bluuebunny/crossref_metadata_2025 huggingface dataset:
A Structure-Related Fine-Grained Deep Learning System With Diversity Data for Universal Glaucoma Visual Field Grading
Authors: Huang Xiaoling , Jin Kai , Zhu Jiazhu , Xue Ying , Si Ke , Zhang Chun , Meng Sukun , Gong Wei , Ye Juan
Published: March 2022

Purpose

Glaucoma is the main cause of irreversible blindness worldwide. However, the diagnosis and treatment of glaucoma remain difficult because of the lack of an effective glaucoma grading measure. In this study, we aimed to propose an artificial intelligence system to provide adequate assessment of glaucoma patients.

Methods

A total of 16,356 visual fields (VFs) measured by Octopus perimeters and Humphrey Field Analyzer (HFA) were collected, from three hospitals in China and the public Harvard database. We developed a fine-grained grading deep learning system, named FGGDL, to evaluate the VF loss, compared to ophthalmologists. Subsequently, we discuss the relationship between structural and functional damage for the comprehensive evaluation of glaucoma level. In addition, we developed an interactive interface and performed a cross-validation study to test its auxiliary ability. The performance was valued by F1 score, overall accuracy and area under the curve (AUC).

Results

The FGGDL achieved a high accuracy of 85 and 90%, and AUC of 0.93 and 0.90 for HFA and Octopus data, respectively. It was significantly superior (p < 0.01) to that of medical students and nearly equal (p = 0.614) to that of ophthalmic clinicians. For the cross-validation study, the diagnosis accuracy was almost improved (p < 0.05).

Conclusion

We proposed a deep learning system to grade VF of glaucoma with a high detection accuracy, for effective and adequate assessment for glaucoma patients. Besides, with the convenient and credible interface, this system can promote telemedicine and be used as a self-assessment tool for patients with long-duration diseases.
Feasibility Study of Intelligent Three-Dimensional Accurate Liver Reconstruction Technology Based on MRI Data
Authors: Cao Shaodong , Li Huan , Dong Suyu , Gao Zhenxuan
Published: March 2022

Intelligent three-dimensional (3D) reconstruction technology plays an important role in the diagnosis and treatment of diseases. It has been widely used in assisted liver surgery. At present, the 3D reconstruction information of liver is mainly obtained based on CT enhancement data. It has also been commercialized. However, there are few reports on the display of 3D reconstruction information of the liver based on MRI. The purpose of this study is to propose a new idea of intelligent 3D liver reconstruction based on MRI technology and verify its feasibility. Two different liver scanning data (CT and MRI) were selected from the same batch of patients at the same time (patients with a time interval of no more than two weeks and without surgery). The results of liver volume, segmentation, tumor, and simulated surgery based on MRI volume data were compared with those based on CT data. The results show that the results of 3D reconstruction based on MRI data are highly consistent with those based on CT 3D reconstruction. At the same time, in addition to providing the information provided by CT 3D reconstruction, it also has its irreplaceable advantages. For example, multi-phase (early, middle and late arterial, hepatobiliary, etc.) scanning of MRI technology can provide more disease information and display of biliary diseases. In a word, MRI technology can be used for 3D reconstruction of the liver. Hence, a new feasible and effective method to show the liver itself and its disease characteristics is proposed.
Insights Into the Concept of Rheumatoid Arthritis Flare
Authors: Bozzalla-Cassione Emanuele , Grignaschi Silvia , Xoxi Blerina , Luvaro Terenzj , Greco Maria Immacolata , Mazzucchelli Iolanda , Bugatti Serena , Montecucco Carlomaurizio , Manzo Antonio
Published: March 2022

Identification of a pathological change in the course of systemic chronic immune-inflammatory diseases is key to delivering effective treatment strategies. In this context, one of the most compelling issues is the concept of flare. The multifaceted expression of disease activity in rheumatoid arthritis (RA) makes it challenging to provide an omni-comprehensive definition of flare, encompassing the pathology's different objective and subjective domains. Our incomplete understanding of the pathophysiological mechanisms underlying this process contributes to the partial comprehension of its potential clinical expression. This review focuses on the proposed pathophysiological processes underlying disease recrudescence in RA and the variable definitions adopted to capture flare in clinical practice through its objective, subjective, and temporal domains. Overall, what emerges is a complex landscape far from being unraveled.
Bacterium-Like Particles Displaying the Rift Valley Fever Virus Gn Head Protein Induces Efficacious Immune Responses in Immunized Mice
Authors: Zhang Shengnan , Yan Feihu , Liu Dongping , Li Entao , Feng Na , Xu Shengnan , Wang Hualei , Gao Yuwei , Yang Songtao , Zhao Yongkun , Xia Xianzhu
Published: March 2022

Rift Valley fever virus (RVFV), a mosquito-borne zoonotic phlebovirus, causes serious disease in humans and ruminants. According to the World Health Organization, Rift Valley fever is classified as a priority disease, and as such, vaccine development is of high priority due to the lack of licensed vaccines. In this study, a bacterium-like particle vaccine (BLP), RVFV-BLPs, is constructed. A novel display system is described, which is based on non-living and non-genetically modified Gram-positive bacterial cells, designated as Gram-positive enhancer matrix (GEM). The RVFV Gn head protein was displayed on the surface of GEM by co-expression with the peptidoglycan-binding domain (protein anchor) at the C-terminus. We determined that the RVFV Gn head-PA fusion protein was successfully displayed on the GEM. Mice immunized with RVFV-BLPs produced humoral and cellular immunity. Interestingly, comparing the production of RVFV Gn head-specific IgG and its subtype by vaccinating with different antigen doses of the RVFV-BLPs determined that the RVFV-BLPs (50 μg) group showed a greater effect than the other two groups. More importantly, antibodies produced by mice immunized with RVFV-BLPs (50 μg) exhibited potent neutralizing activity against RVFV pseudovirus. RVFV-BLPs (50 μg) also could induce IFN-γ and IL-4 in immunized mice; these mice generated memory cells among the proliferating T cell population after immunization with RVFV-BLPs with effector memory T cells as the major population, which means that RVFV-BLPs is an effective vaccine to establish a long-lived population of memory T cells. The findings suggest that the novel RVFV-BLPs subunit vaccine has the potential to be considered a safe and effective candidate vaccine against RVFV infection.
Cordyceps militaris Modulates Intestinal Barrier Function and Gut Microbiota in a Pig Model
Authors: Zheng Hongmei , Cao Haigang , Zhang Deming , Huang Jiahe , Li Jinshu , Wang Shaoying , Lu Junfeng , Li Xiao , Yang Gongshe , Shi Xin’e
Published: March 2022

This study investigated the effects of Cordyceps militaris (CM) on intestinal barrier function and gut microbiota in a pig model. A total of 160 pigs were randomly allocated to either a control group (fed the basal diet) or a CM group (fed the basal diet supplemented with 300 mg/kg CM). CM improved intestinal morphology and increased the numbers of goblet cells and intraepithelial lymphocytes. CM also elevated the expression of zona occluden-1, claudin-1, mucin-2 and secretory immunoglobulin A. Furthermore, the mucosal levels of pro-inflammatory cytokines were downregulated while the levels of anti-inflammatory cytokines were upregulated in the CM group. Mechanistically, CM downregulated the expression of key proteins of the TLR4/MyD88/NF-κB signaling pathway. Moreover, CM altered the colonic microbial composition and increased the concentrations of acetate and butyrate. In conclusion, CM can modulate the intestinal barrier function and gut microbiota, which may provide a new strategy for improving intestinal health.
Diversity and Effect of Increasing Temperature on the Activity of Methanotrophs in Sediments of Fildes Peninsula Freshwater Lakes, King George Island, Antarctica
Authors: Roldán Diego M. , Carrizo Daniel , Sánchez-García Laura , Menes Rodolfo Javier
Published: March 2022

Global warming has a strong impact on polar regions. Particularly, the Antarctic Peninsula and nearby islands have experienced a marked warming trend in the past 50 years. Therefore, higher methane (CH4) emissions from this area could be expected in the future. Since mitigation of these emissions can be carried out by microbial oxidation, understanding this biological process is crucial since to our knowledge, no related studies have been performed in this area before. In this work, the aerobic CH4 oxidation potential of five freshwater lake sediments of Fildes Peninsula (King George Island, South Shetland Islands) was determined with values from 0.07 to 10 μmol CH4 gdw–1 day–1 and revealed up to 100-fold increase in temperature gradients (5, 10, 15, and 20°C). The structure and diversity of the bacterial community in the sediments were analyzed by next-generation sequencing (Illumina MiSeq) of 16S rRNA and pmoA genes. A total of 4,836 ASVs were identified being Proteobacteria, Actinobacteriota, Acidobacteriota, and Bacteroidota the most abundant phyla. The analysis of the pmoA gene identified 200 ASVs of methanotrophs, being Methylobacter Clade 2 (Type I, family Methylococcaceae) the main responsible of the aerobic CH4 oxidation. Moreover, both approaches revealed the presence of methanotrophs of the classes Gammaproteobacteria (families Methylococcaceae and Crenotrichaceae), Alphaproteobacteria (family Methylocystaceae), Verrucomicrobia (family Methylacidiphilaceae), and the candidate phylum of anaerobic methanotrophs Methylomirabilota. In addition, bacterial phospholipid fatty acids (PLFA) biomarkers were studied as a proxy for aerobic methane-oxidizing bacteria and confirmed these results. Methanotrophic bacterial diversity was significantly correlated with pH. In conclusion, our findings suggest that aerobic methanotrophs could mitigate in situ CH4 emissions in a future scenario with higher temperatures in this climate-sensitive area. This study provides new insights into the diversity of methanotrophs, as well as the influence of temperature on the CH4 oxidation potential in sediments of freshwater lakes in polar regions of the southern hemisphere.
Mutations and Phylogenetic Analyses of SARS-CoV-2 Among Imported COVID-19 From Abroad in Nanjing, China
Authors: Zhao Ning , Zhou Nan , Fan Huafeng , Ding Jie , Xu Xingyu , Dong Xiaoqing , Dong Xiaoxiao , Xu Dandan , Min Xiaoyu , Yu Yan , Gong Hongjin , Mao Lingfeng , He Min
Published: March 2022

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a pandemic and is threatening human health globally. The rapid genome sequencing and bioinformatic analysis of SARS-CoV-2 have become a helpful tool in the battle against the COVID-19. Here, we report the genetic characteristics, variations and phylogenetic analysis of SARS-CoV-2 sequenced from 42 clinical specimens. The complete genomes sequencing of SARS-CoV-2 were performed using Oxford Nanopore sequencing. All genomes accumulated mutations compared to the Wuhan-Hu-1 (GenBank Accession No: MN908947.3). Our data of the 42 whole genomes revealed 16 different lineages. The B.1.1 lineage was the most frequent, and 5, 2, 2, 3, and 1 sequences were classified as lineages of B.1.1.7, B.1.351, P.1, B.1.617.2, and C.37, respectively. A total of 328 nucleotide mutation sites were found in 42 genomes, among which A23403G mutation (D614G amino acid change in the spike protein) was the most common substitution. The phylogenetic trees of 42 SARS-CoV-2 sequences and GISAID-available SARS-CoV-2 sequences were constructed and its taxonomic status was supported. These results will provide scientific basis for tracing the source and prevention and control of SARS-CoV-2 imported from abroad in Nanjing, China.
A Shift in Perspective: A Role for the Type I Toxin TisB as Persistence-Stabilizing Factor
Authors: Edelmann Daniel , Berghoff Bork A.
Published: March 2022

Bacterial persistence is a phenomenon that is founded by the existence of a subpopulation of multidrug-tolerant cells. These so-called persister cells endure otherwise lethal stress situations and enable restoration of bacterial populations upon return to favorable conditions. Persisters are especially notorious for their ability to survive antibiotic treatments without conventional resistance genes and to cause infection relapse. The persister state is typically correlated with reduction or inhibition of cellular activity. Early on, chromosomal toxin-antitoxin (TA) systems were suspected to induce the persister state in response to environmental stress. However, this idea has been challenged during the last years. Especially the involvement of toxins from type II TA systems in persister formation is put into question. For toxins from type I TA systems the debate has just started. Here, we would like to summarize recent knowledge gained for the type I TA system tisB/istR-1 from Escherichia coli. TisB is a small, membrane-targeting toxin, which disrupts the proton motive force (PMF), leading to membrane depolarization. Based on experimental data, we hypothesize that TisB primarily stabilizes the persister state through depolarization and further, secondary effects. We will present a simple model that will provide a framework for future directions.
Siglec-9, a Putative Immune Checkpoint Marker for Cancer Progression Across Multiple Cancer Types
Authors: Wu Yuliang , Huang Wei , Xie Yutong , Wang Chunyan , Luo Ning , Chen Yingying , Wang Liefu , Cheng Zhongping , Gao Zhengliang , Liu Shupeng
Published: March 2022

Siglec-9, a cell surface transmembrane receptor mainly expressed on B cells, CD56+ NK cells, and CD4+ and CD8+ T cells, is strongly related to the tumor immune microenvironment. However, the expression pattern of Siglec-9 and its prognostic potential have not been investigated in a pan-cancer perspective. This study aimed to explore the association of Siglec-9 with prognosis, tumor stage, molecular subtype, and the immune microenvironment in pan-cancer. The mRNA expression of Siglec-9 was obtained from The Cancer Genome Atlas (TCGA), the Broad Institute Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx). The relationship between Siglec-9 mRNA expression and prognosis was evaluated by the Kaplan–Meier analysis. The correlation between Siglec-9 and tumor-infiltrating immune cells, immune subtype, and molecular subtype was evaluated on Tumor Immune Estimation Resource (TIMER) and Integrated Repository Portal for Tumor-Immune System Interactions (TISIDB). The correlation between Siglec-9 expression and immune checkpoint, mismatch repair (MMR), DNA methyltransferase (DNMT), tumor mutation burden (TMB), and microsatellite instability (MSI) was also analyzed. It showed that Siglec-9 expression was significantly altered in most TCGA tumors. Siglec-9 expression was associated with the prognosis of patients with adrenocortical carcinoma (ACC), lung adenocarcinoma (LUSC), thymoma (THYM), colon adenocarcinoma (COAD), glioblastoma multiforme (GBM), prostate adenocarcinoma (PRAD), esophageal carcinoma (ESCA), and brain lower-grade glioma (LGG). Particularly, increased Siglec-9 expression was strongly correlated with poor prognosis in LGG. Correlation between Siglec-9 expression and tumor stage was also observed in various cancers. In addition, Siglec-9 was positively associated with infiltration of immune cells including neutrophils, dendritic cells (DCs), macrophage, and CD4+ and CD8+ T cells. Moreover, a significant correlation between Siglec-9 and MSI, TMB, MMR, DNMT, immune checkpoint, immune subtype, molecular subtype, and immunomodulators was observed in multiple cancers. Specifically, poor prognostic value and strong correlation to immune cell infiltration were verified with the LGG dataset from the Chinese Glioma Genome Atlas (CGGA). These findings indicated that Siglec-9 can be a novel biomarker and a potential target for cancer immunotherapy.
Multimodal Deep Learning Models for Detecting Dementia From Speech and Transcripts
Authors: Ilias Loukas , Askounis Dimitris
Published: March 2022

Alzheimer's dementia (AD) entails negative psychological, social, and economic consequences not only for the patients but also for their families, relatives, and society in general. Despite the significance of this phenomenon and the importance for an early diagnosis, there are still limitations. Specifically, the main limitation is pertinent to the way the modalities of speech and transcripts are combined in a single neural network. Existing research works add/concatenate the image and text representations, employ majority voting approaches or average the predictions after training many textual and speech models separately. To address these limitations, in this article we present some new methods to detect AD patients and predict the Mini-Mental State Examination (MMSE) scores in an end-to-end trainable manner consisting of a combination of BERT, Vision Transformer, Co-Attention, Multimodal Shifting Gate, and a variant of the self-attention mechanism. Specifically, we convert audio to Log-Mel spectrograms, their delta, and delta-delta (acceleration values). First, we pass each transcript and image through a BERT model and Vision Transformer, respectively, adding a co-attention layer at the top, which generates image and word attention simultaneously. Secondly, we propose an architecture, which integrates multimodal information to a BERT model via a Multimodal Shifting Gate. Finally, we introduce an approach to capture both the inter- and intra-modal interactions by concatenating the textual and visual representations and utilizing a self-attention mechanism, which includes a gate model. Experiments conducted on the ADReSS Challenge dataset indicate that our introduced models demonstrate valuable advantages over existing research initiatives achieving competitive results in both the AD classification and MMSE regression task. Specifically, our best performing model attains an accuracy of 90.00% and a Root Mean Squared Error (RMSE) of 3.61 in the AD classification task and MMSE regression task, respectively, achieving a new state-of-the-art performance in the MMSE regression task.
Distribution Heterogeneity of Muscle Spindles Across Skeletal Muscles of Lower Extremities in C57BL/6 Mice
Authors: Lian Wenxi , Hao Fei , Hao Peng , Zhao Wen , Gao Yudan , Rao Jia-Sheng , Duan Hongmei , Yang Zhaoyang , Li Xiaoguang
Published: March 2022

Muscle spindles, an important proprioceptor scattered in the skeletal muscle, participate in maintaining muscle tension and the fine regulation of random movement. Although muscle spindles exist in all skeletal muscles, explanations about the distribution and morphology of muscle spindles remain lacking for the indetermination of spindle location across muscles. In this study, traditional time-consuming histochemical technology was utilized to determine the muscle spindle anatomical and morphological characteristics in the lower extremity skeletal muscle in C57BL/6 mice. The relative distance from spindles to nerve-entry points varied from muscles in the ventral-dorsal direction, in which spindles in the lateral of gastrocnemius were not considered to be close to its nerve-entry point. In the longitudinal pattern, the domain with the highest abundance of spindles corresponded to the nerve-entry point, excluding the tibialis anterior. Spindles are mainly concentrated at the middle and rostral domain in all muscles. The results suggest a heterogeneity of the distribution of spindles in different muscles, but the distribution trend generally follows the location pattern of the nerve-entry point. Histochemical staining revealed that the spindle did not have a symmetrical structure along the equator, and this result does not agree with previous findings. Exploring the distribution and structural characteristics of muscle spindles in skeletal muscle can provide some anatomical basis for the study of muscle spindles at the molecular level and treatment of exercise-related diseases and provide a comprehensive understanding of muscle spindle morphology.
Capsaicin Ameliorates the Loosening of Mitochondria-Associated Endoplasmic Reticulum Membranes and Improves Cognitive Function in Rats With Chronic Cerebral Hypoperfusion
Authors: Ouyang Mengqi , Zhang Qi , Shu Jiahui , Wang Zhiqiang , Fan Jin , Yu Ke , Lei Lei , Li Yuxia , Wang Qingsong
Published: March 2022

Based on accumulating evidence, vascular factors contribute to cognitive decline and dementia. Mitochondrial dysfunction is the core pathophysiological mechanism. Mitochondria-associated endoplasmic reticulum membranes (MAMs) are subcellular structures that physically and biologically connect mitochondria with the endoplasmic reticulum (ER) and regulate multiple functions ranging from calcium transfer to mitochondrial dynamics and bioenergetics. MAMs dysfunction has been speculated to be a key factor contributing to the pathogenesis of cognitive disorders and a new therapeutic target. However, the alteration of MAMs in vascular cognitive impairment remains to be revealed. Capsaicin, a specific agonist known to activated the transient receptor potential vanilloid type 1 (TRPV1), is involved in hippocampal synaptic plasticity and memory, but the detailed mechanism is still unclear. In this study, chronic cerebral hypoperfusion (CCH) model rats were created by bilateral common carotid artery occlusion (BCCAO), which is a widely used model to study vascular dementia. We observed that CCH rats showed obvious cognitive deficits, and ER-mitochondria contacts were loosener with lower expression of mitofusin2 (MFN2), a key protein connecting MAMs, in the hippocampal CA1 region, compared to the sham group. After capsaicin treatment for 12 weeks, we found that cognitive deficits induced by CCH were significantly alleviated and loosened ER-mitochondrial interactions were obviously improved. In conclusion, the findings of this study highlight that MAMs may contribute to the pathogenesis of cognitive impairment induced by CCH, and our new evidence that capsaicin improves cognitive function highlights a novel opportunity for drug discovery.
Epidermal Growth Factor Pathway in the Age-Related Decline of Oligodendrocyte Regeneration
Authors: Rivera Andrea D. , Azim Kasum , Macchi Veronica , Porzionato Andrea , Butt Arthur M. , De Caro Raffaele
Published: March 2022

Oligodendrocytes (OLs) are specialized glial cells that myelinate CNS axons. OLs are generated throughout life from oligodendrocyte progenitor cells (OPCs) via a series of tightly controlled differentiation steps. Life-long myelination is essential for learning and to replace myelin lost in age-related pathologies such as Alzheimer’s disease (AD) as well as white matter pathologies such as multiple sclerosis (MS). Notably, there is considerable myelin loss in the aging brain, which is accelerated in AD and underpins the failure of remyelination in secondary progressive MS. An important factor in age-related myelin loss is a marked decrease in the regenerative capacity of OPCs. In this review, we will contextualize recent advances in the key role of Epidermal Growth Factor (EGF) signaling in regulating multiple biological pathways in oligodendroglia that are dysregulated in aging.
Towards a Data-Driven Estimation of Resilience in Networked Dynamical Systems: Designing a Versatile Testbed
Authors: Fischer Tobias , Rings Thorsten , Rahimi Tabar M. Reza , Lehnertz Klaus
Published: March 2022

Estimating resilience of adaptive, networked dynamical systems remains a challenge. Resilience refers to a system’s capacity “to absorb exogenous and/or endogenous disturbances and to reorganize while undergoing change so as to still retain essentially the same functioning, structure, and feedbacks.” The majority of approaches to estimate resilience requires exact knowledge of the underlying equations of motion; the few data-driven approaches so far either lack appropriate strategies to verify their suitability or remain subject of considerable debate. We develop a testbed that allows one to modify resilience of a multistable networked dynamical system in a controlled manner. The testbed also enables generation of multivariate time series of system observables to evaluate the suitability of data-driven estimators of resilience. We report first findings for such an estimator.
Relationship Between the Onset of Ménière's Disease and Sympathetic Hyperactivity
Authors: Ishii Masanori , Ishiyama Gail , Ishiyama Akira , Kato Yujin , Mochizuki Fumihiro , Ito Yusuke
Published: March 2022

Objective

The pathogenesis of Ménière's disease is still largely unknown; however, it is known to be strongly associated with stress. Excessive stress can cause hyperactivity of the sympathetic autonomic nervous system. With the aim of understanding changes in sympathetic hyperactivity before and after Ménière's disease, we compared autonomic nervous function in patients in a stable phase of Ménière's disease and that in healthy adults. We also gathered data over about 10 years on autonomic nervous function immediately before a Ménière's attack.

Study Design

Prospective study.

Patients

Autonomic nervous function was analyzed in 129 patients in a stable phase of Ménière's disease 31 healthy adult volunteers. In nine patients, autonomic nervous function was also measured immediately before and after treatment of a vertigo attack.

Main Outcome Measure

Power spectrum analysis of heart rate variability (HRV) of EEG/ECG and an infrared electronic pupillometer were used. Sympathetic and parasympathetic nervous function was measured.

Results

There were no statistically significant differences in autonomic nervous function determined by HRV and electronic pupillometry between patients in a stable phase of Ménière's disease and healthy adults. Sympathetic function as measured by electronic pupillometry parameters VD and T5 showed no difference between the affected and unaffected sides in the baseline data measured in the stable phase (VD: affected side is 31.02 ± 6.16 mm/sec, unaffected side is 29.25 ± 5.73 mm/sec; T5: affected side is 3.37 ± 0.43 msec, unaffected side is 3.25 ± 0.39 msec). In contrast, all nine patients whose HRV data had been obtained just before an attack showed marked suppression of the parasympathetic nervous system and activation of the sympathetic nervous system. Electronic pupillometry also revealed an overactivation of the sympathetic nervous system on the affected side, just before the attacks. Analysis of sequential changes after the onset of an attack revealed that overactivation on the affected side was reduced after treatment, and no difference between affected and unaffected sides was observed 3 days after treatment.

Conclusion

Detailed analysis of autonomic nervous function showed that immediately before an attack of Ménière's disease, the sympathetic nervous system on the affected side was strongly overactivated.
Alterations of the White Matter in Patients With Knee Osteoarthritis: A Diffusion Tensor Imaging Study With Tract-Based Spatial Statistics
Authors: Cheng Shirui , Dong Xiaohui , Zhou Jun , Tang Chenjian , He Wenhua , Chen Yang , Zhang Xinyue , Ma Peihong , Yin Tao , Hu Yimei , Zeng Fang , Li Zhengjie , Liang Fanrong
Published: March 2022

Background

Functional and structural alterations in the gray matter have been observed in patients with knee osteoarthritis (KOA). However, little is known about white matter changes in KOA. Here, we evaluated fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) to investigate potential alterations in the white matter of patients with KOA.

Methods

A total of 166 patients with KOA, along with 88 age- and sex-matched healthy controls were recruited and underwent brain magnetic resonance imaging (MRI). Diffusion tensor imaging (DTI) data were collected and analyzed using tract-based spatial statistics (TBSS). Statistical significances were determined at p < 0.05 and were corrected by the threshold-free cluster enhancement (TFCE) method. Then, we evaluated potential correlations between FA, MD, AD, RD values and disease duration, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, and visual analog scale (VAS) scores.

Results

FA values for the body of corpus callosum, splenium of corpus callosum, bilateral superior longitudinal fasciculus, cingulum, bilateral superior corona radiata, and right posterior corona radiata were significantly higher in patients with KOA than in healthy controls (p < 0.05, TFCE corrected). Compared with healthy controls, patients with KOA also had significantly lower MD, AD, and RD values of the genu of corpus callosum, body of corpus callosum, splenium of corpus callosum, corona radiata, right posterior thalamic radiation, superior longitudinal fasciculus, and middle cerebellar peduncle (p < 0.05, TFCE corrected). Negative correlations were detected between WOMAC scores and AD values for the body of the corpus callosum and the splenium of the corpus callosum (p < 0.05, FDR corrected).

Conclusion

Patients with KOA exhibited extensive white matter alterations in sensorimotor and pain-related regions. Longitudinal observation studies on the causation between abnormalities in the white matter tracts and KOA is needed in the future.
Adaptation in Gait to Lunar and Martian Gravity Unloading During Long-Term Isolation in the Ground-Based Space Station Model
Authors: Saveko Alina , Brykov Vitaly , Kitov Vladimir , Shpakov Alexey , Tomilovskaya Elena
Published: March 2022

The aim of the experiment was to evaluate the adaptive responses of biomechanical and electromyographic parameters to vertical unloading (Lunar—0.15 G and Martian—0.35 G) when walking during the 4-month isolation experiment SIRIUS-19 in the ground-based space station model (GBI). The study involved 6 healthy international crew members of the SIRIUS-19 project aged 34 ± 6.2 years (3 women and 3 men). Body Weight Unloading (BWU) conditions was created by the h/p/cosmos airwalk system. The locomotor test included walking (3.5 ± 0.3 km/h) with a sequential change of BWU modes: 5-min walking with 0% BWU (1 G), 5-min walking with 65% BWU (0.35 G) and 5-min walking with 85% BWU (0.15 G). Ground Reaction Force was recorded by the h/p/cosmos treadmill device. Muscle Lab Model 4000e device was used to record the electromyographic signals of the hip and shin muscles. The locomotor test was performed twice before GBI, monthly during GBI and 1 week after leaving isolation. The results obtained before GBI demonstrate that the changes of support and proprioceptive afferentation signals play significant role in reorganizing of the biomechanical structure of motor acts and the development of new movement patterns. The results of the study are consistent with the previously obtained results of other studies in this direction. Despite the fact that during the GBI the participants of the experiment performed regular physical training, a decrease in the performance indicators values was detected, especially pronounced after 100 days of GBI. This is probably due to limited space of a space station model, as well as the development of a special motor stereotype in it. Noteworthy are the results obtained after the 4th session of the experiment, indicating the effect of sensorimotor learning. We think that the data obtained in this study will be useful in research both in gravitational physiology and in clinical medicine.
Enhancing Visuospatial Working Memory Performance Using Intermittent Theta-Burst Stimulation Over the Right Dorsolateral Prefrontal Cortex
Authors: Ngetich Ronald , Jin Donggang , Li Wenjuan , Song Bian , Zhang Junjun , Jin Zhenlan , Li Ling
Published: March 2022

Noninvasive brain stimulation provides a promising approach for the treatment of neuropsychiatric conditions. Despite the increasing research on the facilitatory effects of this kind of stimulation on the cognitive processes, the majority of the studies have used the standard stimulation approaches such as the transcranial direct current stimulation and the conventional repetitive transcranial magnetic stimulation (rTMS) which seem to be limited in robustness and the duration of the transient effects. However, a recent specialized type of rTMS, theta-burst stimulation (TBS), patterned to mimic the natural cross-frequency coupling of the human brain, may induce robust and longer-lasting effects on cortical activity. Here, we aimed to investigate the effects of the intermittent TBS (iTBS), a facilitatory form of TBS, over the right DLPFC (rDLPFC), a brain area implicated in higher-order cognitive processes, on visuospatial working memory (VSWM) performance. Therefore, iTBS was applied over either the rDLPFC or the vertex of 24 healthy participants, in two separate sessions. We assessed VSWM performance using 2-back and 4-back visuospatial tasks before iTBS (at the baseline (BL), and after the iTBS. Our results indicate that the iTBS over the rDLPFC significantly enhanced VSWM performance in the 2-back task, as measured by the discriminability index and the reaction time. However, the 4-back task performance was not significantly modulated by iTBS. These findings demonstrate that the rDLPFC plays a critical role in VSWM and that iTBS is a safe and effective approach for investigating the causal role of the specific brain areas.
Hypnotic Induction of Deafness to Elementary Sounds: An Electroencephalography Case-Study and a Proposed Cognitive and Neural Scenario
Authors: Munoz Musat Esteban , Rohaut Benjamin , Sangare Aude , Benhaiem Jean-Marc , Naccache Lionel
Published: March 2022

Hypnosis can be conceived as a unique opportunity to explore how top-down effects can influence various conscious and non-conscious processes. In the field of perception, such modulatory effects have been described in distinct sensory modalities. In the present study we focused on the auditory channel and aimed at creating a radical deafness to elementary sounds by a specific hypnotic suggestion. We report here a single case-study in a highly suggestible healthy volunteer who reported a total hypnotically suggested deafness. We recorded high-density scalp EEG during an auditory odd-ball paradigm before and after hypnotic deafness suggestion. While both early auditory event-related potentials to sounds (P1) and mismatch negativity component were not affected by hypnotic deafness, we observed a total disappearance of the late P3 complex component when the subject reported being deaf. Moreover, a centro-mesial positivity was present exclusively during the hypnotic condition prior to the P3 complex. Interestingly, source localization suggested an anterior cingulate cortex (ACC) origin of this neural event. Multivariate decoding analyses confirmed and specified these findings. Resting state analyses confirmed a similar level of conscious state in both conditions, and suggested a functional disconnection between auditory areas and other cortical areas. Taken together these results suggest the following plausible scenario: (i) preserved early processing of auditory information unaffected by hypnotic suggestion, (ii) conscious setting of an inhibitory process (ACC) preventing conscious access to sounds, (iii) functional disconnection between the modular and unconscious representations of sounds and global neuronal workspace. This single subject study presents several limits that are discussed and remains open to alternative interpretations. This original proof-of-concept paves the way to a larger study that will test the predictions stemming from our theoretical model and from this first report.
tDCS-Induced Memory Reconsolidation Effects: Analysis of Prominent Predicting Factors
Authors: Cotelli Maria , Ferrari Clarissa , Gobbi Elena , Binetti Giuliano , Manenti Rosa , Sandrini Marco
Published: March 2022

Background

Memory impairment is among one of the greatest cognitive complaints in midlife and in old age. Considering the importance of good memory functioning in everyday life, it is crucial to study interventions that can reduce the natural decline in this cognitive function. Transcranial Magnetic Stimulation (TMS) studies have demonstrated that the lateral prefrontal cortex (PFC) plays a causal role in enhancing episodic memory recall through reconsolidation. Using a similar paradigm with transcranial direct current stimulation (tDCS) over the left lateral PFC, facilitation effects were observed in delayed memory retrieval in older adults with subjective memory complaints (SMCs) and amnestic Mild Cognitive Impairment (aMCI). However, it remains unclear which potential factors (i.e., tDCS group, cognitive reserve, education level, diagnosis and encoding performance) directly and/or indirectly modulate the tDCS-induced memory reconsolidation effects.

Methods

We reanalyzed data acquired in our previous tDCS studies with 22 SMC and 18 aMCI participants from the perspective of predicting delayed memory retrieval performance. These studies included a learning session on Day 1, a reactivation by a contextual reminder followed by 15 min of tDCS session on Day 2 (24 h after Day 1), and two retrieval sessions (free recall and recognition) tested on Days 3 and 30 (48 h and 30 Days after Day 1).

Results

Univariate models showed that tDCS group (sham vs. active) significantly predicted memory recognition (but not free recall), evidenced by higher scores in the active tDCS group than in sham group, confirming our previous results. Encoding performance and diagnosis (SMC vs. aMCI) significantly predicted memory retrieval, suggesting higher performances in individuals with SMC than in those with aMCI. Regarding cognitive reserve, higher leisure time activity subscores significantly predicted better memory recognition. Finally, multiple models did not show any tDCS group × predictor interaction effects, indicating that the effects of the predictors on retrieval occurred irrespective of tDCS group.

Conclusion

Our results shed light on predicting factors of episodic memory retrieval in this reconsolidation paradigm in individuals with SMC and aMCI. The findings suggest that multifactorial interventions program may be most promising to slow cognitive decline and delay the onset of dementia.
Reduced Precision Underwrites Ego Dissolution and Therapeutic Outcomes Under Psychedelics
Authors: Stoliker Devon , Egan Gary F. , Razi Adeel
Published: March 2022

Evidence suggests classic psychedelics reduce the precision of belief updating and enable access to a range of alternate hypotheses that underwrite how we make sense of the world. This process, in the higher cortices, has been postulated to explain the therapeutic efficacy of psychedelics for the treatment of internalizing disorders. We argue reduced precision also underpins change to consciousness, known as “ego dissolution,” and that alterations to consciousness and attention under psychedelics have a common mechanism of reduced precision of Bayesian belief updating. Evidence, connecting the role of serotonergic receptors to large-scale connectivity changes in the cortex, suggests the precision of Bayesian belief updating may be a mechanism to modify and investigate consciousness and attention.
Sympathetic Pathways Target Cholinergic Neurons in the Human Colonic Myenteric Plexus
Authors: Parker Dominic R. , Wiklendt Lukasz , Humenick Adam , Chen Bao Nan , Sia Tiong Cheng , Wattchow David A. , Dinning Phil G. , Brookes Simon J. H.
Published: March 2022

Background

The sympathetic nervous system inhibits human colonic motility largely by effects on enteric neurons. Noradrenergic axons, which branch extensively in the myenteric plexus, are integral to this modulatory role, but whether they contact specific types of enteric neurons is unknown. The purpose of this study was to determine the association of noradrenergic varicosities with types of enteric neurons.

Methods

Human colonic tissue from seven patients was fixed and dissected prior to multi-layer immunohistochemistry for human RNA binding proteins C and D (HuC/D) (pan-neuronal cell body labelling), tyrosine hydroxylase (TH, catecholaminergic labelling), Enkephalin (ENK), choline acetyltransferase (ChAT, cholinergic labelling) and/or nitric oxide synthase (NOS, nitrergic labelling) and imaged using confocal microscopy. TH-immunoreactive varicose nerve endings and myenteric cell bodies were reconstructed as three dimensional digital images. Data was exported to a purpose-built software package which quantified the density of varicosities close to the surface of each myenteric cell body.

Results

TH-immunoreactive varicosities had a greater mean density within 1 μm of the surface of ChAT +/NOS− nerve cell bodies compared with ChAT−/NOS + cell bodies. Similarly, ENK-immunoreactive varicosities also had a greater mean density close to ChAT +/NOS− cell bodies compared with ChAT−/NOS + cells.

Conclusion

A method for quantifying close associations between varicosities and nerve cell bodies was developed. Sympathetic axons in the myenteric plexus preferentially target cholinergic excitatory cells compared to nitrergic neurons (which are largely inhibitory). This connectivity is likely to be involved in inhibitory modulation of human colonic motility by the sympathetic nervous system.
Computational Identification of Guillain-Barré Syndrome-Related Genes by an mRNA Gene Expression Profile and a Protein–Protein Interaction Network
Authors: Wang Chunyang , Liao Shiwei , Wang Yiyi , Hu Xiaowei , Xu Jing
Published: March 2022

Background

In the present study, we used a computational method to identify Guillain–Barré syndrome (GBS) related genes based on (i) a gene expression profile, and (ii) the shortest path analysis in a protein–protein interaction (PPI) network.

Materials and Methods

mRNA Microarray analyses were performed on the peripheral blood mononuclear cells (PBMCs) of four GBS patients and four age- and gender-matched healthy controls.

Results

Totally 30 GBS-related genes were screened out, in which 20 were retrieved from PPI analysis of upregulated expressed genes and 23 were from downregulated expressed genes (13 overlap genes). Gene ontology (GO) enrichment and KEGG enrichment analysis were performed, respectively. Results showed that there were some overlap GO terms and KEGG pathway terms in both upregulated and downregulated analysis, including positive regulation of macromolecule metabolic process, intracellular signaling cascade, cell surface receptor linked signal transduction, intracellular non-membrane-bounded organelle, non-membrane-bounded organelle, plasma membrane, ErbB signaling pathway, focal adhesion, neurotrophin signaling pathway and Wnt signaling pathway, which indicated these terms may play a critical role during GBS process.

Discussion

These results provided basic information about the genetic and molecular pathogenesis of GBS disease, which may improve the development of effective genetic strategies for GBS treatment in the future.
Development and Cross-Validation of a Predictive Equation for Fat-Free Mass in Brazilian Adolescents by Bioelectrical Impedance
Authors: Costa Roberto Fernandes da , Silva Analiza M. , Masset Kalina Veruska da Silva Bezerra , Cesário Tatianny de Macêdo , Cabral Breno Guilherme de Araújo Tinoco , Ferrari Gerson , Dantas Paulo Moreira Silva
Published: March 2022

The bioelectrical impedance analysis (BIA) is one of the most commonly used techniques for assessing body composition in a clinical setting and in field approaches, as it has the advantages of easy application, fast, and non-invasive, in addition to its relatively low cost. However, the available predictive equations need to be valid for the evaluated subjects. The aim of this study was to verify the validity of several published BIA equations in estimating fat-free mass (FFM) among Brazilian adolescents, in addition to developing and cross-validating a BIA equation to estimate FFM appropriate for Brazilian adolescents. This is a cross-sectional study with 257 adolescents (128 girls) aged 10–19 years, randomly divided into two groups, namely, development (n = 172) and cross-validation (n = 85). The standard technique for assessing FFM was dual X-ray absorptiometry (DXA). The paired t-test, multiple regression, and the Bland-Altman plots were used to test the validity of the proposed models and to perform cross-validation of the model. The equation derived in this study was as follows: FFM = −17.189 + 0.498 (Height2/Resistance) + 0.226 Weight + 0.071 Reactance − 2.378 Sex + 0.097 Height + 0.222 Age; r2 = 0.92; standard error of the estimate = 2.49 kg; the new equation for FFM showed better agreement when compared with that of the equations developed in other countries. In conclusion, the newly developed equations provide a valid FFM estimation and are recommended for Brazilian adolescents with similar characteristics.
Association of Dietary Insulin Index and Dietary Insulin Load With Metabolic Health Status in Iranian Overweight and Obese Adolescents
Authors: Hajhashemy Zahra , Mirzaei Saeideh , Asadi Ali , Akhlaghi Masoumeh , Saneei Parvane
Published: March 2022

Background

Limited data are available on the association of dietary insulin load (DIL) and dietary insulin index (DII) with health status in pediatrics. We aimed to investigate the relationship of DIL and DII with metabolic health status in Iranian overweight/obese adolescents.

Methods

In this cross-sectional study, using a multistage cluster random-sampling method, 203 overweight/obese adolescents (aged 12 to <18 years) were included. A validated 147-item food frequency questionnaire (FFQ) was used for a dietary intake assessment. Glycemic and lipid profile, blood pressure (BP), and anthropometric indices were measured. Participants were categorized as metabolically healthy obese (MHO) or metabolically unhealthy obese (MUO) using the two methods of the International Diabetes Federation (IDF) and a combination of IDF with Homeostasis Model Assessment Insulin Resistance (HOMA-IR).

Results

According to IDF and IDF/HOMA-IR strategies, 38.9% (n = 79) and 33.0% (n = 67) of participants belonged to MUO category. After adjustments for potential confounders, subjects in the highest tertile of DIL in comparison with those in the lowest tertile had the odds ratio (OR) values of 8.44 (95% CI: 2.24–31.78) and 5.86 (95% CI: 1.39–24.58) for MUO based on IDF and IDF/HOMA-IR definitions, respectively. Moreover, after considering potential confounders, adolescents in the highest tertile of DII, compared to the lowest tertile, were, respectively, 6.93 (OR: 6.93; 95% CI: 2.59–18.57) and 5.26 (OR: 5.26; 95% CI: 1.85–14.97) times more likely to be MUO, based on IDF and IDF/HOMA-IR definitions. A significant decreasing trend was observed for OR of MUO in tertiles of DIL and DII. The stratified analysis revealed that these associations were stronger in obese participants; in overweight subjects, the association was not independent of confounders.

Conclusion

This population-based study revealed that higher DIL and DII were strongly related to increased OR of MUO in Iranian adolescents, especially in obese participants. Further investigations, especially with a prospective design, are needed to affirm these findings.