Physiological and Pathological Signals
Authors: Panes Jessica D. , Saavedra Paulina , Pineda Benjamin , Escobar Kathleen , Cuevas Magdalena E. , Moraga-Cid Gustavo , Fuentealba Jorge , Rivas Coralia I. , Rezaei Human , Muñoz-Montesino Carola
Published: November 2021

After the discovery of prion phenomenon, the physiological role of the cellular prion protein (PrPC) remained elusive. In the past decades, molecular and cellular analysis has shed some light regarding interactions and functions of PrPC in health and disease. PrPC, which is located mainly at the plasma membrane of neuronal cells attached by a glycosylphosphatidylinositol (GPI) anchor, can act as a receptor or transducer from external signaling. Although the precise role of PrPC remains elusive, a variety of functions have been proposed for this protein, namely, neuronal excitability and viability. Although many issues must be solved to clearly define the role of PrPC, its connection to the central nervous system (CNS) and to several misfolding-associated diseases makes PrPC an interesting pharmacological target. In a physiological context, several reports have proposed that PrPC modulates synaptic transmission, interacting with various proteins, namely, ion pumps, channels, and metabotropic receptors. PrPC has also been implicated in the pathophysiological cell signaling induced by β-amyloid peptide that leads to synaptic dysfunction in the context of Alzheimer’s disease (AD), as a mediator of Aβ-induced cell toxicity. Additionally, it has been implicated in other proteinopathies as well. In this review, we aimed to analyze the role of PrPC as a transducer of physiological and pathological signaling.
Low Carbohydrate Diets in Cancer Therapeutics: Current Evidence
Authors: Haskins Christopher , Cohen Justin , Kotecha Rupesh , Kaiser Adeel
Published: November 2021

Low carbohydrate diets have a promising mechanistic rationale in the treatment of cancer with favorable preclinical data. The strongest data suggest synergistic effects of dietary interventions with traditional cancer therapies. Recent prospective clinical trials suggest that low carbohydrate diets are safely and feasibly added within a busy oncology clinic, with hopeful additive effects in treatment enhancement.
Aronia Upregulates Myogenic Differentiation and Augments Muscle Mass and Function Through Muscle Metabolism
Authors: Yun Chae-Eun , So Hyun-Kyung , Vuong Tuan Anh , Na Myung Woo , Anh Subin , Lee Hyo-Keun , Kim Ki Hyun , Kang Jong-Sun , Bae Gyu-Un , Lee Sang-Jin
Published: November 2021

Black chokeberry or aronia (the fruit of Aronia melanocarpa) has been reported to having pharmacological activities against metabolic syndrome, such as hypertension, obesity, diabetes, and pro-inflammatory conditions. However, the effects of aronia on myogenic differentiation and muscle homoeostasis are uncharacterized. In this study, we investigated the effects of aronia (black chokeberry) on myogenic differentiation and muscle metabolic functions in young mice. Aronia extract (AR) promotes myogenic differentiation and elevates the formation of multinucleated myotubes through Akt activation. AR protects dexamethasone (DEX)-induced myotube atrophy through inhibition of muscle-specific ubiquitin ligases mediated by Akt activation. The treatment with AR increases muscle mass and strength in mice without cardiac hypertrophy. AR treatment enhances both oxidative and glycolytic myofibers and muscle metabolism with elevated mitochondrial genes and glucose metabolism-related genes. Furthermore, AR-fed muscle fibers display increased levels of total OxPHOS and myoglobin proteins. Taken together, AR enhances myogenic differentiation and improves muscle mass and function, suggesting that AR has a promising potential as a nutraceutical remedy to intervene in muscle weakness and atrophy.
Use Database to Evaluate the Prevalence of Hunger Among Adolescents in Brazil
Authors: Amorim Ana Laura Benevenuto de , Ribeiro Junior José Raimundo Sousa , Gonçalves Helida Ventura Barbosa , Bandoni Daniel Henrique
Published: November 2021

Food insecurity and malnutrition have become serious problems in many countries. In recent years, Brazil has experienced an increase in the prevalence of food insecurity and hunger. However, there is limited information on the status of these issues, and food security assessments are only performed as household measures. Therefore, the use of available databases is essential to expand information and support decision-making in the fight against food insecurity. This study aimed to evaluate the relationship between reports of hunger among adolescents and their sociodemographic characteristics. We used data from the 2015 National School Health Survey. The main variable of interest was obtained from responses to the following question: “Over the past 30 days, how often have you gone hungry because you did not have enough food at home?”. The responses were separately gathered from those who reported going hungry and those who did not. Socioeconomic characteristics were evaluated simultaneously. For statistical analysis, a Pearson chi-square test and multiple analyses were performed using Poisson regression models. A total of 101,888 adolescents were evaluated. The variable used to measure hunger was associated with maternal education, internet access, and fruit intake. The results showed a positive association between adolescents who reported going hungry and women, black and indigenous adolescent students living in households with more than five people, adolescents not living with their father, and adolescents planning to work or not knowing what they will do after completing the ninth grade. The results demonstrate that it is possible to use secondary data with a single question to assess, monitor, and provide insights into how food security impacts the sociodemographic groups differently.
Intermittent Fasting Reshapes the Gut Microbiota and Metabolome and Reduces Weight Gain More Effectively Than Melatonin in Mice
Authors: Liu Jingliang , Zhong Yifan , Luo Xin M. , Ma Yanfei , Liu Jianxin , Wang Haifeng
Published: November 2021

Background: Intermittent fasting (IF) can reduce energy intake and body weight (BW). Melatonin has many known functions, which include reducing appetite and preventing excessive weight gain.

Objective: This study aimed to investigate the effects of IF on body fat and the gut microbiota and metabolome as well as a potential interaction with melatonin.

Methods: Male C57BL/6J mice (23.0 ± 0.9 g, 6 wk old) were randomly assigned into four groups (12 mice/group): control (C), intermittent fasting (F), melatonin (M), and intermittent fasting plus melatonin (MF). The C and M groups mice were provided with ad libitum access to food and water, while the F and MF groups underwent alternative-day feed deprivation (15 cycles total). Melatonin was administered in the drinking water of the M and MF groups. Blood, epididymal fat, liver tissue, and intestinal tissue and contents were collected for lab measurements, histology, and microbiota and metabolome analysis. Main effects and interactions were tested by 2-factor ANOVA.

Results: IF significantly reduced BW gain and serum glucose, total cholesterol (TC) and triglyceride (TG) levels. Adipocyte size significantly decreased with IF, then the number of adipocytes per square millimeter significantly increased (P < 0.05). Compared to the C group, the M and MF groups had significantly higher serum melatonin levels (17 and 21%, respectively), although melatonin monotherapy had no effect on serum parameters and adipocytes. There was no interaction between IF and melatonin on BW gain and serum parameters except for on adipocyte area and number per square millimeter, Bacteroidetes and Akkermansia bacterial abundance, and the levels of the intestinal metabolites alanine, valine and isoleucine. IF changed the intestinal microbiota structure, with the F and MF groups clearly separating from the C and M groups. Metabolomic analysis showed that there was obvious separation between all four groups.

Conclusions: IF, but neither melatonin nor the interaction between IF and melatonin, could alter intestinal microbiota and metabolism and prevent obesity by reducing BW gain, serum glucose, TC, and TG, and adipocyte size in mice.
Application of Gross Tissue Response System in Gastric Cancer After Neoadjuvant Chemotherapy: A Primary Report of a Prospective Cohort Study
Authors: Yang Hua , Zhang Wei-Han , Ge Rui , Peng Bo-Qiang , Chen Xin-Zu , Yang Kun , Liu Kai , Chen Xiao-Long , He Du , Liu Jian-Ping , Zhang Wei-Wei , Qin Yun , Zhou Zong-Guang , Hu Jian-Kun
Published: November 2021

Objective

We previously established a gross tissue response (GTR) system to evaluate the intraoperative response of perigastric tissue in patients with gastric cancers to neoadjuvant chemotherapy. This prospective cohort study aims to confirm the relationship between gross tissue response and clinicopathological characteristics and explore the possibility of using the GTR system to predict the difficulty of surgery and the occurrence of postoperative complications within 30 days.

Methods

A total of 102 patients with gastric cancer from January 2019 to April 2020 were enrolled in this study. The degrees of fibrosis, edema, and effusion in the perigastric tissues were assessed intraoperatively according to the GTR system. We systematically analyzed the relations between GTR and clinicopathological characteristics, and then a prediction model that includes GTR was established to predict the difficulty of surgery and the occurrence of postoperative complications within 30 days.

Results

Finally, the study included 71 male patients and 31 female patients. The patients had an average age of 58.79 ± 1.03 years, BMI of 22.89 ± 0.29, and tumor diameter of 4.50 ± 0.27 cm. Among these patients, 17 underwent laparoscopic gastrectomy, 85 underwent open gastrectomy, the average operation time was 294.63 ± 4.84 minutes, and the mean volume of intraoperative blood loss was 94.65 ± 5.30 ml. The overall 30-day postoperative complication rate was 19.6% (20/102). The total GTR was significantly related to the primary tumor stage, operation time and 30-day postoperative complication rate (p<0.05). Edema and effusion were significantly related to intraoperative blood loss (p<0.05). The logistic regression analysis identified that the total GTR score (score: 4-9, OR 2.888, 95% CI: 1.035-8.062, p = 0.043) was an independent risk factor for postoperative complications within 30 days, and the total GTR score (score 4-9, OR 3.32, 95% CI 1.219-9.045, p=0.019) was also an independent risk factor for operation time. The AUC of the total GTR score for predicting postoperative complications within 30 days was 0.681.

Conclusion

According to the results of the present study, the gross tissue response (GTR) system is an effective tool that may be used to predict the risk of a difficult operation after neoadjuvant chemotherapy and postoperative complications. Although neoadjuvant chemotherapy improves the therapeutic effect, it also increases the risk of surgical trauma and postoperative complications.

Clinical Trial Registration

ClinicalTrials.gov, identifier NCT03791268.
Integrating Clinical Data and Attentional CT Imaging Features for Esophageal Fistula Prediction in Esophageal Cancer
Authors: Xu Yiyue , Cui Hui , Dong Taotao , Zou Bing , Fan Bingjie , Li Wanlong , Wang Shijiang , Sun Xindong , Yu Jinming , Wang Linlin
Published: November 2021

Background and Purpose

This study aims to develop a risk model to predict esophageal fistula in esophageal cancer (EC) patients by learning from both clinical data and computerized tomography (CT) radiomic features.

Materials and Methods

In this retrospective study, computerized tomography (CT) images and clinical data of 186 esophageal fistula patients and 372 controls (1:2 matched by the diagnosis time of EC, sex, marriage, and race) were collected. All patients had esophageal cancer and did not receive esophageal surgery. 70% patients were assigned into training set randomly and 30% into validation set. We firstly use a novel attentional convolutional neural network for radiographic descriptor extraction from nine views of planes of contextual CT, segmented tumor and neighboring structures. Then clinical factors including general, diagnostic, pathologic, therapeutic and hematological parameters are fed into neural network for high-level latent representation. The radiographic descriptors and latent clinical factor representations are finally associated by a fully connected layer for patient level risk prediction using SoftMax classifier.

Results

512 deep radiographic features and 32 clinical features were extracted. The integrative deep learning model achieved C-index of 0.901, sensitivity of 0.835, and specificity of 0.918 on validation set with superior performance than non-integrative model using CT imaging alone (C-index = 0.857) or clinical data alone (C-index = 0.780).

Conclusion

The integration of radiomic descriptors from CT and clinical data significantly improved the esophageal fistula prediction. We suggest that this model has the potential to support individualized stratification and treatment planning for EC patients.