bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective Efficacy of an Orf Virus-Vector Encoding the Hemagglutinin and the Nucleoprotein of Influenza A Virus in Swine
Authors: Joshi Lok R. , Knudsen David , Piñeyro Pablo , Dhakal Santosh , Renukaradhya Gourapura J. , Diel Diego G.
Published: November 2021

Swine influenza is a highly contagious respiratory disease of pigs caused by influenza A viruses (IAV-S). IAV-S causes significant economic losses to the swine industry and poses challenges to public health given its zoonotic potential. Thus effective IAV-S vaccines are needed and highly desirable and would benefit both animal and human health. Here, we developed two recombinant orf viruses, expressing the hemagglutinin (HA) gene (OV-HA) or the HA and the nucleoprotein (NP) genes of IAV-S (OV-HA-NP). The immunogenicity and protective efficacy of these two recombinant viruses were evaluated in pigs. Both OV-HA and OV-HA-NP recombinants elicited robust virus neutralizing antibody response in pigs, with higher levels of neutralizing antibodies (NA) being detected in OV-HA-NP-immunized animals pre-challenge infection. Although both recombinant viruses elicited IAV-S-specific T-cell responses, the frequency of IAV-S-specific proliferating CD8+ T cells upon re-stimulation was higher in OV-HA-NP-immunized animals than in the OV-HA group. Importantly, IgG1/IgG2 isotype ELISAs revealed that immunization with OV-HA induced Th2-biased immune responses, whereas immunization with OV-HA-NP virus resulted in a Th1-biased immune response. While pigs immunized with either OV-HA or OV-HA-NP were protected when compared to non-immunized controls, immunization with OV-HA-NP resulted in incremental protection against challenge infection as evidenced by a reduced secondary antibody response (NA and HI antibodies) following IAV-S challenge and reduced virus shedding in nasal secretions (lower viral RNA loads and frequency of animals shedding viral RNA and infectious virus), when compared to animals in the OV-HA group. Interestingly, broader cross neutralization activity was also observed in serum of OV-HA-NP-immunized animals against a panel of contemporary IAV-S isolates representing the major genetic clades circulating in swine. This study demonstrates the potential of ORFV-based vector for control of swine influenza virus in swine.
The Pathogenesis of COVID-19 Myocardial Injury: An Immunohistochemical Study of Postmortem Biopsies
Authors: Hartmann Camila , Miggiolaro Anna Flavia Ribeiro dos Santos , Motta Jarbas da Silva , Baena Carstens Lucas , Busatta Vaz De Paula Caroline , Fagundes Grobe Sarah , Hermann de Souza Nunes Larissa , Lenci Marques Gustavo , Libby Peter , Zytynski Moura Lidia , de Noronha Lucia , Pellegrino Baena Cristina
Published: November 2021

Rationale

Myocardial injury associates significantly and independently with mortality in COVID-19 patients. However, the pathogenesis of myocardial injury in COVID-19 remains unclear, and cardiac involvement by SARS-CoV-2 presents a major challenge worldwide.

Objective

This histological and immunohistochemical study sought to clarify the pathogenesis and propose a mechanism with pathways involved in COVID-19 myocardial injury.

Methods and Results

Postmortem minimally invasive autopsies were performed in six patients who died from COVID-19, and the myocardium samples were compared to a control group (n=11). Histological analysis was performed using hematoxylin-eosin and toluidine blue staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: caspase-1, caspase-9, gasdermin-d, ICAM-1, IL-1β, IL-4, IL-6, CD163, TNF-α, TGF-β, MMP-9, type 1 and type 3 collagen. The samples were also assessed for apoptotic cells by TUNEL. Histological analysis showed severe pericardiocyte interstitial edema and higher mast cells counts per high-power field in all COVID-19 myocardium samples. The IHC analysis showed increased expression of caspase-1, ICAM-1, IL-1β, IL-6, MMP-9, TNF-α, and other markers in the hearts of COVID-19 patients. Expression of caspase-9 did not differ from the controls, while gasdermin-d expression was less. The TUNEL assay was positive in all the COVID-19 samples supporting endothelial apoptosis.

Conclusions

The pathogenesis of COVID-19 myocardial injury does not seem to relate to primary myocardiocyte involvement but to local inflammation with associated interstitial edema. We found heightened TGF-β and interstitial collagen expression in COVID-affected hearts, a potential harbinger of chronic myocardial fibrosis. These results suggest a need for continued clinical surveillance of patients for myocardial dysfunction and arrythmias after recovery from the acute phase of COVID-19.
Salmonella Infantis Delays the Death of Infected Epithelial Cells to Aggravate Bacterial Load by Intermittent Phosphorylation of Akt With SopB
Authors: Chu Bing-Xin , Li Ya-Nan , Liu Ning- , Yuan Lan-Xin , Chen Shi-Yan , Zhu Yao-Hong , Wang Jiu-Feng
Published: November 2021

Salmonella Infantis has emerged as a major clinical pathogen causing gastroenteritis worldwide in recent years. As an intracellular pathogen, Salmonella has evolved to manipulate and benefit from the cell death signaling pathway. In this study, we discovered that S. Infantis inhibited apoptosis of infected Caco-2 cells by phosphorylating Akt. Notably, Akt phosphorylation was observed in a discontinuous manner: immediately 0.5 h after the invasion, then before peak cytosolic replication. Single-cell analysis revealed that the second phase was only induced by cytosolic hyper-replicating bacteria at 3–4 hpi. Next, Akt-mediated apoptosis inhibition was found to be initiated by Salmonella SopB. Furthermore, Akt phosphorylation increased mitochondrial localization of Bcl-2 to prevent Bax oligomerization on the mitochondrial membrane, maintaining the mitochondrial network homeostasis to resist apoptosis. In addition, S. Infantis induced pyroptosis, as evidenced by increased caspase-1 (p10) and GSDMS-N levels. In contrast, cells infected with the ΔSopB strain displayed faster but less severe pyroptosis and had less bacterial load. The results indicated that S. Infantis SopB–mediated Akt phosphorylation delayed pyroptosis, but aggravated its severity. The wild-type strain also caused more severe diarrhea and intestinal inflammatory damage than the ΔSopB strain in mice. These findings revealed that S. Infantis delayed the cells’ death by intermittent activation of Akt, allowing sufficient time for replication, thereby causing more severe inflammation.
Hsa-miR-31 Governs T-Cell Homeostasis in HIV Protection via IFN-γ-Stat1-T-Bet Axis
Authors: Zhu Lingyan , Qiu Chao , Dai Lili , Zhang Linxia , Feng Meiqi , Yang Yu , Qiu Chenli , Zhang Anli , Huang Jun , Wang Ying , Wan Ying , Zhao Chen , Wu Hao , Lyu Jianxin , Zhang Xiaoyan , Xu Jianqing
Published: November 2021

It remains poorly defined whether any human miRNAs play protective roles during HIV infection. Here, focusing on a unique cohort of HIV-infected former blood donors, we identified miR-31 (hsa-miR-31) by comparative miRNA profiling as the only miRNA inversely correlating with disease progression. We further validated this association in two prospective cohort studies. Despite conservation during evolution, hsa-miR-31, unlike its mouse counterpart (mmu-miR-31), was downregulated in human T cell upon activation. Our ex vivo studies showed that inhibiting miR-31 in naïve CD4+ T cells promoted a transcriptional profile with activation signature. Consistent with this skewing effect, miR-31 inhibition led to remarkably increased susceptibility to HIV infection. The suppressive nature of miR-31 in CD4+ T cell activation was pinpointed to its ability to decrease T-bet, the key molecule governing IFN-γ production and activation of CD4+ T cells, by directly targeting the upstream STAT1 transcriptional factor for downregulation, thus blunting Th1 response. Our results implicated miR-31 as a useful biomarker for tracking HIV disease progression and, by demonstrating its importance in tuning the activation of CD4+ T cells, suggested that miR-31 may play critical roles in other physiological contexts where the CD4+ T cell homeostasis needs to be deliberately controlled.
The Macrophage Reprogramming Ability of Antifolates Reveals Soluble CD14 as a Potential Biomarker for Methotrexate Response in Rheumatoid Arthritis
Authors: Fuentelsaz-Romero Sara , Barrio-Alonso Celia , García Campos Raquel , Torres Torresano Mónica , Muller Ittai B. , Triguero-Martínez Ana , Nuño Laura , Villalba Alejandro , García-Vicuña Rosario , Jansen Gerrit , Miranda-Carús María-Eugenia , González-Álvaro Isidoro , Puig-Kröger Amaya
Published: November 2021

The identification of “trained immunity/tolerance” in myeloid cells has changed our perception of the performance of monocytes and macrophages during inflammatory and immune responses. Pemetrexed (PMX) and methotrexate (MTX) are blockers of the one-carbon metabolism (OCM) and commonly used therapeutic agents in cancer and rheumatoid arthritis (RA). We have previously showed that MTX promotes trained immunity in human macrophages. In the present manuscript, we have assessed the anti-inflammatory effects of PMX and MTX and found that OCM blockers alter the functional and gene expression profile of human macrophages and that OCM blockade reprograms macrophages towards a state of lipopolysaccharide (LPS) tolerance at the signaling and functional levels. Moreover, OCM blockade reduced macrophage LPS responsiveness by impairing the expression of membrane-bound and soluble CD14 (sCD14). The therapeutic relevance of these results was later confirmed in early RA patients, as MTX-responder RA patients exhibit lower sCD14 serum levels, with baseline sCD14 levels predicting MTX response. As a whole, our results demonstrate that OCM is a metabolic circuit that critically mediates the acquisition of innate immune tolerance and positions sCD14 as a valuable tool to predict MTX response in RA patients.
A Systematic Review of Acoustic Telemetry as a Tool to Gain Insights Into Marine Turtle Ecology and Aid Their Conservation
Authors: Hardin Emily E. , Fuentes Mariana M. P. B.
Published: November 2021

While widely applied in fisheries science, acoustic telemetry remains an underutilized method in the field of marine turtle biotelemetry. However, with the ability to provide fine-scale spatial data (tens to hundreds of meters, depending on array setup and receiver range) at a low cost, acoustic telemetry presents an important tool for obtaining key information on marine turtle ecology. We present a comprehensive and systematic review acknowledging how acoustic telemetry has been used to advance the field of marine turtle ecology and conservation. We identify the extent of current studies and discuss common and novel research approaches while addressing specific limitations of acoustic telemetry. Forty-eight studies were reviewed, representing six of the seven marine turtle species and all life stages, with most individuals identified as juveniles (45%) and hatchlings (36%). Most studies (83%) focused on the spatial distribution of marine turtles, including estimating home ranges, investigating drivers of habitat use, and identifying horizontal movement patterns and vertical space use. Additionally, acoustic telemetry has been used to study hatchling dispersal and marine turtle exposure and response to threats, as well as to monitor physiological parameters. We identified that acoustic telemetry directly or indirectly informs 60% of the top questions and research priorities related to marine turtles identified by experts in the field. With an increase in acoustic telemetry receiver networks and collaborations across taxa, the applicability of acoustic telemetry is growing, not only for marine turtles but for a wide array of marine species. Although there are limitations that need to be considered at a site/project-level, acoustic telemetry is an important, low-cost technology able to address key questions related to marine turtle ecology that can aid in their conservation, and therefore should be considered by researchers as they develop their projects.
Intrinsic Mechanisms Underlying Hypoxia-Tolerant Mitochondrial Phenotype During Hypoxia-Reoxygenation Stress in a Marine Facultative Anaerobe, the Blue Mussel Mytilus edulis
Authors: Sokolov Eugene P. , Adzigbli Linda , Markert Stephanie , Bundgaard Amanda , Fago Angela , Becher Dörte , Hirschfeld Claudia , Sokolova Inna M.
Published: November 2021

Hypoxia is common in marine environments and a major stressor for marine organisms inhabiting benthic and intertidal zones. Several studies have explored the responses of these organisms to hypoxic stress at the whole organism level with a focus on energy metabolism and mitochondrial response, but the instrinsic mitochondrial responses that support the organelle’s function under hypoxia and reoxygenation (H/R) stress are not well understood. We studied the effects of acute H/R stress (10 min anoxia followed by 15 min reoxygenation) on mitochondrial respiration, production of reactive oxygen species (ROS) and posttranslational modifications (PTM) of the proteome in a marine facultative anaerobe, the blue musselMytilus edulis. The mussels’ mitochondria showed increased OXPHOS respiration and suppressed proton leak resulting in a higher coupling efficiency after H/R stress. ROS production decreased in both the resting (LEAK) and phosphorylating (OXPHOS) state indicating thatM. eduliswas able to prevent oxidative stress and mitochondrial damage during reoxygenation. Hypoxia did not lead to rearrangement of the mitochondrial supercomplexes but impacted the mitochondrial phosphoproteome including the proteins involved in OXPHOS, amino acid- and fatty acid catabolism, and protein quality control. This study indicates that mussels’ mitochondria possess intrinsic mechanisms (including regulation via reversible protein phosphorylation) that ensure high respiratory flux and mitigate oxidative damage during H/R stress and contribute to the hypoxia-tolerant mitochondrial phenotype of this metabolically plastic species.
Surface-Functionalized Nanocelluloses as Viscosity-Modifying Agents in Engineered Cementitious Composites
Authors: Liang Long , Yang Junlei , Lv Guowei , Lei Zhen , Li Xiurong , Liu Qiaoling
Published: November 2021

This study investigated the feasibility of using nanofibrilliated celluloses (CNF) (0.1% by weight of binder materials) with three oxidation degrees, no oxidation (NCNF), low oxidation (LCNF), and high oxidation (HCNF), as a viscosity-modifying agent (VMA) to develop polyethylene fiber (PE)-engineered cementitious composites (ECC). Attenuated total reflection-Fourier transform infrared (ATR-FTIR), dynamic light scattering (DLS), and zeta potential were performed to characterize the properties of the CNF with different oxidation degrees. More stable CNF suspensions could be obtained due to the increasing oxidation degree. Rheology tests showed that CNF replacing VMA could modify the plastic viscosity and yield stress of the fresh matrices. With increasing the oxidation degree of CNF, a significant enhancement was seen for the rheological parameters. It was conducted that CNF could increase the compressive strength, the tensile stress, the nominal flexural strength, and the fracture toughness compared with ECC using VMA, and much higher oxidation degrees yielded higher enhancements (HCNF > LCNF > NCNF). ECC using CNF to replace VMA also achieved ultra-high ductility behavior with the tensile strain of over 8% and the saturated multiple cracking pattern. These finds were supplemented by thermal gravimetric analysis (TGA), which showed that the degree of hydration increased with increasing CNF surface oxidation degree. Additionally, the morphology images of PE fibers were observed by scanning electron microscope (SEM).
The Ki-67 Proliferation Index-Related Nomogram to Predict the Response of First-Line Tyrosine Kinase Inhibitors or Chemotherapy in Non-small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor-Mutant Status
Authors: Gu Weiguo , Hu Mingbin , Xu Linlin , Ren Yuanhui , Mei Jinhong , Wang Weijia , Wang Chunliang
Published: November 2021

Background: The correlation between Ki-67 and epidermal growth factor receptor (EGFR)- or Kristen rat sarcoma viral oncogene homolog (KRAS)-mutant status in advanced or postoperative-recurrent non-small cell lung cancer (NSCLC) has fewer studies reported, and the prognostic role of Ki-67 with first-line EGFR-tyrosine kinase inhibitors (TKIs) or chemotherapy remains controversial.

Methods: A total of 295 patients were tested for EGFR-mutant status in advanced or postoperative-recurrent NSCLC and received first-line EGFR-TKIs or chemotherapy for treatment. Ki-67 expression was retrospectively analyzed by immunohistochemistry. The Kaplan-Meier method was used to calculate survival rates. The multivariate Cox proportional hazards model was used to generate a nomogram. The established nomogram was validated using the calibration plots.

Results: The expression levels of Ki-67 were divided into low (<60%, n = 186) and high (≥60%, n = 109) groups, based on the receiver operating characteristic curve. The expression levels of Ki-67 were found to be higher in patients with KRAS mutations when compared to KRAS wildtype, and EGFR wildtype was higher than EGFR mutations. The median overall survival (OS) of the low Ki-67 expression group was significantly longer than that of the high Ki-67 group, no matter in all NSCLC, EGFR mutations, EGFR wildtype, KRAS-mutant status, EGFR-TKIs, or chemotherapy of patients (P < 0.05). Subgroup analysis showed that the KRAS wildtype or EGFR mutations combine with low Ki-67 expression group had the longest median OS than KRAS mutations or EGFR wildtype combine with Ki-67 high expression group (P < 0.05). In the training cohort, the multivariate Cox analysis identified age, serum lactate dehydrogenase (LDH), serum Cyfra211, EGFR mutations, and Ki-67 as independent prognostic factors, and a nomogram was developed based on these covariates. The calibration curve for predicting the 12-, 24-, and 30-month OS showed an optimal agreement between the predicted and actual observed outcomes.

Conclusions: The Ki-67 expression-based nomogram can well predict the efficacy of first-line therapy in NSCLC patients with EGFR- or KRAS-mutant status, high expression levels of Ki-67 correlated with a poor prognosis.
A Carvacrol-Rich Essential Oil Extracted From Oregano (Origanum vulgare “Hot & Spicy”) Exerts Potent Antibacterial Effects Against Staphylococcus aureus
Authors: Hao Yuanpeng , Li Jingyi , Shi Lei
Published: November 2021

Oregano essential oil (OEO), as a natural antimicrobial, has gained increased interest from food researchers and manufacturers. However, a few studies have investigated its possible antibacterial effects against Staphylococcus aureus using the proteomic tool. The present study aimed to explore the antibacterial effect and mechanism of a carvacrol-rich OEO extracted from Origanum vulgare “Hot & Spicy” on the inactivation of S. aureus. The gas chromatography–mass spectrometry analysis of the OEO allowed the detection of 27 compounds; the major constituent was carvacrol (84.38% of total compounds). The average diameter of the inhibitory zone (DIZ) value was 29.10 mm, and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of OEO against S. aureus were 0.125 and 0.25 mg/mL, respectively. The growth curve assay indicated that the OEO prolonged the lag phase of S. aureus. The decrease in cell viability, changes in the integrity of cell membrane, and abnormal cell morphology further reflected the cell damage of S. aureus caused by the OEO. In addition, a label-free proteomic analysis was applied to analyze the regulatory networks of S. aureus in response to 1/2 MIC OEO-treatment stress. Of the 56 differentially expressed proteins (DEPs) identified, 26 were significantly upregulated and 30 downregulated. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the DEPs were mainly involved in pathways of ribosomes; valine, leucine, and isoleucine biosynthesis; and phenylalanine, tyrosine, and tryptophan biosynthesis, which suggested that the growth inhibition of S. aureus might be due to the disordered effect of the OEO on protein synthesis and amino acid metabolism. These findings deepened our understanding regarding S. aureus survival and metabolism responses to the OEO treatment and suggested that the carvacrol-rich OEO could be used in food production environments to effectively control S. aureus.
Roles of Type VI Secretion System in Transport of Metal Ions
Authors: Yang Xiaobing , Liu Hai , Zhang Yanxiong , Shen Xihui
Published: November 2021

The type VI secretion system (T6SS) is a transmembrane protein nanomachine employed by many gram-negative bacteria to directly translocate effectors into adjacent cells or the extracellular milieu, showing multiple functions in both interbacterial competition and bacteria-host interactions. Metal ion transport is a newly discovered T6SS function. This review summarizes the identified T6SS functions and highlights the features of metal ion transport mediated by T6SS and discusses its regulation.
Glycine Transporter 2: Mechanism and Allosteric Modulation
Authors: Frangos Zachary J. , Cantwell Chater Ryan P. , Vandenberg Robert J.
Published: November 2021

Neurotransmitter sodium symporters (NSS) are a subfamily of SLC6 transporters responsible for regulating neurotransmitter signalling. They are a major target for psychoactive substances including antidepressants and drugs of abuse, prompting substantial research into their modulation and structure-function dynamics. Recently, a series of allosteric transport inhibitors have been identified, which may reduce side effect profiles, compared to orthosteric inhibitors. Allosteric inhibitors are also likely to provide different clearance kinetics compared to competitive inhibitors and potentially better clinical outcomes. Crystal structures and homology models have identified several allosteric modulatory sites on NSS including the vestibule allosteric site (VAS), lipid allosteric site (LAS) and cholesterol binding site (CHOL1). Whilst the architecture of eukaryotic NSS is generally well conserved there are differences in regions that form the VAS, LAS, and CHOL1. Here, we describe ligand-protein interactions that stabilize binding in each allosteric site and explore how differences between transporters could be exploited to generate NSS specific compounds with an emphasis on GlyT2 modulation.
In the Model Cell Lines of Moderately and Poorly Differentiated Endometrial Carcinoma, Estrogens Can Be Formed via the Sulfatase Pathway
Authors: Pavlič Renata , Gjorgoska Marija , Hafner Eva , Sinreih Maša , Gajser Kristina , Poschner Stefan , Jäger Walter , Rižner Tea Lanišnik
Published: November 2021

Endometrial cancer (EC) is the most common gynecological malignancy in resource-abundant countries. The majority of EC cases are estrogen dependent but the mechanisms of estrogen biosynthesis and oxidative metabolism and estrogen action are not completely understood. Here, we evaluated formation of estrogens in models of moderately and poorly differentiated EC: RL95-2 and KLE cells, respectively. Results revealed high expression of estrone-sulfate (E1-S) transporters (SLCO1A2, SLCO1B3, SLCO1C1, SLCO3A1, SLC10A6, SLC22A9), and increased E1-S uptake in KLE vs RL95-2 cells. In RL95-2 cells, higher levels of sulfatase and better metabolism of E1-S to E1 were confirmed compared to KLE cells. In KLE cells, disturbed balance in expression of HSD17B genes led to enhanced activation of E1 to E2, compared to RL95-2 cells. Additionally, increased CYP1B1 expression and down-regulation of genes encoding phase II metabolic enzymes: COMT, NQO1, NQO2, and GSTP1 suggested decreased detoxification of carcinogenic metabolites in KLE cells. Results indicate that in model cell lines of moderately and poorly differentiated EC, estrogens can be formed via the sulfatase pathway.
Searching for DNA Damage: Insights From Single Molecule Analysis
Authors: Schaich Matthew A. , Van Houten Bennett
Published: November 2021

DNA is under constant threat of damage from a variety of chemical and physical insults, such as ultraviolet rays produced by sunlight and reactive oxygen species produced during respiration or inflammation. Because damaged DNA, if not repaired, can lead to mutations or cell death, multiple DNA repair pathways have evolved to maintain genome stability. Two repair pathways, nucleotide excision repair (NER) and base excision repair (BER), must sift through large segments of nondamaged nucleotides to detect and remove rare base modifications. Many BER and NER proteins share a common base-flipping mechanism for the detection of modified bases. However, the exact mechanisms by which these repair proteins detect their damaged substrates in the context of cellular chromatin remains unclear. The latest generation of single-molecule techniques, including the DNA tightrope assay, atomic force microscopy, and real-time imaging in cells, now allows for nearly direct visualization of the damage search and detection processes. This review describes several mechanistic commonalities for damage detection that were discovered with these techniques, including a combination of 3-dimensional and linear diffusion for surveying damaged sites within long stretches of DNA. We also discuss important findings that DNA repair proteins within and between pathways cooperate to detect damage. Finally, future technical developments and single-molecule studies are described which will contribute to the growing mechanistic understanding of DNA damage detection.
Aging Affects the Demands and Patterns in Active Control Under Different Sensory-Conflicted Conditions
Authors: Hu Jing , Chien Jung Hung
Published: November 2021

Most falls might be attributed to an unexpected perturbation such as a slip. It might be aggravated by the deterioration of the sensory system as people aged. This deterioration increases the demand in active control. However, what levels of demand in active control do older adults need? This study aimed to answer this question by using a novel assessment. Both young and old adults walked in three conditions: normal, slip, and slip with low light conditions. The amount of step length variability, step width variability, and the 95% confidence interval of the ellipse area of heel contact locations was measured to quantify and distinguish different levels of demand and patterns in active control. The results found that less sensory information led to a higher level of demand in active control in both anterior-posterior and medial-lateral directions. Importantly, different patterns in active control were found among different age groups and perturbation conditions. This study extended the current knowledge and further proposed the possibility of multiple patterns in active control. This study also suggests a new method to quantify the levels and patterns in active control under sensory perturbations, and this innovation can be used to guide age-related fall prevention training.
Association Between Sleep and Motoric Cognitive Risk Syndrome Among Community-Dwelling Older Adults: Results From the China Health and Retirement Longitudinal Study
Authors: Xu Weihao , Bai Anying , Huang Xin , Gao Yinghui , Liu Lin
Published: November 2021

Background: Sleep is increasingly recognized as an important lifestyle contributor to health; however, its relationship with Motoric cognitive risk syndrome (MCR) is still unclear. The present study aimed to examine the associations between sleep duration, sleep quality, and MCR among community-dwelling Chinese older adults.

Methods: We recruited 5,387 participants aged ≥60 years from the China Health and Retirement Longitudinal Study (CHARLS). Sleep-related variables including night sleep duration and sleep quality were assessed via self-reported questionnaires. MCR syndrome was defined as cognitive complaints and slow gait speed without dementia or impaired mobility. Multivariate logistic regression analysis was performed to explore the associations between sleep-related variables and MCR after controlling for all potential confounders including demographic characteristics, lifestyle factors, and comorbidities.

Results: We found that sleep duration was significantly associated with MCR, and the multivariate-adjusted odds ratios (OR) were highest for those with the shortest (<6 h OR = 1.55, 95% CI = 1.18–2.04) and longest (≥10 h OR = 1.73, 95% CI = 1.03–2.91) sleep durations. Moreover, an increasing frequency of self-perceived poor sleep quality was significantly associated with MCR in the adjusted model (3–4 days OR = 1.58, 95% CI = 1.16–2.17; 5–7 days OR = 1.81, 95% CI = 1.37–2.40).

Conclusions: Our study indicated an inverted U-shaped association between night sleep duration and MCR. Poor sleep quality was also associated with higher odds of MCR in community-dwelling Chinese elders. Longitudinal studies with a larger population size are needed to establish causality in the future and further explore potential action mechanisms.
The Differences Between Motor Attempt and Motor Imagery in Brain-Computer Interface Accuracy and Event-Related Desynchronization of Patients With Hemiplegia
Authors: Chen Shugeng , Shu Xiaokang , Wang Hewei , Ding Li , Fu Jianghong , Jia Jie
Published: November 2021

Background: Motor attempt and motor imagery (MI) are two common motor tasks used in brain-computer interface (BCI). They are widely researched for motor rehabilitation in patients with hemiplegia. The differences between the motor attempt (MA) and MI tasks of patients with hemiplegia can be used to promote BCI application. This study aimed to explore the accuracy of BCI and event-related desynchronization (ERD) between the two tasks.

Materials and Methods: We recruited 13 patients with stroke and 3 patients with traumatic brain injury, to perform MA and MI tasks in a self-control design. The BCI accuracies from the bilateral, ipsilesional, and contralesional hemispheres were analyzed and compared between different tasks. The cortical activation patterns were evaluated with ERD and laterality index (LI).

Results: The study showed that the BCI accuracies of MA were significantly (p < 0.05) higher than MI in the bilateral, ipsilesional, and contralesional hemispheres in the alpha-beta (8–30 Hz) frequency bands. There was no significant difference in ERD and LI between the MA and MI tasks in the 8–30 Hz frequency bands. However, in the MA task, there was a negative correlation between the ERD values in the channel CP1 and ipsilesional hemispheric BCI accuracies (r = −0.552, p = 0.041, n = 14) and a negative correlation between the ERD values in channel CP2 and bilateral hemispheric BCI accuracies (r = −0.543, p = 0.045, n = 14). While in the MI task, there were negative correlations between the ERD values in channel C4 and bilateral hemispheric BCI accuracies (r = −0.582, p = 0.029, n = 14) as well as the contralesional hemispheric BCI accuracies (r = −0.657, p = 0.011, n = 14). As for motor dysfunction, there was a significant positive correlation between the ipsilesional BCI accuracies and FMA scores of the hand part in 8–13 Hz (r = 0.565, p = 0.035, n = 14) in the MA task and a significant positive correlation between the ipsilesional BCI accuracies and FMA scores of the hand part in 13–30 Hz (r = 0.558, p = 0.038, n = 14) in the MI task.

Conclusion: The MA task may achieve better BCI accuracy but have similar cortical activations with the MI task. Cortical activation (ERD) may influence the BCI accuracy, which should be carefully considered in the BCI motor rehabilitation of patients with hemiplegia.
An Improved PSO-GWO Algorithm With Chaos and Adaptive Inertial Weight for Robot Path Planning
Authors: Cheng Xuezhen , Li Jiming , Zheng Caiyun , Zhang Jianhui , Zhao Meng
Published: November 2021

The traditional particle swarm optimization (PSO) path planning algorithm represents each particle as a path and evolves the particles to find an optimal path. However, there are problems in premature convergence, poor global search ability, and to the ease in which particles fall into the local optimum, which could lead to the failure of fast optimal path obtainment. In order to solve these problems, this paper proposes an improved PSO combined gray wolf optimization (IPSO-GWO) algorithm with chaos and a new adaptive inertial weight. The gray wolf optimizer can sort the particles during evolution to find the particles with optimal fitness value, and lead other particles to search for the position of the particle with the optimal fitness value, which gives the PSO algorithm higher global search capability. The chaos can be used to initialize the speed and position of the particles, which can reduce the prematurity and increase the diversity of the particles. The new adaptive inertial weight is designed to improve the global search capability and convergence speed. In addition, when the algorithm falls into a local optimum, the position of the particle with the historical best fitness can be found through the chaotic sequence, which can randomly replace a particle to make it jump out of the local optimum. The proposed IPSO-GWO algorithm is first tested by function optimization using ten benchmark functions and then applied for optimal robot path planning in a simulated environment. Simulation results show that the proposed IPSO-GWO is able to find an optimal path much faster than traditional PSO-GWO based methods.
Abnormal Network Homogeneity in the Right Superior Medial Frontal Gyrus in Cervical Dystonia
Authors: Wei Shubao , Chen Xiuqiong , Xiao Yousheng , Jiang Wenyan , Yin Qiong , Lu Chunhui , Yang Lu , Wei Jing , Liu Yang , Li Wenmei , Tang Jingqun , Guo Wenbin , Luo Shuguang
Published: November 2021

Background: Increasing evidence from modern neuroimaging has confirmed that cervical dystonia (CD) is caused by network abnormalities. Specific brain networks are known to be crucial in patients suffering from CD. However, changes in network homogeneity (NH) in CD patients have not been characterized. Therefore, the purpose of this study was to investigate the NH of patients with CD.

Methods: An automated NH method was used to analyze resting-state functional magnetic resonance (fMRI) data from 19 patients with CD and 21 gender- and age-matched healthy controls (HC). Correlation analysis were conducted between NH, illness duration and symptom severity measured by the Tsui scale.

Results: Compared with the HC group, CD patients showed a lower NH in the right superior medial frontal gyrus. No significant correlations were found between abnormal NH values and illness duration or symptom severity.

Conclusion: Our findings suggest the existence of abnormal NH in the default mode network (DMN) of CD patients, and thereby highlight the importance of the DMN in the pathophysiology of CD.
Prospective Quantitative Neuroimaging Analysis of Putative Temporal Lobe Epilepsy
Authors: Elisevich Kost , Davoodi-Bojd Esmaeil , Heredia John G. , Soltanian-Zadeh Hamid
Published: November 2021

Purpose: A prospective study of individual and combined quantitative imaging applications for lateralizing epileptogenicity was performed in a cohort of consecutive patients with a putative diagnosis of mesial temporal lobe epilepsy (mTLE).

Methods: Quantitative metrics were applied to MRI and nuclear medicine imaging studies as part of a comprehensive presurgical investigation. The neuroimaging analytics were conducted remotely to remove bias. All quantitative lateralizing tools were trained using a separate dataset. Outcomes were determined after 2 years. Of those treated, some underwent resection, and others were implanted with a responsive neurostimulation (RNS) device.

Results: Forty-eight consecutive cases underwent evaluation using nine attributes of individual or combinations of neuroimaging modalities: 1) hippocampal volume, 2) FLAIR signal, 3) PET profile, 4) multistructural analysis (MSA), 5) multimodal model analysis (MMM), 6) DTI uncertainty analysis, 7) DTI connectivity, and 9) fMRI connectivity. Of the 24 patients undergoing resection, MSA, MMM, and PET proved most effective in predicting an Engel class 1 outcome (>80% accuracy). Both hippocampal volume and FLAIR signal analysis showed 76% and 69% concordance with an Engel class 1 outcome, respectively.

Conclusion: Quantitative multimodal neuroimaging in the context of a putative mTLE aids in declaring laterality. The degree to which there is disagreement among the various quantitative neuroimaging metrics will judge whether epileptogenicity can be confined sufficiently to a particular temporal lobe to warrant further study and choice of therapy. Prediction models will improve with continued exploration of combined optimal neuroimaging metrics.
Benefit of Action Naming Over Object Naming for Visualization of Subcortical Language Pathways in Navigated Transcranial Magnetic Stimulation-Based Diffusion Tensor Imaging-Fiber Tracking
Authors: Ohlerth Ann-Katrin , Bastiaanse Roelien , Negwer Chiara , Sollmann Nico , Schramm Severin , Schröder Axel , Krieg Sandro M.
Published: November 2021

Visualization of functionally significant subcortical white matter fibers is needed in neurosurgical procedures in order to avoid damage to the language network during resection. In an effort to achieve this, positive cortical points revealed during preoperative language mapping with navigated transcranial magnetic stimulation (nTMS) can be employed as regions of interest (ROIs) for diffusion tensor imaging (DTI) fiber tracking. However, the effect that the use of different language tasks has on nTMS mapping and subsequent DTI-fiber tracking remains unexplored. The visualization of ventral stream tracts with an assumed lexico-semantic role may especially benefit from ROIs delivered by the lexico-semantically demanding verb task, Action Naming. In a first step, bihemispheric nTMS language mapping was administered in 18 healthy participants using the standard task Object Naming and the novel task Action Naming to trigger verbs in a small sentence context. Cortical areas in which nTMS induced language errors were identified as language-positive cortical sites. In a second step, nTMS-based DTI-fiber tracking was conducted using solely these language-positive points as ROIs. The ability of the two tasks’ ROIs to visualize the dorsal tracts Arcuate Fascicle and Superior Longitudinal Fascicle, the ventral tracts Inferior Longitudinal Fascicle, Uncinate Fascicle, and Inferior Fronto-Occipital Fascicle, the speech-articulatory Cortico-Nuclear Tract, and interhemispheric commissural fibers was compared in both hemispheres. In the left hemisphere, ROIs of Action Naming led to a significantly higher fraction of overall visualized tracts, specifically in the ventral stream’s Inferior Fronto-Occipital and Inferior Longitudinal Fascicle. No difference was found between tracking with Action Naming vs. Object Naming seeds for dorsal stream tracts, neither for the speech-articulatory tract nor the inter-hemispheric connections. While the two tasks appeared equally demanding for phonological-articulatory processes, ROI seeding through the task Action Naming seemed to better visualize lexico-semantic tracts in the ventral stream. This distinction was not evident in the right hemisphere. However, the distribution of tracts exposed was, overall, mirrored relative to those in the left hemisphere network. In presurgical practice, mapping and tracking of language pathways may profit from these findings and should consider inclusion of the Action Naming task, particularly for lesions in ventral subcortical regions.
Involvement of Visual Mismatch Negativity in Access Processing to Visual Awareness
Authors: Kurita Yuki , Urakawa Tomokazu , Araki Osamu
Published: November 2021

Psychophysiological studies with electroencephalography, focusing on the dynamical aspect of neural correlate of consciousness, reported that visual awareness negativity and P3 enhancement are observed at a latency, 200–300 ms after the visual stimulus onset, when the visual stimulus is consciously perceived. However, access processing to visual awareness (APVA) immediately before conscious perception still remains at the earlier stage of visual sensory processing, though there is little known regarding this subject. The present study hypothesized that visual mismatch negativity (vMMN), which reflects automatic change detection at a latency of 130–250 ms, might be involved in the APVA. In a previous study, vMMN was reported to be evoked by the deviant stimulus that is not consciously perceived in binocular rivalry. To clarify whether the visual change detection affects APVA, we conducted a modified experiment of oddball paradigm on binocular rivalry. The results showed a significant correlation between enhancement of vMMN amplitude and facilitation of perceptual alternation when the unconscious deviant was presented. This implies that vMMN is relevant to the APVA, which is a novel role of vMMN. In early visual processing, the attentional mechanism associated with vMMN is suggested to play an important role in unconscious neural processing at an earlier stage of visual awareness.
Improving Motor Imagery-Based Brain-Computer Interface Performance Based on Sensory Stimulation Training: An Approach Focused on Poorly Performing Users
Authors: Park Sangin , Ha Jihyeon , Kim Da-Hye , Kim Laehyun
Published: November 2021

The motor imagery (MI)-based brain-computer interface (BCI) is an intuitive interface that provides control over computer applications directly from brain activity. However, it has shown poor performance compared to other BCI systems such as P300 and SSVEP BCI. Thus, this study aimed to improve MI-BCI performance by training participants in MI with the help of sensory inputs from tangible objects (i.e., hard and rough balls), with a focus on poorly performing users. The proposed method is a hybrid of training and imagery, combining motor execution and somatosensory sensation from a ball-type stimulus. Fourteen healthy participants participated in the somatosensory-motor imagery (SMI) experiments (within-subject design) involving EEG data classification with a three-class system (signaling with left hand, right hand, or right foot). In the scenario of controlling a remote robot to move it to the target point, the participants performed MI when faced with a three-way intersection. The SMI condition had a better classification performance than did the MI condition, achieving a 68.88% classification performance averaged over all participants, which was 6.59% larger than that in the MI condition (p < 0.05). In poor performers, the classification performance in SMI was 10.73% larger than in the MI condition (62.18% vs. 51.45%). However, good performers showed a slight performance decrement (0.86%) in the SMI condition compared to the MI condition (80.93% vs. 81.79%). Combining the brain signals from the motor and somatosensory cortex, the proposed hybrid MI-BCI system demonstrated improved classification performance, this phenomenon was predominant in poor performers (eight out of nine subjects). Hybrid MI-BCI systems may significantly contribute to reducing the proportion of BCI-inefficiency users and closing the performance gap with other BCI systems.
Imaging Features of Hepatocellular Carcinoma With Bile Duct Tumor Thrombus: A Multicenter Study
Authors: Wu Jun-Yi , Huang Li-Ming , Bai Yan-Nan , Wu Jia-Yi , Wei Yong-Gang , Zhang Zhi-Bo , Yan Mao-Lin
Published: November 2021

Objectives

There are still challenging problems in diagnosis of hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) before operation. This study aimed to analyze the imaging features of HCC with B1–B3 BDTT.

Materials and Methods

The clinicopathological data and imaging findings of 30 HCC patients with B1–B3 BDTT from three high-volume institutions were retrospectively reviewed. A total of 631 patients without BDTT who were randomly collected from each of the enrolled centers were recorded as the control group to analyze the differences in clinicopathological characteristics and imaging features between the two groups. A total of 453 HCC patients who underwent surgical treatment in the three institutions from January 2020 to December 2020 were collected for a blinded reading test as the validation group.

Results

HCC patients with B1–B3 BDTT had more advanced tumor stages and adverse clinicopathological features. HCC lesions were detected in all patients, and intrahepatic bile duct dilation was observed in 28 (93.3%) patients with B1–B3 BDTT and 9 (1.43%) patients in HCC without BDTT. The intrahepatic bile duct dilation showed no enhancement at hepatic arterial phase (HAP) and no progressively delayed enhancement at portal venous phase (PVP), but it was more obvious at PVP on CT. In the reports of the 30 HCC patients with B1–B3 BDTT generated for the image when the scan was done, BDTT was observed in all 13 B3 patients and 3 of 12 B2 patients, but none of the 5 B1 patients. Fourteen patients were misdiagnosed before surgery. However, when using intrahepatic bile duct dilation in HCC patients as a potential biomarker for BDTT diagnosis, the sensitivity and specificity for BDTT diagnosis were 93.33% and 98.57%, respectively. The blinded reading test showed that intrahepatic bile duct dilation in CT and MRI scans could be for separating HCC patients with B1–B3 BDTT from HCC patients without BDTT.

Conclusions

The HCC lesions and intrahepatic bile duct dilation on CT or MRI scans are imaging features of HCC with BDTT, which might facilitate the early diagnosis of B1–B3 BDTT.
Clinical Value of Machine Learning-Based Ultrasomics in Preoperative Differentiation Between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: A Multicenter Study
Authors: Ren Shanshan , Li Qian , Liu Shunhua , Qi Qinghua , Duan Shaobo , Mao Bing , Li Xin , Wu Yuejin , Zhang Lianzhong
Published: November 2021

Objective

This study aims to explore the clinical value of machine learning-based ultrasomics in the preoperative noninvasive differentiation between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).

Methods

The clinical data and ultrasonic images of 226 patients from three hospitals were retrospectively collected and divided into training set (n = 149), test set (n = 38), and independent validation set (n = 39). Manual segmentation of tumor lesion was performed with ITK-SNAP, the ultrasomics features were extracted by the pyradiomics, and ultrasomics signatures were generated using variance filtering and lasso regression. The prediction models for preoperative differentiation between HCC and ICC were established by using support vector machine (SVM). The performance of the three models was evaluated by the area under curve (AUC), sensitivity, specificity, and accuracy.

Results

The ultrasomics signatures extracted from the grayscale ultrasound images could successfully differentiate between HCC and ICC (p < 0.05). The combined model had a better performance than either the clinical model or the ultrasomics model. In addition to stability, the combined model also had a stronger generalization ability (p < 0.05). The AUC (along with 95% CI), sensitivity, specificity, and accuracy of the combined model on the test set and the independent validation set were 0.936 (0.806–0.989), 0.900, 0.857, 0.868, and 0.874 (0.733–0.961), 0.889, 0.867, and 0.872, respectively.

Conclusion

The ultrasomics signatures could facilitate the preoperative noninvasive differentiation between HCC and ICC. The combined model integrating ultrasomics signatures and clinical features had a higher clinical value and a stronger generalization ability.