bluuebunny/crossref_metadata_2025 huggingface dataset:
Perturbations in the T cell receptor β repertoire during malaria infection in children: A preliminary study
Authors: Frimpong Augustina , Ofori Michael Fokuo , Degoot Abdoelnaser M. , Kusi Kwadwo Asamoah , Gershom Buri , Quartey Jacob , Kyei-Baafour Eric , Nguyen Nhi , Ndifon Wilfred
Published: October 2022

The changes occurring in the T cell repertoire during clinical malaria infection in children remain unknown. In this study, we undertook the first detailed comparative study of the T cell repertoire in African children with and without clinical malaria to test the hypothesis that clonotypic expansions that occur during P. falciparum infection will contribute to the generation of a T cell repertoire that is unique to each disease state. We profiled the complementarity-determining region 3 (CDR3) of the TCRβ chain sequences from children with Plasmodium falciparum infections (asymptomatic, uncomplicated and severe malaria) and compared these with sequences from healthy children. Interestingly, we discovered that children with symptomatic malaria have a lower TCR diversity and frequency of shared (or “public”) TCR sequences compared to asymptomatic children. Also, TCR diversity was inversely associated with parasitemia. Furthermore, by clustering TCR sequences based on their predicted antigen specificities, we identified a specificity cluster, with a 4-mer amino acid motif, that is overrepresented in the asymptomatic group compared to the diseased groups. Further investigations into this finding may help in delineating important antigenic targets for vaccine and therapeutic development. The results show that the T cell repertoire in children is altered during malaria, suggesting that exposure to P. falciparum antigens disrupts the adaptive immune response, which is an underlying feature of the disease.
Prognostic analysis and validation of diagnostic marker genes in patients with osteoporosis
Authors: Wang Xing , Pei Zhiwei , Hao Ting , Ariben Jirigala , Li Siqin , He Wanxiong , Kong Xiangyu , Chang Jiale , Zhao Zhenqun , Zhang Baoxin
Published: October 2022

Backgrounds

As a systemic skeletal dysfunction, osteoporosis (OP) is characterized by low bone mass and bone microarchitectural damage. The global incidences of OP are high.

Methods

Data were retrieved from databases like Gene Expression Omnibus (GEO), GeneCards, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Gene Expression Profiling Interactive Analysis (GEPIA2), and other databases. R software (version 4.1.1) was used to identify differentially expressed genes (DEGs) and perform functional analysis. The Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression and random forest algorithm were combined and used for screening diagnostic markers for OP. The diagnostic value was assessed by the receiver operating characteristic (ROC) curve. Molecular signature subtypes were identified using a consensus clustering approach, and prognostic analysis was performed. The level of immune cell infiltration was assessed by the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm. The hub gene was identified using the CytoHubba algorithm. Real-time fluorescence quantitative PCR (RT-qPCR) was performed on the plasma of osteoporosis patients and control samples. The interaction network was constructed between the hub genes and miRNAs, transcription factors, RNA binding proteins, and drugs.

Results

A total of 40 DEGs, eight OP-related differential genes, six OP diagnostic marker genes, four OP key diagnostic marker genes, and ten hub genes (TNF, RARRES2, FLNA, STXBP2, EGR2, MAP4K2, NFKBIA, JUNB, SPI1, CTSD) were identified. RT-qPCR results revealed a total of eight genes had significant differential expression between osteoporosis patients and control samples. Enrichment analysis showed these genes were mainly related to MAPK signaling pathways, TNF signaling pathway, apoptosis, and Salmonella infection. RT-qPCR also revealed that the MAPK signaling pathway (p38, TRAF6) and NF-kappa B signaling pathway (c-FLIP, MIP1β) were significantly different between osteoporosis patients and control samples. The analysis of immune cell infiltration revealed that monocytes, activated CD4 memory T cells, and memory and naïve B cells may be related to the occurrence and development of OP.

Conclusions

We identified six novel OP diagnostic marker genes and ten OP-hub genes. These genes can be used to improve the prognostic of OP and to identify potential relationships between the immune microenvironment and OP. Our research will provide insights into the potential therapeutic targets and pathogenesis of osteoporosis.
Identification and exploration of pharmacological pyroptosis-related biomarkers of ulcerative colitis
Authors: Chen Kaiwei , Shang Shipeng , Yu Shengnan , Cui Luwen , Li Shangyong , He Ningning
Published: October 2022

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD). Its etiology is unclear. Much evidence suggests that the death of abnormal intestinal epithelial cells (IECs) leads to intestinal barrier disruption, and the subsequent inflammatory response plays a vital role in UC. Pyroptosis is a form of programmed inflammatory cell death, and the role of pyroptosis in UC etiology remains to be explored. This study identified 10 hub genes in pyroptosis by gene expression profiles obtained from the GSE87466 dataset. Meanwhile, the biomarkers were screened based on gene significance (GS) and module membership (MM) through the Weighted Gene Co-Expression Network Analysis (WGCNA). The following analysis indicated that hub genes were closely associated with the UC progression and therapeutic drug response. The single-cell RNA (scRNA) sequencing data from UC patients within the GSE162335 dataset indicated that macrophages were most related to pyroptosis. Finally, the expression of hub genes and response to the therapeutic drug [5-aminosalicylic acid (5-ASA)] were verified in dextran sulfate sodium (DSS)-induced colitis mice. Our study identified IL1B as the critical pyroptosis-related biomarker in UC. The crosstalk between macrophage pyroptosis and IEC pyroptosis may play an essential role in UC, deserving further exploration.
Monitoring the marine invasive alien species Rugulopteryx okamurae using unmanned aerial vehicles and satellites
Authors: Roca Mar , Dunbar Martha Bonnet , Román Alejandro , Caballero Isabel , Zoffoli Maria Laura , Gernez Pierre , Navarro Gabriel
Published: October 2022

Rugulopteryx okamurae is a species of brown macroalgae belonging to the Dictyotaceae family and native to the north-western Pacific. As an Invasive Alien Species (IAS), it was first detected in the Strait of Gibraltar in 2015. Since then, R. okamurae has been spreading rapidly through the submerged euphotic zone, colonizing from 0 to 50 m depth and generating substantial economic and environmental impacts on the Andalusian coasts (southern Spain). More than 40% of marine IAS in the European Union (EU) are macroalgae, representing one of the main threats to biodiversity and ecosystem functioning in coastal habitats. This study presents a monitoring pilot of beached R. okamurae and fresh R. okamurae down to 5 m depth in Tarifa (Cadiz, Spain), combining multispectral remote sensing data collected by sensors on-board Unmanned Aerial Vehicles (UAVs) and satellites, and how this information can be used to support decision-making and policy. We used an UAV flight carried out at Bolonia beach (Tarifa, Spain) on 1st July 2021 and Sentinel-2 (S2) and Landsat-8 (L8) image acquisitions close to the drone flight date. In situ data were also measured on the same date of the flight, and they were used to train the supervised classification Super Vector Machine (SVM) method based on the spectral information obtained for each substrate cover. The results obtained show how multispectral images allow the detection of beached R. okamurae, and the classification accuracy for water, land vegetation, sand and R. okamurae depending on the image resolution (8.3 cm/pixel for UAV flight, 10 m/pixel for S2 and 30 m/pixel for L8). While the UAV imagery precisely delimited the area occupied by this macroalgae, satellite data were capable of detecting its presence, and able to generate early warnings. This study demonstrates the usefulness of multispectral remote sensing techniques to be incorporated in continuous monitoring programmes of the marine IAS R. okamurae in coastal areas. This information is also key to supporting regional, national and European policies in order to adapt strategic management of invasive marine macrophytes.
RNA-based drugs and regulation: Toward a necessary evolution of the definitions issued from the European union legislation
Authors: Guerriaud Mathieu , Kohli Evelyne
Published: October 2022

Many RNA-based drugs, both vaccines and non-vaccines, are under development or even approved. They include coding mRNAs and non-coding (nc) RNAs among them antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), micro-RNAs (miRNAs), small activating RNAs (saRNAs), RNA aptamers and RNA guides. According to the European Union (EU) legislation, these products can be currently categorized into different regulatory statuses, depending, for vaccines, on their target (infectious disease or not) and, for other drugs, on how they are obtained (chemically or biologically). This classification is fundamental to the type of marketing authorization (MA), and therefore to the controls to be performed, from preclinical stages through clinical trials to pharmacovigilance, to meet the safety requirements for patients. However, the current rules raise several problems, in particular the risk, because technology is evolving, to have similar RNA drugs being covered by very different legal statuses and the lack of international harmonization. The objectives of this study are (i) to review how RNA medicinal products are currently legally categorized in the EU and especially whether they fall under the status of gene therapy medicinal products (GTMP), a regulatory status belonging to advanced therapy medicinal products (ATMP), (ii) to discuss the issues generated by this classification, with a focus on the heterogeneity of statuses of these products, the differences with the American and ICH definitions and the potential impact on the safety requirements.
Stereoscopic vs. monoscopic photographs on optic disc evaluation and glaucoma diagnosis among general ophthalmologists: A cloud-based real-world multicenter study
Authors: Yang Jingyuan , Qu Yi , Zhao Jianchun , Cong Jingwu , Sun Zixi , Du Yunfeng , Yang Gang , Ding Dayong , Chen Youxin , Cheng Gangwei
Published: October 2022

Purpose

To investigate whether stereoscopic vs. monoscopic viewing condition influences the evaluation of optic disc photographs for morphologic features and glaucoma likelihood in a general ophthalmologist population from multicenters on a cloud-based platform.

Methods

A cross-sectional study of 519 pairs of stereoscopic and monoscopic photographs of optic discs with adequate quality were selected and presented using a cloud-based platform. A total of 21 general ophthalmologists from 14 centers assessed 15 morphologic features based on 5R's rules and estimated glaucoma likelihood for each assigned photograph. There were 93 pairs of stereoscopic and monoscopic photographs evaluated by a panel of glaucoma specialists and set as ground truth. The main outcome measures were the agreement between estimates and ground truth and the inter-grader agreements.

Results

There were good agreements between ground truth and both monoscopic and stereoscopic estimates (stereo κ 0.532 and mono κ 0.494). There was also a substantial intra-grader agreement between monoscopic and stereoscopic evaluation of glaucoma likelihood (κ 0.636). In eyes with probable glaucoma, the accuracy of the stereo method was greater than that of the mono method (stereo 0.238 vs. mono 0.118) When compared with ground truth, stereoscopic photographs had a better agreement for disc size (stereo κ 0.447 vs. mono κ 0.183), disc color (stereo κ 0.612 vs. mono κ 0.549), neuroretinal rim shape (stereo κ 0.356 vs. mono κ 0.274) on the whole. The stereoscopic method also had a better inter-grade agreement for disc size, disc color, neuroretinal rim shape, and glaucoma likelihood (stereo κ 0.402 vs. mono κ 0.359) on the whole.

Conclusions

In the evaluation of optic disc photographs for morphologic features and glaucoma likelihood, the stereoscopic method showed superiority compared to the monoscopic method for general ophthalmologists. The stereoscopic method is more likely to identify glaucomatous eyes which need medical intervention.
Temporal dynamics of total and active root-associated diazotrophic communities in field-grown rice
Authors: Luo Xue , Ye Xianfeng , Wang Wenhui , Chen Yang , Li Zhoukun , Wang Yanxin , Huang Yan , Ran Wei , Cao Hui , Cui Zhongli
Published: October 2022

Plant-associated nitrogen-fixing microorganisms (diazotrophs) are essential to host nutrient acquisition, productivity and health, but how host growth affects the succession characteristics of crop diazotrophic communities is still poorly understood. Here, Illumina sequencing of DNA- and RNA-derived nifH genes was employed to investigate the dynamics of total and active diazotrophic communities across rhizosphere soil and rice roots under four fertilization regimes during three growth periods (tillering, heading and mature stages) of rice in 2015 and 2016. Our results indicated that 71.9–77.2% of the operational taxonomic units (OTUs) were both detected at the DNA and RNA levels. According to the nonmetric multidimensional scaling ordinations of Bray–Curtis distances, the variations in community composition of active rhizosphere diazotrophs were greater than those of total rhizosphere diazotrophs. The community composition (β-diversity) of total and active root-associated diazotrophs was shaped predominantly by microhabitat (niche; R2 ≥ 0.959, p < 0.001), followed by growth period (R2 ≥ 0.15, p < 0.001). The growth period had a stronger effect on endophytic diazotrophs than on rhizosphere diazotrophs. From the tillering stage to the heading stage, the α-diversity indices (Chao1, Shannon and phylogenetic diversity) and network topological parameters (edge numbers, average clustering coefficient and average degree values) of total endophytic diazotrophic communities increased. The proportions of OTUs shared by the total rhizosphere and endophytic diazotrophs in rhizosphere diazotrophs gradually increased during rice growth. Moreover, total diazotrophic α-diversity and network complexity decreased from rhizosphere soil to roots. Collectively, compared with total diazotrophic communities, active diazotrophic communities were better indicators of biological response to environmental changes. The host microhabitat profoundly drove the temporal dynamics of total and active root-associated diazotrophic communities, followed by the plant growth period.
Identification and characterization of nanobodies specifically against African swine fever virus major capsid protein p72
Authors: Yang Jifei , Jing Mengyao , Niu Qingli , Wang Jinming , Zhao Yaru , Liu Meng , Guan Guiquan , Luo Jianxun , Yin Hong , Liu Zhijie
Published: October 2022

African swine fever virus (ASFV) is a large and very complex DNA virus. The major capsid protein p72 is the most predominant structural protein and constitutes the outmost icosahedral capsid of the virion. In the present study, the nanobodies against ASFV p72 protein were screened from a camelid immune VHH library by phage display technique. Nine distinct nanobodies were identified according to the amino acid sequences of the complementary determining regions (CDRs), and contain typical amino acid substitutions in the framework region 2 (FR2). Six nanobodies were successfully expressed in E. coli, and their specificity and affinity to p72 protein were further evaluated. The results showed that nanobodies Nb25 had the best affinity to both recombinant and native p72 protein of ASFV. The Nb25 possesses an extremely long CDR3 with 23 amino acids compared with other nanobodies, which may allow this nanobody to access the hidden epitopes of target antigen. Furthermore, the Nb25 can specifically recognize the virus particles captured by polyclonal antibody against ASFV in a sandwich immunoassay, and its application as a biosensor to target virus in PAM cells was verified by an immunofluorescence assay. Nanobodies have been proven to possess many favorable properties with small size, high affinity and specificity, easier to produce, low costs and deep tissue penetration that make them suitable for various biotechnological applications. These findings suggest that nanobody Nb25 identified herein could be a valuable alternative tool and has potential applications in diagnostic and basic research on ASFV.
BosR: A novel biofilm-specific regulator in Pseudomonas aeruginosa
Authors: Dostert Melanie , Belanger Corrie R. , Pedraz Lucas , Alford Morgan A. , Blimkie Travis M. , Falsafi Reza F. , Bains Manjeet , Dhillon Bhavjinder Kaur , Haney Cara H. , Lee Amy H. , Hancock Robert E. W.
Published: October 2022

Biofilms are the most common cause of bacterial infections in humans and notoriously hard to treat due to their ability to withstand antibiotics and host immune defenses. To overcome the current lack of effective antibiofilm therapies and guide future design, the identification of novel biofilm-specific gene targets is crucial. In this regard, transcriptional regulators have been proposed as promising targets for antimicrobial drug design. Therefore, a Transposon insertion sequencing approach was employed to systematically identify regulators phenotypically affecting biofilm growth in Pseudomonas aeruginosa PA14 using the TnSeq analysis tools Bio-TraDIS and TRANSIT. A screen of a pool of 300,000 transposon insertion mutants identified 349 genes involved in biofilm growth on hydroxyapatite, including 47 regulators. Detection of 19 regulatory genes participating in well-established biofilm pathways validated the results. An additional 28 novel prospective biofilm regulators suggested the requirement for multiple one-component transcriptional regulators. Biofilm-defective phenotypes were confirmed for five one-component transcriptional regulators and a protein kinase, which did not affect motility phenotypes. The one-component transcriptional regulator bosR displayed a conserved role in P. aeruginosa biofilm growth since its ortholog in P. aeruginosa strain PAO1 was also required for biofilm growth. Microscopic analysis of a chromosomal deletion mutant of bosR confirmed the role of this regulator in biofilm growth. Overall, our results highlighted that the gene network driving biofilm growth is complex and involves regulators beyond the primarily studied groups of two-component systems and cyclic diguanylate signaling proteins. Furthermore, biofilm-specific regulators, such as bosR, might constitute prospective new drug targets to overcome biofilm infections.
Prevalence and genotyping distribution of Enterocytozoon bieneusi in diarrheic pigs in Chongqing and Sichuan provinces, China
Authors: Ghebremichael Samson Teweldeberhan , Meng Xianzhi , Wei Junhong , Yang Yujiao , Huang Qingyuan , Luo Lie , Xiang Heng , Chen Jie , Abo-Kadoum M. A. , Li Tian , Liu Xiao , Bao Jialing , Zhou Zeyang , Pan Guoqing
Published: October 2022

The microsporidian fungal pathogen Enterocytozoon bieneusi is a unicellular parasite that infects humans and various animals, including pigs. Currently, there are few data on E. bieneusi infection a in diarrheic pigs in Chongqing and Sichuan Provinces, China. This study aims to determine the prevalence and genotype distribution of E. bieneusi in diarrheic pigs. In total, 514 fecal samples from diarrheic pigs were obtained from 14 large-scale farms in Chongqing and Sichuan Provinces (326 suckling pigs, 17 weaned pigs, 65 fattening pigs, and 106 sows). To identify the E. bieneusi genotypes, genomic DNA was isolated from the samples and tested by nested PCR, targeting the internal transcribed spacer region of the rRNA followed by DNA sequence analysis. The overall prevalence of E. bieneusi was 79.8% (410/514), with rates of 84.9% (90/106) in sows and 64.7% (11/17) in weaned pigs. We found 61 different genotypes, including seven known genotypes (E, F, CHG1, Peru8, CAF1, B, and BEB17) and 54 novel genotypes. These 54 new genotypes are variants of eight known genotypes (SDD2, A, B, HLJD-IV, PigSpEb1, O, JLD-I, and BEB17) based on their sequence similarities. Phylogenetically, all of the identified genotypes clustered with counterparts belonging to Group 1 and Group 2 of E. bieneusi. Therefore, we found a higher prevalence of E. bieneusi in sows than in preweaned and weaned pigs. These findings indicate that diarrheic pigs could be a potential reservoir host, which can contaminate the environment and be a source of microsporidia in humans and other animals.
Biocontrol potential of Pseudomonas rhodesiae GC-7 against the root-knot nematode Meloidogyne graminicola through both antagonistic effects and induced plant resistance
Authors: Ye Shan , Yan Rui , Li Xinwen , Lin Yufeng , Yang Zhuhong , Ma Yihang , Ding Zhong
Published: October 2022

Plant-parasitic nematodes (PPNs) cause serious damage to agricultural production worldwide. Currently, because of a lack of effective and environmental-friendly chemical nematicides, the use of microbial nematicides has been proposed as an eco-friendly management strategy to control PPNs. A nematicidal bacterium GC-7 was originally isolated from the rice rhizosphere, and was identified as Pseudomonas rhodesiae. Treatment with the fermentation supernatant of GC-7 in vitro showed a highly lethal effect on second-stage juveniles of Meloidogyne graminicola, with the mortality rate increasing to 95.82% at 24 h and egg hatching significantly inhibited, with a hatch inhibition rate of 60.65% at 96 h. The bacterium significantly reduced the level of damage caused by M. graminicola infestations to rice (Oryza sativa) in greenhouse and field experiments. Under greenhouse conditions, the GC-7 culture efficiently reduced the gall index and nematode population in rice roots and soils, as well as inhibited nematode development compared to the control. Under field conditions, application of the GC-7 consistently showed a high biocontrol efficacy against M. graminicola (with a control efficiency of 58.85%) and promoted plant growth. In addition, the inoculation of GC-7 in M. graminicola-infested rice plant fields significantly suppressed final nematode populations in soil under natural conditions. Furthermore, activities of plant defense-related enzymes, peroxidase, polyphenol oxidase, and phenylalanine ammonia-lyase were remarkably increased in plant roots treated with GC-7 compared with roots that were challenge to M. graminicola. Moreover, quantitative real-time PCR analysis showed that GC-7 significantly enhanced the expression of defense genes (PR1a, WRKY45, JaMYB, AOS2, ERF1, and ACS1) related to salicylic acid, jasmonic acid, and ethylene signaling pathways in rice roots after inoculation with GC-7 at different levels. The results indicated that GC-7 could be an effective biological component in the integrated management of M. graminicola infecting rice.
Microbial diversity and functional genes of red vinasse acid based on metagenome analysis
Authors: Lv Jianman , Ye Yaolu , Zhong Yuan , Liu Wukang , Chen Meilin , Guo Ailing , Lv Jun , Ma Huawei
Published: October 2022

Red vinasse acid has a distinct flavor and a vivid red color that are directly tied to the intricate metabolic activities of microorganisms that produce it. In this study, metagenomic technology was used to mine its functional genes and examine the microbial diversity of red vinasse acid. The findings revealed the identification of 2,609 species, 782 genera, and 63 phyla of microorganisms, and the dominant genus was Lactobacillus. Amino acid metabolism and carbohydrate metabolism were significant activities among the 16,093 and 49,652 genes that were annotated in the evolutionary genealogy of genes: Non-supervised Orthologous Groups (eggNOG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively. In gluconeogenesis, red vinasse acid encodes 194 genes controlling the transporter protein systems of different sugars and has key enzyme genes that catalyze the conversion of intracellular sugars into glycolytic intermediates. In amino acid flavor formation, red vinasse acid contains 32 control genes for branched-chain aminotransferase (BCAT), 27 control genes for aromatic-amino-acid transaminase (ArAT), 60 control genes for keto acid invertase, 123 control genes for alcohol/aldehyde dehydrogenase, and 27 control genes for acetyl esterase, which have the basis for the formation of strong flavor substances from amino acids.
Monocytohigh-density lipoprotein ratio has a high predictive value for the diagnosis of multiple system atrophy and the differentiation from Parkinson’s disease
Authors: Jiang Lijuan , Zhong Zhen , Huang Juan , Bian Hetao , Huang Wei
Published: October 2022

Background and purpose

Inflammation is closely related to the pathogenesis of multiple system atrophy (MSA). As markers of inflammation, the monocyte to high-density lipoprotein ratio (MHR), neutrophil to lymphocyte ratio (NLR), and red cell distribution width to platelet ratio (RPR) have been proven to be associated with a large variety of diseases. The aim of this study was to explore the association between inflammatory markers (MHR, NLR, and RPR) and MSA, and the difference between MSA and Parkinson’s disease (PD) was further compared by these inflammatory markers.

Materials and methods

This study was divided into three groups: 47 patients with MSA, 125 patients with PD, and 124 healthy controls. The corresponding laboratory indicators of subjects were collected and analyzed to obtain MHR, NLR, and RPR values.

Results

Compared with healthy controls, the MHR, NLR, and RPR were higher in the MSA group (P < 0.05), and the MHR was higher in the MSA group than in the PD group (P < 0.001). Multivariate logistic regression analysis showed that MHR*10 (corrected OR = 1.312, 95% CI 1.093–1.575) and RPR*100 (corrected OR = 1.262, 95% CI 1.055–1.509) were positively correlated with the risk of MSA. The receiver operating characteristic (ROC) curve indicated that the areas under the curve (AUCs) of the MHR, NLR, and RPR for predicting MSA were 0.651 (95% CI 0.562–0.74; P < 0.05), 0.6 (95% CI 0.501–0.699; P < 0.05), and 0.612 (95% CI 0.516–0.708; P < 0.05), respectively. The AUC of MSA and PD predicted by the MHR was 0.727 (P < 0.001). When the cut-off value was 0.38, the sensitivity and specificity were 60 and 77%, respectively. Spearman correlation analysis showed that the MHR was significantly and positively correlated with the course of MSA cerebellar type (MSA-C) patients.

Conclusion

There may be peripheral inflammation in patients with MSA. Compared with NLR and RPR, MHR has higher predictive value for the diagnosis and differential diagnosis of MSA.
No evidence for a difference in lateralization and distinctiveness level of transcranial magnetic stimulation-derived cortical motor representations over the adult lifespan
Authors: Hehl Melina , Swinnen Stephan P. , Van Malderen Shanti , Cuypers Koen
Published: October 2022

This study aimed to investigate the presence and patterns of age-related differences in TMS-based measures of lateralization and distinctiveness of the cortical motor representations of two different hand muscles. In a sample of seventy-three right-handed healthy participants over the adult lifespan, the first dorsal interosseus (FDI) and abductor digiti minimi (ADM) cortical motor representations of both hemispheres were acquired using transcranial magnetic stimulation (TMS). In addition, dexterity and maximum force levels were measured. Lateralization quotients were calculated for homolog behavioral and TMS measures, whereas the distinctiveness between the FDI and ADM representation within one hemisphere was quantified by the center of gravity (CoG) distance and cosine similarity. The presence and patterns of age-related changes were examined using linear, polynomial, and piecewise linear regression. No age-related differences could be identified for the lateralization quotient of behavior or cortical motor representations of both intrinsic hand muscles. Furthermore, no evidence for a change in the distinctiveness of the FDI and ADM representation with advancing age was found. In conclusion this work showed that lateralization and distinctiveness of cortical motor representations, as determined by means of TMS-based measures, remain stable over the adult lifespan.
Electroacupuncture of the trigeminal nerve causes N-methyl-D-aspartate receptors to mediate blood-brain barrier opening and induces neuronal excitatory changes
Authors: Gong Peng , Zhang Shanshan , Ren Li , Zhang Jiangsong , Zhao Yibin , Mao Xuqing , Gan Lin , Wang Hao , Ma Congcong , Lin Yubo , Ye Qinyu , Qian Kecheng , Lin Xianming
Published: October 2022

The blood-brain barrier (BBB) is an important structure for maintaining environmental stability in the central nervous system (CNS). Our previous study showed that specific parameters of electroacupuncture (EA) at the head points Shuigou (GV26) and Baihui (GV20) can open the BBB; however, the mechanism by which stimulation of body surface acupuncture points on the head results in peripheral stimulation and affects the status of the central BBB and the neuronal excitatory changes has not been elucidated. We used laser spectroscopy, the In Vivo Imaging System (IVIS), immunofluorescence and immunoblotting to verified the role of the trigeminal nerve in BBB opening during EA, and we applied the central N-methyl-D-aspartate (NMDA) receptors blocker MK-801 to verify the mediating role of NMDA receptors in EA-induced BBB opening. Next, electroencephalogram (EEG) and in vivo calcium imaging techniques were applied to verify the possible electrical patterns of BBB opening promoted by different intensities of EA stimulation. The results showed that the trigeminal nerve plays an important role in the alteration of BBB permeability promoted by EA stimulation of the head acupoints. Brain NMDA receptors play a mediating role in promoting BBB permeability during EA of the trigeminal nerve, which may affect the expression of the TJ protein occludin, and thus alter BBB permeability. The analysis of the electrical mechanism showed that there was no significant change in the rhythm of local field potentials (LFP) in different brain regions across frequency bands immediately after EA of the trigeminal nerve at different intensities. However, the local primary somatosensory (S1BF) area corresponding to the trigeminal nerve showed a transient reduction in the delta rhythm of LFP with no change in the high-frequency band, and the action potential (spike) with short inter spike interval (ISI) varied with EA intensity. Meanwhile, EA of the trigeminal nerve resulted in rhythmic changes in calcium waves in the S1BF region, which were influenced by different EA intensities. This study provides a research perspective and a technical approach to further explore the mechanism of EA-induced BBB opening and its potential clinical applications.
Brain and spinal cord paired stimulation coupled with locomotor training facilitates motor output in human spinal cord injury
Authors: Pulverenti Timothy S. , Zaaya Morad , Grabowski Ewelina , Grabowski Monika , Knikou Maria
Published: October 2022

Combined interventions for neuromodulation leading to neurorecovery have gained great attention by researchers to resemble clinical rehabilitation approaches. In this randomized clinical trial, we established changes in the net output of motoneurons innervating multiple leg muscles during stepping when transcranial magnetic stimulation (TMS) of the primary motor cortex was paired with transcutaneous spinal (transspinal) stimulation over the thoracolumbar region during locomotor training. TMS was delivered before (TMS-transspinal) or after (transspinal-TMS) transspinal stimulation during the stance phase of the less impaired leg. Ten individuals with chronic incomplete or complete SCI received at least 20 sessions of training. Each session consisted of 240 paired stimuli delivered over 10-min blocks for 1 h during robotic assisted step training on a motorized treadmill. Body weight support, leg guidance force and treadmill speed were adjusted based on each subject's ability to step without knee buckling or toe dragging. Most transspinal evoked potentials (TEPs) recorded before and after each intervention from ankle and knee muscles during assisted stepping were modulated in a phase-dependent pattern. Transspinal-TMS and locomotor training affected motor neuron output of knee and ankle muscles with ankle TEPs to be modulated in a phase-dependent manner. TMS-transspinal and locomotor training increased motor neuron output for knee but not for ankle muscles. Our results support that targeted brain and spinal cord stimulation alters responsiveness of neurons over multiple spinal segments in people with chronic SCI. Noninvasive stimulation of the brain and spinal cord along with locomotor training is a novel neuromodulation method that can become a promising modality for rehabilitation in humans after SCI.
Dose-staged Gamma Knife radiosurgery for meningiomas: A retrospective study in a single center
Authors: Gong Xiu , Ding Jianbo , Knisely Jonathan P. S. , Wang Enmin , Pan Li , Wang Binjiang , Zhang Nan , Wu Hanfeng , Dai Jiazhong , Yu Tonggang , Tang Xuqun
Published: October 2022

Objective

This study aimed to study the efficiency and safety of a dose-staged Gamma Knife radiosurgery strategy for large meningiomas or meningiomas close to important nerve structures.

Methods

This study evaluates the outcome of a prospectively accrued series of 71 consecutive patients with meningiomas treated with staged dose-fractionated Gamma Knife radiosurgery. The average peripheral doses for the first and second fractions were 9.0 ± 0.9 Gy (8–12 Gy) and 8.6 ± 0.7 Gy (range, 7–10 Gy), respectively. The interval between fractions was 6.1 ± 1.9 months (range, 3–12 months). The median follow-up time was 36 months (12–96 months).

Results

During the follow-up period after the second fraction, 97.2% achieved tumor control in our series. A total of 2 patients exhibited local recurrence at 30 and 60 months after the second fraction, respectively. No treatment-related complications or new long-term neurological dysfunctions were reported. MRIs observed slightly or moderately increased peritumoral edema in six patients, but no specific neurological complaints are attributed to this finding.

Conclusion

This study investigates the efficiency and safety of dose-staged Gamma Knife radiosurgery as an alternative option for meningiomas that were large in volume, adjacent to crucial structures, or in patients with contraindications to craniotomy.
Surgical quadriceps lengthening can reduce quadriceps spasticity in chronic stroke patients. A case-control study
Authors: Merlo Andrea , Galletti Martina , Zerbinati Paolo , Prati Paolo , Mascioli Francesca , Basini Giacomo , Rambelli Chiara , Masiero Stefano , Mazzoli Davide
Published: October 2022

Background

Muscle overactivity is one of the positive signs of upper motor neuron lesions. In these patients, the loss of muscle length and extensibility resulting from soft tissue rearrangement has been suggested as a contributing cause of muscle overactivity in response to stretching.

Objective

To assess the effects of surgical lengthening of the quadriceps femoris (QF) muscle-tendon unit by aponeurectomy on muscle spasticity.

Methods

This is a case-control study on chronic stroke patients with hemiparesis that have undergone lower limb functional surgery over a 8-year period. CASEs underwent corrective surgery for both the foot and knee deviations, inclusive of a QF aponeurectomy. Controls (CTRLs) underwent corrective surgery for foot deviations only. QF spasticity was assessed with the Modified Tardieu Scale (MTS) before and 1 month after surgery. The Wilcoxon test was used to assess MTS variations over time and the Mann–Whitney test was used to verify the presence of group differences at the 1 month mark.

Results

Ninety-three patients were included: 57 cases (30F, 1–34 years from lesion) and 36 controls (12F, 1–35 years from lesion). Before surgery, both CASEs and CTRLs had similar MTS scores (median MTS = 3) and functional characteristics. One month after surgery, QF spasticity was significantly lower in the CASEs compared to CTRLs (p = 0.033) due to a significant reduction of the median MTS score from 3 to 0 in the CASE group (p < 0.001) and no variations in the CTRL group (p = 0.468). About half of the cases attained clinically significant MTS reductions and complete symptom relief even many years from the stroke.

Conclusions

Functional surgery inclusive of QF aponeurectomy can be effective in reducing or suppressing spasticity in chronic stroke patients. This is possibly a result of the reduction in neuromuscular spindle activation due to a decrease in muscle shortening, passive tension, and stiffness.
Early nutritional intake influences the serum levels of nerve growth factor (NGF) and brain-derived neurotrophic factor in preterm newborns
Authors: De Nardo Maria Chiara , Petrella Carla , Di Chiara Maria , Di Mario Chiara , Deli Giorgia , Travaglia Elisa , Baldini Laura , Russo Alessia , Parisi Pasquale , Fiore Marco , Terrin Gianluca
Published: October 2022

Introduction

Parenteral nutrition (PN) may have detrimental effects on neurodevelopment in preterm newborns. Moreover, enteral nutrition (EN) seems to be protective. To understand the mechanisms of how neurological development can be influenced by the route of administration of nutritional intake, we investigated the relationship between the serum levels of the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and nutritional intake received in early life by preterm newborns.

Materials and methods

Specimens of blood were obtained at 28 days of life (DOL) for NGF/BDNF determination in neonates <32 weeks of gestation and/or with birth weight <1,500 g, consecutively observed in the neonatal intensive care unit. We analyzed the relation between amino acid content and energy intake and NGF/BDNF measurements at 28 DOL. PN protein intake was referred to as the total amounts of amino acid intake received daily.

Results

We enrolled 20 newborns (gestational age 30.45 ± 1.76 weeks, birth weight 1,340 ± 352.63 g). Serum NGF value at 28 DOL was positively correlated with enteral protein and energy intake (r = 0.767; r = 0.746, p < 0.001), whereas, negatively correlated with parenteral amino acid and energy intake (r = −0.652, p < 0.001; r = −0.466, p < 0.05). Similar significant correlations were described between BDNF level at 28 DOL and enteral energy intake (r = 0.493, p < 0.05). Multivariate regression analysis showed that NGF level at 28 DOL depends on enteral protein and energy intake administrated in the 1st week of life.

Conclusion

Neurotrophin values varied according to the route of nutrition administration in preterm newborns. NGF/BDNF serum levels are influenced positively and negatively by EN and PN, respectively.
Noise exposure in early adulthood causes age-dependent and brain region-specific impairments in cognitive function
Authors: Patel Salonee V. , DeCarlo Courtney M. , Book Shae A. , Schormans Ashley L. , Whitehead Shawn N. , Allman Brian L. , Hayes Sarah H.
Published: October 2022

Hearing loss is a chronic health condition that affects millions of people worldwide. In addition to age-related hearing impairment, excessive noise exposure is a leading cause of hearing loss. Beyond the devastating effects of hearing impairment itself, epidemiological studies have identified hearing loss as a major risk factor for age-related cognitive decline, including dementia. At present, we currently lack a full understanding of the brain regions and underlying molecular changes that are responsible for mediating the link between hearing loss and cognitive impairment across aging. In the present study, we exposed 6-month-old rats to an occupational-like noise (100 dB SPL, 4 h/day × 30 days) or sham exposure and investigated both hippocampal-dependent (i.e., spatial learning and memory, assessed using the Morris water maze) and striatal-dependent (i.e., visuomotor associative learning, assessed using an operant-conditioning task) cognitive function across aging at 7, 10, and 13 months of age. We also investigated brain region-specific changes in microglial expression following noise/sham exposure in order to assess the potential contribution of this cell type to noise-induced cognitive impairments. Consistent with human studies, the occupational-like noise exposure resulted in high-frequency hearing loss, evidenced by a significant increase in hearing thresholds at 20 kHz. Ultimately, our results suggest that not all higher-level cognitive tasks or their associated brain regions appear to be equally susceptible to noise-induced deficits during aging, as the occupational-like noise exposure caused an age-dependent deficit in spatial but not visuomotor associative learning, as well as altered microglial expression in the hippocampus but not the striatum. Interestingly, we found no significant relationships between spatial learning ability and the level of hearing loss or altered microglial density in the hippocampus following noise exposure, suggesting that other changes in the brain likely contribute to hippocampal-dependent cognitive dysfunction following noise exposure. Lastly, we found that a subset of younger animals also showed noise-induced deficits in spatial learning; findings which suggest that noise exposure may represent an increased risk for cognitive impairment in vulnerable subjects. Overall, our findings highlight that even a mild occupational-like noise exposure earlier in adulthood can have long lasting implications for cognitive function later in life.
Brain Interleukin-17A contributes to neuroinflammation and cardiac dysfunction in rats with myocardial infarction
Authors: Yu Yang , Weiss Robert M. , Wei Shun-Guang
Published: October 2022

Proinflammatory cytokines produced outside the central nervous system can act in the brain to promote sympathetic activation that contributes to the progression of heart failure (HF). Interleukin (IL)-17A, a key inflammatory regulator which orchestrates immune responses to promote chronic inflammation, has been implicated in the pathophysiology of HF. We previously reported that IL-17A acts within the brain, particularly in the hypothalamic paraventricular nucleus (PVN), to increase expression of inflammatory mediators and, consequently, sympathetic outflow. The present study sought to determine whether IL-17A levels are elevated in a rat model of HF induced by myocardial infarction and, if so, whether increased expression of IL-17A in the brain itself contributes to neuroinflammation and cardiac dysfunction in this disease setting. Male SD rats underwent coronary artery ligation (CL) to induce HF or sham operation (SHAM). Compared with SHAM rats, HF rats exhibited significantly increased IL-17A levels in plasma, beginning within 1 week with a peak increase at 4 weeks after CL. IL-17A levels in cerebrospinal fluid (CSF) were also increased in HF rats and correlated with IL-17A levels in the plasma. The mRNA expression of IL-17A and its receptor IL-17RA, but not IL-17RC, was markedly upregulated in the PVN of HF when compared with SHAM rats. Genetic knockdown of IL-17RA by bilateral PVN microinjections of an IL-17RA siRNA AAV virus attenuated mRNA expression of proinflammatory cytokines and chemokines, and ameliorated sympathetic activation and cardiac function in HF rats. These data indicate that elevated expression of IL-17A in the brain in HF contributes to the excessive central inflammatory state and cardiac dysfunction in HF. Interventions to suppress IL-17A/IL-17RA axis in the brain have the potential for treating HF.
Comparisons of tri-ponderal mass index and body mass index in discriminating hypertension at three separate visits in adolescents: A retrospective cohort study
Authors: Hu Jia , Zhong Yi , Ge WenXin , Lv Huiling , Ding Ziyao , Han Di , Hai Bo , Shen Hui , Yin Jieyun , Gu Aihua , Yang Haibing
Published: October 2022

Objective

To estimate whether the new obesity indicator tri-ponderal mass index (TMI) has a better capacity to predict adolescent hypertension (HTN) and HTN subtypes at three separate blood pressure (BP) visits than the conventionally used body mass index (BMI).

Methods

A total of 36,950 adolescents who had initial normal BP from 2012 to 2019 were included in Suzhou, China. HTN was defined as having three separate visits of elevated BP in 2020. The area under the receiver-operating characteristic curve (AUC), false-positive rate, false-negative rate, total misclassification rates, net reclassification improvement (NRI), and integrated discrimination improvement were calculated to compare the discriminative ability of HTN between BMI and TMI.

Results

TMI had better predictive abilities than BMI among all of the participants when predicting HTN (difference in AUC = 0.019, 95% CI = 0.007–0.031; NRI = 0.067, 95% CI = 0.008–0.127) and isolated systolic hypertension (difference in AUC = 0.021, 95% CI = 0.005–0.036; NRI = 0.106, 95% CI = 0.029–0.183). The difference in prediction abilities between BMI and TMI was more obvious in the subgroup of age ≥16. Also, TMI outperformed BMI in predicting adolescent HTN in girls but not in boys.

Conclusion

Compared with BMI, TMI may have a better predictive capacity for HTN, particularly in girls and older adolescents. TMI has the potential to be used as an effective predictor for HTN in clinic practice. Further studies are needed to verify the utility of TMI.
Spatial transcriptomics technology in cancer research
Authors: Yu Qichao , Jiang Miaomiao , Wu Liang
Published: October 2022

In recent years, spatial transcriptomics (ST) technologies have developed rapidly and have been widely used in constructing spatial tissue atlases and characterizing spatiotemporal heterogeneity of cancers. Currently, ST has been used to profile spatial heterogeneity in multiple cancer types. Besides, ST is a benefit for identifying and comprehensively understanding special spatial areas such as tumor interface and tertiary lymphoid structures (TLSs), which exhibit unique tumor microenvironments (TMEs). Therefore, ST has also shown great potential to improve pathological diagnosis and identify novel prognostic factors in cancer. This review presents recent advances and prospects of applications on cancer research based on ST technologies as well as the challenges.