bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantification of Fat Metaplasia in the Sacroiliac Joints of Patients With Axial Spondyloarthritis by Chemical Shift-Encoded MRI: A Diagnostic Trial
Authors: Liu Dong , Lin Churong , Liu Budian , Qi Jun , Wen Huiquan , Tu Liudan , Wei Qiujing , Kong Qingcong , Xie Ya , Gu Jieruo
Published: January 2022

Objective

To study the diagnostic performance of chemical shift-encoded MRI (CSE-MRI) in the diagnosis of axial spondyloarthritis (axSpA).

Methods

CSE-MRI images were acquired for consecutive patients complaining of back pain as well as healthy volunteers. Proton density fat fraction (PDFF) values were measured independently by two readers. Diagnostic performance of CSE-MRI was analyzed by sensitivity analysis and ROC curve analysis. Logistic regression analysis was employed to investigate the risk factors of extensive fat deposition in the SIJs.

Results

A total of 52 r-axSpA patients, 37 nr-axSpA patients, 24 non-SpA patients and 34 healthy volunteers were included. Mean PDFF values in the SIJs of patients with r-axSpA and nr-axSpA (72.7% and 64.5%) were significantly higher than non-SpA patients and healthy volunteers (56.0% and 57.6%) (p<0.001). By defining extensive fat deposition in the SIJs as ≥8 ROIs with PDFF values over 70%, its sensitivity and specificity in diagnosing axSpA reached 72.47% and 86.21%%. By joining bone marrow edema (BME) with ≥8 ROIs (PDFF>70%), 22 (24.71%) and 23 (25.84%) more axSpA patients were classified as SIJ MRI (+) by reader 1 and 2, but specificities decreased by 15.52% and 10.34%. Multivariate logistic regression analysis confirmed longer disease duration as the independent risk factor of extensive fat deposition in SIJs (OR=1.15, 95%CI[1.03, 1.32]), while bDMARDs medication was a protective factor (OR=0.15, 95%CI[0.04, 0.51]).

Conclusion

CSE-MRI is a reliable tool to quantitively assess the fat metaplasia in the SIJs of axSpA patients. Extensive fat deposition in the SIJs could add incremental diagnostic value to BME, but at the cost of decreased specificities.
Dysregulation of SAA1, TUBA8 and Monocytes Are Key Factors in Ankylosing Spondylitis With Femoral Head Necrosis
Authors: Jiang Jie , Zhan Xinli , Liang Tuo , Chen Liyi , Huang Shengsheng , Sun Xuhua , Jiang Wenyong , Chen Jiarui , Chen Tianyou , Li Hao , Yao Yuanlin , Wu Shaofeng , Zhu Jichong , Liu Chong
Published: January 2022

Introduction

The mechanism of ankylosing spondylitis with femoral head necrosis is unknown, and our study aimed investigate the effects of genetic and immune cell dysregulation on ankylosing spondylitis.

Materials and Methods

The protein expression of all ligaments in ankylosing spondylitis with femoral head necrosis was obtained using label-free quantification protein park analysis of six pairs of specimens. The possible pathogenesis was explored using differential protein analysis, weighted gene co-expression network analysis, recording intersections with hypoxia-related genes, immune cell correlation analysis, and drug sensitivity analysis. Finally, routine blood test data from 502 AS and 162 healthy controls were collected to examine immune cell differential analysis.

Results

SAA1 and TUBA8 were significantly expressed differentially in these two groups and correlated quite strongly with macrophage M0 and resting mast cells (P < 0.05). Routine blood data showed that monocytes were significantly more expressed in AS than in healthy controls (P < 0.05). SAA1 and TUBA8 were closely related to the sensitivity of various drugs, which might lead to altered drug sensitivity.

Conclusion

Dysregulation of SAA1, TUBA8 and monocytes are key factors in ankylosing spondylitis with femoral head necrosis.
Surgical Trauma in Mice Modifies the Content of Circulating Extracellular Vesicles
Authors: Mkrtchian Souren , Ebberyd Anette , Veerman Rosanne E. , Méndez-Lago María , Gabrielsson Susanne , Eriksson Lars I. , Gómez-Galán Marta
Published: January 2022

Surgical interventions rapidly trigger a cascade of molecular, cellular, and neural signaling responses that ultimately reach remote organs, including the brain. Using a mouse model of orthopedic surgery, we have previously demonstrated hippocampal metabolic, structural, and functional changes associated with cognitive impairment. However, the nature of the underlying signals responsible for such periphery-to-brain communication remains hitherto elusive. Here we present the first exploratory study that tests the hypothesis of extracellular vesicles (EVs) as potential mediators carrying information from the injured tissue to the distal organs including the brain. The primary goal was to investigate whether the cargo of circulating EVs after surgery can undergo quantitative changes that could potentially trigger phenotypic modifications in the target tissues. EVs were isolated from the serum of the mice subjected to a tibia surgery after 6, 24, and 72 h, and the proteome and miRNAome were investigated using mass spectrometry and RNA-seq approaches. We found substantial differential expression of proteins and miRNAs starting at 6 h post-surgery and peaking at 24 h. Interestingly, one of the up-regulated proteins at 24 h was α-synuclein, a pathogenic hallmark of certain neurodegenerative syndromes. Analysis of miRNA target mRNA and corresponding biological pathways indicate the potential of post-surgery EVs to modify the extracellular matrix of the recipient cells and regulate metabolic processes including fatty acid metabolism. We conclude that surgery alters the cargo of circulating EVs in the blood, and our results suggest EVs as potential systemic signal carriers mediating remote effects of surgery on the brain.
Bioaccumulation of PCBs, OCPs and PBDEs in Marine Mammals From West Antarctica
Authors: Khairy Mohammed , Brault Emily , Dickhut Rebecca , Harding Karin C. , Harkonen Tero , Karlsson Olle , Lehnert Kristine , Teilmann Jonas , Lohmann Rainer
Published: January 2022

Graphical Abstract

POPs in Antarctic Mammals.
Assessments of Nitrate Budgets in the Yellow Sea Based on a 3D Physical-Biogeochemical Coupled Model
Authors: Tak Yong-Jin , Cho Yang-Ki , Hwang Jeomshik , Kim Yong-Yub
Published: January 2022

Nitrate (NO3–) plays an important role in ecosystems and aquaculture in the Yellow Sea (YS). Sparse observational data suggest that ocean currents and nitrification are crucial to NO3– flux in the YS; however, a quantitative assessment of these fluxes has not yet been performed. This study investigates seasonal and spatial variations in NO3– flux via currents and biological processes in the YS from 2006 to 2019 using a physical-biogeochemical coupled model. The model results show that the current-driven fluxes exceeded biological processes in the eastern and central regions of the YS, unlike in the western and northern regions. Advection of NO3– in the YS is mainly driven by cyclonic circulation in summer and fall, and anticyclonic circulation in spring and winter. The Subei Coastal Current along the coast of China plays a primary role in net advective influx of NO3– to the YS year round. The NO3– influx by the Yellow Sea Warm Current along the lower layer of the southcentral YS is offset by outflux through wind-driven surface currents in winter. The southward movements of the Yellow Sea Bottom Cold Water in summer and the Korean Coastal Current in winter are major NO3– outfluxes to the East China Sea. In terms of biological processes, NO3– is mainly consumed by phytoplankton during the spring bloom and supplied through organic matter decomposition and nitrification. Net supply of NO3– by biological processes was the greatest in the southcentral YS where the Yellow Sea Bottom Cold Water is present.
Development of High-Entropy Alloy Coating by Additive Technology
Authors: Kocsis Bence , Gulyás Gábor , Varga Lajos Károly
Published: January 2022

In this research study, various additively fabricated coatings and bulk 3D-printed parts were prepared, using the mechanical and corrosion-resistant properties of CrMnFeCoNi (Cantor alloy) and AlCrMnFeNi high-entropy alloys (HEAs). The coatings were applied to an EN 1.0038 carbon steel substrate using direct metal laser sintering. We attempted to optimize the 3D printing parameters of HEA alloys. The effect of volumetric energy density (VED) on the microstructure was investigated by scanning electron microscopy. We also examined the change of relative concentration of alloys in the direction of 3D printing (z-axis) as well as the volumetric failures (cracks and gaps). Standard salt spray tests were performed to test the corrosion resistance of various coatings after 3D printing. The use of both raw materials applied as thick films was successful; they retained their corrosion-resistant properties even with a change in their composition. Regarding the crystal structure, no difference was found between the base material and the material applied as a coating on the basis of X-ray diffraction investigations. Bulk HEA printing experiments need further optimization concerning their structural integrity and density in the case of the Cantor alloy. Bulk 3D printing experiments of the AlCrMnFeNi alloy did not yield satisfactory results because of the formation of dendritic microstructure and brittle BCC phase, and the residual internal stress resulted in part distortion and improper printing.
Numerical Analysis of Thermal Shock Cracking Behaviors of Ceramics Based on the Force-Heat Equivalence Energy Density Principle
Authors: Li Dingyu , Pang Yong , Lu Tao , Liu Zhongshuai , Chen Shiwei
Published: January 2022

Thermal shock is one of the main causes for the fracture of ceramic materials due to their inherent brittleness. Aiming to explore the mechanism of thermal shock cracking behavior of ceramics under different thermal shock conditions, a novel temperature-dependent failure criterion of thermal shock fracture of the ceramic materials was deduced based on the force-heat equivalence energy density principle. Combining this failure criterion and the finite element method, the thermal shock cracking behaviors of the thin circular and rectangular ceramic slabs under different thermal shock initial temperature were simulated. Results show that the morphology, periodicity, hierarchy, and number of thermal shock cracks obtained by numerical simulation are in good agreement with the experimental results. These essential characteristics verify the validity of the temperature-dependent failure criterion for thermal shock fracture. Furthermore, the strain energy of tension produced by thermal shock is proved to be the dominated mechanism for thermal shock-induced fracture.
Deep Learning Algorithms for the Prediction of Posttransplant Renal Function in Deceased-Donor Kidney Recipients: A Preliminary Study Based on Pretransplant Biopsy
Authors: Luo You , Liang Jing , Hu Xiao , Tang Zuofu , Zhang Jinhua , Han Lanqing , Dong Zhanwen , Deng Weiming , Miao Bin , Ren Yong , Na Ning
Published: January 2022

Background

Posttransplant renal function is critically important for kidney transplant recipients. Accurate prediction of graft function would greatly help in deciding acceptance or discard of allocated kidneys.

Methods

: Whole-slide images (WSIs) of H&E-stained donor kidney biopsies at × 200 magnification between January 2015 and December 2019 were collected. The clinical characteristics of each donor and corresponding recipient were retrieved. Graft function was indexed with a stable estimated glomerular filtration rate (eGFR) and reduced graft function (RGF). We used convolutional neural network (CNN)-based models, such as EfficientNet-B5, Inception-V3, and VGG19 for the prediction of these two outcomes.

Results

In total, 219 recipients with H&E-stained slides of the donor kidneys were included for analysis [biopsies from standard criteria donor (SCD)/expanded criteria donor (ECD) was 191/28]. The results showed distinct improvements in the prediction performance of the deep learning algorithm plus the clinical characteristics model. The EfficientNet-B5 plus clinical data model showed the lowest mean absolute error (MAE) and root mean square error (RMSE). Compared with the clinical data model, the area under the receiver operating characteristic (ROC) curve (AUC) of the clinical data plus image model for eGFR classification increased from 0.69 to 0.83. In addition, the predictive performance for RGF increased from 0.66 to 0.80. Gradient-weighted class activation mappings (Grad-CAMs) showed that the models localized the areas of the tubules and interstitium near the glomeruli, which were discriminative features for RGF.

Conclusion

Our results preliminarily show that deep learning for formalin-fixed paraffin-embedded H&E-stained WSIs improves graft function prediction accuracy for deceased-donor kidney transplant recipients.
In vivo Gene Therapy to the Liver and Nervous System: Promises and Challenges
Authors: Cantore Alessio , Fraldi Alessandro , Meneghini Vasco , Gritti Angela
Published: January 2022

In vivo genetic engineering has recently shown remarkable potential as a novel effective treatment for an ever-growing number of diseases, as also witnessed by the recent marketing authorization of several in vivo gene therapy products. In vivo genetic engineering comprises both viral vector-mediated gene transfer and the more recently developed genome/epigenome editing strategies, as long as they are directly administered to patients. Here we first review the most advanced in vivo gene therapies that are commercially available or in clinical development. We then highlight the major challenges to be overcome to fully and broadly exploit in vivo gene therapies as novel medicines, discussing some of the approaches that are being taken to address them, with a focus on the nervous system and liver taken as paradigmatic examples.
Metabolomic Alterations in the Tear Fluids of Patients With Superior Limbic Keratoconjunctivitis
Authors: Zong Yan , Cheng Chao , Li Kunke , Xue Ran , Chen Ziyan , Liu Xiuping , Wu Kaili
Published: January 2022

Purpose

Superior limbic keratoconjunctivitis (SLK) is a bilateral, chronic inflammatory disease that recurs for up to several years; however, the fundamental processes involved in its pathogenic mechanisms remain unknown. We aimed to investigate the metabolomic alterations in the tear fluids of patients with superior limbic keratoconjunctivitis (SLK) compared with those of healthy volunteers (Ctrl group).

Methods

We performed a cross-sectional study involving 42 subjects. Tear fluid was taken from one eye of 24 SLK patients (40.13 ± 14.55 years, 83.33% female) and 18 healthy volunteers (Ctrl, 39.89 ± 9.2 years, 72.22% female) using Schirmer strips. After the liquid extraction of tear metabolites, samples were infused into the QE HFX Orbitrap mass spectrometer in both positive and negative ion mode. Metabolites were quantitatively analyzed and matched with entries in the HMDB database. Metabolic differences between the SLK group and the control group were identified based on multivariate statistical analysis. Open database sources, including SMPDB and MetaboAnalyst, were used to identify metabolic pathways.

Results

Among 179 metabolites retained for annotation, 133 metabolites were finally identified, among which 50 were found to be significantly changed in SLK patients. Of these 50 metabolites, 31 metabolites significantly increased and 19 metabolites decreased in SLK patients. The altered metabolites are mainly involved in α linolenic acid and linoleic acid metabolism, ketone body metabolism, butyrate metabolism, mitochondrial electron transport chain, carnitine synthesis, and so on. The most significantly changed pathway was linoleic acid metabolism. To explore the utility of tear biomarkers, a model combining 9 metabolites (phenol, ethyl glucuronide, eicosapentaenoic acid, 12-keto-leukotriene B4, linoleic acid, hypoxanthine, triethanolamine, 1-nitrohexane, and terephthalic acid) was selected as a candidate biomarker.

Conclusion

The results reveal that SLK has a specific metabolomic profile, of which some key elements can serve as potential biomarkers of SLK for diagnostic and prognostic purposes. The findings of this study are novel and provide a basis for further investigations of the mechanism of SLK.
Development and Validation of a Personalized Prognostic Prediction Model for Patients With Spinal Cord Astrocytoma
Authors: Yang Sheng , Yang Xun , Wang Huiwen , Gu Yuelin , Feng Jingjing , Qin Xianfeng , Feng Chaobo , Li Yufeng , Liu Lijun , Fan Guoxin , Liao Xiang , He Shisheng
Published: January 2022

Background

The study aimed to investigate the prognostic factors of spinal cord astrocytoma (SCA) and establish a nomogram prognostic model for the management of patients with SCA.

Methods

Patients diagnosed with SCA between 1975 and 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training and testing datasets (7:3). The primary outcomes of this study were overall survival (OS) and cancer-specific survival (CSS). Cox hazard proportional regression model was used to identify the prognostic factors of patients with SCA in the training dataset and feature importance was obtained. Based on the independent prognostic factors, nomograms were established for prognostic prediction. Calibration curves, concordance index (C-index), and time-dependent receiver operating characteristic (ROC) curves were used to evaluate the calibration and discrimination of the nomogram model, while Kaplan-Meier (KM) survival curves and decision curve analyses (DCA) were used to evaluate the clinical utility. Web-based online calculators were further developed to achieve clinical practicability.

Results

A total of 818 patients with SCA were included in this study, with an average age of 30.84 ± 21.97 years and an average follow-up time of 117.57 ± 113.51 months. Cox regression indicated that primary site surgery, age, insurance, histologic type, tumor extension, WHO grade, chemotherapy, and post-operation radiotherapy (PRT) were independent prognostic factors for OS. While primary site surgery, insurance, tumor extension, PRT, histologic type, WHO grade, and chemotherapy were independent prognostic factors for CSS. For OS prediction, the calibration curves in the training and testing dataset illustrated good calibration, with C-indexes of 0.783 and 0.769. The area under the curves (AUCs) of 5-year survival prediction were 0.82 and 0.843, while 10-year survival predictions were 0.849 and 0.881, for training and testing datasets, respectively. Moreover, the DCA demonstrated good clinical net benefit. The prediction performances of nomograms were verified to be superior to that of single indicators, and the prediction performance of nomograms for CSS is also excellent.

Conclusions

Nomograms for patients with SCA prognosis prediction demonstrated good calibration, discrimination, and clinical utility. This result might benefit clinical decision-making and patient management for SCA. Before further use, more extensive external validation is required for the established web-based online calculators.
Lung Adenocarcinoma Cells Promote Self-Migration and Self-Invasion by Activating Neutrophils to Upregulate Notch3 Expression of Cancer Cells
Authors: Peng Weidong , Sheng Youjing , Xiao Han , Ye Yuanzi , Kwantwi Louis Boafo , Cheng Lanqing , Wang Yuanchong , Xu Jiegou , Wu Qiang
Published: January 2022

Background: Invasion and migration of cancer cells play a key role in lung cancer progression and metastasis. Tumor-associated neutrophils (TANs) are related to poor prognosis in many types of cancer. However, the role of TANs in lung cancer is controversial. In this study, we investigated the effect of TANs on the invasion and migration of lung adenocarcinoma.

Methods: Immunohistochemistry was performed to detect the density of infiltrating TANs and the expression of Notch3 in 100 lung adenocarcinoma tissues. Flow cytometry was used to observe the viability of neutrophils, which were isolated from healthy peripheral blood and then exposed to the supernatant of cultured lung adenocarcinoma cell lines. After treating with tumor-associated neutrophils culture supernatant, NeuCS (supernatant of cultured neutrophils), tumor cells culture supernatant, Medium (serum-free medium), respectively, the migration and invasion of the lung cancer cells before and after transfected by si-Notch3 were detected by transwell assay and wound healing assay. Kaplan-Meier plotter (http://kmplot.com/analysis/index.php?p) was used to analyze the prognostic role of the density of TANs on lung adenocarcinoma and TIMER ((http://cistrome.dfci.harvard.edu/TIMER/) was used to detect the expression of Notch3 on lung adenocarcinoma.

Results: The infiltration of TANs was observed in the parenchyma and stroma of the lung adenocarcinoma, the density of TANs was positively related to the TNM stage and negatively related to the differentiation and prognosis. Notch3 expression of cancer cells was negatively related to the tumor differentiation and prognosis. Compared to quiescent neutrophils, the viability of TCCS-activated neutrophils was enhanced. Both migration and invasion of A549 and PC9 cells were significantly promoted by TANs, while after knocking down Notch3, the migration and invasion of the cancer cells were not affected by TANs. Bioinformatics analysis showed that the density of TANs and the expression of Notch3 were related to the poor prognosis.

Conclusion: The results indicated that lung adenocarcinoma cells promote self-invasion and self-migration by activating neutrophils to upregulate the Notch3 expression of cancer cells. The density of infiltrating TANs may be a novel marker for the poor prognosis of lung adenocarcinoma. Targeting TANs might be a potential therapeutic strategy for lung cancer treatment.
The Tissue Distribution of SARS-CoV-2 in Transgenic Mice With Inducible Ubiquitous Expression of hACE2
Authors: Dolskiy Alexander A. , Gudymo Andrey S. , Taranov Oleg S. , Grishchenko Irina V. , Shitik Ekaterina M. , Prokopov Dmitry Yu , Soldatov Vladislav O. , Sobolevskaya Elvira V. , Bodnev Sergey A. , Danilchenko Natalia V. , Moiseeva Anastasia A. , Torzhkova Polina Y. , Bulanovich Yulia A. , Onhonova Galina S. , Ivleva Elena K. , Kubekina Marina V. , Belykh Andrey E. , Tregubchak Tatiana V. , Ryzhikov Alexander B. , Gavrilova Elena V. , Maksyutov Rinat A. , Deykin Alexey V. , Yudkin Dmitry V.
Published: January 2022

The novel coronavirus disease COVID-19 has become one of the most socially significant infections. One of the main models for COVID-19 pathogenesis study and anti-COVID-19 drug development is laboratory animals sensitive to the virus. Herein, we report SARS-CoV-2 infection in novel transgenic mice conditionally expressing human ACE2 (hACE2), with a focus on viral distribution after intranasal inoculation. Transgenic mice carrying hACE2 under the floxed STOP cassette [(hACE2-LoxP(STOP)] were mated with two types of Cre-ERT2 strains (UBC-Cre and Rosa-Cre). The resulting offspring with temporal control of transgene expression were treated with tamoxifen to induce the removal of the floxed STOP cassette, which prevented hACE2 expression. Before and after intranasal inoculation, the mice were weighed and clinically examined. On Days 5 and 10, the mice were sacrificed for isolation of internal organs and the further assessment of SARS-CoV-2 distribution. Intranasal SARS-CoV-2 inoculation in hACE2-LoxP(STOP)×UBC-Cre offspring resulted in weight loss and death in 6 out of 8 mice. Immunostaining and focus formation assays revealed the most significant viral load in the lung, brain, heart and intestine samples. In contrast, hACE2-LoxP(STOP) × Rosa-Cre offspring easily tolerated the infection, and SARS-CoV-2 was detected only in the brain and lungs, whereas other studied tissues had null or negligible levels of the virus. Histological examination revealed severe alterations in the lungs, and mild changes were observed in the brain tissues. Notably, no changes were observed in mice without tamoxifen treatment. Thus, this novel murine model with the Cre-dependent activation of hACE2 provides a useful and safe tool for COVID-19 studies.
Which Exercise Interventions Can Most Effectively Improve Reactive Balance in Older Adults? A Systematic Review and Network Meta-Analysis
Authors: Kim Youngwook , Vakula Michael N. , Bolton David A. E. , Dakin Christopher J. , Thompson Brennan J. , Slocum Timothy A. , Teramoto Masaru , Bressel Eadric
Published: January 2022

Background

Reactive balance is the last line of defense to prevent a fall when the body loses stability, and beneficial effects of various exercise-based interventions on reactive balance in older adults have been reported. However, their pooled evidence on the relative effects has yet to be described.

Objective

To review and evaluate the comparative effectiveness of various exercise-based interventions on reactive balance in older adults.

Methods

Nine electronic databases and reference lists were searched from inception to August 2021. Eligibility criteria according to PICOS criteria were as follows: (1) population: older adults with the mean age of 65 years or above; (2) intervention and comparison: at least two distinct exercise interventions or one exercise intervention with a no-exercise controlled intervention (NE) compared in each trial; (3) outcome: at least one measure of reactive balance; (4) study: randomized controlled trial. The main network meta-analysis was performed on data from the entire older adult population, involving all clinical conditions as well as healthy older adults. Subgroup analyses stratified by characteristics of participants (healthy only) and reactive balance outcomes (simulated slip or trip while walking, simulated forward falls, being pushed or pulled, and movable platform) were also conducted.

Results

Thirty-nine RCTs (n = 1388) investigating 17 different types of exercise interventions were included in the network meta-analysis. Reactive balance training as a single intervention presented the highest probability (surface under the cumulative ranking (SUCRA) score) of being the best intervention for improving reactive balance and the greatest relative effects vs. NE in the entire sample involving all clinical conditions [SUCRA = 0.9; mean difference (95% Credible Interval): 2.7 (1.0 to 4.3)]. The results were not affected by characteristics of participants (i.e., healthy older adults only) or reactive balance outcomes.

Summary/Conclusion

The findings from the NMA suggest that a task-specific reactive balance exercise could be the optimal intervention for improving reactive balance in older adults, and power training can be considered as a secondary training exercise.
Intermediate Effects of Body Mass Index and C-Reactive Protein on the Serum Cotinine- Leukocyte Telomere Length Association
Authors: Gao Xiao , Kong Yawei , Li Shengxu , Dong Shiqiu , Huang Xinyu , Qi Deyu , Zhang Tao , Yan Yinkun , Chen Wei
Published: January 2022

We aimed to examine the association between serum cotinine and leukocyte telomere length (LTL) and the intermediate effects of body mass index (BMI) and C-reactive protein (CRP) on modulating the association. This study included 4,047 adults from the 1999 to 2002 National Health and Nutrition Examination Survey. In the combined sample, after adjusting for age, race, sex, physical activity, and alcohol use, the total effect of serum cotinine on LTL was significant (standardized regression coefficient, β = −0.049, p = 0.001) without BMI and CRP included in the model. With inclusion of BMI but without CRP in the model, the direct effect of cotinine on LTL in its absolute value increased to β = −0.053 (p < 0.001), and the suppression effect of BMI was estimated at 8.8%. With inclusion of CRP but without BMI in the model, the direct effect of cotinine on LTL in its absolute value decreased to β = −0.040 (p = 0.008), and the mediation effect of CRP was estimated at 16.9%. With inclusion of both BMI and CRP in the model, BMI and CRP still had significant suppression and mediation effects, respectively, on the cotinine-LTL association. These findings suggest that weight and inflammation have different roles in the inverse association between serum cotinine and LTL.
Combined fMRI Region- and Network-Analysis Reveal New Insights of Top-Down Modulation of Bottom-Up Processes in Auditory Laterality
Authors: Kazimierczak Katarzyna , Craven Alexander R. , Ersland Lars , Specht Karsten , Dumitru Magda L. , Sandøy Lydia B. , Hugdahl Kenneth
Published: January 2022

Dichotic listening along with the right-ear advantage (REA) has been a standard method of investigating auditory laterality ever since it was first introduced into neuropsychology in the early 1960s. Beginning in the 1980s, authors reported that it was possible to modulate the bottom-up driven perceptual REA by instructing subjects to selectively attend to and report only from the right or left ear. In the present study, we investigated neuronal correlates of both the bottom-up and top-down modulation of the REA through two fMRI analysis approaches: a traditional region approach and a network connectivity approach. Blood-Oxygenation-Level-Dependent (BOLD) fMRI data were acquired while subjects performed the standard forced-attention paradigm. We asked two questions, could the behavioral REA be replicated in unique brain markers, and second if the profound instruction-induced modulation of the REA found in behavioral data would correspond to a similar modulation of brain activation, both region- and network-specific modulations. The subjects were 70 healthy adult right-handers, about half men and half women. fMRI data were acquired in a 3T MR scanner, and the behavioral results replicated previous findings with a REA in the non-forced (NF) and forced-right (FR) conditions, and a tendency for a left-ear advantage (LEA) in the FL-condition. The fMRI data showed unique activations in the speech perception areas of the left temporal lobe when directly contrasted with activations in the homologous right side. However, there were no remaining unique activations when the FR- and FL-conditions were contrasted against each other, and with the NF-condition, using a conservative significance thresholding. The fMRI results are conceptualized within a network connectivity frame of reference, especially with reference to the extrinsic mode network (EMN). The EMN is a generalized task-positive network that is upregulated whenever the task demands exceed a certain threshold irrespective of the specifics and demands of the task. This could explain the similarity of activations for the FR- and FL-conditions, despite the clear differences in behavior.
High-Frequency Head Impact Disrupts Hippocampal Neural Ensemble Dynamics
Authors: Chapman Daniel P. , Sloley Stephanie S. , Caccavano Adam P. , Vicini Stefano , Burns Mark P.
Published: January 2022

We have recently shown that the cognitive impairments in a mouse model of high-frequency head impact (HFHI) are caused by chronic changes to synaptic physiology. To better understand these synaptic changes occurring after repeat head impact, we used Thy1-GcCAMP6f mice to study intracellular and intercellular calcium dynamics and neuronal ensembles in HFHI mice. We performed simultaneous calcium imaging and local field potential (LFP) recordings of the CA1 field during an early-LTP paradigm in acute hippocampal slice preparations 24 h post-impact. As previously reported, HFHI causes a decrease in early-LTP in the absence of any shift in the input-output curve. Calcium analytics revealed that HFHI hippocampal slices have similar numbers of active ROIs, however, the number of calcium transients per ROI was significantly increased in HFHI slices. Ensembles consist of coordinated activity between groups of active ROIs. We exposed the CA1 ensemble to Schaffer-collateral stimulation in an abbreviated LTP paradigm and observed novel coordinated patterns of post stimulus calcium ensemble activity. HFHI ensembles displayed qualitatively similar patterns of post-stimulus ensemble activity to shams but showed significant changes in quantitative ensemble inactivation and reactivation. Previous in vivo and in vitro reports have shown that ensemble activity frequently occurs through a similar set of ROIs firing in a repeating fashion. HFHI slices showed a decrease in such coordinated firing patterns during post stimulus ensemble activity. The present study shows that HFHI alters synaptic activity and disrupts neuronal organization of the ensemble, providing further evidence of physiological synaptic adaptation occurring in the brain after a high frequency of non-pathological head impacts.
Metformin Alleviates Neuroinflammation Following Intracerebral Hemorrhage in Mice by Regulating Microglia/Macrophage Phenotype in a Gut Microbiota-Dependent Manner
Authors: Yu Xiaobo , Fu Xiongjie , Wu Xinyan , Tang Wenwen , Xu Lei , Hu Libin , Xu Chaoran , Zhou Hang , Zhou Guoyang , Li Jianru , Cao Shenglong , Liu Jiang , Yan Feng , Wang Lin , Liu Fuyi , Chen Gao
Published: January 2022

The gut microbiota plays a key role in regulating intracerebral hemorrhage (ICH)-induced neuroinflammation. The anti-neuroinflammatory effects of metformin (Met) have been reported in many central nervous system (CNS) diseases. However, whether Met regulates neuroinflammation through the gut microbiota in ICH-induced brain injury remains unknown. We found that Met treatment substantially alleviated neurological dysfunction and reduced neuroinflammation by inhibiting pro-inflammatory polarization of microglia/macrophages in mice with ICH. Moreover, Met treatment altered the microbiota composition and improved intestinal barrier function. The expression of lipopolysaccharide-binding protein (LBP), a biomarker of intestinal barrier damage, was also significantly reduced by Met treatment. Neuroinflammation was also potently ameliorated after the transplantation of fecal microbiota from Met-treated ICH mice. The neuroprotective effects of fecal microbiota transplantation (FMT) were similar to those of oral Met treatment. However, suppression of the gut microbiota negated the neuroprotective effects of Met in ICH mice. Therefore, Met is a promising therapeutic agent for neuroinflammation owing to ICH-induced imbalance of the gut microbiota.
Overtraining Syndrome as a Complex Systems Phenomenon
Authors: Armstrong Lawrence E. , Bergeron Michael F. , Lee Elaine C. , Mershon James E. , Armstrong Elizabeth M.
Published: January 2022

The phenomenon of reduced athletic performance following sustained, intense training (Overtraining Syndrome, and OTS) was first recognized more than 90 years ago. Although hundreds of scientific publications have focused on OTS, a definitive diagnosis, reliable biomarkers, and effective treatments remain unknown. The present review considers existing models of OTS, acknowledges the individualized and sport-specific nature of signs/symptoms, describes potential interacting predisposing factors, and proposes that OTS will be most effectively characterized and evaluated via the underlying complex biological systems. Complex systems in nature are not aptly characterized or successfully analyzed using the classic scientific method (i.e., simplifying complex problems into single variables in a search for cause-and-effect) because they result from myriad (often non-linear) concomitant interactions of multiple determinants. Thus, this review 1) proposes that OTS be viewed from the perspectives of complex systems and network physiology, 2) advocates for and recommends that techniques such as trans-omic analyses and machine learning be widely employed, and 3) proposes evidence-based areas for future OTS investigations, including concomitant multi-domain analyses incorporating brain neural networks, dysfunction of hypothalamic-pituitary-adrenal responses to training stress, the intestinal microbiota, immune factors, and low energy availability. Such an inclusive and modern approach will measurably help in prevention and management of OTS.
Characteristics of Brain White Matter Microstructure in HIV Male Patients With Primary Syphilis Co-Infection
Authors: Qi Yu , Li Rui-Li , Wang Yuan-Yuan , Wang Wei , Liu Xu-Ze , Liu Jing , Li Xing , Zhang Xiao-Dong , Yu Wen , Liu Jiao-Jiao , Guo Yi-Fan , Rao Bo , Li Hong-Jun
Published: January 2022

Purpose: To investigate the effect of syphilis infection on the microstructure of white matter (WM) in HIV-infected male patients using diffusion tensor imaging (DTI).

Methods: Twenty-seven HIV-infected male patients with current syphilis or a history of syphilis (HIV +/syphilis +), twenty-nine HIV-infected male patients without syphilis co-infection (HIV +/syphilis–), and twenty-nine healthy controls (HC) were enrolled. All participants received DTI, and all patients received comprehensive neuropsychological assessment. Tract-based spatial statistics (TBSS) was adopted to analyze the DTI measures: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Correlation analysis was conducted to investigate the relationships between DTI measures and cognitive performance.

Results: There were no significant differences in DTI measures between HIV+/syphilis– and HC. Compared with HC, lower FA was found in body of corpus callosum (BCC), splenium of corpus callosum (SCC), genu of corpus callosum (GCC), the bilateral anterior corona radiata (ACR), superior corona radiata (SCR), posterior corona radiata (PCR), and posterior thalamic radiation (PTR) in HIV+/syphilis+ (p < 0.05). Higher RD was found in BCC and SCC (p < 0.05). Compared with HIV+/syphilis–, lower scores were found in complex motor skills (CMS) in HIV+/syphilis+, lower FA was found in BCC, SCC, GCC, the bilateral ACR, SCR, PCR, PTR, cingulate gyrus (CGC), the right inferior fronto-occipital fasciculus (IFO), the retrolenticular part of internal capsule (RLIC), sagittal stratum (SS), external capsule (EC) in HIV+/syphilis+ (p < 0.01). Correlation analysis uncorrected for multiple comparisons showed there was a positive correlation between FA in GCC and CMS, FA in BCC, and CMS in HIV+/syphilis+.

Conclusions: Syphilis co-infection can have an additive or synergistic effect on the brain WM in HIV-infected subjects. HIV-infected patients without syphilis should be actively treated to avoid syphilis infection.
Efficacy of Anti-seizure Medications, Quinidine, and Ketogenic Diet Therapy for KCNT1-Related Epilepsy and Genotype-Efficacy Correlation Analysis
Authors: Lin Zehong , Sang Tian , Yang Ying , Wu Yuan , Dong Yan , Ji Taoyun , Zhang Yuehua , Wu Ye , Gao Kai , Jiang Yuwu
Published: January 2022

Aim

To evaluate the efficacy of anti-seizure medications (ASMs), quinidine, and ketogenic diet therapy (KDT) for KCNT1-related epilepsy and to explore genotype-efficacy correlations.

Methods

We collected the data for KCNT1-related epilepsy cases from our hospital's medical records and the literature. In total, 50 patients received quinidine, 23 received classical KDT, and 15 received ASMs; all ASM data were from our hospital owing to the lack of detailed ASM data in the literature. The efficacy rates (ERs) of the treatments were compared; an ER that reduced the number of seizures by ≥50% was considered positive. Efficacy according to genotype was also assessed.

Results

The ERs for the 30 patients at our hospital were 40, 26.7, 30, and 44.4% for all treatments, ASMs, quinidine, and KDT, respectively. For all patients (ours and those in previous reports), the overall ERs for quinidine and KDT were 26.0 and 43.5%, respectively (P = 0.135). The ERs for quinidine and KDT in functional domain variant-related epilepsy differed significantly (20.6 vs. 53.8%; P = 0.037).

Interpretation

KDT may be better at treating KCNT1-related epilepsy than quinidine; ASMs were the least effective. KDT is a viable treatment option for functional domain variant-related epilepsy.
Frailty Syndrome and Oxidative Stress as Possible Links Between Age-Related Hearing Loss and Alzheimer’s Disease
Authors: Alvarado Juan Carlos , Fuentes-Santamaría Verónica , Juiz José M.
Published: January 2022

As it is well known, a worldwide improvement in life expectancy has taken place. This has brought an increase in chronic pathologies associated with aging. Cardiovascular, musculoskeletal, psychiatric, and neurodegenerative conditions are common in elderly subjects. As far as neurodegenerative diseases are concerned dementias and particularly, Alzheimer’s disease (AD) occupy a central epidemiological position given their high prevalence and their profound negative impact on the quality of life and life expectancy. The amyloid cascade hypothesis partly explains the immediate cause of AD. However, limited therapeutical success based on this hypothesis suggests more complex remote mechanisms underlying its genesis and development. For instance, the strong association of AD with another irreversible neurodegenerative pathology, without curative treatment and complex etiology such as presbycusis, reaffirms the intricate nature of the etiopathogenesis of AD. Recently, oxidative stress and frailty syndrome have been proposed, independently, as key factors underlying the onset and/or development of AD and presbycusis. Therefore, the present review summarizes recent findings about the etiology of the above-mentioned neurodegenerative diseases, providing a critical view of the possible interplay among oxidative stress, frailty syndrome, AD and presbycusis, that may help to unravel the common mechanisms shared by both pathologies. This knowledge would help to design new possible therapeutic strategies that in turn, will improve the quality of life of these patients.
Effect of Gum Tragacanth-Sodium Alginate Active Coatings Incorporated With Epigallocatechin Gallate and Lysozyme on the Quality of Large Yellow Croaker at Superchilling Condition
Authors: Pei Juxin , Mei Jun , Yu Huijie , Qiu Weiqiang , Xie Jing
Published: January 2022

This research was done to investigate the synergistic interactions of the gum tragacanth (GT)–sodium alginate (SA) active coatings, incorporated with epigallocatechin gallate and lysozyme, on the quality of large yellow croaker (Larimichthys crocea) during superchilling storage at −3°C. Results showed that the GT-SA active coatings, containing epigallocatechin gallate [EGCG (E), 0.32% w/v], and lysozyme [LYS (L), 0.32% w/v] have reduced the total viable count, psychrophilic bacteria, and Pseudomonas spp. by about 1.55 log CFU/g, 0.49 log CFU/g, and 1.64 log CFU/g compared to the control at day 35. The GT-SA active coatings containing EGCG and LYS were effective in lowering the formations of off-odor compounds such as total volatile basic nitrogen (TVB-N), malondialdehyde (MDA), and off-favor amino acid (histidine). The solid phase microextraction gas chromatography-mass spectrometer (SPME-GC/MS) was applied to characterize and to quantify the volatile compounds of large yellow croaker samples during superchilling storage, while the relative content of the fishy flavor compounds (including 1-octen-3-ol and acetoin) was significantly reduced in the active coatings treated samples. Furthermore, the GT-SA active coatings containing EGCG and LYS treatments was found to be more effective in retarding the migration of water based on magnetic resonance imaging (MRI) results and in maintaining the organoleptic quality of large yellow croaker in superchilling storage at −3°C according to the sensory evaluation results. The results showed that the GT-SA active coating containing EGCG and LYS was effective to be used as a fish preservative to improve the quality and to prolong the shelf life of large yellow croaker in a superchilling storage for at least 7 days.
Effects of High-Temperature, High-Pressure, and Ultrasonic Treatment on the Physicochemical Properties and Structure of Soluble Dietary Fibers of Millet Bran
Authors: Wei Chunhong , Ge Yunfei , Liu Dezhi , Zhao Shuting , Wei Mingzhi , Jiliu Junchen , Hu Xin , Quan Zhigang , Wu Yunjiao , Su Youtao , Wang Yifei , Cao Longkui
Published: January 2022

Objectives

The effects of high-temperature, high-pressure, and ultrasonic treatment on the physicochemical properties and structure of soluble dietary fibers in millet bran were studied to provide a comprehensive reference for the utilization of millet bran.

Methods

Different physical methods were used to treat millet bran dietary fibers, and their microstructures and Fourier-transform infrared spectra before and after modification were compared. The physicochemical properties (water-holding capacity, swelling capacity, oil-holding capacity, fat-binding capacity, cation exchange capacity), total antioxidant capacity, and thermal characteristics were also analyzed.

Results

There were no significant changes in the chemical groups of millet bran's soluble dietary fibers after modification, but cracks appeared on the surface of the fibers and the structure became loose and porous. Fiber agglomeration was observed, as well as improved thermal stability. After modification, the water-holding capacity, swelling capacity, oil-holding capacity, fat-binding capacity, and cation exchange capacity of millet bran were improved. When compared to the original soluble dietary fibers, ultrasound-treated fibers showed the most substantial improvement in all four capabilities, with increases of 140, 50, 78.1, 65.7, and 37.8%, respectively, compared with the original soluble dietary fibers (P < 0.05). The total antioxidant capacity of the ultrasound-treated fibers was found to be higher than those of the fibers that underwent the other three treatments (P < 0.05).

Conclusions

The physicochemical qualities and structural characteristics of the soluble dietary fibers in millet bran are affected by all three physical modification methods; however, the physicochemical properties of the ultrasound-treated fibers are most significantly improved.
Combined Association of Tumoral PD-L1 Expression and Pretreatment Presence of Epstein-Barr Virus DNA With Risk Stratification and Prognosis of Patients With Nasopharyngeal Carcinoma
Authors: Li Xiaoyu , Peng Xingchen , Zhao Sha , Zhang Hong , Jiang Yong , Liu Fei , Ai Ping
Published: January 2022

Background

Little is known about whether the combination of tumor programmed death-ligand 1 (PD-L1) expression and pretreatment EBV DNA status can help stratify nasopharyngeal carcinoma (NPC) patients by risk of metastasis or predict prognosis.

Methods

PD-L1 expression was assessed using immunohistochemical staining of 78 non-keratinizing NPC patients with clinical data. Survival outcomes and independent prognostic factors were identified.

Results

Seventy-eight patients were included, high PD-L1 expression was observed in 25 of 43 patients (58%) with metastasis, while it was observed only in 7 of 35 patients (20%) without metastasis. Multivariate analyses showed that progression-free survival (PFS) was independently predicted by tumoral PD-L1 expression and pretreatment EBV DNA status. When combining, 93.75% patients with high PD-L1 and EBV infection developed distant metastasis, and those patients were associated with worse PFS.

Conclusions

Both PD-L1 expression and pretreatment EBV DNA are closely related to metastasis and prognosis of NPC patients. Their combination can facilitate risk stratification and prognosis prediction, which may improve disease treatment and management.