bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Molecular Diagnosis of Extra-Pulmonary Tuberculosis by Xpert/RIF Ultra
Authors: Rindi Laura
Published: May 2022

Rapid detection of Mycobacterium tuberculosis complex and determination of drug resistance are essential for early diagnosis and treatment of tuberculosis (TB). Xpert MTB/RIF Ultra (Xpert Ultra), a molecular test that can simultaneously identify M. tuberculosis complex and resistance to rifampicin directly on clinical samples, is currently used. Xpert Ultra represents a helpful tool for rapid pulmonary TB diagnosis, especially in patients with paucibacillary infection. The aim of this review is to provide an overview of the diagnostic performance of Xpert Ultra in detection of extra-pulmonary tuberculosis.
Ms1 RNA Interacts With the RNA Polymerase Core in Streptomyces coelicolor and Was Identified in Majority of Actinobacteria Using a Linguistic Gene Synteny Search
Authors: Vaňková Hausnerová Viola , Marvalová Olga , Šiková Michaela , Shoman Mahmoud , Havelková Jarmila , Kambová Milada , Janoušková Martina , Kumar Dilip , Halada Petr , Schwarz Marek , Krásný Libor , Hnilicová Jarmila , Pánek Josef
Published: May 2022

Bacteria employ small non-coding RNAs (sRNAs) to regulate gene expression. Ms1 is an sRNA that binds to the RNA polymerase (RNAP) core and affects the intracellular level of this essential enzyme. Ms1 is structurally related to 6S RNA that binds to a different form of RNAP, the holoenzyme bearing the primary sigma factor. 6S RNAs are widespread in the bacterial kingdom except for the industrially and medicinally important Actinobacteria. While Ms1 RNA was identified in Mycobacterium, it is not clear whether Ms1 RNA is present also in other Actinobacteria species. Here, using a computational search based on secondary structure similarities combined with a linguistic gene synteny approach, we identified Ms1 RNA in Streptomyces. In S. coelicolor, Ms1 RNA overlaps with the previously annotated scr3559 sRNA with an unknown function. We experimentally confirmed that Ms1 RNA/scr3559 associates with the RNAP core without the primary sigma factor HrdB in vivo. Subsequently, we applied the computational approach to other Actinobacteria and identified Ms1 RNA candidates in 824 Actinobacteria species, revealing Ms1 RNA as a widespread class of RNAP binding sRNAs, and demonstrating the ability of our multifactorial computational approach to identify weakly conserved sRNAs in evolutionarily distant genomes.
Eukaryogenesis: The Rise of an Emergent Superorganism
Authors: Bell Philip J. L.
Published: May 2022

Although it is widely taught that all modern life descended via modification from a last universal common ancestor (LUCA), this dominant paradigm is yet to provide a generally accepted explanation for the chasm in design between prokaryotic and eukaryotic cells. Counter to this dominant paradigm, the viral eukaryogenesis (VE) hypothesis proposes that the eukaryotes originated as an emergent superorganism and thus did not evolve from LUCA via descent with incremental modification. According to the VE hypothesis, the eukaryotic nucleus descends from a viral factory, the mitochondrion descends from an enslaved alpha-proteobacteria and the cytoplasm and plasma membrane descend from an archaeal host. A virus initiated the eukaryogenesis process by colonising an archaeal host to create a virocell that had its metabolism reprogrammed to support the viral factory. Subsequently, viral processes facilitated the entry of a bacterium into the archaeal cytoplasm which was also eventually reprogrammed to support the viral factory. As the viral factory increased control of the consortium, the archaeal genome was lost, the bacterial genome was greatly reduced and the viral factory eventually evolved into the nucleus. It is proposed that the interaction between these three simple components generated a superorganism whose emergent properties allowed the evolution of eukaryotic complexity. If the radical tenets of the VE hypothesis are ultimately accepted, current biological paradigms regarding viruses, cell theory, LUCA and the universal Tree of Life (ToL) should be fundamentally altered or completely abandoned.
The Improvement of Semen Quality by Dietary Fiber Intake Is Positively Related With Gut Microbiota and SCFA in a Boar Model
Authors: Lin Yan , Wang Ke , Che Lianqiang , Fang Zhengfeng , Xu Shengyu , Feng Bin , Zhuo Yong , Li Jian , Wu Caimei , Zhang Junjie , Xiong Haoyu , Yu Chenglong , Wu De
Published: May 2022

Although fiber-rich diets have been positively associated with sperm quality, there have not been any studies that have examined the effects of dietary fiber and its metabolites on sperm quality in young or pre-pubescent animals. In this study, we aimed to explore the effect of dietary fiber supplementation on semen quality and the underlying mechanisms in a boar model. Sixty purebred Yorkshire weaning boars were randomly divided into the four groups (T1–T4). Groups T1, T2, and T3 boars were fed diets with different levels of fiber until reaching 160 days of age and were then fed the same diet, while group T4 boars were fed a basal diet supplemented with butyrate and probiotics. Compared with T1 boars, sperm motility and effective sperm number were significantly higher among T3 boars. Meanwhile, at 240 days of age, the acetic acid and total short-chain fatty acid (SCFA) contents in the sera of T3 and T4 boars were significantly higher than those in T1 boars. The abundance of microbiota in T2 and T3 boars was significantly higher than that in T1 boars (P < 0.01). Moreover, dietary fiber supplementation increased “beneficial gut microbes” such as UCG-005, Rumenococcus, Rikenellaceae_RC9_gut_group and Lactobacillus and decreased the relative abundance of “harmful microbes” such as Clostridium_sensu_stricto_1, Romboutsia and Turicibacter. Collectively, the findings of this study indicate that dietary fiber supplementation improves gut microbiota and promotes SCFA production, thereby enhancing spermatogenesis and semen quality. Moreover, the effects of dietary fiber are superior to those of derived metabolites.
The Alternative Sigma Factor SigL Influences Clostridioides difficile Toxin Production, Sporulation, and Cell Surface Properties
Authors: Clark Andrew E. , Adamson Chelsea C. , Carothers Katelyn E. , Roxas Bryan Angelo P. , Viswanathan V. K. , Vedantam Gayatri
Published: May 2022

The alternative sigma factor SigL (Sigma-54) facilitates bacterial adaptation to the extracellular environment by modulating the expression of defined gene subsets. A homolog of the gene encoding SigL is conserved in the diarrheagenic pathogen Clostridioides difficile. To explore the contribution of SigL to C. difficile biology, we generated sigL-disruption mutants (sigL::erm) in strains belonging to two phylogenetically distinct lineages—the human-relevant Ribotype 027 (strain BI-1) and the veterinary-relevant Ribotype 078 (strain CDC1). Comparative proteomics analyses of mutants and isogenic parental strains revealed lineage-specific SigL regulons. Concomitantly, loss of SigL resulted in pleiotropic and distinct phenotypic alterations in the two strains. Sporulation kinetics, biofilm formation, and cell surface-associated phenotypes were altered in CDC1 sigL::erm relative to the isogenic parent strain but remained unchanged in BI-1 sigL::erm. In contrast, secreted toxin levels were significantly elevated only in the BI-1 sigL::erm mutant relative to its isogenic parent. We also engineered SigL overexpressing strains and observed enhanced biofilm formation in the CDC1 background, and reduced spore titers as well as dampened sporulation kinetics in both strains. Thus, we contend that SigL is a key, pleiotropic regulator that dynamically influences C. difficile's virulence factor landscape, and thereby, its interactions with host tissues and co-resident microbes.
Virological and Histopathological Findings in Boars Naturally Infected With Porcine Reproductive and Respiratory Syndrome Virus Type 1
Authors: Pedersen Kasper , Blirup-Plum Sophie Amalie , Kristensen Charlotte Sonne , Kvisgaard Lise Kirstine , Skade Lotte , Jensen Henrik Elvang , Larsen Lars Erik
Published: May 2022

Major geographical transmission of porcine reproductive and respiratory syndrome virus (PRRSV) occursviasemen when a boar stud is infected. This happened in Denmark in 2019, providing an opportunity to compare previous experimental PRRSV boar studies with natural PRRSV-1 infection in boars. The aim of this study was to investigate the association between the presence of PRRSV RNA in serum, semen, testicles, and epididymis of boars naturally infected with PRRSV and to describe the histological lesions in the testes and epididymis combined with direct visualisation of PRRSV-infected cells by immunohistochemical staining (IHC). The exact timing of infection of each boar was not determined, but based on serology the boars were divided into two groups: acute and late infections. All boars included were sampled the same day. In this study, 35 boars and 10 healthy boars from another PRRSV-negative boar stud were included as histological controls. PRRSV RNA was found most often in serum (51%) and least frequently in semen (22%) and was more often detected in the reproductive tract in the acute phase of infection (p< 0.0001; RR: 2.58). Mononuclear cells and multinuclear giant cells were present in the adluminal compartment of the testis and epididymis in PRRSV-infected boars, but not in control boars (p< 0.05), which supports the hypothesis that macrophages are involved in the venereal spread of the virus.
Systematic Comparison of Nanopore and Illumina Sequencing for the Detection of Plant Viruses and Viroids Using Total RNA Sequencing Approach
Authors: Pecman Anja , Adams Ian , Gutiérrez-Aguirre Ion , Fox Adrian , Boonham Neil , Ravnikar Maja , Kutnjak Denis
Published: May 2022

High-throughput sequencing (HTS) has become an important tool for plant virus detection and discovery. Nanopore sequencing has been rapidly developing in the recent years and offers new possibilities for fast diagnostic applications of HTS. With this in mind, a study was completed, comparing the most established HTS platform (MiSeq benchtop sequencer—Illumina), with the MinION sequencer (Oxford Nanopore Technologies) for the detection of plant viruses and viroids. Method comparisons were performed on five selected samples, containing two viroids, which were sequenced using nanopore technology for the first time and 11 plant viruses with different genome organizations. For all samples, sequencing libraries for the MiSeq were prepared from ribosomal RNA-depleted total RNA (rRNA-depleted totRNA) and for MinION sequencing, direct RNA sequencing of totRNA was used. Moreover, for one of the samples, which contained five different plant viruses and a viroid, three additional variations of sample preparation for MinION sequencing were also used: direct RNA sequencing of rRNA-depleted totRNA, cDNA-PCR sequencing of totRNA, and cDNA-PCR sequencing of rRNA-depleted totRNA. Whilst direct RNA sequencing of total RNA was the quickest of the tested approaches, it was also the least sensitive: using this approach, we failed to detect only one virus that was present in a sample at an extremely low titer. All other MinION sequencing approaches showed improved performance with outcomes similar to Illumina sequencing, with cDNA-PCR sequencing of rRNA-depleted totRNA showing the best performance amongst tested nanopore MinION sequencing approaches. Moreover, when enough sequencing data were generated, high-quality consensus viral genome sequences could be reconstructed from MinION sequencing data, with high identity to the ones generated from Illumina data. The results of this study implicate that, when an appropriate sample and library preparation are selected, nanopore MinION sequencing could be used for the detection of plant viruses and viroids with similar performance as Illumina sequencing. Taken as a balance of practicality and performance, this suggests that MinION sequencing may be an ideal tool for fast and affordable virus diagnostics.
The Relationship Between Gut Microbiome and Bile Acids in Primates With Diverse Diets
Authors: Li Xinyue , Wang Xiaochen , Wang Ziming , Zhang Mingyi , Wang Song , Xiang Zuofu , Pan Huijuan , Li Ming
Published: May 2022

Primates have evolved a variety of feeding habits and intestinal physiological structure. Gut microbiome act as metabolic organs in many biological processes and play a vital role in adaptation to dietary niches. Gut microbiome also convert primary bile acids (BAs) to secondary. BAs profile and gut microbiome are together influenced by diets and play a significant role in nutrient absorption. The regulation between gut microbiome and BAs metabolism is bidirectional although the relationship in primates consuming diverse diets is still unclear. Here, we investigated gut microbiome structures, fecal BAs profile, and their relationship in primates preferring three distinct diets. We found that gut microbiome communities are well differentiated among dietary groups. Folivorous primates had higher Firmicutes abundance and lower Prevotella to Bacaeroides ratios, possibly related to fiber consumption. Frugivorous primates are colonized predominantly by Prevotella and Bacteroides, pointing to an increased adaptation to high-sugar and simple carbohydrate diets. Likewise, BA profiles differ according to diet in a manner predictable from the known effects of BAs on metabolism. Folivorous primates have high conjugated bile acid levels and low unconjugated to conjugated BA ratios, consistent with their fiber-rich leaf-eating diet. Much of the differentiation in secondary and unconjugated BAs is associated with microbiome composition shifts and individual bile acid concentrations are correlated with the abundance of distinct bacterial taxonomic groups. Omnivores have higher concentrations of secondary BAs, mainly lithocholic acid (LCA). These levels are significantly positively correlated with the presence of Clostrida species, showing that the digestion requirements of omnivores are different from plant-eating primates. In conclusion, gut microbiome and BAs can respond to changes in diet and are associated with nutrient component consumption in each diet primate group. Our study is the first to demonstrate BA profile differentiation among primates preferring diverse diets. BAs thus appear to work with gut microbiome to help primates adapt to their diet.
The Expression Modulation of the Key Enzyme Acc for Highly Efficient 3-Hydroxypropionic Acid Production
Authors: Wang Sumeng , Jin Xin , Jiang Wei , Wang Qian , Qi Qingsheng , Liang Quanfeng
Published: May 2022

3-Hydroxypropionic acid (3-HP) is a promising high value-added chemical. Acetyl-CoA carboxylase (Acc) is a vital rate-limiting step in 3-HP biosynthesis through the malonyl-CoA pathway. However, Acc toxicity in cells during growth blocks its ability to catalyze acetyl-CoA to malonyl-CoA. The balancing of Acc and malonyl-CoA reductase (MCR) expression is another an unexplored but key process in 3-HP production. To solve these problems, in the present study, we developed a method to mitigate Acc toxicity cell growth through Acc subunits (AccBC and DtsR1) expression adjustment. The results revealed that cell growth and 3-HP production can be accelerated through the adjustment of DtsR1 and AccBC expression. Subsequently, the balancing Acc and MCR expression was also employed for 3-HP production, the engineered strain achieved the highest titer of 6.8 g/L, with a high yield of 0.566 g/g glucose and productivity of 0.13 g/L/h, in shake-flask fermentation through the malonyl-CoA pathway. Likewise, the engineered strain also had the highest productivity (1.03 g/L/h) as well as a high yield (0.246 g/g glucose) and titer (up to 38.13 g/L) in fed-batch fermentation, constituting the most efficient strain for 3-HP production through the malonyl-CoA pathway using a cheap carbon source. This strategy might facilitate the production of other malonyl-CoA-derived chemical compounds in the future.
Pan-Cancer Analysis of the Characteristics of LY96 in Prognosis and Immunotherapy Across Human Cancer
Authors: Nie Kechao , Li Jing , Peng Luqi , Zhang Mei , Huang Wei
Published: May 2022

Lymphocyte antigen 96 (LY96) is implicated in tumorigenesis by modulating host immunity. However, an integrated pan-cancer analysis of LY96 in prognosis and immunotherapy across human cancers is still lacking. Therefore, we analyzed the LY96 expression and its prognostic role in tumors by multiple databases. We also investigated the correlation between LY96 and copy number, DNA methylation, somatic mutation, microsatellite instability (MSI), tumor mutation burden (TMB), tumor microenvironment (TME), and immune cell infiltration across human cancers. In addition, the biological processes related to LY96 across various tumors and the correlation between LY96 and 50% inhibitive concentration (IC50) of various drugs were investigated. We found that LY96 was differently expressed between tumor and normal tissues and was significantly upregulated in most types of cancers. LY96 was gradually upregulated from stages I to IV in several cancers. Moreover, we found LY96 may play a prognostic role in most cancers, and patients with high or low LY96 expression often show different clinical outcomes. LY96 was also associated with copy number, DNA methylation, somatic mutation, MSI, TMB, TME characteristics, and immune cell infiltration in cancers. LY96 may also regulate classic tumor-associated pathways in several cancers and is related to drug resistance. This article may help to elucidate the role of LY96 in tumorigenesis, which may promote the development of immunotherapy and targeted therapy in cancers.
Phase Separation Drives SARS-CoV-2 Replication: A Hypothesis
Authors: Vandelli Andrea , Vocino Giovanni , Tartaglia Gian Gaetano
Published: May 2022

Identifying human proteins that interact with SARS-CoV-2 genome is important to understand its replication and to identify therapeutic strategies. Recent studies have unveiled protein interactions of SARS-COV-2 in different cell lines and through a number of high-throughput approaches. Here, we carried out a comparative analysis of four experimental and one computational studies to characterize the interactions of SARS-CoV-2 genomic RNA. Although hundreds of interactors have been identified, only twenty-one appear in all the experiments and show a strong propensity to bind. This set of interactors includes stress granule forming proteins, pre-mRNA regulators and elements involved in the replication process. Our calculations indicate that DDX3X and several editases bind the 5′ end of SARS-CoV-2, a regulatory region previously reported to attract a large number of proteins. The small overlap among experimental datasets suggests that SARS-CoV-2 genome establishes stable interactions only with few interactors, while many proteins bind less tightly. In analogy to what has been previously reported for Xist non-coding RNA, we propose a mechanism of phase separation through which SARS-CoV-2 progressively sequesters human proteins hijacking the host immune response.
Sex-Specific Causes and Consequences of White Matter Damage in a Middle-Aged Cohort
Authors: Bonberg Nadine , Wulms Niklas , Dehghan-Nayyeri Mahboobeh , Berger Klaus , Minnerup Heike
Published: May 2022

Objective

To evaluate potential sex-specific effects of multiple cardiovascular risk factors on white matter pathology in normal aging men and women, as well as potential sex-differences in the association of white matter pathology and cognitive functions.

Methods

We analyzed cross-sectional data of 581 participants (median age: 53 years, 54% women) of the population-based cohort of the BiDirect Study who completed clinical examinations, five neuropsychological tests, and an 3T MRI examination. White matter pathology was determined by the extent of white matter hyperintensities (WMH) on FLAIR images as well as the magnitude of global fractional anisotropy (FA) based on diffusion tensor imaging. Main effects, interaction as well as sex-stratified generalized linear regression models were used to evaluate the moderating effect of sex on the association of hypertension, diabetes mellitus, smoking, and obesity with WMH and FA, respectively. Associations of imaging markers with cognitive test results were determined with linear regression models.

Results

Hypertension showed stronger associations with more extensive WMH and less FA in women compared to men. Current smoking was associated with more severe WMH in women only. Adjusted for age and education, WMH were not significantly associated with cognitive tests, but higher FA was associated with better performance in motor function in both sexes and with executive functions in men, even after adjustment for cardiovascular risk factors.

Conclusion

We observed a stronger association of hypertension and smoking with white matter damage in women, suggesting a higher susceptibility for vascular pathology in women. However, there was no association of WMH with cognition, and FA was associated with executive function tests only in men, suggesting a higher cognitive reserve in women.
Multi-Concept Frailty Predicts the Late-Life Occurrence of Cognitive Decline or Dementia: An Updated Systematic Review and Meta-Analysis of Longitudinal Studies
Authors: Guo Chun-Yan , Sun Zhen , Tan Chen-Chen , Tan Lan , Xu Wei
Published: May 2022

Background

Frailty is a multidimensional syndrome that increases an individual’s vulnerability for developing adverse health outcomes, which include dementia. It might serve as a promising target for dementia prevention. However, there are currently no studies summarizing the association between multi-concept frailty and the risk of cognitive disorders. This study aims to summarize the evidence of associations between multi-concept frailty and cognitive disorders based on longitudinal studies.

Methods

Scopus, The Cochrane Library, PsycINFO, CINAHL, PubMed, and EMBASE databases were searched from inception to January 2, 2022. Longitudinal studies, which explored the association of frailty with incident risk of cognitive decline or dementia, were included. The multivariable-adjusted effect estimates were pooled by random-effects models. The evidence credibility was depicted according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method.

Results

A total of 30 longitudinal studies were included. Four types of frailty concepts were involved, including physical, cognitive, social, and biopsychosocial frailty. The meta-analysis comprised 20 studies of 252,571 older adults (mean age: 64.1–80.4 years), among whom 7,388 participants developed cognitive decline or dementia. Physical frailty was associated with higher risk of developing cognitive disorders [pooled relative risk (pRR) = 1.52, 95% confidence interval (CI): 1.28–1.80, I2 = 21.2%, pRR = 1.62 for cognitive decline, 95% CI: 1.07–2.45, I2 = 40.2%, pRR = 1.37 for all-cause dementia (ACD), 95% CI: 1.13–1.66, I2 = 0.0%]. Cognitive frailty (pRR = 2.90, 95% CI: 1.28–6.55, I2 = 78.1%) and pre-frailty (pRR = 4.24, 95% CI: 2.74–6.56, I2 = 30.2%) were linked to higher risk of ACD. Biopsychosocial frailty could predict a 41% (pRR = 1.41, 95% CI: 1.17–1.71) elevated risk of cognitive decline or dementia [pRR = 1.53 (95% CI: 1.19–1.96) for ACD and 1.11 (95% CI: 1.05–1.17) for Alzheimer’s disease (AD)]. In the systematic review, social frailty was associated with a 53% higher risk of AD. Preventing frailty could avoid a maximum of 9.9% cognitive disorders globally. The overall evidence strength is rated as low-to-moderate. Inconsistency and imprecision are major sources of bias.

Conclusion

Frailty in late life is a promising risk factor for cognitive disorders. Frail elderly should be monitored for their cognitive dynamics and initiate early prevention of dementia.

Systematic Review Registration

www.ClinicalTrials.gov, identifier CRD4202127 3434.
Electroencephalographic Measurement on Post-stroke Sensory Deficiency in Response to Non-painful Cold Stimulation
Authors: Huang Yanhuan , Jiao Jiao , Hu Junyan , Hsing Chihchia , Lai Zhangqi , Yang Yang , Li Zengyong , Hu Xiaoling
Published: May 2022

Background

Reduced elementary somatosensation is common after stroke. However, the measurement of elementary sensation is frequently overlooked in traditional clinical assessments, and has not been evaluated objectively at the cortical level. This study designed a new configuration for the measurement of post-stroke elementary thermal sensation by non-painful cold stimulation (NPCS). The post-stroke cortical responses were then investigated during elementary NPCS on sensory deficiencyviaelectroencephalography (EEG) when compared with unimpaired persons.

Method

Twelve individuals with chronic stroke and fifteen unimpaired controls were recruited. A 64-channel EEG system was used to investigate the post-stroke cortical responses objectively during the NPCS. A subjective questionnaire of cold sensory intensity was also administeredviaa numeric visual analog scale (VAS). Three water samples with different temperatures (i.e., 25, 10, and 0°C) were applied to the skin surface of the ventral forearm for 3 sviaglass beaker, with a randomized sequence on either the left or right forearm of a participant. EEG relative spectral power (RSP) and topography were used to evaluate the neural responses toward NPCS with respect to the independent factors of stimulation side and temperature.

Results

For unimpaired controls, NPCS initiated significant RSP variations, mainly located in the theta band with the highest discriminative resolution on the different temperatures (P< 0.001). For stroke participants, the distribution of significant RSP spread across all EEG frequency bands and the temperature discrimination was lower than that observed in unimpaired participants (P< 0.05). EEG topography showed that the NPCS could activate extensive and bilateral sensory cortical areas after stroke. Significant group differences on RSP intensities were obtained in each EEG band (P< 0.05). Meanwhile, significant asymmetry cortical responses in RSP toward different upper limbs were observed during the NPCS in both unimpaired controls and participants with stroke (P< 0.05). No difference was found between the groups in the VAS ratings of the different temperatures (P> 0.05).

Conclusion

The post-stroke cortical responses during NPCS on sensory deficiency were characterized by the wide distribution of representative RSP bands, lowered resolution toward different temperatures, and extensive activated sensory cortical areas.
Application of Table Tennis Ball Trajectory and Rotation-Oriented Prediction Algorithm Using Artificial Intelligence
Authors: Liu Qiang , Ding Hairong
Published: May 2022

The present work aims to accelerate sports development in China and promote technological innovation in the artificial intelligence (AI) field. After analyzing the application and development of AI, it is introduced into sports and applied to table tennis competitions and training. The principle of the trajectory prediction of the table tennis ball (TTB) based on AI is briefly introduced. It is found that the difficulty of predicting TTB trajectories lies in rotation measurement. Accordingly, the rotation and trajectory of TTB are predicted using some AI algorithms. Specifically, a TTB detection algorithm is designed based on the Feature Fusion Network (FFN). For feature exaction, the cross-layer connection network is used to strengthen the learning ability of convolutional neural networks (CNNs) and streamline network parameters to improve the network detection response. The experimental results demonstrate that the trained CNN can reach a detection accuracy of over 98%, with a detection response within 5.3 ms, meeting the requirements of the robot vision system of the table tennis robot. By comparison, the traditional Color Segmentation Algorithm has advantages in detection response, with unsatisfactory detection accuracy, especially against TTB's color changes. Thus, the algorithm reported here can immediately hit the ball with high accuracy. The research content provides a reference for applying AI to TTB trajectory and rotation prediction and has significant value in popularizing table tennis.
Increased miR-155 in Microglial Exosomes Following Heat Stress Accelerates Neuronal Autophagy via Their Transfer Into Neurons
Authors: Li Ping , Luo Xue , Luo Zhen , He Gen-Lin , Shen Ting-Ting , Yu Xue-Ting , Wang Ze-Ze , Tan Yu-Long , Liu Xiao-Qian , Yang Xue-Sen
Published: May 2022

Background

Heat stroke is the outcome of excessive heat stress, which results in core temperatures exceeding 40°C accompanied by a series of complications. The brain is particularly vulnerable to damage from heat stress. In our previous studies, both activated microglia and increased neuronal autophagy were found in the cortices of mice with heat stroke. However, whether activated microglia can accelerate neuronal autophagy under heat stress conditions is still unknown. In this study, we aimed to investigate the underlying mechanism that caused neuronal autophagy upregulation in heat stroke from the perspective of exosome-mediated intercellular communication.

Methods

In this study, BV2 and N2a cells were used instead of microglia and neurons, respectively. Exosomes were extracted from BV2 culture supernatants by ultracentrifugation and then characterized via transmission electron microscopy, nanoparticle tracking analysis and Western blotting. N2a cells pretreated with/without miR-155 inhibitor were cocultured with microglial exosomes that were treated with/without heat stress or miR-155 overexpression and subsequently subjected to heat stress treatment. Autophagy in N2a cells was assessed by detecting autophagosomes and autophagy-related proteins through transmission electron microscopy, immunofluorescence, and Western blotting. The expression of miR-155 in BV2 and BV2 exosomes and N2a cells was measured using real-time reverse transcription polymerase chain reaction. Target binding analysis was verified via a dual-luciferase reporter assay.

Results

N2a autophagy moderately increased in response to heat stress and accelerated by BV2 cells through transferring exosomes to neurons. Furthermore, we found that neuronal autophagy was positively correlated with the content of miR-155 in microglial exosomes. Inhibition of miR-155 partly abolished autophagy in N2a cells, which was increased by coculture with miR-155-upregulated exosomes. Mechanistic analysis confirmed that Rheb is a functional target of miR-155 and that microglial exosomal miR-155 accelerated heat stress-induced neuronal autophagy mainly by regulating the Rheb-mTOR signaling pathway.

Conclusion

Increased miR-155 in microglial exosomes after heat stroke can induce neuronal autophagy via their transfer into neurons. miR-155 exerted these effects by targeting Rheb, thus inhibiting the activity of mTOR signaling. Therefore, miR-155 could be a promising target for interventions of neuronal autophagy after heat stroke.
B81 Bone Vibrator-Induced Vestibular-Evoked Myogenic Potentials: Normal Values and the Effect of Age
Authors: Zhang Yuzhong , Chen Zichen , Zhao Huandi , Shen Jiali , Zhong Bo , Wu Qiong , Yang Jun , Jin Yulian , Zhang Qing , Ren Pengyu
Published: May 2022

Objective

To define the normal values and examine the influence of aging on B81 bone vibrator-induced cervical vestibular-evoked myogenic potentials (B81-cVEMPs) and ocular vestibular-evoked myogenic potentials (B81-oVEMPs).

Methods

Seventy healthy subjects, divided into seven groups according to their ages, were enrolled in this study. The 4–9-, 10–19-, 20–29-, 30–39-, 40–49-, 50–59-, and 60–70-year-old participants were divided into groups I–VII, respectively. B81-cVEMP and B81-oVEMP were recorded in each group.

Results

The B81-cVEMP response rates for groups I–VII were 100, 100, 100, 100, 95, 95, and 75%, respectively, with significant differences only between groups I–VI and group VII (p = 0.047, p < 0.05). The B81-oVEMP response rates for groups I–VII were 100, 100, 100, 100, 70, 65, and 40%, respectively, with significant differences only between groups I–IV and groups V–VII (p = 0.020, p = 0.008, p = 0.000; p < 0.05). The threshold, P13, and N23 latencies of B81-cVEMP positively correlated with age (r = 0.756, p = 0.000; r = 0.357, p = 0.003; r = 0.316, p = 0.009; p < 0.05). The raw amplitudes and corrected amplitudes negatively correlated with age (r = −0.641, p = 0.000; r = −0.609, p = 0.000, p < 0.05). For B81-oVEMP, the corrected amplitudes negatively correlated with age (r = −0.638, p = 0.000, p<0.05), but the threshold and N10 latency positively correlated with age (r = 0.768, p = 0.000; r = 0.334, p = 0.009, p < 0.05). Moreover, the interaural asymmetry ratio did not significantly correlate with age for B81-cVEMP and B81-oVEMP.

Conclusion

As age increased, the B81-cVEMP response rate decreased, the thresholds increased, P13 and N23 latencies were prolonged, and the raw amplitude and corrected amplitude decreased. The B81-oVEMP response rate and corrected amplitude decreased, the thresholds increased, and N10 latency was prolonged with age. These changes are probably due to the occurrence of morphological and functional changes in the vestibular system with aging. Therefore, we suggest establishing different reference values according to different age groups when evaluating the VEMP results in patients with vestibular diseases.
A Modular Workflow for Performance Benchmarking of Neuronal Network Simulations
Authors: Albers Jasper , Pronold Jari , Kurth Anno Christopher , Vennemo Stine Brekke , Haghighi Mood Kaveh , Patronis Alexander , Terhorst Dennis , Jordan Jakob , Kunkel Susanne , Tetzlaff Tom , Diesmann Markus , Senk Johanna
Published: May 2022

Modern computational neuroscience strives to develop complex network models to explain dynamics and function of brains in health and disease. This process goes hand in hand with advancements in the theory of neuronal networks and increasing availability of detailed anatomical data on brain connectivity. Large-scale models that study interactions between multiple brain areas with intricate connectivity and investigate phenomena on long time scales such as system-level learning require progress in simulation speed. The corresponding development of state-of-the-art simulation engines relies on information provided by benchmark simulations which assess the time-to-solution for scientifically relevant, complementary network models using various combinations of hardware and software revisions. However, maintaining comparability of benchmark results is difficult due to a lack of standardized specifications for measuring the scaling performance of simulators on high-performance computing (HPC) systems. Motivated by the challenging complexity of benchmarking, we define a generic workflow that decomposes the endeavor into unique segments consisting of separate modules. As a reference implementation for the conceptual workflow, we develop beNNch: an open-source software framework for the configuration, execution, and analysis of benchmarks for neuronal network simulations. The framework records benchmarking data and metadata in a unified way to foster reproducibility. For illustration, we measure the performance of various versions of the NEST simulator across network models with different levels of complexity on a contemporary HPC system, demonstrating how performance bottlenecks can be identified, ultimately guiding the development toward more efficient simulation technology.
Mental Workload in Neuropsychology: An Example With the NASA-TLX in Adults With HIV
Authors: Hardy David J. , Hinkin Charles H.
Published: May 2022

A preliminary set of analyses are presented, where workload was examined in 32 adults infected with the human immunodeficiency virus (HIV). Like the current COVID-19 pandemic (caused by the SARS-CoV-2 virus), HIV can produce a wide variety of symptoms, including various levels of cognitive dysfunction. In fact, a recent meta-analysis estimates that of the 39 million adults infected globally with HIV, 42.6% exhibit some form of HIV-associated neurocognitive disorder. A common cognitive symptom in HIV is decline in attention and executive functioning. Though typically examined by clinicians with less precise traditional paper-and-pencil neuropsychological tests, we examined this aspect of cognitive functioning using a more psychometrically sophisticated task as we had HIV-positive adults perform a computerized tracking task in single, dual, and tri-task conditions via the Multi-Attribute Task (MAT) Battery. Also assessed was mental workload, with the NASA-Task Load Index (NASA-TLX), rarely used in neuropsychology but a standard tool in human factors and neuroergonomics research. As expected, tracking performance declined with task condition difficulty (p < 0.001). Although no direct statistical comparisons were made, MAT performance here appeared worse than the MAT performance of various other groups reported in the research literature and in our laboratory. Ratings of workload also tended to increase as a function of task condition difficulty (p < 0.001). Plotting MAT tracking performance against the Mental Demand subscale scores, large individual differences in this aspect of workload were evident in both optimal and sub-optimal tracking performance. To examine likely variables with a potential impact on Mental Demand, a variety of variables (nadir CD4 count, viral load, depression symptoms, diagnosis of AIDS, presence of opportunistic infection, general cognitive status, etc.) were examined in relation to the Mental Demand scale, with age showing a significant association (r = 0.41, p = 0.022) and a diagnosis of AIDS showing trend associations (ps ≥ 0.066). Findings suggesting a deficit in metacognition or insight are also discussed. It is argued that assessment of workload (and its various aspects or components) can provide valuable additional information in neuropsychology.
Testing Links of Food-Related Olfactory Perception to Peripheral Ghrelin and Leptin Concentrations
Authors: Ginieis Rachel , Abeywickrema Sashie , Oey Indrawati , Peng Mei
Published: May 2022

The peptide hormones ghrelin and leptin play major roles in the regulation of appetite and food intake. However, the precise effects of these hormones on sensory processing remain a subject of debate, particularly with food related stimuli and its small body of evidence. Here, we test for relationships between ghrelin and leptin levels against olfactory performance with multiple food-related odours. Specifically, a total of 94 Caucasian males were tested for their supra-threshold sensitivity (i.e., d′), intensity, and valence perception to three odour compounds (i.e., vanilla, potato, and dairy odours). These sensory data were then analysed against peripheral ghrelin and leptin levels, both assessed in plasma samples. Participants’ body adiposity measures were also obtained. Results lent strong support to one of our original hypotheses, with ghrelin levels being positively correlated to the supra-threshold sensitivity of the dairy odour, (r = 0.241, p = 0.020), and intensity ratings to most of the food odours tested [dairy (r = 0.216, p = 0.037) and vanilla (r = 0.241, p = 0.020)]. By contrast, peripheral leptin levels were not significantly linked to any of the olfactory measures (p > 0.05). These relationships remained similar after controlling for variabilities of adiposity measures. The present study brings novel insights by identifying positive links between supra-threshold olfactory perception and ghrelin. This new knowledge is highly relevant for future research linking olfactory shifts to hormonal dysregulation and obesity.
Ghrelin Levels in Children With Intestinal Failure Receiving Long-Term Parenteral Nutrition
Authors: Vlug Lotte E. , Delhanty Patric J. D. , Neelis Esther G. , Huisman Martin , Visser Jenny A. , Rings Edmond H. H. M. , Wijnen René M. H. , Nagelkerke Sjoerd C. J. , Tabbers Merit M. , Hulst Jessie M. , de Koning Barbara A. E.
Published: May 2022

Background

Children with intestinal failure (IF) require parenteral nutrition (PN). Transition to oral and enteral nutrition (EN) can be difficult also due to abnormal gastrointestinal motility. The gut hormone ghrelin is increased in states of negative energy balance, functioning to preserve euglycemia, and also has appetite stimulating and prokinetic properties. We aimed to evaluate and compare ghrelin levels in children with IF, and to assess the relationship with PN-dependency.

Methods

In this exploratory prospective multicenter study, plasma acylated (AG) and unacylated (UAG) ghrelin levels were measured in children with short bowel syndrome (SBS) and with functional IF (pseudo-obstruction or any enteropathy) and compared with healthy control subjects. Spearman’s rho (rs) was used to assess correlations of AG and UAG with PN-dependency (%PN) and parenteral glucose intake.

Results

Sixty-four samples from 36 IF-patients were analyzed. Median baseline AG and UAG levels were respectively 279.2 and 101.0 pg/mL in children with SBS (n = 16), 126.4 and 84.5 pg/mL in children with functional IF (n = 20) and 82.4 and 157.3 pg/mL in healthy children (n = 39). AG levels were higher in children with SBS and functional IF than in healthy children (p = 0.002 and p = 0.023, respectively). In SBS, AG positively correlated with %PN (rs = 0.5, p = 0.005) and parenteral glucose intake (rs = 0.6, p = 0.003). These correlations were not observed in functional IF.

Conclusion

Children with IF had raised AG levels which could be related to starvation of the gut. The positive correlation between AG and glucose infusion rate in SBS suggests an altered glucoregulatory function.
Structural Characterization and Anti-breast Cancer Activity in vitro of a Novel Polysaccharide From Cymbopogon citratus
Authors: Chen Yi , Qiao Saifeng , Liu Huiping , Xing Huizhen , Chen Pei
Published: May 2022

Cymbopogon citratus is an important functional food, widely used for flavoring in Africa and South America. In this study, a novel high-molecular-weight polysaccharide (CCP) from C. citratus was extracted, and its structural characteristics and anti-breast cancer activity in vitro were investigated. CCP contained both α and β configurations and mainly composed of galactose (36.89%), arabinose (23.97%), glucose (18.35%) and rhamnose (9.36%) with an average molecular weight of 1.98 × 106 Da. The main glycosyl residues of CCP detected by methylation analysis were 1,3,6-linked Galp, 1,3-linked Glcp, 1,5-linked Araf , T-Araf , and T-Rhap. In vitro experiments suggested that CCP significantly inhibited the proliferation of MDA-MB-231 cells, decreased the expressions of cyclin D1 and CDK4 and stocked cells at G0/G1 phase. Meanwhile, the typical morphological features of apoptotic cells were also observed. Combining with the consequences of Annexin V-FITC/PI staining, Hoechst 33258 staining and western blot analysis, CCP induced apoptosis of MDA-MB-231 cells by triggering the Fas/FasL-mediated death receptor pathway. Overall, these results provide a theoretical basis for the application of C. citratus polysaccharide as a potential anti-breast cancer agent in functional food and medicine.
Single-Cell Proteomics and Tumor RNAseq Identify Novel Pathways Associated With Clofazimine Sensitivity in PI- and IMiD- Resistant Myeloma, and Putative Stem-Like Cells
Authors: Kumar Harish , Mazumder Suman , Sharma Neeraj , Chakravarti Sayak , Long Mark D. , Meurice Nathalie , Petit Joachim , Liu Song , Chesi Marta , Sanyal Sabyasachi , Stewart A. Keith , Kumar Shaji , Bergsagel Leif , Rajkumar S. Vincent , Baughn Linda B. , Van Ness Brian G. , Mitra Amit Kumar
Published: May 2022

Multiple myeloma (MM) is an incurable plasma cell malignancy with dose-limiting toxicities and inter-individual variation in response/resistance to the standard-of-care/primary drugs, proteasome inhibitors (PIs), and immunomodulatory derivatives (IMiDs). Although newer therapeutic options are potentially highly efficacious, their costs outweigh the effectiveness. Previously, we have established that clofazimine (CLF) activates peroxisome proliferator-activated receptor-γ, synergizes with primary therapies, and targets cancer stem-like cells (CSCs) in drug-resistant chronic myeloid leukemia (CML) patients. In this study, we used a panel of human myeloma cell lines as in vitro model systems representing drug-sensitive, innate/refractory, and clonally-derived acquired/relapsed PI- and cereblon (CRBN)-negative IMiD-resistant myeloma and bone marrow-derived CD138+ primary myeloma cells obtained from patients as ex vivo models to demonstrate that CLF shows significant cytotoxicity against drug-resistant myeloma as single-agent and in combination with PIs and IMiDs. Next, using genome-wide transcriptome analysis (RNA-sequencing), single-cell proteomics (CyTOF; Cytometry by time-of-flight), and ingenuity pathway analysis (IPA), we identified novel pathways associated with CLF efficacy, including induction of ER stress, autophagy, mitochondrial dysfunction, oxidative phosphorylation, enhancement of downstream cascade of p65-NFkB-IRF4-Myc downregulation, and ROS-dependent apoptotic cell death in myeloma. Further, we also showed that CLF is effective in killing rare refractory subclones like side populations that have been referred to as myeloma stem-like cells. Since CLF is an FDA-approved drug and also on WHO’s list of safe and effective essential medicines, it has strong potential to be rapidly re-purposed as a safe and cost-effective anti-myeloma drug.
Nomograms Predicting Survival of Cervical Cancer Patients Treated With Concurrent Chemoradiotherapy Based on the 2018 FIGO Staging System
Authors: Meng Qingyu , Wang Weiping , Liu Xiaoliang , Wang Dunhuang , Zhang Fuquan
Published: May 2022

Background

In 2018, a revised staging system was released for cervical cancer, which defined pelvic and paraaortic lymph node metastasis as stages IIIC1 and IIIC2, respectively. In this study, we constructed and validated nomograms to predict the 3- and 5-year survival of patients with cervical cancer based on the revised International Federation of Gynecology and Obstetrics (FIGO) staging system.

Methods

We retrospectively examined patients with 2009 FIGO stage IB–IVA cervical cancer who were treated at our institute between 2011 and 2015. Patients were randomized into the model development and validation cohorts (2:1). Univariate and multivariate analyses were conducted for the model development cohort to identify prognostic factors. In the multivariate analysis, nomograms were built to predict overall survival (OS) and disease-free survival (DFS) using significant variables. The nomograms were assessed based on the discrimination and calibration in both cohorts. Discrimination was assessed using the concordance index. Calibration was performed by comparing the mean nomogram estimated survival and the mean observed survival.

Results

We included 1,192 patients, with 795 and 397 patients in the model development and validation cohorts, respectively. In the model development cohort, the median follow-up period was 49.2 months. After multivariate analysis, age, histology, 2018 FIGO stage, and pelvic lymph node number were independent factors for OS. Histology, 2018 FIGO stage, squamous cell carcinoma antigen, and pelvic lymph node number were significant predictors of DFS. The nomograms constructed to predict OS and DFS were based on these factors. In both model cohorts, the concordance index for the nomogram-predicted OS and DFS was 0.78 and 0.75 and 0.74 and 0.67, respectively. The calibration curve revealed good agreement between the nomogram predictions and actual values.

Conclusion

We constructed robust nomograms to predict the OS and DFS of patients with cervical cancer undergoing treatment with concurrent chemoradiotherapy based on the 2018 FIGO staging system.