bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Surface Fatigue Crack Nucleation and Microstructurally Small Crack Growth in High Strength Aluminum Alloys
Authors: Fleishel Robert , Cauthen Cole , Daniewicz Steven , Baker Andrew , Jordon J. Brian , TerMaath Stephanie
Published: February 2021

It is well established that fatigue crack nucleation and small crack growth in high strength aluminum alloys are highly influenced by the surrounding microstructure including grain boundaries, texture, inclusion barriers, among other factors. As such, specific and targeted experimental and computational methods are necessary to accurately capture and predict the discrete behavior of microstructurally small fatigue cracks. In this study, surface fatigue crack nucleation and microstructurally small crack growth in high strength aluminum alloys, commonly used in aerospace applications, are evaluated through a holistic approach encompassing fatigue testing, crack measurement, and computational prediction of crack growth rates. During fatigue testing, crack shapes and growth are quantified using a novel surface replication technique that is applied to investigate crack nucleation, as well as to collect validation data that includes an accurate description of crack shape during crack propagation, a challenging and essential component in predicting crack growth. Computational simulation of fatigue crack growth in non-straight, complex surface crack arrays typically requires high fidelity analysis using computationally expensive methods to account for the mathematical and geometrical complexities inherent in the solution. A dislocation distribution based technique has been previously demonstrated to rapidly and accurately predict the stress intensity factors for through cracks of complex shape. This method was expanded and investigated as an approach for rapidly predicting the crack growth rate of kinked and tortuous surface crack arrays, using the crack configuration and bulk material properties as inputs. To investigate the accuracy and effectiveness of this characterization approach, surface crack growth in AA7075-T7351 was experimentally analyzed and modeled under high cycle and low cycle fatigue conditions. This comprehensive approach was determined to be an expedient and applicable method for characterizing and evaluating the nucleation and crack growth rate of non-planar microstructurally small and short crack configurations.
Olive Stone Delignification Toward Efficient Adsorption of Metal Ions
Authors: Gao Ying , Aliques Tomas Maria del Carmen , Garemark Jonas , Sheng Xia , Berglund Lars , Li Yuanyuan
Published: February 2021

Olive stone is an important biomaterial waste product generated in large amount. As a lignocellulose material, olive stone could be a sustainable resource for biosorbents. In this work, olive stone powder delignification using sodium chlorite (NaClO2) was performed to enhance metal ion adsorption capacity. The influence of the treatment on olive stone powder physical-chemical properties was studied, including specific surface area, surface chemistry, morphology, etc. The white, delignified olive stone powder was applied for metal ions (Fe3+, Cu2+, and Zn2+) adsorption. Olive stone delignification not only increases the accessibility of the olive stone powder but also broadens the applications to materials design with optical functions by the generation of a white powder.
Influence of Coarse Mg3Bi2 Particles on Deformation Behaviors of Mg-Bi Alloys
Authors: Guo Tingting , Lu Xuerong , Varma Ramesh Kumar , Zhao Cheng , Wang Jun , You Jianwei , Chen Jian
Published: February 2021

Mg-Bi binary alloys with concentrations of 1, 3, 6, and 9 wt% Bi and ternary Mg-9Bi-2.5Zn alloy were prepared by casting and hot extrusion. The results show that alloying with Bi refined as-cast grains of Mg alloys and the refinement efficiency of Bi is in between Al and Zr. It was also found that a critical value for the area fraction of constituent Mg3Bi2 particles seems to appear, which influences the dynamic recrystallization mechanism during extrusion. This influence results in either uniform or heterogenetic distribution of grain size and different extrusion texture intensities. Furthermore, the addition of Zn affected both the grain size and the area fraction/size of Mg3Bi2. Mechanical results and microstructure/fractography observation suggest that Mg3Bi2 particles do not impact the tensile nor compression yielding stress but act as fracture sources.
Evaluation of a Double-Entry Turbine Model Coupled With a One-Dimensional Calibrated Engine Model at Engine Full Load Curves
Authors: Galindo José , Serrano José Ramón , De La Morena Joaquín , Samala Vishnu , Guilain Stéphane , Batard Samuel
Published: February 2021

Turbocharging is one of the foremost ways of engine downsizing and represents the leading technology for reducing the engine CO2emission standards in gasoline engine application. Turbocharger turbine always faces high unsteadiness of flow coming from the reciprocating internal combustion engines. Besides, increasing levels of engine downsizing include rising degrees of pulse charging. Utilization of pulse energy in the engine exhaust and reducing the interferences between the cylinders using the double-entry turbines is a vital element in solving the low-end-torque targets and improving rated power in highly boosted four-cylinder engines. The present paper describes a model of double-entry turbines. The model’ aim is to accommodate an efficient boundary condition to turbocharged engine models with zero and one-dimensional gas dynamic codes. The model is based on the simple procedure of testing and systematizing the performance maps of these turbines with different flow admission conditions. However, the described model in the present paper is capable of extrapolating operating conditions that differ from those included in the turbine maps because a turbocharger turbine with an engine usually works instantaneously and away from the narrow range of data that are measured in the gas stand. The described model has been implemented in a one-dimensional gas dynamic code and has been used to calculate unsteady operating conditions coming from the engine. The results obtained from the whole engine simulation show that the model can produce all the full load engine variables such as air mass flow and brake torque in a reasonable degree of agreement with the experimental data that are obtained from the engine test bench.
Prevalence and Characteristics of Hypoxic Hepatitis in COVID-19 Patients in the Intensive Care Unit: A First Retrospective Study
Authors: Huang Haijun , Li Hong , Chen Shanshan , Zhou Xianlong , Dai Xuan , Wu Jia , Zhang Jun , Shao Lina , Yan Rong , Wang Mingshan , Wang Jiafeng , Tu Yuexing , Ge Minghua
Published: February 2021

Purpose: Coronavirus disease 2019 (COVID-19) has been associated with acute liver injury in reports worldwide. But no studies to date have described hypoxic hepatitis (HH) in patients with COVID-19. We aim to identify the prevalence of and possible mechanisms of HH in COVID-19 patients in the Intensive Care Unit (ICU).

Methods: This retrospective study was conducted on 51 patients with confirmed SARS-CoV-2 infection in the ICU at Zhongnan Hospital of Wuhan University from December 21, 2019, to March 11, 2020. Information on clinical features of enrolled patients was collected for analysis.

Results: HH was observed in 5.88% of the ICU patients with SARS-CoV-2 infection. All HH patients were progressing to respiratory failure and peak alanine aminotransferase (ALT) values were 1665, 1414, and 1140 U/L during hospitalization, respectively. All patients with HH died as a result of the deterioration of multiple organ failure (MOF). The dynamic changes of ALT, aspartate transaminase (AST), and total bilirubin (TBIL) levels were more dramatic in HH groups. Levels of TBIL, C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6(IL-6) showed statistically significant elevation in HH cases compared with that in non-HH cases (P < 0.001). Besides, the median survival time of the HH group was significantly shorter than the non-HH group (P < 0.05).

Conclusions: In ICU, HH was not a rare condition in patients with severe COVID-19 and has a high mortality. The main causes of HH are respiratory and cardiac failure and may be associated with the immune-mediated inflammatory response. Clinicians should search for any underlying hemodynamic or respiratory instability even in patients with normal ALT levels on admission.
Molecular Analysis of IL-5 Receptor Subunit Alpha as a Possible Pharmacogenetic Biomarker in Asthma
Authors: Elena-Pérez Sandra , Heredero-Jung David Hansoe , García-Sánchez Asunción , Estravís Miguel , Martin Maria J. , Ramos-González Jacinto , Triviño Juan Carlos , Isidoro-García María , Sanz Catalina , Dávila Ignacio
Published: February 2021

Background: Asthma is a heterogeneous syndrome with a broad clinical spectrum and high drug response variability. The inflammatory response in asthma involves multiple effector cells and mediator molecules. Based on asthma immunopathogenesis, precision medicine can be a promising strategy for identifying biomarkers. Biologic therapies acting on the IL-5/IL-5 receptor axis have been developed. IL-5 promotes proliferation, differentiation and activation of eosinophils by binding to the IL-5 receptor, located on the surface of eosinophils and basophils. This study aimed to investigate the expression of IL5RA in patients with several types of asthma and its expression after treatment with benralizumab, a biologic directed against IL-5 receptor subunit alpha.

Methods: Sixty peripheral blood samples, 30 from healthy controls and 30 from asthmatic patients, were selected for a transcriptomic RNAseq study. Differential expression analysis was performed by statistical assessment of fold changes and P-values. A validation study of IL5RA expression was developed using qPCR in 100 controls and 187 asthmatic patients. The effect of benralizumab on IL5RA expression was evaluated in five patients by comparing expression levels between pretreatment and after 3 months of treatment. The IL5RA mRNA levels were normalized to GAPDH and TBP expression values for each sample. Calculations were made by the comparative ΔΔCt method. All procedures followed the MIQE guidelines.

Results:IL5RA was one of the most differentially overexpressed coding transcripts in the peripheral blood of asthmatic patients (P = 8.63E-08 and fold change of 2.22). In the qPCR validation study, IL5RA expression levels were significantly higher in asthmatic patients than in controls (P < 0.001). Significant expression differences were present in different asthmatic types. In the biological drug study, patients treated with benralizumab showed a significant decrease in IL5RA expression and blood eosinophil counts. A notable improvement in ACT and lung function was also observed in these patients.

Conclusions: These results indicate that IL5RA is overexpressed in patients with different types of asthma. It could help identify which asthmatic patients will respond more efficiently to benralizumab, moving toward a more personalized asthma management. Although further studies are required, IL5RA could play a role as a biomarker and pharmacogenetic factor in asthma.
Shortages Without Frontiers: Antimicrobial Drug and Vaccine Shortages Impact Far Beyond the Individual!
Authors: Beraud Guillaume
Published: February 2021

Among increasingly common drug shortages, antimicrobial drug and vaccine shortages are the most frequently reported. This could be related to the smaller size of the market, compared to statins or antidepressant drugs. But there are multiple causes to shortages, such as flawed manufacturing processes, modification of quality control processes and scarcity of raw materials. Besides, concentration of manufacturing in emerging economies, dependence on a single producer and pressure on profit margins amplify the consequences of any manufacturing problem. Antimicrobial drug shortages have an impact on patient outcomes and antimicrobial resistance (AMR) by leading to choices of alternatives with an inadequately large spectrum, and consequently with deleterious side effects and increased costs. Moreover, vaccine shortages result in controversies exacerbated by the antivax community. Given the transmissibility of infectious diseases, antimicrobial drug and vaccine shortages will impact both individual and population health through herd effect. For these reasons, they represent a worldwide threat that goes beyond impact at the individual level. There has been no coordinated response to this threat hitherto. In order to provide an adequate response plan, precise data on shortage occurrences and their causes are a prerequisite. Moreover, efficient action will not be possible without a transnational will. Examples of useful actions could be: Incorporating a standardized survey into the WHO surveillance programs on antimicrobial use; creating a communication channel between pharmaceutical companies, providers and national agencies so as to recognize upcoming shortages; licensing some laboratories to manufacture out-of-stock drugs, for the duration of the shortage.
Early Detection of Sepsis With Machine Learning Techniques: A Brief Clinical Perspective
Authors: Giacobbe Daniele Roberto , Signori Alessio , Del Puente Filippo , Mora Sara , Carmisciano Luca , Briano Federica , Vena Antonio , Ball Lorenzo , Robba Chiara , Pelosi Paolo , Giacomini Mauro , Bassetti Matteo
Published: February 2021

Sepsis is a major cause of death worldwide. Over the past years, prediction of clinically relevant events through machine learning models has gained particular attention. In the present perspective, we provide a brief, clinician-oriented vision on the following relevant aspects concerning the use of machine learning predictive models for the early detection of sepsis in the daily practice: (i) the controversy of sepsis definition and its influence on the development of prediction models; (ii) the choice and availability of input features; (iii) the measure of the model performance, the output, and their usefulness in the clinical practice. The increasing involvement of artificial intelligence and machine learning in health care cannot be disregarded, despite important pitfalls that should be always carefully taken into consideration. In the long run, a rigorous multidisciplinary approach to enrich our understanding in the application of machine learning techniques for the early recognition of sepsis may show potential to augment medical decision-making when facing this heterogeneous and complex syndrome.
Conjugative DNA Transfer From E. coli to Transformation-Resistant Lactobacilli
Authors: Samperio Sara , Guzmán-Herrador Dolores L. , May-Cuz Rigoberto , Martín Maria Cruz , Álvarez Miguel A. , Llosa Matxalen
Published: February 2021

Lactic acid bacteria (LAB) belonging to the genus classically known as Lactobacillus, recently split into 25 different genera, include many relevant species for the food industry. The well-known properties of lactobacilli as probiotics make them an attractive model also for vaccines and therapeutic proteins delivery in humans. However, scarce tools are available to accomplish genetic modification of these organisms, and most are only suitable for laboratory strains. Here, we test bacterial conjugation as a new tool to introduce genetic modifications into many biotechnologically relevant laboratory and wild type lactobacilli. Using mobilizable shuttle plasmids from a donor Escherichia coli carrying either RP4 or R388 conjugative systems, we were able to get transconjugants to all tested Lactocaseibacillus casei strains, including many natural isolates, and to several other genera, including Lentilactobacillus parabuchneri, for which no transformation protocol has been reported. Transconjugants were confirmed by the presence of the oriT and 16S rRNA gene sequencing. Serendipitously, we also found transconjugants into researcher-contaminant Staphylococcus epidermidis. Conjugative DNA transfer from E. coli to S. aureus was previously described, but at very low frequencies. We have purified this recipient strain and used it in standard conjugation assays, confirming that both R388 and RP4 conjugative systems mediate mobilization of plasmids into S. epidermidis. This protocol could be assayed to introduce DNA into other Gram-positive microorganisms which are resistant to transformation.
Improved in vitro Efficacy of Baloxavir Marboxil Against Influenza A Virus Infection by Combination Treatment With the MEK Inhibitor ATR-002
Authors: Hamza Hazem , Shehata Mahmoud M. , Mostafa Ahmed , Pleschka Stephan , Planz Oliver
Published: February 2021

Currently, all available antiviral drugs against influenza virus (IV) that target the virus proteins directly, like Baloxavir acid (BXA), lead to viral resistance. Therefore, cellular mechanisms and factors essential for IV replication are promising antiviral targets. As IV strongly depends on the virus-induced Raf/MEK/ERK signal pathway for efficient generation of infectious progeny virions, this pathway represents an important target. We aimed to determine whether the MEK inhibitor ATR-002 (PD0184264) is able to impair replication of BXA-resistant influenza A virus (IAV) and whether a treatment combining BXA and ATR-002 improves the therapeutic efficiency in vitro. A549 cells infected with different IAV strains including BXA-resistant variants were treated with ATR-002 or BXA and the effect on virus titer reduction was determined. The synergistic effect of ATR-002 and BXA was also analyzed using different evaluation methods. The data demonstrated that ATR-002 has a significant and dose-dependent inhibitory effect on IAV replication across different strains and subtypes. IAV with the PA-I38T mutation shows resistance against BXA, but is still susceptible toward ATR-002. The combination of ATR-002 and BXA exhibited a synergistic potency reflected by low combination index values. In conclusion, we show that ATR-002 permits to counteract the limitations of BXA against BXA-resistant IAV. Moreover, the results support the use of ATR-002 (i) in a mono-therapy, as well as (ii) in a combined approach together with BXA. These findings might also apply to the treatment of infections with IAV, resistant against other direct-acting antiviral compounds.
Assembly Patterns of the Rhizosphere Microbiome Along the Longitudinal Root Axis of Maize (Zea mays L.)
Authors: Rüger Lioba , Feng Kai , Dumack Kenneth , Freudenthal Jule , Chen Yan , Sun Ruibo , Wilson Monica , Yu Peng , Sun Bo , Deng Ye , Hochholdinger Frank , Vetterlein Doris , Bonkowski Michael
Published: February 2021

It is by now well proven that different plant species within their specific root systems select for distinct subsets of microbiota from bulk soil – their individual rhizosphere microbiomes. In maize, root growth advances several centimeters each day, with the locations, quality and quantity of rhizodeposition changing. We investigated the assembly of communities of prokaryotes (archaea and bacteria) and their protistan predators (Cercozoa, Rhizaria) along the longitudinal root axis of maize (Zea mays L.). We grew maize plants in an agricultural loamy soil and sampled rhizosphere soil at distinct locations along maize roots. We applied high-throughput sequencing, followed by diversity and network analyses in order to track changes in relative abundances, diversity and co-occurrence of rhizosphere microbiota along the root axis. Apart from a reduction of operational taxonomic unit (OTU) richness and a strong shift in community composition between bulk soil and root tips, patterns of microbial community assembly along maize-roots were more complex than expected. High variation in beta diversity at root tips and the root hair zone indicated substantial randomness of community assembly. Root hair zone communities were characterized by massive co-occurrence of microbial taxa, likely fueled by abundant resource supply from rhizodeposition. Further up the root where lateral roots emerged processes of community assembly appeared to be more deterministic (e.g., through competition and predation). This shift toward significance of deterministic processes was revealed by low variability of beta diversity, changes in network topology, and the appearance of regular phylogenetic co-occurrence patterns in bipartite networks between prokaryotes and their potential protistan predators. Such patterns were strongest in regions with fully developed laterals, suggesting that a consistent rhizosphere microbiome finally assembled. For the targeted improvement of microbiome function, such knowledge on the processes of microbiome assembly on roots and its temporal and spatial variability is crucially important.
Monthly Variation in the Macromolecular Composition of Phytoplankton Communities at Jang Bogo Station, Terra Nova Bay, Ross Sea
Authors: Kim Kwanwoo , Park Jisoo , Jo Naeun , Park Sanghoon , Yoo Hyeju , Kim Jaehong , Lee Sang Heon
Published: February 2021

Organic carbon fixed by photosynthesis of phytoplankton during the polar growing period could be important for their survival and consumers during the long polar night. Differences in biochemical traits of phytoplankton between ice-free and polar night periods were investigated in biweekly water samples obtained at the Korean “Jang Bogo Station” located in Terra Nova Bay, Antarctica. The average concentration of total Chl-a from phytoplankton dominated by micro-sized species from the entire sampling period was 0.32 μg L–1 (SD = ± 0.88 μg L–1), with the highest concentration of 4.29 μg L–1 in February and the lowest concentration of 0.01 μg L–1 during the ice-covered polar night (April–October) in 2015. The highest protein concentration coincided with the peak Chl-a concentration in February and decreased rapidly relative to the carbohydrate and lipid concentrations in the early part of polar night. Among the different biochemical components, carbohydrates were the predominant constituent, accounting for 69% (SD = ± 14%) of the total particulate organic matter (POM) during the entire study period. The carbohydrate contributions to the total POM markedly increased from 39 ± 8% during the ice-free period to 73 ± 9% during the polar night period. In comparison, while we found a significant negative correlation (r2 = 0.92, p < 0.01) between protein contributions and carbohydrate contributions, lipid contributions did not show any particular trend with relatively small temporal variations during the entire observation period. The substantial decrease in the average weight ratio of proteins to carbohydrates from the ice-free period (mean ± SD = 1.0 ± 0.3) to the ice-covered period (mean ± SD = 0.1 ± 0.1) indicates a preferential loss of nitrogen-based proteins compared to carbohydrates during the polar night period. Overall, the average food material (FM) concentration and calorific contents of FM in this study were within the range reported previously from the Southern Ocean. The results from this study may serve as important background data for long-term monitoring of the regional and interannual variations in the physiological state and biochemical compositions of phytoplankton resulting from future climate change in Antarctica.
An Optimized High-Throughput Immuno-Plaque Assay for SARS-CoV-2
Authors: Amarilla Alberto A. , Modhiran Naphak , Setoh Yin Xiang , Peng Nias Y. G. , Sng Julian D. J. , Liang Benjamin , McMillan Christopher L. D. , Freney Morgan E. , Cheung Stacey T. M. , Chappell Keith J. , Khromykh Alexander A. , Young Paul R. , Watterson Daniel
Published: February 2021

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been identified as the causative agent of coronavirus disease 2019 and is capable of human-to-human transmission and rapid global spread. The rapid emergence and global spread of SARS-CoV-2 has encouraged the establishment of a rapid, sensitive, and reliable viral detection and quantification methodology. Here, we present an alternative assay, termed immuno-plaque assay (iPA), which utilizes a combination of plaque assay and immunofluorescence techniques. We have extensively optimized the conditions for SARS-CoV-2 infection and demonstrated the great flexibility of iPA detection using several antibodies and dual-probing with two distinct epitope-specific antibodies. In addition, we showed that iPA could be utilized for ultra-high-throughput viral titration and neutralization assay within 24 h and is amenable to a 384-well format. These advantages will significantly accelerate SARS-CoV-2 research outcomes during this pandemic period.
AOA-2 Derivatives as Outer Membrane Protein A Inhibitors for Treatment of Gram-Negative Bacilli Infections
Authors: Ayerbe-Algaba Rafael , Bayó Nuria , Verdú Ester , Parra-Millán Raquel , Seco Jesús , Teixidó Meritxell , Pachón Jerónimo , Giralt Ernest , Smani Younes
Published: February 2021

Previously, we identified that a cyclic hexapeptide AOA-2 inhibited the interaction of Gram-negative bacilli (GNB) like Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli to host cells thereby preventing the development of infection in vitro and in a murine sepsis peritoneal model. In this work, we aimed to evaluate in vitro a library of AOA-2 derivatives in order to improve the effect of AOA-2 against GNB infections. Ten AOA-2 derivatives were synthetized for the in vitro assays. Their toxicities to human lung epithelial cells (A549 cells) for 24 h were evaluated by determining the A549 cells viability using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of these peptide derivatives and AOA-2 at 250, 125, 62.5, and 31.25 μg/mL on the attachment of A. baumannii ATCC 17978, P. aeruginosa PAO1 and E. coli ATCC 25922 strains to A549 cells was characterized by adherence and viability assays. None of the 10 derivatives showed toxicity to A549 cells. RW01 and RW06 have reduced more the adherence of ATCC 17978, PAO1 and ATCC 2599 strains to A549 cells when compared with the original compound AOA-2. Moreover, both peptides have increased slightly the viability of infected A549 cells by PAO1 and ATCC 25922 than those observed with AOA-2. Finally, RW01 and RW06 have potentiated the activity of colistin against ATCC 17978 strain in the same level with AOA-2. The optimization program of AOA-2 has generated two derivatives (RW01 and RW06) with best effect against interaction of GNB with host cells, specifically against P. aeruginosa and E. coli.
The Association Between the Gut Microbiota and Parkinson's Disease, a Meta-Analysis
Authors: Shen Ting , Yue Yumei , He Tingting , Huang Cong , Qu Boyi , Lv Wen , Lai Hsin-Yi
Published: February 2021

Patients with Parkinson's disease (PD) were often observed with gastrointestinal symptoms, which preceded the onset of motor symptoms. Neuropathology of PD has also been found in the enteric nervous system (ENS). Many studies have reported significant PD-related alterations of gut microbiota. This meta-analysis was performed to evaluate the differences of gut microbiota between patients with PD and healthy controls (HCs) across different geographical regions. We conducted a systematic online search for case-control studies detecting gut microbiota in patients with PD and HCs. Mean difference (MD) and 95% confidence interval (CI) were calculated to access alterations in the abundance of certain microbiota families in PD. Fifteen case-control studies were included in this meta-analysis study. Our results showed significant lower abundance levels of Prevotellaceae (MD = −0.37, 95% CI = −0.62 to −0.11), Faecalibacterium (MD = −0.41, 95% CI: −0.57 to −0.24), and Lachnospiraceae (MD = −0.34, 95% CI = −0.59 to −0.09) in patients with PD compared to HCs. Significant higher abundance level of Bifidobacteriaceae (MD = 0.38, 95%; CI = 0.12 to 0.63), Ruminococcaceae (MD = 0.58, 95% CI = 0.07 to 1.10), Verrucomicrobiaceae (MD = 0.45, 95% CI = 0.21 to 0.69), and Christensenellaceae (MD = 0.20, 95% CI = 0.07 to 0.34) was also found in patients with PD. Thus, shared alterations of certain gut microbiota were detected in patients with PD across different geographical regions. These PD-related gut microbiota dysbiosis might lead to the impairment of short-chain fatty acids (SCFAs) producing process, lipid metabolism, immunoregulatory function, and intestinal permeability, which contribute to the pathogenesis of PD.
Place Cells in Head-Fixed Mice Navigating a Floating Real-World Environment
Authors: Go Mary Ann , Rogers Jake , Gava Giuseppe P. , Davey Catherine E. , Prado Seigfred , Liu Yu , Schultz Simon R.
Published: February 2021

The hippocampal place cell system in rodents has provided a major paradigm for the scientific investigation of memory function and dysfunction. Place cells have been observed in area CA1 of the hippocampus of both freely moving animals, and of head-fixed animals navigating in virtual reality environments. However, spatial coding in virtual reality preparations has been observed to be impaired. Here we show that the use of a real-world environment system for head-fixed mice, consisting of an air-floating track with proximal cues, provides some advantages over virtual reality systems for the study of spatial memory. We imaged the hippocampus of head-fixed mice injected with the genetically encoded calcium indicator GCaMP6s while they navigated circularly constrained or open environments on the floating platform. We observed consistent place tuning in a substantial fraction of cells despite the absence of distal visual cues. Place fields remapped when animals entered a different environment. When animals re-entered the same environment, place fields typically remapped over a time period of multiple days, faster than in freely moving preparations, but comparable with virtual reality. Spatial information rates were within the range observed in freely moving mice. Manifold analysis indicated that spatial information could be extracted from a low-dimensional subspace of the neural population dynamics. This is the first demonstration of place cells in head-fixed mice navigating on an air-lifted real-world platform, validating its use for the study of brain circuits involved in memory and affected by neurodegenerative disorders.
The Connectivity Fingerprints of Highly-Skilled and Disordered Reading Persist Across Cognitive Domains
Authors: McNorgan Chris
Published: February 2021

The capacity to produce and understand written language is a uniquely human skill that exists on a continuum, and foundational to other facets of human cognition. Multivariate classifiers based on support vector machines (SVM) have provided much insight into the networks underlying reading skill beyond what traditional univariate methods can tell us. Shallow models like SVM require large amounts of data, and this problem is compounded when functional connections, which increase exponentially with network size, are predictors of interest. Data reduction using independent component analyses (ICA) mitigates this problem, but conventionally assumes linear relationships. Multilayer feedforward networks, in contrast, readily find optimal low-dimensional encodings of complex patterns that include complex nonlinear or conditional relationships. Samples of poor and highly-skilled young readers were selected from two open access data sets using rhyming and mental multiplication tasks, respectively. Functional connectivity was computed for the rhyming task within a functionally-defined reading network and used to train multilayer feedforward classifier models to simultaneously associate functional connectivity patterns with lexicality (word vs. pseudoword) and reading skill (poor vs. highly-skilled). Classifiers identified validation set lexicality with significantly better than chance accuracy, and reading skill with near-ceiling accuracy. Critically, a series of replications used pre-trained rhyming-task models to classify reading skill from mental multiplication task participants' connectivity with near-ceiling accuracy. The novel deep learning approach presented here provides the clearest demonstration to date that reading-skill dependent functional connectivity within the reading network influences brain processing dynamics across cognitive domains.
The Potential of Exosomal RNAs in Atherosclerosis Diagnosis and Therapy
Authors: Yang Wenzhi , Pan Xudong , Ma Aijun
Published: February 2021

Atherosclerosis is an inflammatory disease that can lead to cardiovascular disorders and stroke. In the atherosclerosis microenvironment, exosomes secreted from various cells, especially macrophage-derived exosomes, play an important role in cell–cell communication and cellular biological functions. In this article, we review previous studies on exosomal RNAs and discuss their potential value in atherosclerosis diagnosis and therapy. Based on our research, we concluded that macrophage exosomes have potential value in atherosclerosis diagnosis and therapy. However, there is a need for future studies to further investigate methods of exosome isolation and targeting.
Characteristics of Clinical and Electrophysiological Pattern in a Large Cohort of Chinese Patients With Charcot-Marie-Tooth 4C
Authors: Duan Xiaohui , Ma Yan , Fan Dongsheng , Liu Xiaoxuan
Published: February 2021

The “Src homology 3 (SH3) domain and tetratricopeptide repeats 2” (SH3TC2) gene is mutated in individuals with Charcot-Marie-Tooth disease (CMT) and considered relevant to a demyelinating or intermediate subtype of CMT disease, CMT4C. In this study, we screened a cohort of 465 unrelated Chinese CMT patients alongside 650 controls. We used Sanger, next-generation, or whole-exome sequencing to analyze SH3TC2 and other CMT-related genes and identified 12 SH3TC2 variants (eight novel) in seven families. Of the eight novel variants, seven were likely pathogenic (c.280–2 A > G, c.732–1 G > A, c.1177+6 T > C, c.3328–1 G > A, G299S, R548W, L1048P), and 1 had uncertain significance (S221P). The CMT4C frequency was calculated to be 4.24% in demyelinating or intermediate CMT patients without PMP22 duplication. Additionally, we detected variant R954* in the Chinese cohort in our study, indicating that this variant may be present among Asians, albeit with a relatively low frequency. The onset age varied among the eight patients, three of whom presented scoliosis. We summarized phenotypes in the Chinese CMT cohort and concluded that the absence of scoliosis, cranial nerve involvement, or late-onset symptoms does not necessarily preclude SH3TC2 involvement in a given case.
A New Software for Quantifying Motor Deficit After Stroke: A Case–Control Feasibility Pilot Study
Authors: Gutiérrez Zúñiga Raquel , Alonso de Leciñana María , Díez Alejandro , Torres Iglesias Gabriel , Pascual Alejandro , Higashi Ariaki , Rodríguez Pardo Jorge , Hernández Herrero David , Fuentes Blanca , Díez Tejedor Exuperio
Published: February 2021

Introduction: The degree of disability after stroke needs to be objectively measured to implement adequate rehabilitation programs. Here, we evaluate the feasibility of a custom-built software to assess motor status after stroke.

Methods: This is a prospective, case–control pilot study comparing stroke patients with healthy volunteers. A workout evaluation that included trunk and upper limb movement was captured with Kinect® and kinematic metrics were extracted with Akira®. Trunk and joint angles were analyzed and compared between cases and controls. Patients were evaluated within the first week from stroke onset using the National Institutes of Health Stroke Scale (NIHSS), Fulg-Meyer Assessment (FMA), and modified Rankin Scale (mRS) scales; the relationship with kinematic measurements was explored.

Results: Thirty-seven patients and 33 controls were evaluated. Median (IQR) NIHSS of cases was 2 (0–4). The kinematic metrics that showed better discriminatory capacity were body sway during walking (less in cases than in controls, p = 0.01) and the drift in the forearm–trunk angle during shoulder abduction in supination (greater in cases than in controls, p = 0.01). The body sway during walking was moderately correlated with NIHSS score (Rho = −0.39; p = 0.01) but better correlated with mRS score (Rho = −0.52; p < 0.001) and was associated with the absence of disability (mRS 0–1) (OR = 0.64; p = 0.02). The drift in the forearm–trunk angle in supination was associated with the presence of disability (mRS >1) (OR = 1.27; p = 0.04).

Conclusion: We present a new software that detects even mild motor impairment in stroke patients underestimated by clinical scales but with an impact on patient functionality.
Disrupted Neural Activity in Individuals With Iridocyclitis Using Regional Homogeneity: A Resting-State Functional Magnetic Resonance Imaging Study
Authors: Tong Yan , Huang Xin , Qi Chen-Xing , Shen Yin
Published: February 2021

Objective: This study used the regional homogeneity (ReHo) technique to explore whether spontaneous brain activity is altered in patients with iridocyclitis.

Methods: Twenty-six patients with iridocyclitis (14 men and 12 women) and 26 healthy volunteers (15 men and 11 women) matched for sex and age were enrolled in this study. The ReHo technique was used to comprehensively assess changes in whole-brain synchronous neuronal activity. The diagnostic ability of the ReHo method was evaluated by means of receive operating characteristic (ROC) curve analysis. Moreover, associations of average ReHo values in different brain areas and clinical characteristics were analyzed using correlation analysis.

Result: Compared with healthy volunteers, reduced ReHo values were observed in patients with iridocyclitis in the following brain regions: the right inferior occipital gyrus, bilateral calcarine, right middle temporal gyrus, right postcentral gyrus, left superior occipital gyrus, and left precuneus. In contrast, ReHo values were significantly enhanced in the right cerebellum, left putamen, left supplementary motor area, and left inferior frontal gyrus in patients with iridocyclitis, compared with healthy volunteers (false discovery rate correction, P < 0.05).

Conclusion: Patients with iridocyclitis exhibited disturbed synchronous neural activities in specific brain areas, including the visual, motor, and somatosensory regions, as well as the default mode network. These findings offer a novel image-guided research strategy that might aid in exploration of neuropathological or compensatory mechanisms in patients with iridocyclitis.
Dynamic Changes of Amplitude of Low-Frequency Fluctuations in Patients With Diabetic Retinopathy
Authors: Huang Xin , Wen Zhi , Qi Chen-Xing , Tong Yan , Shen Yin
Published: February 2021

Background: Growing evidence demonstrate that diabetic retinopathy (DR) patients have a high risk of cognitive decline and exhibit abnormal brain activity. However, neuroimaging studies thus far have focused on static cerebral activity changes in DR patients. The characteristics of dynamic cerebral activity in patients with DR are poorly understood.

Purpose: The purpose of the study was to investigate the dynamic cerebral activity changes in patients with DR using the dynamic amplitude of low-frequency fluctuation (dALFF) method.

Materials and methods: Thirty-four DR patients (18 men and 16 women) and 38 healthy controls (HCs) (18 males and 20 females) closely matched in age, sex, and education were enrolled in this study. The dALFF method was used to investigate dynamic intrinsic brain activity differences between the DR and HC groups.

Results: Compared with HCs, DR patients exhibited increased dALFF variability in the right brainstem, left cerebellum_8, left cerebellum_9, and left parahippocampal gyrus. In contrast, DR patients exhibited decreased dALFF variability in the left middle occipital gyrus and right middle occipital gyrus.

Conclusion: Our study highlighted that DR patients showed abnormal variability of dALFF in the visual cortices, cerebellum, and parahippocampal gyrus. These findings suggest impaired visual and motor and memory function in DR individuals. Thus, abnormal dynamic spontaneous brain activity might be involved in the pathophysiology of DR.
Cognitive Impairments and Risk Factors After Ruptured Anterior Communicating Artery Aneurysm Treatment in Low-Grade Patients Without Severe Complications: A Multicenter Retrospective Study
Authors: Ma Ning , Feng Xin , Wu Zhongxue , Wang Daming , Liu Aihua
Published: February 2021

Background: Cognitive impairment is the main factor affecting quality of life in patients with low-grade aneurysmal subarachnoid hemorrhage.

Objective: We explored cognitive impairments and risk factors after treatment for ruptured anterior communicating artery (AComA) aneurysms in low-grade (Hunt-Hess grade of 1–3) patients without severe complications.

Methods: One-hundred-twenty-six patients with a Hunt-Hess grade of 1–3 who underwent microsurgical clipping or endovascular embolization for ruptured AComA aneurysm treatment at three academic institutions in China from January 2015 to December 2017 were assessed with the modified Telephone Interview for Cognitive Status (TICS-m), the modified Rankin Scale (mRS), and the instrumental activities of daily living (IADL) scale 2 or more years after microsurgical clipping or endovascular coiling. Multiple cox-regression analysis was used to identify variables independently associated with cognitive impairment.

Results: Of the total of 126 patients, 115 (91.3%) achieved good clinical outcomes (mRS score 0–2) and 109 (86.5%) had excellent quality of life (IADL score 8). Twenty-eight (22.2%) patients showed cognitive impairments (TICS-m≤27). The multivariate COX regression analysis showed that the female patients and longer duration of loss of consciousness at onset of subarachnoid hemorrhage (SAH) were independently associated with cognitive impairment. Cognitive outcome at the latest follow-up was not significantly different between patients treated after surgical clipping and coiling.

Conclusion: About one in five patients showed cognitive impairments after treatment for ruptured AComA aneurysms. Patients who are of the female sex, and who have a longer duration of a loss of consciousness at the onset of SAH may be at risk of cognitive impairment.
Case Report: Neuronal Intranuclear Inclusion Disease With Oromandibular Dystonia Onset
Authors: Deng Wei-Ping , Yang Zhao , Huang Xiao-Jun , Jiang Jing-Wen , Luan Xing-Hua , Cao Li
Published: February 2021

Background: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Because of variable clinical manifestations, NIID was often misdiagnosed. According to published case reports, the common clinical manifestations of NIID include dementia, muscle weakness, autonomic impairment, sensory disturbance, rigidity, ataxia convulsions, etc. However, no cases of oromandibular dystonia were mentioned.

Case Presentation: We describe a case of a 58-year-old woman presenting with mouth involuntary chewing initially. She started to show hand tremors, ataxia, and walking instability until 2 years later. Diffusion-weighted imaging showed high intensity signal along the corticomedullary junction. Fluid-attenuated inversion recovery imaging showed white matter hyperintensity. Electromyography (EMG) indicated peripheral nerve degeneration. Neuropsychological testing showed memory loss. Finally, skin biopsy and GGC repeat expansions in the NOTCH2NLC (Notch 2 N-terminal like C) gene confirmed the diagnosis of NIID.

Conclusion: This case demonstrated that oromandibular dystonia could be the first symptom of NIID. This case report provides new characteristics of NIID and broadens its clinical spectrum.
MRI Texture Analysis Reveals Brain Abnormalities in Medically Refractory Trigeminal Neuralgia
Authors: Danyluk Hayden , Ishaque Abdullah , Ta Daniel , Yang Yee Hong , Wheatley B. Matthew , Kalra Sanjay , Sankar Tejas
Published: February 2021

Background: Several neuroimaging studies report structural alterations of the trigeminal nerve in trigeminal neuralgia (TN). Less attention has been paid to structural brain changes occurring in TN, even though such changes can influence the development and response to treatment of other headache and chronic pain conditions. The purpose of this study was to apply a novel neuroimaging technique—texture analysis—to identify structural brain differences between classical TN patients and healthy subjects.

Methods: We prospectively recruited 14 medically refractory classical TN patients and 20 healthy subjects. 3-Tesla T1-weighted brain MRI scans were acquired in all participants. Three texture features (autocorrelation, contrast, energy) were calculated within four a priori brain regions of interest (anterior cingulate, insula, thalamus, brainstem). Voxel-wise analysis was used to identify clusters of texture difference between TN patients and healthy subjects within regions of interest (p < 0.001, cluster size >20 voxels). Median raw texture values within clusters were also compared between groups, and further used to differentiate TN patients from healthy subjects (receiver-operator characteristic curve analysis). Median raw texture values were correlated with pain severity (visual analog scale, 1–100) and illness duration.

Results: Several clusters of texture difference were observed between TN patients and healthy subjects: right-sided TN patients showed reduced autocorrelation in the left brainstem, increased contrast in the left brainstem and right anterior insula, and reduced energy in right and left anterior cingulate, right midbrain, and left brainstem. Within-cluster median raw texture values also differed between TN patients and healthy subjects: TN patients could be segregated from healthy subjects using brainstem autocorrelation (p = 0.0040, AUC = 0.84, sensitivity = 89%, specificity = 70%), anterior insula contrast (p = 0.0002, AUC = 0.92, sensitivity = 78%, specificity = 100%), and anterior cingulate energy (p = 0.0004, AUC = 0.92, sensitivity = 78%, specificity = 100%). Additionally, anterior insula contrast and duration of TN were inversely correlated (p = 0.030, Spearman r = −0.73).

Conclusions: Texture analysis reveals distinct brain abnormalities in TN, which relate to clinical features such as duration of illness. These findings further implicate structural brain changes in the development and maintenance of TN.