bluuebunny/crossref_metadata_2025 huggingface dataset:
Feeding Ecology of Three Euphausiid Species in the North Pacific Ocean Inferred From 18S V9 Metabarcoding and Stable Isotope Analysis
Authors: Zhou Fanyu , Hirai Junya , Hamasaki Koji , Horii Sachiko , Tsuda Atsushi
Published: October 2021

Euphausiids are abundant micronekton and important links between higher and lower trophic levels in marine ecosystems; however, their detailed diets cannot be fully understood by conventional microscopy, especially in subtropical areas. Here, we report the euphausiid community structure in the California Current (CC) area and the eastern/western North Pacific subtropical gyre (ESG and WSG) and detail the feeding ecology of the dominant species (Euphausia pacifica, E. brevis, and E. hemigibba) in each region using a combined approach of gut content analysis via 18S V9 metabarcoding and stable carbon and nitrogen isotope analysis. A pronounced omnivorous feeding of all studied euphausiid species was supported by both methods: phytoplanktonic taxonomic groups (Dinophyta, Stramenopiles, and Archaeplastida), Copepoda, and Hydrozoa were detected in the gut contents; all the three euphausiid species displayed an intermediate trophic position between the net plankton (0.2–1.0 mm) and the myctophid fish (15.2–85.5 mm). However, Hydrozoa found in euphausiid gut contents likely derived from a potential cod-end feeding, based on isotope analysis. E. pacifica in the CC province ingested more autotrophic prey, including pelagophyte and green algae, due to a greater abundance of Stramenopiles and Archaeplastida in shallow layers of CC water. On the other hand, non-autotrophic prey such as mixotrophic Kareniaceae dinoflagellates, Pontellidae and Clausocalanidae copepods, and Sphaerozoidae rhizarian contributed more to the diets of E. brevis and E. hemigibba because of a lower chlorophyll a concentration or potentially a scarcity of autotrophic prey availability in ESG and WSG. The feeding patterns of dominant euphausiid species conducting filter feeding were thus largely determined by phytoplankton prey availability in the environments. Dietary difference across three species was also indicated by stable isotope analysis, with a lower mean trophic level of E. pacifica (2.32) than E. brevis (2.48) and E. hemigibba (2.57). These results verify direct trophic interactions between euphausiids and primary production and suggest that the omnivorous feeding habit is a favorable character for dominant Euphausia species.
Monoculture or Mixed Culture? Relevance of Fine Root Dynamics to Carbon Sequestration Oriented Mangrove Afforestation and Restoration
Authors: He Ziying , Sun Huaye , Yu Xiaoli , Yin Zhushi , Wu Mengxing , Zhao Lili , Hu Zhan , Peng Yisheng , Lee Shing Yip
Published: October 2021

Fine root dynamics have the potential to contribute to ecosystem biogeochemical cycling, especially for carbon. This is particularly true in mangroves which are the most productive and carbon-rich ecosystems of the world. However, few studies comprehensively evaluated the contribution of mangrove fine root dynamics to soil organic carbon accumulation. In southern China, while the introduced fast-growing Sonneratia apetala and native shrubby Kandelia obovata have been widely used in mangrove reforestation/afforestation programs since the mid-1980s, their implications and ecosystem services are still unclear. Here we show distinct differences in fine root dynamic among 12-year-old S. apetala, K. obovata monocultures, and their mixed stand using root coring, ingrowth core, and intact-core methods. Soil organic carbon storage was examined by soil coring method. One-year observation showed significant differences among the three mangrove plantations in fine root biomass, necromass, turnover rate, and decomposition decay rate constant. Soil organic carbon stock was 15.8 ± 0.8, 7.8 ± 0.5, and 11.9 ± 1.6 Mg C ha–1 for K. obovata, S. apetala monocultures and their mixed stand, respectively. Live fine root biomass, fine root necromass, annual fine root production and fine root mass decay rate constant are significantly correlated to soil organic carbon content across plantations. We suggest that mangrove fine root dynamics were mainly affected by soil nutrient conditions and species composition. Mixed stands may not have higher soil organic carbon storage than monocultures. The functional trait of different mangrove species is responsible to determine the carbon storage function of mixed stands. Fine roots play an important role in carbon storage, and fine root dynamics have a significant effect on carbon sequestration in mangrove ecosystems. The shrubby native K. obovata had a higher potential for belowground carbon sequestration and storage than the tall introduced S. apetala.
Frequency-Diverse Holographic Metasurface Antenna for Near-Field Microwave Computational Imaging
Authors: Han Jiaqi , Li Long , Tian Shuncheng , Ma Xiangjin , Feng Qiang , Liu Haixia , Zhao Yu , Liao Guisheng
Published: October 2021

This article presents a holographic metasurface antenna with stochastically distributed surface impedance, which produces randomly frequency-diverse radiation patterns. Low mutual coherence electric field patterns generated by the holographic metasurface antenna can cover the K-band from 18 to 26 GHz with 0.1 GHz intervals. By utilizing the frequency-diverse holographic metasurface (FDHM) antenna, we build a near-field microwave computational imaging system based on reflected signals in the frequency domain. A standard horn antenna is adopted to acquire frequency domain signals radiated from the proposed FDHM antenna. A detail imaging restoration process is presented, and the desired targets are correctly reconstructed using the 81 frequency-diverse patterns through full-wave simulation studies. Compressed sensing technique and iterative shrinkage/thresholding algorithms are applied for the imaging reconstruction. The achieved compressive ratio of this computational imaging system on the physical layer is 30:1.
Comparison of the IOLMaster 700 and the Pentacam in the Analysis of the Lens Nuclear Density Before the Cataract Surgery
Authors: Li Bowen , Liu Yuqi , Hu Yiping , Shi Mingyu
Published: October 2021

Purpose: To evaluate the difference of the lens nuclear density measured before and after mydriasis by using the IOLMaster 700 (Carl Zeiss Meditec AG, Jena, Germany) and the Pentacam Scheimpflug imaging (Pentacam HR, Oculus Incorporation, Wetzlar, Germany) and investigate the relationship between the measurement data and the phacoemulsification parameters.

Methods: Patients with age-related nuclear cataracts diagnosed on the slit-lamp examination were enrolled in the age range of 53–76 years. No patient had a history of ocular surgery, laser treatment, or general disorders affecting vision. The mean optical density (OD) was measured by the IOLMaster 700 by using the Image-Pro® Plus software before and after mydriasis. The Pentacam nucleus densitometry (PND) was obtained automatically from the Pentacam Scheimpflug imaging and compared with OD. The correlation between OD and effective phacoemulsification time (EPT), PND, and EPT were analyzed, respectively.

Results: In this study, 53 eyes of 52 patients were evaluated. Before and after mydriasis, the mean OD values were 64.34 ± 23.31 and 63.81 ± 23.21 pixel units, respectively; the mean PND values were 28.51 ± 11.42 and 25.41 ± 11.31, respectively; and the mean EPT value was 6.24 ± 3.49. The Bland–Altman analysis showed that the lens nuclear densities of the two devices were highly consistent. There was no significant difference in the OD values (t = 0.455, p > 0.05) before and after mydriasis, but the difference has existed in the PND values (t = 2.509, p < 0.05). The OD and PND values were positively correlated with EPT before and after mydriasis (rOD−Before = 0.604, rOD−After = 0.593, rPND−Before = 0.701, and rPND−After = 0.891, p < 0.01).

Conclusion: The combination of the IOLMaster 700 and the Image-Pro® Plus software can quantitatively evaluate the degree of the cataract lens opacification. It has good consistency with the Pentacam and is positively correlated with the phacoemulsification parameters. It is expected to become a new method to predict the phacoemulsification parameters before and during cataract surgery.
Iron Isotopic Composition of Biological Standards Relevant to Medical and Biological Applications
Authors: Kubik Edith , Moynier Frédéric , Paquet Marine , Siebert Julien
Published: October 2021

Iron isotopes are fractionated by multiple biological processes, which offers a novel opportunity to study iron homeostasis. The determination of Fe isotope composition in biological samples necessitates certified biological reference materials with known Fe isotopic signature in order to properly assess external reproducibility and data quality between laboratories. We report the most comprehensive study on the Fe isotopic composition for widely available international biological reference materials. They consist of different terrestrial and marine animal organs (bovine, porcine, tuna, and mussel) as well as apple leaves and human hair (ERC-CE464, NIST1515, ERM-DB001, ERM-BB186, ERM-BB184, ERM-CE196, BCR668, ERM-BB185, ERM-BB124). Previously measured Fe isotopic compositions were available for only two of these reference materials (ERC-CE464 tuna fish and ERM-BB186 pig kidney) and these literature data are in excellent agreement with our data. The Fe isotopic ratios are reported as the permil deviation of the 56Fe/54Fe ratio from the IRMM-014 standard. All reference materials present δ56Fe ranging from −2.27 to −0.35%0. Combined with existing data, our results suggest that animal models could provide useful analogues of the human body regarding the metabolic pathways affecting Fe isotopes, with many potential applications to medicine.
Pansclerotic Morphea Following COVID-19: A Case Report and Review of Literature on Rheumatologic and Non-rheumatologic Dermatologic Immune-Mediated Disorders Induced by SARS-CoV-2
Authors: Lotfi Zahra , Haghighi Anousheh , Akbarzadehpasha Amirhossein , Mozafarpoor Samaneh , Goodarzi Azadeh
Published: October 2021

While mucocutaneous manifestations of COVID-19 have been frequently reported and added to our knowledge every day during the pandemic, another issue is the COVID-related diseases that can present as intensified lesions of underlying diseases, a new disease, or changes in the behavior of an old lesion. Given that immune system overreaction and cytokine storm are among the most prominent events in COVID-19, the incidence of autoimmune diseases is expected to increase after COVID-19, as confirmed in several reports. To increase the body of knowledge about short- and long-term outcomes of COVID-19 for specialists, it is essential that similar cases be reported and collected for years to come. The present study investigated a case of pansclerotic morphea that rapidly progressed a few weeks after infection with COVID-19 in a 57-year-old woman with no history of any autoimmune skin or rheumatic diseases. She was prescribed outpatient COVID-19 treatment of azithromycin, vitamins D and C, and then quarantined for 2 weeks. The manifestations of the disease were exacerbated at each follow-up and sampling visit at short intervals. This kind of pansclerotic morphea is reported for the first time.
Identification of Genetic Signature Associated With Aging in Pulmonary Fibrosis
Authors: Lu Yanjiao , Chen Jinkun , Wang Shanshan , Tian Zhen , Fan Yan , Wang Meijia , Zhao Jianping , Tang Kun , Xie Jungang
Published: October 2021

Background: Aging is a strong risk factor and an independent prognostic factor in idiopathic pulmonary fibrosis (IPF). In this study, we aimed to conduct a comprehensive analysis based on gene expression profiles for the role of aging in pulmonary fibrosis.

Method: Four datasets (GSE21411, GSE24206, GSE47460, and GSE101286) for patients with clinical IPF and one dataset for bleomycin (BLM)-induced pulmonary fibrosis (BIPF) mouse model (GSE123293) were obtained from Gene Expression Omnibus (GEO). According to different age ranges, both patients with IPF and BIPF mice were divided into young and aged groups. The differently expressed genes (DEGs) were systemically analyzed using Gene Ontology (GO) functional, Kyoto Encyclopedia of Genes and Genomes (KEGG), and hub genes analysis. Finally, we verified the role of age and core genes associated with age in vivo.

Results:Via the expression profile comparisons of aged and young patients with IPF, we identified 108 aging-associated DEGs, with 21 upregulated and 87 downregulated. The DEGs were associated with “response to glucocorticoid,” “response to corticosteroid,” and “rhythmic process” in GO biological process (BP). For KEGG analysis, the top three significantly enriched KEGG pathways of the DEGs included “IL-17 signaling pathway,” “Mineral absorption,” and “HIF-1-signaling pathway.” Through the comparisons of aged and young BIPF mice, a total number of 778 aging-associated DEGs were identified, with 453 genes increased and 325 genes decreased. For GO and KEGG analysis, the DEGs were enriched in extracellular matrix (ECM) and collagen metabolism. The common DEGs of patients with IPF and BIPF mice were enriched in the BP category, including “induction of bacterial agglutination,” “hyaluronan biosynthetic process,” and “positive regulation of heterotypic cell-cell adhesion.” We confirmed that aged BIPF mice developed more serious pulmonary fibrosis. Finally, the four aging-associated core genes (Slc2a3, Fga, Hp, and Thbs1) were verified in vivo.

Conclusion: This study provides new insights into the impact of aging on pulmonary fibrosis. We also identified four aging-associated core genes (Slc2a3, Fga, Hp, and Thbs1) related to the development of pulmonary fibrosis.
Epidemiology and Regional Predictors of COVID-19 Clusters: A Bayesian Spatial Analysis Through a Nationwide Contact Tracing Data
Authors: Hong Kwan , Yum Sujin , Kim Jeehyun , Yoo Daesung , Chun Byung Chul
Published: October 2021

Purpose: Revealing the clustering risks of COVID-19 and prediction is essential for effective quarantine policies, since clusters can lead to rapid transmission and high mortality in a short period. This study aimed to present which regional and social characteristics make COVID-19 cluster with high risk.

Methods: By analyzing the data of all confirmed cases (14,423) in Korea between January 10 and August 3, 2020, provided by the Korea Disease Control and Prevention Agency, we manually linked each case and discovered clusters. After classifying the cases into clusters as nine types, we compared the duration and size of clusters by types to reveal high-risk cluster types. Also, we estimated odds for the risk factors for COVID-19 clustering by a spatial autoregressive model using the Bayesian approach.

Results: Regarding the classified clusters (n = 539), the mean size was 19.21, and the mean duration was 9.24 days. The number of clusters was high in medical facilities, workplaces, and nursing homes. However, multilevel marketing, religious facilities, and restaurants/business-related clusters tended to be larger and longer when an outbreak occurred. According to the spatial analysis in COVID-19 clusters of more than 20 cases, the global Moran's I statistics value was 0.14 (p < 0.01). After adjusting for population size, the risks of COVID-19 clusters were related to male gender (OR = 1.29) and low influenza vaccination rate (OR = 0.87). After the spatial modeling, the predicted probability of forming clusters was visualized and compared with the actual incidence and local Moran's I statistics 2 months after the study period.

Conclusions: COVID-19 makes different sizes of clusters in various contact settings; thus, precise epidemic control measures are needed. Also, when detecting and screening for COVID-19 clusters, regional risks such as vaccination rate should be considered for predicting risk to control the pandemic cost-effectively.
Abundance and Diversity of Ophiostomatoid Fungi Associated With the Great Spruce Bark Beetle (Dendroctonus micans) in the Northeastern Qinghai-Tibet Plateau
Authors: Wang Zheng , Zhou Qinzheng , Zheng Guiheng , Fang Jiaxing , Han Fuzhong , Zhang Xingyao , Lu Quan
Published: October 2021

The role of several virulent tree pathogens in host death has been overlooked because of the aggressiveness of their associated bark beetles. The great spruce bark beetle (Dendroctonus micans) is a widely distributed beetle that infests coniferous plants in Eurasia; however, its associated fungi have been poorly studied. Therefore, in this study, we elucidated the diversity of ophiostomatoid fungi associated with D. micans in the northeastern Qinghai-Tibet Plateau through field investigation, laboratory isolation, and culture analyses. A total of 220 strains of ophiostomatoid fungi were isolated from adults and tunnel galleries of D. micans infesting Picea crassifolia. We identified that the isolated strains belonged to eight ophiostomatoid species, including five new species (Ophiostoma huangnanense sp. nov., Ophiostoma maixiuense sp. nov., Ophiostoma sanum sp. nov., Leptographium sanjiangyuanense sp. nov., and Leptographium zekuense sp. nov.), one undefined species (Ophiostoma sp. 1), and two known species (Ophiostoma bicolor and Endoconidiophora laricicola), using phylogenetic analysis of multigene DNA sequences and morphological characteristics. This is the first time that E. laricicola, a pioneer invader and virulent pathogen, has been reported in China. We found that E. laricicola was the dominant species, accounting for 40.91% of the total number of ophiostomatoid communities. This study enriched the knowledge of the fungal associates of D. micans and elucidated that it carried the virulent pathogen E. laricicola at a surprisingly high frequency. Our findings show increased species association between D. micans and ophiostomatoid fungi and provide a basis for understanding the occurrence of forest diseases and pests.
Dining in Blue Light Impairs the Appetite of Some Leaf Epiphytes
Authors: Alsanius Beatrix W. , Vaas Lea , Gharaie Samareh , Karlsson Maria E. , Rosberg Anna Karin , Wohanka Walter , Khalil Sammar , Windstam Sofia
Published: October 2021

Background:The phyllosphere is subjected to fluctuating abiotic conditions. This study examined the phenotypic plasticity (PP) of four selected non-phototrophic phyllosphere bacteria [control strain:Pseudomonassp. DR 5-09;Pseudomonas agarici,Bacillus thuringiensisserovarisraeliensis(Bti), andStreptomyces griseoviridis(SG)] regarding their respiration patterns and surfactant activity as affected by light spectrum and nutrient supply.

Methods:The PP of the strains was examined under four light regimes [darkness (control); monochromatic light-emitting diodes (LED) at 460 nm (blue) and 660 nm (red); continuously polychromatic white LEDs], in the presence of 379 substrates and conditions.

Results:Light treatment affected the studied bacterial strains regarding substrate utilization (Pseudomonasstrains > SG > Bti). Blue LEDs provoked the most pronounced impact on the phenotypic reaction norms of thePseudomonasstrains and Bti. The two Gram-positive strains Bti and SG, respectively, revealed inconsistent biosurfactant formation in all cases. Biosurfactant formation by bothPseudomonasstrains was supported by most substrates incubated in darkness, and blue LED exposure altered the surface activity profoundly. Blue and white LEDs enhanced biofilm formation in PA in highly utilized C-sources. Putative blue light receptor proteins were found in bothPseudomonasstrains, showing 91% similarity with the sequence from NCBI accession numberWP_064119393.

Conclusion:Light quality–nutrient interactions affect biosurfactant activity and biofilm formation of some non-phototrophic phyllosphere bacteria and are, thus, crucial for dynamics of the phyllosphere microbiome.
Quantitative PCR to Discriminate Between Pneumocystis Pneumonia and Colonization in HIV and Non-HIV Immunocompromised Patients
Authors: Sarasombath Patsharaporn T. , Thongpiya Jerapas , Chulanetra Monrat , Wijit Sirirat , Chinabut Pisith , Ongrotchanakun Jeerawan , Jitmuang Anupop , Wanachiwanawin Darawan
Published: October 2021

Pneumocystispneumonia (PCP) is an opportunistic infection that commonly occurs in immunocompromised individuals. A definite diagnosis of PCP can be made only when the organism is identified in a respiratory specimen. It remains unclear whether qPCR can differentiate patients with PCP from those withPneumocystis jiroveciicolonization. In this study, we retrospectively collected data from HIV and non-HIV patients during 2013–2019. A diagnosis of definite, probable PCP, or PCP excluded was made based on clinical criteria, radiological reports, and three standard laboratory staining methods with blinding to qPCR data. Data from qPCR that was performed to determine the fungal burden (DNA copies/μl) in the BAL specimens of 69 HIV and 286 non-HIV patients were then obtained and reviewed. Receiver Operating Characteristic (ROC) curve analysis was performed to determine the upper and lower cut-off values for PCP diagnosis in HIV and non-HIV groups. In the non-HIV group, the lower cut-off value of 1,480 DNA copies/μl yielded a sensitivity of 100% (95% confidence interval [CI], 91.0–100), specificity of 72.9% (95% CI, 64.0–80.7), a positive predictive value (PPV) of 54.9% (95% CI, 47.6–62.1), and a negative predictive value (NPV) of 100% with Youden index of 0.73 for PCP diagnosis. In this group, the upper cut-off value of 9,655 DNA copies/μl showed the sensitivity of 100% (95% CI, 91.0–100) and specificity of 95.8% (95% CI, 90.4–98.6) with PPV of 88.6% (95% CI, 76.8–94.8) and a NPV of 100% with Youden index of 0.96 for PCP diagnosis. Regarding the HIV group, the lower cut-off value of 1,480 DNA copies/μl showed the sensitivity of 100% (95% CI, 92.5–100%) and specificity of 91.7% (95% CI, 61.5–99.8) with PPV of 97.9% (95% CI, 87.8–99.7) and a NPV of 100% with Youden index of 0.92 for PCP diagnosis. The sensitivity and specificity of the upper cut-off value of 12,718 DNA copies/μl in this group were 97.9% (95%CI, 88.7–100) and 100% (95%CI, 73.5–100), respectively. The values above the upper cut-off point had a PPV of 100% (95% CI, N/A) and a NPV of 92.3% (95% CI, 63.3–98.8) with Youden index of 0.98 for PCP diagnosis in the HIV group.
Functional Severe Acute Respiratory Syndrome Coronavirus 2 Virus-Like Particles From Insect Cells
Authors: Naskalska Antonina , Dabrowska Agnieszka , Szczepanski Artur , Jasik Krzysztof P. , Gromadzka Beata , Pyrc Krzysztof
Published: October 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a major epidemic threat since the beginning of 2020. Efforts to combat the virus and the associated coronavirus disease 2019 (COVID-19) disease are being undertaken worldwide. To facilitate the research on the virus itself, a number of surrogate systems have been developed. Here, we report the efficient production of SARS-CoV-2 virus-like particles (VLPs) in insect cells. Contrary to widely used pseudovirus particles, where only one coronaviral protein is displayed within a heterologous scaffold, developed VLPs are structurally similar to the native virus and allow for more throughput studies on the biology of the infection. On the other hand, being devoid of the viral genome, VLPs are unable to replicate and thus safe to work with. Importantly, this is the first report showing that SARS-CoV-2 VLPs can be efficiently produced in insect cells and purified using scalable affinity chromatography.
A New Protocruzia Species (Ciliophora: Protocruziida) Isolated From the Mariana Trench Area
Authors: Liang Chen , Wang Wei , Dong Liang , Mukhtar Irum , Wang Fengping , Chen Jianming
Published: October 2021

A new species of Protocruzia, isolated from the deep-sea Pacific Ocean (>3,000-m depth) in the vicinity of the Mariana Trench, is described based on morphological and molecular data. The systematic status of the ciliate genus Protocruzia has long been highly ambiguous, and Protocruzia species have been assigned to an independent class until recently. In the present study, we described Protocruzia marianaensis sp. n. as a small (25–32 × 14–17 μm in vivo) drop-shaped ciliate, with longitudinal furrows along the ciliary rows on the right side, six adoral membranelles, eight somatic kineties, and one macronucleus comprising 7–11 nuclear globules. Phylogenetic analyses inferred from small subunit rRNA gene sequences revealed that seven Protocruzia species in the phylogenetic tree formed a fully supported clade representing an independent class. Protocruzia marianaensis sp. n. was established to be most closely related to Protocruzia adhaerens, with a sequence similarity of 96.64%, and was found to be able to survive at both atmospheric pressure and hydrostatic pressure of 320 bar, thereby indicating effective barotolerance.
On the Cluster Formation of α-Synuclein Fibrils
Authors: Dubackic Marija , Idini Ilaria , Lattanzi Veronica , Liu Yun , Martel Anne , Terry Ann , Haertlein Michael , Devos Juliette M. , Jackson Andrew , Sparr Emma , Linse Sara , Olsson Ulf
Published: October 2021

The dense accumulation of α-Synuclein fibrils in neurons is considered to be strongly associated with Parkinson’s disease. These intracellular inclusions, called Lewy bodies, also contain significant amounts of lipids. To better understand such accumulations, it should be important to study α-Synuclein fibril formation under conditions where the fibrils lump together, mimicking what is observed in Lewy bodies. In the present study, we have therefore investigated the overall structural arrangements of α-synuclein fibrils, formed under mildly acidic conditions, pH = 5.5, in pure buffer or in the presence of various model membrane systems, by means of small-angle neutron scattering (SANS). At this pH, α-synuclein fibrils are colloidally unstable and aggregate further into dense clusters. SANS intensities show a power law dependence on the scattering vector,q, indicating that the clusters can be described as mass fractal aggregates. The experimentally observed fractal dimension wasd= 2.6 ± 0.3. We further show that this fractal dimension can be reproduced using a simple model of rigid-rod clusters. The effect of dominatingly attractive fibril-fibril interactions is discussed within the context of fibril clustering in Lewy body formation.
Sleep Quality Mediates the Association Between Cerebral Small Vessel Disease Burden and Frailty: A Community-Based Study
Authors: Zhao Jing , Qu Wensheng , Zhou Xirui , Guo Yinping , Zhang Yi , Wu Lingshan , Yu Zhiyuan , Huang Hao , Luo Xiang
Published: October 2021

Background: Physical frailty is a common problem among older adults which usually leads to adverse health outcomes. The imaging markers of cerebral small vessel disease (CSVD) are associated with frailty, but the underlying mechanisms remain unclear. The present study aimed to investigate the mediating role of sleep quality in the relationship between CSVD burden and frailty.

Methods: We performed a cross-sectional study and enrolled community residents. Frailty and sleep quality were measured using the Fried frailty phenotype and the Pittsburgh Sleep Quality Index (PSQI), respectively. A multivariate linear regression analysis and a Bootstrap analysis were performed to examine the association among the key variables and the mediating role of sleep quality.

Results: Of the 726 participants (mean age: 65.5 ± 6.5 years, 59.8% female), the numbers (percentages) of the frail, prefrail, and robust residents were 49 (6.7%), 310 (42.7%), and 367 (50.6%), respectively. After adjusting for covariates, the CSVD burden and PSQI score were significantly associated with the frailty score. In addition, sleep quality played a partial mediating role in the association between CSVD burden and physical frailty. The mediating effect was 21.9%.

Conclusion: The present study suggests that sleep quality is a mediator of this association between CSVD and frailty in community-dwelling older adults. Improving sleep quality might be helpful to mitigate the risk of frailty in CSVD patients.
Methamphetamine and Modulation Functionality of the Prelimbic Cortex for Developing a Possible Treatment of Alzheimer’s Disease in an Animal Model
Authors: Shyu Bai-Chuang , Gao Zhi-Yue , Wu José Jiun-Shian , He Alan Bo Han , Cheng Cai-N , Huang Andrew Chih Wei
Published: October 2021

Alzheimer’s disease (AD) is a progressive neurodegenerative condition that causes cognitive impairment and other neuropsychiatric symptoms. Previously, little research has thus far investigated whether methamphetamine (MAMPH) can enhance cognitive function or ameliorate AD symptoms. This study examined whether a low dose of MAMPH can induce conditioned taste aversion (CTA) learning, or can increase plasma corticosterone levels, neural activity, and neural plasticity in the medial prefrontal cortex (mPFC) (responsible for cognitive function), the nucleus accumbens (NAc) and the amygdala (related to rewarding and aversive emotion), and the hippocampus (responsible for spatial learning). Furthermore, the excitations or lesions of the prelimbic cortex (PrL) can affect MAMPH-induced CTA learning, plasma corticosterone levels, and neural activity or plasticity in the mPFC [i.e., PrL, infralimbic cortex (IL), cingulate cortex 1 (Cg1)], the NAc, the amygdala [i.e., basolateral amygdala (BLA) and central amygdala (CeA)], and the hippocampus [i.e., CA1, CA2, CA3, and dentate gyrus (DG)]. In the experimental procedure, the rats were administered either saline or NMDA solutions, which were injected into the PrL to excite or destroy PrL neurons. Additionally, rats received 0.1% saccharin solution for 15 min, followed by intraperitoneal injections of either normal saline or 1 mg/kg MAMPH to induce CTA. A one-way ANOVA was performed to analyze the effects of saccharin intake on CTA, plasma corticosterone levels, and the expression of c-Fos and p-ERK. The results showed that the MAMPH induced CTA learning and increased plasma corticosterone levels. The mPFC, and particularly the PrL and IL and the DG of the hippocampus, appeared to show increased neural activity in c-Fos expression or neural plasticity in p-ERK expression. The excitation of the PrL neurons upregulated neural activity in c-Fos expression and neural plasticity in p-ERK expression in the PrL and IL. In summary, MAMPH may be able to improve cognitive and executive function in the brain and reduce AD symptoms. Moreover, the excitatory modulation of the PrL with MAMPH administration can facilitate MAMPH-induced neural activity and plasticity in the PrL and IL of the mPFC. The present data provide clinical implications for developing a possible treatment for AD in an animal model.
Role of Glia-Derived Extracellular Vesicles in Neurodegenerative Diseases
Authors: Li Tianbai , Tan Xiang , Li Song , Al-Nusaif Murad , Le Weidong
Published: October 2021

Extracellular vesicles (EVs), as nano-sized vesicles secreted by almost all cells, have been recognized as the essential transmitter for cell-to-cell communication and participating in multiple biological processes. Neurodegenerative diseases (ND), such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, share common mechanisms of the aggregation and propagation of distinct pathologic proteins among cells in the nervous systems and neuroinflammatory reactions mediated by glia during the pathogenic process. This feature indicates the vital role of crosstalk between neurons and glia in the pathogenesis of ND. In recent years, glia-derived EVs have been investigated as potential mediators of signals between neurons and glia, which provides a new direction and strategy for understanding ND. By a comprehensive summary, it can be concluded that glia-derived EVs have both a beneficial and/or a detrimental effect in the process of ND. Therefore, this review article conveys the role of glia-derived EVs in the pathogenesis of ND and raises current limitations of their potential application in the diagnosis and treatment of ND.
Functional Brain Networks in Mild Cognitive Impairment Based on Resting Electroencephalography Signals
Authors: Youssef Nadia , Xiao Shasha , Liu Meng , Lian Haipeng , Li Renren , Chen Xi , Zhang Wei , Zheng Xiaoran , Li Yunxia , Li Yingjie
Published: October 2021

The oscillatory patterns of electroencephalography (EEG), during resting states, are informative and helpful in understanding the functional states of brain network and their contribution to behavioral performances. The aim of this study is to characterize the functional brain network alterations in patients with amnestic mild cognitive impairment (aMCI). To this end, rsEEG signals were recorded before and after a cognitive task. Functional connectivity metrics were calculated using debiased weighted phase lag index (DWPLI). Topological features of the functional connectivity network were analyzed using both the classical graph approach and minimum spanning tree (MST) algorithm. Subsequently, the network and connectivity values together with Mini-Mental State Examination cognitive test were used as features to classify the participants. Results showed that: (1) across the pre-task condition, in the theta band, the aMCI group had a significantly lower global mean DWPLI than the control group; the functional connectivity patterns were different in the left hemisphere between two groups; the aMCI group showed significantly higher average clustering coefficient and the remarkably lower global efficiency than the control. (2) Analysis of graph measures under post-task resting state, unveiled that for the percentage change of post-task vs. pre-task in beta EEG, a significant increase in tree hierarchy was observed in aMCI group (2.41%) than in normal control (−3.89%); (3) Furthermore, the classification analysis of combined measures of functional connectivity, brain topology, and MMSE test showed improved accuracy compared to the single method, for which the connectivity patterns and graph metrics were used as separate inputs. The classification accuracy obtained for the case of post-task resting state was 87.2%, while the one achieved under pre-task resting state was found to be 77.7%. Therefore, the functional network alterations in aMCI patients were more prominent during the post-task resting state. This study suggests that the disintegration observed in MCI functional network during the resting states, preceding and following a task, might be possible biomarkers of cognitive dysfunction in aMCI patients.
Abnormal Cerebral Blood Flow and Functional Connectivity Strength in Subjects With White Matter Hyperintensities
Authors: Huang Hao , Zhao Kun , Zhu Wenzhen , Li Hui , Zhu Wenhao
Published: October 2021

White matter hyperintensities (WMHs) are common neuroimaging findings in the aging population and are associated with various clinical symptoms, especially cognitive impairment. Abnormal global cerebral blood flow (CBF) and specific functional connections have been reported in subjects with higher WMH loads. Nevertheless, the comprehensive functional mechanisms underlying WMH are yet to be established. In this study, by combining resting-state functional magnetic resonance imaging and arterial spin labeling, we investigated the neurovascular dysfunction in subjects with WMH in CBF, functional connectivity strength (FCS), and CBF–FCS coupling. The whole-brain alterations of all these measures were explored among non-dementia subjects with different WMH loads using a fine-grained Human Brainnetome Atlas. In addition, exploratory mediation analyses were conducted to further determine the relationships between these neuroimaging indicators, WMH load, and cognition. The results showed that subjects with higher WMH loads displayed decreased CBF and FCS mainly in regions involving the cognitive- and emotional-related brain networks, including the default mode network, salience network, and central executive network. Notably, subjects with higher WMH loads also showed an abnormal regional CBF–FCS coupling in several regions of the thalamus, posterior cingulate cortex, and parahippocampal gyrus involving the default mode network. Furthermore, regional CBF in the right inferior temporal gyrus and right dorsal caudate may mediate the relationship between WMH load and cognition in WMH subjects. These findings indicated characteristic changes in cerebral blood supply, brain activity, and neurovascular coupling in regions involving specific brain networks with the development of WMH, providing further information on pathophysiology underpinnings of the WMH and related cognitive impairment.
Distribution of Diagnoses and Clinical and Imaging Characteristics in 1,322 Consecutive Suspected Stroke Patients
Authors: Sporns Peter B. , Brehm Alex , Hilgers Caroline , Ntoulias Nikolaos , Tsogkas Ioannis , Psychogios Marios
Published: October 2021

Background: Endovascular thrombectomy (EVT) has become the standard of care for large-vessel occlusion strokes, but several barriers for implementing an optimal organization of stroke management remain. Major issues include the lack of reliable data on the percentage of stroke patients potentially eligible for EVT especially in times of expanding indications for EVT. Our aim was therefore to study the frequencies of possible EVT-eligible patients such as patients with medium-vessel occlusions, patients with low Alberta Stroke Program Early Computed Tomography Scores (ASPECTS), patients presenting in an extended time window after onset of symptoms, and patients with mild symptoms at presentation (National Institutes of Health Stroke Scale, NIHSS ≤ 5). We also give detailed imaging and clinical information about the patients presenting with intracranial hemorrhage and other ischemic stroke mimics stratified by symptoms at presentation.

Methods: Cohort study of all consecutive patients with suspected acute stroke presenting to a tertiary care center in Germany between September 1, 2016, and August 31, 2017. Baseline and follow-up clinical and imaging characteristics were collected from patients' medical charts.

Results: Of 1,322 patients with a suspected acute stroke, 592 (44.8%) had ischemic strokes, 221 (16.7%) had hemorrhagic strokes, 190 (10.9%) had transient ischemic attacks (TIAs), and 319 (24.1%) were classified as stroke mimics. Stroke severity was mild (NIHSS ≤ 5) in 866 (65.5%) patients; 15.7% of the patients with an occlusion of the anterior circulation had an ASPECTS ≤ 5, 17.4% of the patients with an ischemic stroke had distal vessel occlusions, and 49% of the patients presented later than 6 h after onset of symptoms.

Conclusion: Our results help to plan resources in thrombectomy-capable centers in times of expanding indications for EVT where resources will have to be adjusted to patients with low-NIHSS, low-ASPECTS, and distal occlusions, and patients presenting in the extended time window, which may altogether account for an additional 20% of all ischemic stroke patients.
Classification of Obsessive-Compulsive Disorder Using Distance Correlation on Resting-State Functional MRI Images
Authors: Luo Qian , Liu Weixiang , Jin Lili , Chang Chunqi , Peng Ziwen
Published: October 2021

Both the Pearson correlation and partial correlation methods have been widely used in the resting-state functional MRI (rs-fMRI) studies. However, they can only measure linear relationship, although partial correlation excludes some indirect effects. Recent distance correlation can discover both the linear and non-linear dependencies. Our goal was to use the multivariate pattern analysis to compare the ability of such three correlation methods to distinguish between the patients with obsessive-compulsive disorder (OCD) and healthy control subjects (HCSs), so as to find optimal correlation method. The main process includes four steps. First, the regions of interest are defined by automated anatomical labeling (AAL). Second, functional connectivity (FC) matrices are constructed by the three correlation methods. Third, the best discriminative features are selected by support vector machine recursive feature elimination (SVM-RFE) with a stratified N-fold cross-validation strategy. Finally, these discriminative features are used to train a classifier. We had a total of 128 subjects out of which 61 subjects had OCD and 67 subjects were normal. All the three correlation methods with SVM have achieved good results, among which distance correlation is the best [accuracy = 93.01%, specificity = 89.71%, sensitivity = 95.08%, and area under the receiver-operating characteristic curve (AUC) = 0.94], followed by Pearson correlation and partial correlation is the last. The most discriminative regions of the brain for distance correlation are right dorsolateral superior frontal gyrus, orbital part of left superior frontal gyrus, orbital part of right middle frontal gyrus, right anterior cingulate and paracingulate gyri, left the supplementary motor area, and right precuneus, which are the promising biomarkers of OCD.
Consciousness as a Product of Evolution: Contents, Selector Circuits, and Trajectories in Experience Space
Authors: Lacalli Thurston
Published: October 2021

Conscious experience can be treated as a complex unified whole, but to do so is problematic from an evolutionary perspective if, like other products of evolution, consciousness had simple beginnings, and achieved complexity only secondarily over an extended period of time as new categories of subjective experience were added and refined. The premise here is twofold, first that these simple beginnings can be investigated regardless of whether the ultimate source of subjective experience is known or understood, and second, that of the contents known to us, the most accessible for investigation will be those that are, or appear, most fundamental, in the sense that they resist further deconstruction or analysis. This would include qualia as they are usually defined, but excludes more complex experiences (here, formats) that are structured, or depend on algorithmic processes and/or memory. Vision and language for example, would by this definition be formats. More formally, qualia, but not formats, can be represented as points, lines, or curves on a topological experience space, and as domains in a configuration space representing a subset of neural correlates of consciousness, the selector circuits (SCs), responsible for ensuring that a particular experience is evoked rather than some other. It is a matter of conjecture how points in SC-space map to experience space, but both will exhibit divergence, insuring that a minimal distance separates points in experience space representing different qualia and the SCs that evoke them. An analysis of how SCs evolve over time is used to highlight the importance of understanding patterns of descent among putative qualia, i.e., their homology across species, and whether this implies descent from an ancestral experience, or ur-quale, that combines modes of experience that later came to be experienced separately. The analysis also provides insight into the function of consciousness as viewed from an evolutionary perspective, defined here in terms of the access it allows to regions of SC-space that would otherwise be unavailable to real brains, to produce consciously controlled behaviors that could otherwise not occur.
SMRT: Randomized Data Transformation for Cancer Subtyping and Big Data Analysis
Authors: Nguyen Hung , Tran Duc , Tran Bang , Roy Monikrishna , Cassell Adam , Dascalu Sergiu , Draghici Sorin , Nguyen Tin
Published: October 2021

Cancer is an umbrella term that includes a range of disorders, from those that are fast-growing and lethal to indolent lesions with low or delayed potential for progression to death. The treatment options, as well as treatment success, are highly dependent on the correct subtyping of individual patients. With the advancement of high-throughput platforms, we have the opportunity to differentiate among cancer subtypes from a holistic perspective that takes into consideration phenomena at different molecular levels (mRNA, methylation, etc.). This demands powerful integrative methods to leverage large multi-omics datasets for a better subtyping. Here we introduce Subtyping Multi-omics using a Randomized Transformation (SMRT), a new method for multi-omics integration and cancer subtyping. SMRT offers the following advantages over existing approaches: (i) the scalable analysis pipeline allows researchers to integrate multi-omics data and analyze hundreds of thousands of samples in minutes, (ii) the ability to integrate data types with different numbers of patients, (iii) the ability to analyze un-matched data of different types, and (iv) the ability to offer users a convenient data analysis pipeline through a web application. We also improve the efficiency of our ensemble-based, perturbation clustering to support analysis on machines with memory constraints. In an extensive analysis, we compare SMRT with eight state-of-the-art subtyping methods using 37 TCGA and two METABRIC datasets comprising a total of almost 12,000 patient samples from 28 different types of cancer. We also performed a number of simulation studies. We demonstrate that SMRT outperforms other methods in identifying subtypes with significantly different survival profiles. In addition, SMRT is extremely fast, being able to analyze hundreds of thousands of samples in minutes. The web application is available at http://SMRT.tinnguyen-lab.com. The R package will be deposited to CRAN as part of our PINSPlus software suite.
Proteomics-Based Identification of Candidate Exosomal Glycoprotein Biomarkers and Their Value for Diagnosing Colorectal Cancer
Authors: Sun Zujun , Ji Shurong , Wu Junlu , Tian Jiale , Quan Wenqiang , Shang Anquan , Ji Ping , Xiao Weidong , Liu Ding , Wang Xuan , Li Dong
Published: October 2021

Early diagnosis and treatment of colorectal cancer (CRC) significantly improves the survival rate and quality of life. Here we screened for differences in glycoproteins associated with tumor-derived exosomes and validated their clinical value to serve as liquid biopsy biomarkers to diagnosed early CRC. Exosomes were extracted from paracancerous tissues, cancer tissues, and plasma. LC-MS/MS proteomic and glycoproteomics analyses were performed using an LTQ-Orbitrap Elite mass spectrometer. The differences in glycoproteins associated with exosomes of paracancerous tissues and cancer tissue were determined, and their levels in plasma exosomes were determined. Statistical analysis was performed to evaluate the diagnostic efficacy of exosome-associated glycoproteins for CRC. We found that the levels of fibrinogen beta chain (FGB) and beta-2-glycoprotein 1 (β2-GP1) in the exosome of CRC tissue were significantly higher compared with those of paracancerous tissues exosome. The areas under the receiver operating characteristic (ROC) curves of plasma exosomal FGB and β2-GP1 as biomarkers for CRC were 0.871 (95% CI = 0.786–0.914) and 0.834 (95% CI = 0.734–0.901), respectively, compared with those of the concentrations of carcinoembryonic antigen concentration [0.723 (95% CI = 0.679–0.853)] and carbohydrate antigen19-9 concentration [0.614 (95% CI = 0.543–0.715)]. Comprehensive proteomics analyses of plasma exosomal biomarkers in CRC identified biomarkers with significant diagnostic efficacy for early CRC, which can be measured using relatively non-invasive techniques.