bluuebunny/crossref_metadata_2025 huggingface dataset:
Plant Glycan Metabolism by Bifidobacteria
Authors: Kelly Sandra M. , Munoz-Munoz Jose , van Sinderen Douwe
Published: February 2021

Members of the genus Bifidobacterium, of which the majority have been isolated as gut commensals, are Gram-positive, non-motile, saccharolytic, non-sporulating, anaerobic bacteria. Many bifidobacterial strains are considered probiotic and therefore are thought to bestow health benefits upon their host. Bifidobacteria are highly abundant among the gut microbiota of healthy, full term, breast-fed infants, yet the relative average abundance of bifidobacteria tends to decrease as the human host ages. Because of the inverse correlation between bifidobacterial abundance/prevalence and health, there has been an increasing interest in maintaining, increasing or restoring bifidobacterial populations in the infant, adult and elderly gut. In order to colonize and persist in the gastrointestinal environment, bifidobacteria must be able to metabolise complex dietary and/or host-derived carbohydrates, and be resistant to various environmental challenges of the gut. This is not only important for the autochthonous bifidobacterial species colonising the gut, but also for allochthonous bifidobacteria provided as probiotic supplements in functional foods. For example, Bifidobacterium longum subsp. longum is a taxon associated with the metabolism of plant-derived poly/oligosaccharides in the adult diet, being capable of metabolising hemicellulose and various pectin-associated glycans. Many of these plant glycans are believed to stimulate the metabolism and growth of specific bifidobacterial species and are for this reason classified as prebiotics. In this review, bifidobacterial carbohydrate metabolism, with a focus on plant poly-/oligosaccharide degradation and uptake, as well as its associated regulation, will be discussed.
The Structure of Rhizosphere Fungal Communities of Wild and Domesticated Rice: Changes in Diversity and Co-occurrence Patterns
Authors: Chang Jingjing , Sun Yu , Tian Lei , Ji Li , Luo Shasha , Nasir Fahad , Kuramae Eiko E. , Tian Chunjie
Published: February 2021

The rhizosphere fungal community affects the ability of crops to acquire nutrients and their susceptibility to pathogen invasion. However, the effects of rice domestication on the diversity and interactions of rhizosphere fungal community still remain largely unknown. Here, internal transcribed spacer amplicon sequencing was used to systematically analyze the structure of rhizosphere fungal communities of wild and domesticated rice. The results showed that domestication increased the alpha diversity indices of the rice rhizosphere fungal community. The changes of alpha diversity index may be associated with the enrichment of Acremonium, Lecythophora, and other specific rare taxa in the rhizosphere of domesticated rice. The co-occurrence network showed that the complexity of wild rice rhizosphere fungal community was higher than that of the domesticated rice rhizosphere fungal community. Arbuscular mycorrhizal fungi (AMF) and soilborne fungi were positively and negatively correlated with more fungi in the wild rice rhizosphere, respectively. For restructuring the rhizomicrobial community of domesticated crops, we hypothesize that microbes that hold positive connections with AMF and negative connections with soilborne fungi can be used as potential sources for bio-inoculation. Our findings provide a scientific basis for reshaping the structure of rhizomicrobial community and furthermore create potential for novel intelligent and sustainable agricultural solutions.
Soil Texture, Sampling Depth and Root Hairs Shape the Structure of ACC Deaminase Bacterial Community Composition in Maize Rhizosphere
Authors: Gebauer Lucie , Bouffaud Marie-Lara , Ganther Minh , Yim Bunlong , Vetterlein Doris , Smalla Kornelia , Buscot François , Heintz-Buschart Anna , Tarkka Mika T.
Published: February 2021

Preservation of the phytostimulatory functions of plant growth-promoting bacteria relies on the adaptation of their community to the rhizosphere environment. Here, an amplicon sequencing approach was implemented to specifically target microorganisms with 1-aminocyclopropane-1-carboxylate deaminase activity, carrying the acdS gene. We stated the hypothesis that the relative phylogenetic distribution of acdS carrying microorganisms is affected by the presence or absence of root hairs, soil type, and depth. To this end, a standardized soil column experiment was conducted with maize wild type and root hair defective rth3 mutant in the substrates loam and sand, and harvest was implemented from three depths. Most acdS sequences (99%) were affiliated to Actinobacteria and Proteobacteria, and the strongest influence on the relative abundances of sequences were exerted by the substrate. Variovorax, Acidovorax, and Ralstonia sequences dominated in loam, whereas Streptomyces and Agromyces were more abundant in sand. Soil depth caused strong variations in acdS sequence distribution, with differential levels in the relative abundances of acdS sequences affiliated to Tetrasphaera, Amycolatopsis, and Streptomyces in loam, but Burkholderia, Paraburkholderia, and Variovorax in sand. Maize genotype influenced the distribution of acdS sequences mainly in loam and only in the uppermost depth. Variovorax acdS sequences were more abundant in WT, but Streptomyces, Microbacterium, and Modestobacter in rth3 rhizosphere. Substrate and soil depth were strong and plant genotype a further significant single and interacting drivers of acdS carrying microbial community composition in the rhizosphere of maize. This suggests that maize rhizosphere acdS carrying bacterial community establishes according to the environmental constraints, and that root hairs possess a minor but significant impact on acdS carrying bacterial populations.
Temporal Patterns and Intra- and Inter-Cellular Variability in Carbon and Nitrogen Assimilation by the Unicellular Cyanobacterium Cyanothece sp. ATCC 51142
Authors: Polerecky Lubos , Masuda Takako , Eichner Meri , Rabouille Sophie , Vancová Marie , Kienhuis Michiel V. M. , Bernát Gabor , Bonomi-Barufi Jose , Campbell Douglas Andrew , Claquin Pascal , Červený Jan , Giordano Mario , Kotabová Eva , Kromkamp Jacco , Lombardi Ana Teresa , Lukeš Martin , Prášil Ondrej , Stephan Susanne , Suggett David , Zavřel Tomas , Halsey Kimberly H.
Published: February 2021

Unicellular nitrogen fixing cyanobacteria (UCYN) are abundant members of phytoplankton communities in a wide range of marine environments, including those with rapidly changing nitrogen (N) concentrations. We hypothesized that differences in N availability (N2 vs. combined N) would cause UCYN to shift strategies of intracellular N and C allocation. We used transmission electron microscopy and nanoscale secondary ion mass spectrometry imaging to track assimilation and intracellular allocation of 13C-labeled CO2 and 15N-labeled N2 or NO3 at different periods across a diel cycle in Cyanothece sp. ATCC 51142. We present new ideas on interpreting these imaging data, including the influences of pre-incubation cellular C and N contents and turnover rates of inclusion bodies. Within cultures growing diazotrophically, distinct subpopulations were detected that fixed N2 at night or in the morning. Additional significant within-population heterogeneity was likely caused by differences in the relative amounts of N assimilated into cyanophycin from sources external and internal to the cells. Whether growing on N2 or NO3, cells prioritized cyanophycin synthesis when N assimilation rates were highest. N assimilation in cells growing on NO3 switched from cyanophycin synthesis to protein synthesis, suggesting that once a cyanophycin quota is met, it is bypassed in favor of protein synthesis. Growth on NO3 also revealed that at night, there is a very low level of CO2 assimilation into polysaccharides simultaneous with their catabolism for protein synthesis. This study revealed multiple, detailed mechanisms underlying C and N management in Cyanothece that facilitate its success in dynamic aquatic environments.
Introduction of Colonic and Fecal Microbiota From an Adult Pig Differently Affects the Growth, Gut Health, Intestinal Microbiota and Blood Metabolome of Newborn Piglets
Authors: Qi Renli , Zhang Zhuo , Wang Jing , Qiu Xiaoyu , Wang Qi , Yang Feiyun , Huang Jinxiu , Liu Zuohua
Published: February 2021

Microbiota transplantation is a rapid and effective method for changing and reshaping the intestinal microbiota and metabolic profile in humans and animals. This study compared the different influences of the introduction of fecal microbes and colonic microbes from a fat, adult pig in newborn pigs. Both colonic microbiota transplantation (CMT) and fecal microbiota transplantation (FMT) promoted growth and improved gut functions in suckling pigs up to weaning. FMT was more beneficial for body weight gain and body fat deposition in piglets, while CMT was more beneficial for intestinal health and mucosal immunity. 16S rDNA sequence analysis indicated that both CMT and FMT significantly increased the abundances of beneficial or functional bacteria, such as Lactobacillus and Prevotella_2 genera, in the piglets, and reduced the abundances of harmful bacteria, such as Escherichia–Shigella. Blood metabolome analysis showed that transplantation, especially FMT, enhanced lipid metabolism in piglets. In addition, while CMT also changed amino acid metabolism and increased anti-inflammatory metabolites such as 3-indoleacetic acid and 3-indolepropionic acid in piglets, FMT did not. Of note, FMT damaged the intestinal barrier of piglets to a certain extent and increased the levels of inflammatory factors in the blood that are potentially harmful to the health of pigs. Taken together, these results suggested that intestinal and fecal microbiota transplantations elicited similar but different physiological effects on young animals, so the application of microbiota transplantation in animal production requires the careful selection and evaluation of source bacteria.
Outer Membrane Vesicle Induction and Isolation for Vaccine Development
Authors: Balhuizen Melanie D. , Veldhuizen Edwin J. A. , Haagsman Henk P.
Published: February 2021

Gram-negative bacteria release vesicular structures from their outer membrane, so called outer membrane vesicles (OMVs). OMVs have a variety of functions such as waste disposal, communication, and antigen or toxin delivery. These vesicles are the promising structures for vaccine development since OMVs carry many surface antigens that are identical to the bacterial surface. However, isolation is often difficult and results in low yields. Several methods to enhance OMV yield exist, but these do affect the resulting OMVs. In this review, our current knowledge about OMVs will be presented. Different methods to induce OMVs will be reviewed and their advantages and disadvantages will be discussed. The effects of the induction and isolation methods used in several immunological studies on OMVs will be compared. Finally, the challenges for OMV-based vaccine development will be examined and one example of a successful OMV-based vaccine will be presented.
Species Diversity and Molecular Phylogeny of Cyanosporus (Polyporales, Basidiomycota)
Authors: Liu Shun , Shen Lu-Lu , Wang Yan , Xu Tai-Min , Gates Genevieve , Cui Bao-Kai
Published: February 2021

Cyanosporus is a cosmopolitan brown-rot fungal genus, recognizable by blue-tinted basidiocarps. Species in this genus were usually treated as belonging to the Postia caesia complex, however, recent phylogenetic analyses showed that this complex represents an independent genus. During further studies on Cyanosporus, five new species were discovered based on morphological features and molecular data. Phylogenetic analyses of Cyanosporus were conducted using the internal transcribed spacer (ITS) regions, the large subunit of nuclear ribosomal RNA gene (nLSU), the small subunit of nuclear ribosomal RNA gene (nSSU), the small subunit of mitochondrial rRNA gene (mtSSU), the largest subunit of RNA polymerase II (RPB1), the second largest subunit of RNA polymerase II (RPB2), and the translation elongation factor 1-α gene (TEF); illustrated descriptions of the new species are provided. In addition, fifteen species previously belonging to the Postia caesia complex are transferred to Cyanosporus and proposed as new combinations.
Community Structure of Protease-Producing Bacteria Cultivated From Aquaculture Systems: Potential Impact of a Tropical Environment
Authors: Wei Yali , Bu Jun , Long Hao , Zhang Xiang , Cai Xiaoni , Huang Aiyou , Ren Wei , Xie Zhenyu
Published: February 2021

Protease-producing bacteria play vital roles in degrading organic matter of aquaculture system, while the knowledge of diversity and bacterial community structure of protease-producing bacteria is limited in this system, especially in the tropical region. Herein, 1,179 cultivable protease-producing bacterial strains that belonged to Actinobacteria, Firmicutes, and Proteobacteria were isolated from tropical aquaculture systems, of which the most abundant genus was Bacillus, followed by Vibrio. The diversity and relative abundance of protease-producing bacteria in sediment were generally higher than those in water. Twenty-one genera from sediment and 16 genera from water were identified, of which Bacillus dominated by Bacillus hwajinpoensis in both and Vibrio dominated by Vibrio owensii in water were the dominant genera. The unique genera in sediment or water accounted for tiny percentage may play important roles in the stability of community structure. Eighty V. owensii isolates were clustered into four clusters (ET-1–ET-4) at 58% of similarity by ERIC-PCR (enterobacterial repetitive intergenic consensus-polymerase chain reaction), which was identified as a novel branch of V. owensii. Additionally, V. owensii strains belonged to ET-3 and ET-4 were detected in most aquaculture ponds without outbreak of epidemics, indicating that these protease-producing bacteria may be used as potential beneficial bacteria for wastewater purification. Environmental variables played important roles in shaping protease-producing bacterial diversity and community structure in aquaculture systems. In sediment, dissolved oxygen (DO), chemical oxygen demand (COD), and salinity as the main factors positively affected the distributions of dominant genus (Vibrio) and unique genera (Planococcus and Psychrobacter), whereas temperature negatively affected that of Bacillus (except B. hwajinpoensis). In water, Alteromonas as unique genus and Photobacterium were negatively affected by NO3−-N and NO2−-N, respectively, whereas pH as the main factor positively affected the distribution of Photobacterium. These findings will lay a foundation for the development of protease-producing bacterial agents for wastewater purification and the construction of an environment-friendly tropical aquaculture model.
Viral Release Threshold in the Salivary Gland of Leafhopper Vector Mediates the Intermittent Transmission of Rice Dwarf Virus
Authors: Chen Qian , Liu Yuyan , Long Zhirun , Yang Hengsong , Wei Taiyun
Published: February 2021

Numerous piercing-sucking insects can persistently transmit viral pathogens in combination with saliva to plant phloem in an intermittent pattern. Insect vectors maintain viruliferous for life. However, the reason why insect vectors discontinuously transmit the virus remains unclear. Rice dwarf virus (RDV), a plant reovirus, was found to replicate and assemble the progeny virions in salivary gland cells of the leafhopper vector. We observed that the RDV virions moved into saliva-stored cavities in the salivary glands of leafhopper vectors via an exocytosis-like mechanism, facilitating the viral horizontal transmission to plant hosts during the feeding of leafhoppers. Interestingly, the levels of viral accumulation in the salivary glands of leafhoppers during the transmitting period were significantly lower than those of viruliferous individuals during the intermittent period. A putative viral release threshold, which was close to 1.79 × 104 copies/μg RNA was proposed from the viral titers in the salivary glands of 52 leafhoppers during the intermittent period. Thus, the viral release threshold was hypothesized to mediate the intermittent release of RDV from the salivary gland cells of leafhoppers. We anticipate that viral release threshold-mediated intermittent transmission by insect vectors is the conserved strategy for the epidemic and persistence of vector-borne viruses in nature.
Aspirin Use on Incident Dementia and Mild Cognitive Decline: A Systematic Review and Meta-Analysis
Authors: Li Hui , Li Wan , Zhang Xun , Ma Xiao-Chuan , Zhang Rong-Wei
Published: February 2021

Background:More people with cognitive dysfunction and dementia also fall into the category of high vascular risk, for which aspirin is one of the most frequently used drugs. However, previous studies reporting that aspirin buffers against mild cognitive decline (MCI) and dementia remain controversial. We thus conducted an updated systematic review and meta-analysis to evaluate the association of aspirin use with the risk of MCI and dementia in older adults.

Methods:Data sources from PubMed, Embase, Web of Science, and the Cochrane Database for randomized controlled trails (RCTs) and cohort studies (published between January 1, 2000 and April 11, 2020). Relative risks (RRs) and 95% confidence intervals (95% CIs) were used to pool data on the occurrence of dementia and MCI with random-effects models.

Results:Of 3,193 identified articles, 15 studies (12 cohort studies and three RCTs) were eligible and were included in our analysis, which involved a total of 100,909 participants without cognitive dysfunctions or dementia at baseline. In pooled cohort studies, aspirin use did not reduce the incidence of MCI and dementia (the pooled RR = 0.97; 95% CI = 0.85–1.11;Ifor heterogeneity2= 65%) compared with non-users. However, low-dose aspirin (75–100 mg/day) was associated with a decreased likelihood of developing dementia or MCI (the pooled RR = 0.75; 95% CI = 0.63–0.9;Ifor heterogeneity2= 50.5%). This association existed in studies including all-cause dementia (the pooled RR = 0.82; 95% CI = 0.71–0.96) and Alzheimer's disease (AD) (the pooled RR = 0.54; 95% CI = 0.33–0.89), but not in MCI (the pooled RR = 0.58; 95% CI = 0.31–1.08). In RCTs, low-dose aspirin use was not significantly associated with less prevalence of dementia or MCI (RR = 0.94; 95% CI = 0.84–1.05;Ifor heterogeneity2= 0.0%).

Conclusions:In cohort studies, we found that low-dose aspirin use had a higher likelihood of reducing the incidence of dementia, which was not supported by RCTs. The evidence was insufficient to fully evaluate the effect of aspirin on cognitive function and dementia. Well-designed studies and innovative approaches are therefore needed to clarify whether the use of aspirin improves cognitive function and reduces the risk of dementia.
Alterations of Brain Structural Network Connectivity in Type 2 Diabetes Mellitus Patients With Mild Cognitive Impairment
Authors: Li Chang , Zhang Jingna , Qiu Mingguo , Liu Kaijun , Li Yang , Zuo Zhiwei , Yin Xuntao , Lai Yuqi , Fang Jingqin , Tong Haipeng , Guo Yu , Wang Jian , Chen Xiao , Xiong Kunlin
Published: February 2021

Patients with type 2 diabetes mellitus (T2DM) are highly susceptible to developing dementia, especially for those with mild cognitive impairment (MCI), but its underlying cause is still unclear. This study aims to investigate the early detection of white matter structural network changes in T2DM patients with MCI and assess the relationship between cognitive impairment and structural network alterations in T2DM patients. In this study, we performed a battery of neuropsychological tests and diffusion tensor MRI in 30 T2MD-MCI patients, 30 T2DM patients with normal cognition (T2DM-NC) and 30 age-, sex-, and education-matched healthy control (HC) individuals. Cognitive performance exhibited obvious differences among the three groups. The structural network was significantly disrupted in both global and regional levels in T2DM patients. The T2DM-MCI group showed more severe impairment of global network efficiency, and lower nodal efficiency and fewer connections within multiple regions like the limbic system, basal ganglia, and several cortical structures. Moreover, a subnetwork impaired in T2DM-MCI patients was characterized by cortical-limbic fibers, and commissural fibers and pathways within the frontal, temporal, and occipital lobes. These altered global and nodal parameters were significantly correlated with cognitive function in T2DM-MCI patients. In particular, executive dysfunction and working memory impairment in T2DM-MCI patients correlated with nodal efficiency in the right opercular part and triangular part of the inferior frontal gyrus, which indicated that white matter disruption in these regions may act as potential biomarkers for T2DM-associated MCI detection. Our investigation provides a novel insight into the neuropathological effects of white matter network disruption on cognition impairments induced by T2DM.
Potential Therapies for Cerebral Edema After Ischemic Stroke: A Mini Review
Authors: Yao Yi , Zhang Yonggang , Liao Xiaoyang , Yang Rong , Lei Yi , Luo Jianzhao
Published: February 2021

Stroke is the leading cause of global mortality and disability. Cerebral edema and intracranial hypertension are common complications of cerebral infarction and the major causes of mortality. The formation of cerebral edema includes three stages (cytotoxic edema, ionic edema, and vasogenic edema), which involve multiple proteins and ion channels. A range of therapeutic agents that successfully target cerebral edema have been developed in animal studies, some of which have been assessed in clinical trials. Herein, we review the mechanisms of cerebral edema and the research progress of anti-edema therapies for use after ischemic stroke.
One Hour-Post-load Plasma Glucose ≥155 mg/dl in Healthy Glucose Normotolerant Subjects Is Associated With Subcortical Brain MRI Alterations and Impaired Cognition: A Pilot Study
Authors: Perticone Maria , Di Lorenzo Cherubino , Arabia Gennarina , Arturi Franco , Caroleo Benedetto , Tassone Bruno , Pujia Roberta , Fiorentino Teresa Vanessa , Chiriaco Carmelina , Sesti Giorgio , Quattrone Aldo , Perticone Francesco
Published: February 2021

Background: Glucose alterations are associated with impaired cognition. The 1-h-post-load plasma glucose ≥155 mg/dl in non-diabetic subjects confers an increased risk of cardiovascular events and diabetes. This pilot study aimed to investigate whether the 1-h-post-load plasma glucose ≥155 mg/dl negatively affects the subcortical regions of the brain and the cognitive functions.

Methods: We enrolled 32 non-diabetic subjects. Patients were divided into two groups based on 1-h- post-load plasma glucose value > or < 155 mg/dl: normal glucose tolerance (NGT) 1-h-high and NGT 1-h-low subjects. All subjects underwent 3 Tesla MRI and standard neuropsychological tests.

Results: NGT 1-h-high subjects showed significantly lower values of both right (4.9 ± 0.9 vs. 5.1 ± 0.9 ml) and left (4.8 ± 1.1 vs. 5.1 ± 1.1 ml) hippocampal hemisphere volume, while right hemisphere hippocampal diffusivity was lower in the NGT 1-h-high group (10.0 ± 0.6 vs. 10.6 ± 0.5 10−4 mm2s−1). NGT 1-h-high subjects also showed a poorer memory performance. In particular, for both Rey Auditory Verbal Learning Task (RAVLT)—immediate-recall and Free and Cued Selective Reminding Test (FCSRT)—delayed total recall, we found lower cognitive test scores in the NGT-1 h-high group (26.5 ± 6.3 and 10.4 ± 0.3, respectively).

Conclusions: One-hour-post-load hyperglycemia is associated with morpho-functional subcortical brain alterations and poor memory performance tests.
Grip Strength and the Risk of Cognitive Decline and Dementia: A Systematic Review and Meta-Analysis of Longitudinal Cohort Studies
Authors: Cui Mengzhao , Zhang Siwen , Liu Yujia , Gang Xiaokun , Wang Guixia
Published: February 2021

Purpose: Loss of grip strength and cognitive impairment are prevalent in the elderly, and they may share the pathogenesis in common. Several original studies have investigated the association between them, but the results remained controversial. In this systematic review and meta-analysis, we aimed to quantitatively determine the relationship between baseline grip strength and the risk of cognitive impairment and provide evidence for clinical work.

Methods: We performed a systematic review using PubMed, EMBASE, Cochrane, and Web of Science up to March 23, 2020, and focused on the association between baseline grip strength and onset of cognitive impairment. Next, we conducted a meta-analysis using a hazard ratio (HR) and 95% confidence interval (CI) as effect measures. Heterogeneity between the studies was examined using I2 and p-value. Sensitivity analyses and subgroup analyses were also performed, and publication bias was assessed by Begg's and Egger's tests.

Results: Fifteen studies were included in this systematic review. After sensitivity analyses, poorer grip strength was associated with more risk of cognitive decline and dementia (HR = 1.99, 95%CI: 1.71–2.32; HR = 1.54, 95%CI: 1.32–1.79, respectively). Furthermore, subgroup analysis indicated that people with poorer strength had more risk of Alzheimer's disease (AD) and non-AD dementia (HR = 1.41, 95%CI: 1.09–1.81; HR = 1.45, 95%CI: 1.10–1.91, respectively).

Conclusions: Lower grip strength is associated with more risk of onset of cognitive decline and dementia despite of subtype of dementia. We should be alert for the individuals with poor grip strength and identify cognitive dysfunction early.
Self-Learning Event Mistiming Detector Based on Central Pattern Generator
Authors: Szadkowski Rudolf , Prágr Miloš , Faigl Jan
Published: February 2021

A repetitive movement pattern of many animals, a gait, is controlled by the Central Pattern Generator (CPG), providing rhythmic control synchronous to the sensed environment. As a rhythmic signal generator, the CPG can control the motion phase of biomimetic legged robots without feedback. The CPG can also act in sensory synchronization, where it can be utilized as a sensory phase estimator. Direct use of the CPG as the estimator is not common, and there is little research done on its utilization in the phase estimation. Generally, the sensory estimation augments the sensory feedback information, and motion irregularities can reveal from comparing measurements with the estimation. In this work, we study the CPG in the context of phase irregularity detection, where the timing of sensory events is disturbed. We propose a novel self-supervised method for learning mistiming detection, where the neural detector is trained by dynamic Hebbian-like rules during the robot walking. The proposed detector is composed of three neural components: (i) the CPG providing phase estimation, (ii) Radial Basis Function neuron anticipating the sensory event, and (iii) Leaky Integrate-and-Fire neuron detecting the sensory mistiming. The detector is integrated with the CPG-based gait controller. The mistiming detection triggers two reflexes: the elevator reflex, which avoids an obstacle, and the search reflex, which grasps a missing foothold. The proposed controller is deployed and trained on a hexapod walking robot to demonstrate the mistiming detection in real locomotion. The trained system has been examined in the controlled laboratory experiment and real field deployment in the Bull Rock cave system, where the robot utilized mistiming detection to negotiate the unstructured and slippery subterranean environment.
Genomic Association Study for Cognitive Impairment in Parkinson's Disease
Authors: Park Kye Won , Jo Sungyang , Kim Mi Sun , Jeon Sang Ryong , Ryu Ho-Sung , Kim Jinhee , Park Young-Min , Koh Seong-Beom , Lee Jae-Hong , Chung Sun Ju
Published: February 2021

Background: Cognitive impairment is very common in Parkinson's disease (PD) and constitutes the most debilitating complication of this disease. However, to date, few studies have investigated a genome-wide association in the development of cognitive impairment of PD. We aimed to identify the genetic loci associated with cognitive impairment in patients with sporadic PD by ethnicity-specific genotyping.

Materials and methods: We recruited 1,070 patients with PD and performed a genome-wide association study using the Korean Chip, a microarray chip containing 827,400 single-nucleotide polymorphisms (SNPs) optimized for the Korean population. Multiple logistic regression models adjusting for age, sex, years of education, and disease duration were used to compare between patients with and without cognitive impairment, which was defined using the Mini-Mental Status Examination (MMSE) score (MMSE score ≥ 26 vs. < 26) or the Montreal Cognitive Assessment (MoCA) score (MoCA score ≥24 vs. < 24).

Results:RYR2 SNP rs10495397 was most significantly associated with cognitive impairment based on the MMSE scores (OR = 3.21; 95% CI = 1.96–5.25, P = 3.36 × 10−6) and CASC17 showed the strongest association with cognitive impairment based on the MoCA scores. However, none of the SNPs were statistically significant after Bonferroni correction.

Conclusion:RYR2 may play a role in cognitive impairment in PD by the pathogenic mechanism of neuroinflammation. However, more studies are needed to replicate and validate the results of our functional study.
Functional Dystonia: Differentiation From Primary Dystonia and Multidisciplinary Treatments
Authors: Frucht Lucy , Perez David L. , Callahan Janet , MacLean Julie , Song Phillip C. , Sharma Nutan , Stephen Christopher D.
Published: February 2021

Dystonia is a common movement disorder, involving sustained muscle contractions, often resulting in twisting and repetitive movements and abnormal postures. Dystonia may be primary, as the sole feature (isolated) or in combination with other movement disorders (combined dystonia), or as one feature of another neurological process (secondary dystonia). The current hypothesis is that dystonia is a disorder of distributed brain networks, including the basal ganglia, cerebellum, thalamus and the cortex resulting in abnormal neural motor programs. In comparison, functional dystonia (FD) may resemble other forms of dystonia (OD) but has a different pathophysiology, as a subtype of functional movement disorders (FMD). FD is the second most common FMD and amongst the most diagnostically challenging FMD subtypes. Therefore, distinguishing between FD and OD is important, as the management of these disorders is distinct. There are also different pathophysiological underpinnings in FD, with for example evidence of involvement of the right temporoparietal junction in functional movement disorders that is believed to serve as a general comparator of internal predictions/motor intentions with actual motor events resulting in disturbances in self-agency. In this article, we present a comprehensive review across the spectrum of FD, including oromandibular and vocal forms and discuss the history, clinical clues, evidence for adjunctive “laboratory-based” testing, pathophysiological research and prognosis data. We also provide the approach used at the Massachusetts General Hospital Dystonia Center toward the diagnosis, management and treatment of FD. A multidisciplinary approach, including neurology, psychiatry, physical, occupational therapy and speech therapy, and cognitive behavioral psychotherapy approaches are frequently required; pharmacological approaches, including possible targeted use of botulinum toxin injections and inpatient programs are considerations in some patients. Early diagnosis and treatment may help prevent unnecessary investigations and procedures, while facilitating the appropriate management of these highly complex patients, which may help to mitigate frequently poor clinical outcomes.
Timing and Outcomes of Intracranial Stenting in the Post-SAMMPRIS Era: A Systematic Review
Authors: Yu Yanying , Wang Tao , Yang Kun , Zhang Xiao , Yu Simon Chun Ho , Luo Jichang , Yang Bin , Wang Yabing , Ma Yan , Gao Peng , Jiao Liqun
Published: February 2021

Objective: To investigate the impact of timing on the safety and efficacy of stenting for ICAS, we reviewed high-volume randomized controlled trials or prospective cohort studies of stenting for intracranial atherosclerotic artery stenosis (ICAS) after the SAMMPRIS trial.

Methods: We included randomized controlled trials or prospective cohort studies since 2011 (the publication of the SAMMPRIS trial), evaluating the outcomes of intracranial stenting for ICAS patients. The primary outcomes were perioperative and 1-year stroke or death rate. The interaction of timing and outcomes were shown on trend plots. Overall meta-analysis and subgroup analysis by timing of intracranial stenting were conducted.

Results: Fourteen studies with a total of 1,950 patients were included. The perioperative and post-operative stroke or death rates decreased with the time of stenting to the qualifying events. The perioperative stroke rate was significantly higher in patients treated within 21 days after the qualifying events, compared to those beyond 21 days (IRR = 1.60, 95%CI: 1.10–2.33; p = 0.014), similar relationships were obtained for both post-procedural (IRR = 1.61, 95%CI: 1.02–2.55; p = 0.042) and 1-year (IRR = 1.51, 95%CI: 1.10–2.08; p = 0.012) stroke or death rate.

Conclusions: The timing of intracranial stenting may influence the safety and efficacy outcomes of stenting. Intracranial stenting within 21 days from the qualifying events may confer a higher risk of stroke or death. More studies are needed to confirm the impact of timing and the proper cut-off value.
Neural Correlates of Knee Extension and Flexion Force Control: A Kinetically-Instrumented Neuroimaging Study
Authors: Grooms Dustin R. , Criss Cody R. , Simon Janet E. , Haggerty Adam L. , Wohl Timothy R.
Published: February 2021

Background: The regulation of muscle force is a vital aspect of sensorimotor control, requiring intricate neural processes. While neural activity associated with upper extremity force control has been documented, extrapolation to lower extremity force control is limited. Knowledge of how the brain regulates force control for knee extension and flexion may provide insights as to how pathology or intervention impacts central control of movement.

Objectives: To develop and implement a neuroimaging-compatible force control paradigm for knee extension and flexion.

Methods: A magnetic resonance imaging (MRI) safe load cell was used in a customized apparatus to quantify force (N) during neuroimaging (Philips Achieva 3T). Visual biofeedback and a target sinusoidal wave that fluctuated between 0 and 5 N was provided via an MRI-safe virtual reality display. Fifteen right leg dominant female participants (age = 20.3 ± 1.2 years, height = 1.6 ± 0.10 m, weight = 64.8 ± 6.4 kg) completed a knee extension and flexion force matching paradigm during neuroimaging. The force-matching error was calculated based on the difference between the visual target and actual performance. Brain activation patterns were calculated and associated with force-matching error and the difference between quadriceps and hamstring force-matching tasks were evaluated with a mixed-effects model (z > 3.1, p < 0.05, cluster corrected).

Results: Knee extension and flexion force-matching tasks increased BOLD signal among cerebellar, sensorimotor, and visual-processing regions. Increased knee extension force-matching error was associated with greater right frontal cortex and left parietal cortex activity and reduced left lingual gyrus activity. Increased knee flexion force-matching error was associated with reduced left frontal and right parietal region activity. Knee flexion force control increased bilateral premotor, secondary somatosensory, and right anterior temporal activity relative to knee extension. The force-matching error was not statistically different between tasks.

Conclusion: Lower extremity force control results in unique activation strategies depending on if engaging knee extension or flexion, with knee flexion requiring increased neural activity (BOLD signal) for the same level of force and no difference in relative error. These fMRI compatible force control paradigms allow precise behavioral quantification of motor performance concurrent with brain activity for lower extremity sensorimotor function and may serve as a method for future research to investigate how pathologies affect lower extremity neuromuscular function.
Relationship of Visceral Adipose Tissue With Dilated Perivascular Spaces
Authors: Qi Yunli , Lin Mengqi , Yang Yunjun , Li Yanxuan
Published: February 2021

Background

Dilated perivascular spaces (dPVS) are considered to be a type of cerebral small vessel disease (CSVD) as well as an important part of the glymphatic system. Although obesity has been shown to play a significant role in the development of CSVD, there are no studies addressing the correlation between obesity and dPVS. We aimed to study the relationship between abdominal fat distribution and dPVS in neurologically healthy cohorts.

Methods

A total of 989 subjects, who were examined during a health examination project, were included in this study. We measured both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas using abdominal computed tomography. The dPVS scores were also evaluated in the basal ganglia (BG) and the centrum semiovale (CSO).

Results

In a multivariate ordinal regression analysis, the relationship between VAT area and CSO-dPVS scores remained significant (β [95% confidence interval {CI} = 0.00003395] [0.00001074–0.00005716], P = 0.004), especially in male cohorts (β [95% CI] = 0.00004325 [0.00001772–0.00006878], P = 0.001) after adjusting for age; sex; and glucose, creatinine, uric acid, high-density lipoprotein, and low-density lipoprotein levels, while no association was found between SAT area and dPVS scores. The effects of quartile VAT area on CSO-dPVS were also significant in male cohorts (odds ratio [95% CI] = 1.33 [1.139 – 1.557], P < 0.001).

Conclusion

We demonstrated a positive association between VAT and CSO-dPVS scores in a healthy cohort, which was more prominent in males.
Effects of Excess Brain-Derived Human α-Synuclein on Synaptic Vesicle Trafficking
Authors: Román-Vendrell Cristina , Medeiros Audrey T. , Sanderson John B. , Jiang Haiyang , Bartels Tim , Morgan Jennifer R.
Published: February 2021

α-Synuclein is a presynaptic protein that regulates synaptic vesicle trafficking under physiological conditions. However, in several neurodegenerative diseases, including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy, α-synuclein accumulates throughout the neuron, including at synapses, leading to altered synaptic function, neurotoxicity, and motor, cognitive, and autonomic dysfunction. Neurons typically contain both monomeric and multimeric forms of α-synuclein, and it is generally accepted that disrupting the balance between them promotes aggregation and neurotoxicity. However, it remains unclear how distinct molecular species of α-synuclein affect synapses where α-synuclein is normally expressed. Using the lamprey reticulospinal synapse model, we previously showed that acute introduction of excess recombinant monomeric or dimeric α-synuclein impaired distinct stages of clathrin-mediated synaptic vesicle endocytosis, leading to a loss of synaptic vesicles. Here, we expand this knowledge by investigating the effects of native, physiological α-synuclein isolated from the brain of a neuropathologically normal human subject, which comprised predominantly helically folded multimeric α-synuclein with a minor component of monomeric α-synuclein. After acute introduction of excess brain-derived human α-synuclein, there was a moderate reduction in the synaptic vesicle cluster and an increase in the number of large, atypical vesicles called “cisternae.” In addition, brain-derived α-synuclein increased synaptic vesicle and cisternae sizes and induced atypical fusion/fission events at the active zone. In contrast to monomeric or dimeric α-synuclein, the brain-derived multimeric α-synuclein did not appear to alter clathrin-mediated synaptic vesicle endocytosis. Taken together, these data suggest that excess brain-derived human α-synuclein impairs intracellular vesicle trafficking and further corroborate the idea that different molecular species of α-synuclein produce distinct trafficking defects at synapses. These findings provide insights into the mechanisms by which excess α-synuclein contributes to synaptic deficits and disease phenotypes.
The Regulatory Functions of lncRNAs on Angiogenesis Following Ischemic Stroke
Authors: Gan Li , Liao Shengtao , Xing Yu , Deng Shixiong
Published: February 2021

Ischemic stroke is one of the leading causes of global mortality and disability. It is a multi-factorial disease involving multiple factors, and gene dysregulation is considered as the major molecular mechanisms underlying disease progression. Angiogenesis can promote collateral circulation, which helps the restoration of blood supply in the ischemic area and reduces ischemic necrosis following ischemic injury. Aberrant expression of long non-coding RNAs (lncRNAs) in ischemic stroke is associated with various biological functions of endothelial cells and serves essential roles on the angiogenesis of ischemic stroke. The key roles of lncRNAs on angiogenesis suggest their potential as novel therapeutic targets for future diagnosis and treatment. This review elucidates the detailed regulatory functions of lncRNAs on angiogenesis following ischemic stroke through numerous mechanisms, such as interaction with target microRNAs, downstream signaling pathways and target molecules.
Oral Administration of Flavonifractor plautii, a Bacteria Increased With Green Tea Consumption, Promotes Recovery From Acute Colitis in Mice via Suppression of IL-17
Authors: Mikami Ayane , Ogita Tasuku , Namai Fu , Shigemori Suguru , Sato Takashi , Shimosato Takeshi
Published: February 2021

Flavonifractor plautii (FP) has been reported to participate in the metabolism of catechins in the human gut. However, there is limited information on the immune regulatory effects of this bacterium. We confirmed that the administration of green tea increases the abundance of FP in the gut microbiota and investigated the effect of FP in a mouse colitis model. Mice were orally administered FP for 10 consecutive days; colonic inflammation was evaluated daily on the basis of stool consistency, gross rectal bleeding, and body weight. In the dextran sodium sulfate model, FP-exposed animals exhibited lower levels of inflammation and strong inhibition of interleukin (IL)-17 signaling. Moreover, lipoteichoic acid from FP was identified as the active component mediating IL-17 suppression. Thus, oral administration of FP appears to modulate gut inflammation and represents a viable and inexpensive oral microbial therapeutic.
Background Parenchymal Enhancement on Breast MRI as a Prognostic Surrogate: Correlation With Breast Cancer Oncotype Dx Score
Authors: Zhang Michelle , Sadinski Meredith , Haddad Dana , Bae Min Sun , Martinez Danny , Morris Elizabeth A. , Gibbs Peter , Sutton Elizabeth J.
Published: February 2021

Purpose

Breast MRI background parenchymal enhancement (BPE) can potentially serve as a prognostic marker, by possible correlation with molecular subtype. Oncotype Dx, a gene assay, is a prognostic and predictive surrogate for tumor aggressiveness and treatment response. The purpose of this study was to investigate the association between contralateral non-tumor breast magnetic resonance imaging (MRI) background parenchymal enhancement and tumor oncotype score.

Methods

In this retrospective study, patients with ER+ and HER2− early stage invasive ductal carcinoma who underwent preoperative breast MRI, oncotype risk scoring, and breast conservation surgery from 2008–2010 were identified. After registration, BPE from the pre and three post-contrast phases was automatically extracted using a k-means clustering algorithm. Four metrics were calculated: initial enhancement (IE) relative to the pre-contrast signal, late enhancement, overall enhancement (OE), and area under the enhancement curve (AUC). Histogram analysis was performed to determine first order metrics which were compared to oncotype risk score groups using Mann–Whitney tests and Spearman rank correlation analysis.

Results

This study included 80 women (mean age = 51.1 ± 10.3 years); 46 women were categorized as low risk (≤17) and 34 women were categorized as intermediate/high risk (≥18) according to Oncotype Dx. For the mean of the top 10% pixels, significant differences were noted for IE (p = 0.032), OE (p = 0.049), and AUC (p = 0.044). Using the risk score as a continuous variable, correlation analysis revealed a weak but significant correlation with the mean of the top 10% pixels for IE (r = 0.26, p = 0.02), OE (r = 0.25, p = 0.02), and AUC (r = 0.27, p = 0.02).

Conclusion

BPE metrics of enhancement in the non-tumor breast are associated with tumor Oncotype Dx recurrence score, suggesting that the breast microenvironment may relate to likelihood of recurrence and magnitude of chemotherapy benefit.
Prediction of Pathological Upgrading at Radical Prostatectomy in Prostate Cancer Eligible for Active Surveillance: A Texture Features and Machine Learning-Based Analysis of Apparent Diffusion Coefficient Maps
Authors: Xie Jinke , Li Basen , Min Xiangde , Zhang Peipei , Fan Chanyuan , Li Qiubai , Wang Liang
Published: February 2021

Objective

To evaluate a combination of texture features and machine learning-based analysis of apparent diffusion coefficient (ADC) maps for the prediction of Grade Group (GG) upgrading in Gleason score (GS) ≤6 prostate cancer (PCa) (GG1) and GS 3 + 4 PCa (GG2).

Materials and methods

Fifty-nine patients who were biopsy-proven to have GG1 or GG2 and underwent MRI examination with the same MRI scanner prior to transrectal ultrasound (TRUS)-guided systemic biopsy were included. All these patients received radical prostatectomy to confirm the final GG. Patients were divided into training cohort and test cohort. 94 texture features were extracted from ADC maps for each patient. The independent sample t-test or Mann−Whitney U test was used to identify the texture features with statistically significant differences between GG upgrading group and GG non-upgrading group. Texture features of GG1 and GG2 were compared based on the final pathology of radical prostatectomy. We used the least absolute shrinkage and selection operator (LASSO) algorithm to filter features. Four supervised machine learning methods were employed. The prediction performance of each model was evaluated by area under the receiver operating characteristic curve (AUC). The statistical comparison between AUCs was performed.

Results

Six texture features were selected for the machine learning models building. These texture features were significantly different between GG upgrading group and GG non-upgrading group (P < 0.05). The six features had no significant difference between GG1 and GG2 based on the final pathology of radical prostatectomy. All machine learning methods had satisfactory predictive efficacy. The diagnostic performance of nearest neighbor algorithm (NNA) and support vector machine (SVM) was better than random forests (RF) in the training cohort. The AUC, sensitivity, and specificity of NNA were 0.872 (95% CI: 0.750−0.994), 0.967, and 0.778, respectively. The AUC, sensitivity, and specificity of SVM were 0.861 (95%CI: 0.732−0.991), 1.000, and 0.722, respectively. There had no significant difference between AUCs in the test cohort.

Conclusion

A combination of texture features and machine learning-based analysis of ADC maps could predict PCa GG upgrading from biopsy to radical prostatectomy non-invasively with satisfactory predictive efficacy.