bluuebunny/crossref_metadata_2025 huggingface dataset:
Turnover in Life-Strategies Recapitulates Marine Microbial Succession Colonizing Model Particles
Authors: Pascual-García Alberto , Schwartzman Julia , Enke Tim N. , Iffland-Stettner Arion , Cordero Otto X. , Bonhoeffer Sebastian
Published: June 2022

Particulate organic matter (POM) in the ocean sustains diverse communities of bacteria that mediate the remineralization of organic complex matter. However, the variability of these particles and of the environmental conditions surrounding them present a challenge to the study of the ecological processes shaping particle-associated communities and their function. In this work, we utilize data from experiments in which coastal water communities are grown on synthetic particles to ask which are the most important ecological drivers of their assembly and associated traits. Combining 16S rRNA amplicon sequencing with shotgun metagenomics, together with an analysis of the full genomes of a subset of isolated strains, we were able to identify two-to-three distinct community classes, corresponding to early vs. late colonizers. We show that these classes are shaped by environmental selection (early colonizers) and facilitation (late colonizers) and find distinctive traits associated with each class. While early colonizers have a larger proportion of genes related to the uptake of nutrients, motility, and environmental sensing with few pathways enriched for metabolism, late colonizers devote a higher proportion of genes for metabolism, comprising a wide array of different pathways including the metabolism of carbohydrates, amino acids, and xenobiotics. Analysis of selected pathways suggests the existence of a trophic-chain topology connecting both classes for nitrogen metabolism, potential exchange of branched chain amino acids for late colonizers, and differences in bacterial doubling times throughout the succession. The interpretation of these traits suggests a distinction between early and late colonizers analogous to other classifications found in the literature, and we discuss connections with the classical distinction between r- and K-strategists.
How Metabolomics Provides Novel Insights on Celiac Disease and Gluten-Free Diet: A Narrative Review
Authors: Vacca Mirco , Porrelli Annalisa , Calabrese Francesco Maria , Lippolis Tamara , Iacobellis Ilaria , Celano Giuseppe , Pinto Daniela , Russo Francesco , Giannelli Gianluigi , De Angelis Maria
Published: June 2022

Celiac disease (CD) is an inflammatory autoimmune disorder triggered by the ingestion of gluten from wheat and other cereals. Nowadays, its positive diagnosis is based on invasive approaches such as the histological examination of intestinal biopsies and positive serology screening of antibodies. After proven diagnosis, the only admissible treatment for CD individuals is strict life-long adherence to gluten-free diet (GFD), although it is not a conclusive therapy. Acting by different mechanisms and with different etiologies, both CD and GFD have a great impact on gut microbiota that result in a different taxa composition. Altered production of specific metabolites reflects these microbiota changes. In this light, the currently available literature reports some suggestions about the possible use of specific metabolites, detected by meta-omics analyses, as potential biomarkers for a CD non-invasive diagnosis. To highlight insights about metabolomics application in CD study, we conducted a narrative dissertation of selected original articles published in the last decade. By applying a systematic search, it clearly emerged how the metabolomic signature appears to be contradictory, as well as poorly investigated.
Dengue Virus-2 Infection Affects Fecundity and Elicits Specific Transcriptional Changes in the Ovaries of Aedes aegypti Mosquitoes
Authors: Feitosa-Suntheimer Fabiana , Zhu Zheng , Mameli Enzo , Dayama Gargi , Gold Alexander S. , Broos-Caldwell Aditi , Troupin Andrea , Rippee-Brooks Meagan , Corley Ronald B. , Lau Nelson C. , Colpitts Tonya M. , Londoño-Renteria Berlin
Published: June 2022

Dengue fever (DF), caused by the dengue virus (DENV), is the most burdensome arboviral disease in the world, with an estimated 400 million infections each year. The Aedes aegypti mosquito is the main vector of DENV and transmits several other human pathogens, including Zika, yellow fever, and chikungunya viruses. Previous studies have shown that the pathogen infection of mosquitoes can alter reproductive fitness, revealing specific vector-pathogen interactions that are key determinants of vector competence. However, only a handful of studies have examined the effect of DENV infection in A. aegypti, showing a reduction in lifespan and fecundity over multiple blood meals. To provide a more comprehensive analysis of the impact of DENV infection on egg laying and fecundity, we assessed egg laying timing in DENV-2 blood-fed mosquitoes (infected group) compared to mock blood-fed mosquitoes (control group). We confirmed a significant decrease in fecundity during the first gonadotrophic cycle. To further investigate this phenotype and the underlying DENV-2 infection-dependent changes in gene expression, we conducted a transcriptomic analysis for differentially expressed genes in the ovaries of A. aegypti infected with DENV-2 vs. mock-infected mosquitoes. This analysis reveals several DENV-2-regulated genes; among them, we identified a group of 12 metabolic genes that we validated using reverse transcription-quantitative PCR (RT-qPCR). Interestingly, two genes found to be upregulated in DENV-infected mosquito ovaries exhibited an antiviral role for DENV-2 in an Aedes cell line. Altogether, this study offers useful insights into the virus-vector interface, highlighting the importance of gene expression changes in the mosquito’s ovary during DENV-2 infection in the first gonadotrophic  cycle,  triggering  antiviral  responses  that  may  possibly  interfere  with mosquito reproduction. This information is extremely relevant for further investigation of A. aegypti’s ability to tolerate viruses since virally infected mosquitoes in nature constitute a powerful source of supporting viruses during intra-epidemic periods, causing a huge burden on the public health system.
Antimicrobial Potential of Endophytic Fungi From Artemisia argyi and Bioactive Metabolites From Diaporthe sp. AC1
Authors: Gu Haiping , Zhang Shikai , Liu Lin , Yang Zhengyou , Zhao Fengchun , Tian Yuan
Published: June 2022

Endophytic fungi of medicinal plants are important sources of active natural products. In this study, 26 fungi were isolated from Artemisia argyi, which were belonging to eight genera, namely, Alternaria, Fusarium, Chaetomium, Phoma, Diaporthe, Trichoderma, Gibberella, and Colletotrichum. The antimicrobial activities of all fungal extracts were tested by using the cup-plate method against Staphylococcus aureus, Salmonella enteritidis, and Fusarium graminearum. The results demonstrated that 25 extracts (96%) exhibited inhibitory activity against at least one of the tested pathogenic microorganisms. The strain Diaporthe sp. AC1, which showed good antimicrobial activity and high yield of crude extract from fermentation, was selected for the study of secondary metabolites. The crude extract of strain AC1 was purified by silica gel column chromatography, Sephadex LH-20 gel column chromatography, and HPLC, and finally, a new compound phomopsolide G (1), together with three known phomopsolides (2–4) and four other known compounds (5–8), was obtained. The structures of the compounds were elucidated by NMR and/or HR-MS spectroscopy. Microdilution method and MTT colorimetry were used to determine the bioactivity of the compounds. The study demonstrated that the new compound 1 had moderate antifungal activity against F. graminearum, Fusarium moniliforme, and Botrytis cinerea and weak antibacterial activity against Staphylococcus aureus. Compound 1 also showed weak cytotoxicity against HepG2, A549, and MDA-MB-231, with IC50 values of 89.91, 107.65, and 53.97 μM. Additionally, other compounds also exhibited antimicrobial and/or cytotoxic activities. The findings provided the basis for searching drug and agricultural lead compounds from A. argyi-associated fungi resources.
Characterizing the Microbial Consortium L1 Capable of Efficiently Degrading Chlorimuron-Ethyl via Metagenome Combining 16S rDNA Sequencing
Authors: Li Xiang , Lu Changming , Dai Yumeng , Yu Zhixiong , Gu Wu , Li Tingting , Li Xinyu , Li Xu , Wang Xiujuan , Su Zhencheng , Xu Mingkai , Zhang Huiwen
Published: June 2022

Excessive application of the herbicide chlorimuron-ethyl (CE) severely harms subsequent crops and poses severe risks to environmental health. Therefore, methods for efficiently decreasing and eliminating CE residues are urgently needed. Microbial consortia show potential for bioremediation due to their strong metabolic complementarity and synthesis. In this study, a microbial consortium entitled L1 was enriched from soil contaminated with CE by a “top-down” synthetic biology strategy. The consortium could degrade 98.04% of 100 mg L−1 CE within 6 days. We characterized it from the samples at four time points during the degradation process and a sample without degradation activity via metagenome and 16S rDNA sequencing. The results revealed 39 genera in consortium L1, among which Methyloversatilis (34.31%), Starkeya (28.60%), and Pseudoxanthomonas (7.01%) showed relatively high abundances. Temporal succession and the loss of degradability did not alter the diversity and community composition of L1 but changed the community structure. Taxon-functional contribution analysis predicted that glutathione transferase [EC 2.5.1.18], urease [EC 3.5.1.5], and allophanate hydrolase [EC 3.5.1.54] are relevant for the degradation of CE and that Methyloversatilis, Pseudoxanthomonas, Methylopila, Hyphomicrobium, Stenotrophomonas, and Sphingomonas were the main degrading genera. The degradation pathway of CE by L1 may involve cleavage of the CE carbamide bridge to produce 2-amino-4-chloro-6-methoxypyrimidine and ethyl o-sulfonamide benzoate. The results of network analysis indicated close interactions, cross-feeding, and co-metabolic relationships between strains in the consortium, and most of the above six degrading genera were keystone taxa in the network. Additionally, the degradation of CE by L1 required not only “functional bacteria” with degradation capacity but also “auxiliary bacteria” without degradation capacity but that indirectly facilitate/inhibit the degradation process; however, the abundance of “auxiliary bacteria” should be controlled in an appropriate range. These findings improve the understanding of the synergistic effects of degrading bacterial consortia, which will provide insight for isolating degrading bacterial resources and constructing artificial efficient bacterial consortia. Furthermore, our results provide a new route for pollution control and biodegradation of sulfonylurea herbicides.
Prevalence of Livestock-Associated MRSA ST398 in a Swine Slaughterhouse in Guangzhou, China
Authors: Li Xiaoshen , Xie Longfei , Huang Honghao , Li Zhi , Li Guihua , Liu Peng , Xiao Danyu , Zhang Xucai , Xiong Wenguang , Zeng Zhenling
Published: June 2022

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is an important zoonotic microorganism that is increasingly causing public health concern worldwide. The objective of this study was to determine the transmission and occurrence of MRSA in a slaughterhouse environment and evaluate its antimicrobial resistance and genetic characterization. In this study, we conducted a comprehensive epidemiological survey of S. aureus by spa typing and whole-genome sequencing (WGS) of samples obtained from the pork production chain, the environment, and community residents. To clarify the evolutionary relationships of MRSA sequence type (ST) 398 in this study and global isolates, 197 published whole-genome sequences data of MRSA ST398 strains were downloaded from the GenBank database and included in the phylogenetic analysis. A total of 585 porcine samples (snout and carcass swabs), 78 human nasal samples, and 136 environmental samples were collected. The MRSA isolates were detected at higher frequencies in samples from swine (15.0%) than carcasses (10.0%), slaughterhouse workers (8.0%), community residents (0%), and environment samples (5.9%). The spa typing results showed that t571 accounted for a higher proportion than other spa types. Closely related isolates from the samples of swine, slaughterhouse workers, carcasses, carrier vehicle, and surrounding fishpond water indicate that MRSA ST398 strains may spread among swine, humans, and the environment. MRSA ST398-t571 isolates were genetically different from global strains, except for two Korean isolates, which showed genetic closeness with it. In addition, a MRSA ST398 isolate recovered from an infected patient in Europe differed by only 31 SNPs from the airborne dust-associated strain isolated in this study, thereby suggesting potential transmission among different countries. Antimicrobial susceptibility testing results demonstrated that 99.0% (96/97) of MRSA and 95.1% (231/243) of methicillin-sensitive S. aureus (MSSA) showed multidrug-resistant (MDR) phenotypes. According to WGS analysis, the poxtA-carrying segment (IS431mec-optrA-IS1216-fexB-IS431mec) was reported in MRSA ST398 isolates for the first time. The coexistence of cfr and optrA in a plasmid was first detected in MRSA ST398. The potential transmission of MRSA among humans, animals, and the environment is a cause for concern. The emergence and transmission of LA-MRSA ST398 with high levels of resistance profiles highlight the urgent need for LA-MRSA surveillance.
Overexpression of the Mitochondrial Malic Enzyme Genes (malC and malD) Improved the Lipid Accumulation in Mucor circinelloides WJ11
Authors: Fazili Abu Bakr Ahmad , Shah Aabid Manzoor , Albeshr Mohammed Fahad , Naz Tahira , Dar Mohammad Abass , Yang Wu , Garre Victoriano , Fazili Khalid Majid , Bhat Eijaz Ahmed , Song Yuanda
Published: June 2022

Mucor circinelloides serves as a model organism to investigate the lipid metabolism in oleaginous microorganisms. It is considered as an important producer of γ-linolenic acid (GLA) that has vital medicinal benefits. In this study, we used WJ11, a high lipid-producing strain of M. circinelloides (36% w/w lipid, cell dry weight, CDW), to examine the role in lipid accumulation of two mitochondrial malic enzyme (ME) genes malC and malD. The homologous overexpression of both malC and malD genes enhanced the total lipid content of WJ11 by 41.16 and 32.34%, respectively. In parallel, the total content of GLA was enhanced by 16.73 and 46.76% in malC and malD overexpressing strains, respectively, because of the elevation of total lipid content. The fact that GLA content was enhanced more in the strain with lower lipid content increase and vice versa, indicated that engineering of mitochondrial MEs altered the fatty acid profile. Our results reveal that mitochondrial ME plays an important role in lipid metabolism and suggest that future approaches may involve simultaneous overexpression of distinct ME genes to boost lipid accumulation even further.
Differential Patterns of Domain-Specific Cognitive Complaints and Awareness Across the Alzheimer’s Disease Spectrum
Authors: Cacciamani Federica , Godefroy Valérie , Brambati Simona M. , Migliaccio Raffaella , Epelbaum Stéphane , Montembeault Maxime
Published: June 2022

Background: Characterizing self- and informant-reported cognitive complaints, as well as awareness of cognitive decline (ACD), is useful for an early diagnosis of Alzheimer’s disease (AD). However, complaints and ACD related to cognitive functions other than memory are poorly studied. Furthermore, it remains unclear which source of information is the most useful to distinguish various groups on the AD spectrum.

Methods: Self- and informant-reported complaints were measured with the Everyday Cognition questionnaire (ECog-Subject and ECog-StudyPartner) in four domains (memory, language, visuospatial, and executive). ACD was measured as the subject-informant discrepancy in the four ECog scores. We compared the ECog and ACD scores across cognitive domains between four groups: 71 amyloid-positive individuals with amnestic AD, 191 amnestic mild cognitive impairment (MCI), or 118 cognitively normal (CN), and 211 amyloid-negative CN controls, selected from the ADNI database. Receiver operating characteristic curves analysis was performed to evaluate the accuracy of the ECog and ACD scores in discriminating clinical groups.

Results: Self- and informant-reported complaints were generally distributed as follows: memory, language, executive, and visuospatial (from the most severe to the least severe). Both groups of CN participants presented on average more memory and language complaints than their informant. MCI participants showed good agreement with their informants. AD participants presented anosognosia in all domains, but especially for the executive domain. The four ECog-StudyPartner sub-scores allowed excellent discrimination between groups in almost all classifications and performed significantly better than the other two classifiers considered. The ACD was excellent in distinguishing the participants with AD from the two groups of CN participants. The ECog-Subject was the least accurate in discriminating groups in four of the six classifications performed.

Conclusion: In research, the study of complaint and anosognosia should not be reduced solely to the memory domain. In clinical practice, non-amnestic complaints could also be linked to Alzheimer’s disease. The presence of an informant also seems necessary given its accuracy as a source of information.
The Periodontal Pathogen Fusobacterium nucleatum Exacerbates Alzheimer’s Pathogenesis via Specific Pathways
Authors: Wu Hongle , Qiu Wei , Zhu Xiaofang , Li Xiangfen , Xie Zhongcong , Carreras Isabel , Dedeoglu Alpaslan , Van Dyke Thomas , Han Yiping W. , Karimbux Nadeem , Tu Qisheng , Cheng Lei , Chen Jake
Published: June 2022

Alzheimer’s Disease (AD) is the most common form of dementia in older adults and has a devastating impact on the patient’s quality of life, which creates a significant socio-economic burden for the affected individuals and their families. In recent years, studies have identified a relationship between periodontitis and AD. Periodontitis is an infectious/inflammatory disease that destroys the supporting periodontal structure leading to tooth loss. Dysbiosis of the oral microbiome plays a significant role in the onset and development of periodontitis exhibiting a shift to overgrowth of pathobionts in the normal microflora with increasing local inflammation. Fusobacterium nucleatum is a common pathogen that significantly overgrows in periodontitis and has also been linked to various systemic diseases. Earlier studies have reported that antibodies to F. nucleatum can be detected in the serum of patients with AD or cognitive impairment, but a causal relationship and a plausible mechanism linking the two diseases have not been identified. In this study, we conducted both in vivo and in vitro experiments and found that F. nucleatum activates microglial cells causing morphological changes, accelerated proliferation and enhanced expression of TNF-α and IL-1β in microglial cells. In our in vivo experiments, we found that F. nucleatum-induced periodontitis resulted in the exacerbation of Alzheimer’s symptoms in 5XFAD mice including increased cognitive impairment, beta-amyloid accumulation and Tau protein phosphorylation in the mouse cerebrum. This study may suggest a possible link between a periodontal pathogen and AD and F. nucleatum could be a risk factor in the pathogenesis of AD. We are currently further identifying the pathways through which F. nucleatum modulates molecular elements in enhancing AD symptoms and signs. Data are available via ProteomeXchange with identifier PXD033147.
Altered Coupling Between Cerebral Blood Flow and Voxel-Mirrored Homotopic Connectivity Affects Stroke-Induced Speech Comprehension Deficits
Authors: Zhang Jie , Shang Desheng , Ye Jing , Ling Yi , Zhong Shuchang , Zhang Shuangshuang , Zhang Wei , Zhang Li , Yu Yamei , He Fangping , Ye Xiangming , Luo Benyan
Published: June 2022

The neurophysiological basis of the association between interhemispheric connectivity and speech comprehension processing remains unclear. This prospective study examined regional cerebral blood flow (CBF), homotopic functional connectivity, and neurovascular coupling, and their effects on comprehension performance in post-stroke aphasia. Multimodal imaging data (including data from functional magnetic resonance imaging and arterial spin labeling imaging) of 19 patients with post-stroke aphasia and 22 healthy volunteers were collected. CBF, voxel-mirrored homotopic connectivity (VMHC), CBF-VMHC correlation, and CBF/VMHC ratio maps were calculated. Between-group comparisons were performed to identify neurovascular changes, and correlation analyses were conducted to examine their relationship with the comprehension domain. The correlation between CBF and VMHC of the global gray matter decreased in patients with post-stroke aphasia. The total speech comprehension score was significantly associated with VMHC in the peri-Wernicke area [posterior superior temporal sulcus (pSTS): r = 0.748, p = 0.001; rostroventral area 39: r = 0.641, p = 0.008]. The decreased CBF/VMHC ratio was also mainly associated with the peri-Wernicke temporoparietal areas. Additionally, a negative relationship between the mean CBF/VMHC ratio of the cingulate gyrus subregion and sentence-level comprehension was observed (r = −0.658, p = 0.006). These findings indicate the contribution of peri-Wernicke homotopic functional connectivity to speech comprehension and reveal that abnormal neurovascular coupling of the cingulate gyrus subregion may underly comprehension deficits in patients with post-stroke aphasia.
Secondary Brain Injury by Oxidative Stress After Cerebral Hemorrhage: Recent Advances
Authors: Shao Linqian , Chen Sichao , Ma Li
Published: June 2022

Intracerebral hemorrhage (ICH) is a clinical syndrome in which blood accumulates in the brain parenchyma because of a nontraumatic rupture of a blood vessel. Because of its high morbidity and mortality rate and the lack of effective therapy, the treatment of ICH has become a hot research topic. Meanwhile, Oxidative stress is one of the main causes of secondary brain injury(SBI) after ICH. Therefore, there is a need for an in-depth study of oxidative stress after ICH. This review will discuss the pathway and effects of oxidative stress after ICH and its relationship with inflammation and autophagy, as well as the current antioxidant therapy for ICH with a view to deriving better therapeutic tools or targets for ICH.
Insertion Guidance Based on Impedance Measurements of a Cochlear Electrode Array
Authors: Salkim Enver , Zamani Majid , Jiang Dai , Saeed Shakeel R. , Demosthenous Andreas
Published: June 2022

The cochlear implantable neuromodulator provides substantial auditory perception to those with severe or profound impaired hearing. Correct electrode array positioning in the cochlea is one of the important factors for quality hearing, and misplacement may lead to additional injury to the cochlea. Visual inspection of the progress of electrode insertion is limited and mainly relies on the surgeon's tactile skills, and there is a need to detect in real-time the electrode array position in the cochlea during insertion. The available clinical measurement presently provides very limited information. Impedance measurement may be used to assist with the insertion of the electrode array. Using computational modeling of the cochlea, and its local tissue layers merging with the associated neuromodulator electrode array parameters, the impedance variations at different insertion depths and the proximities to the cochlea walls have been analyzed. In this study, an anatomical computational model of the temporal region of a patient is used to derive the relationship between impedance variations and the electrode proximity to the cochlea wall and electrode insertion depth. The aim was to examine whether the use of electrode impedance variations can be an effective marker of electrode proximity and electrode insertion depth. The proposed anatomical model simulates the quasi-static electrode impedance variations at different selected points but at considerable computation cost. A much less computationally intensive geometric model (~1/30) provided comparative impedance measurements with differences of <2%. Both use finite element analysis over the entire cross-section area of the scala tympani. It is shown that the magnitude of the impedance varies with both electrode insertion depth and electrode proximity to the adjacent anatomical layers (e.g., cochlea wall). In particular, there is a 1,400% increase when the electrode array is moved very close to the cochlea wall. This may help the surgeon to find the optimal electrode position within the scala tympani by observation of such impedance characteristics. The misplacement of the electrode array within the scala tympani may be eliminated by using the impedance variation metric during electrode array insertion if the results are validated with an experimental study.
The Value of First-Order Features Based on the Apparent Diffusion Coefficient Map in Evaluating the Therapeutic Effect of Low-Intensity Pulsed Ultrasound for Acute Traumatic Brain Injury With a Rat Model
Authors: Du Dan , Gao Yajuan , Zheng Tao , Yang Linsha , Wang Zhanqiu , Shi Qinglei , Wu Shuo , Liang Xin , Yao Xinyu , Lu Jiabin , Liu Lanxiang
Published: June 2022

Purpose

In order to evaluate the neuroprotective effect of low-intensity pulsed ultrasound (LIPUS) for acute traumatic brain injury (TBI), we studied the potential of apparent diffusion coefficient (ADC) values and ADC-derived first-order features regarding this problem.

Methods

Forty-five male Sprague Dawley rats (sham group: 15, TBI group: 15, LIPUS treated: 15) were enrolled and underwent magnetic resonance imaging. Scanning layers were acquired using a multi-shot readout segmentation of long variable echo trains (RESOLVE) to decrease distortion. The ultrasound transducer was applied to the designated region in the injured cortical areas using a conical collimator and was filled with an ultrasound coupling gel. Regions of interest were manually delineated in the center of the damaged cortex on the diffusion weighted images (b = 800 s/mm2) layer by layer for the TBI and LIPUS treated groups using the open-source software ITK-SNAP. Before analysis and modeling, the features were normalized using a z-score method, and a logistic regression model with a backward filtering method was employed to perform the modeling. The entire process was completed using the R language.

Results

During the observation time, the ADC values ipsilateral to the trauma in the TBI and LIPUS groups increased rapidly up to 24 h. After statistical analysis, the 10th percentile, 90th percentile, mean, skewness, and uniformity demonstrated a significant difference among three groups. The receiver operating characteristic curve (ROC) analysis shows that the combined LR model exhibited the highest area under the curve value (AUC: 0.96).

Conclusion

The combined LR model of first-order features based on the ADC map can acquire a higher diagnostic performance than each feature only in evaluating the neuroprotective effect of LIPUS for TBI. Models based on first-order features may have potential value in predicting the therapeutic effect of LIPUS in clinical practice in the future.
Mild Traumatic Brain Injury Results in Significant and Lasting Cortical Demyelination
Authors: Mahoney Sean O. , Chowdhury Nahian F. , Ngo Van , Imms Phoebe , Irimia Andrei
Published: June 2022

Despite contributing to neurocognitive deficits, intracortical demyelination after traumatic brain injury (TBI) is understudied. This study uses magnetic resonance imaging (MRI) to map intracortical myelin and its change in healthy controls and after mild TBI (mTBI). Acute mTBI involves reductions in relative myelin content primarily in lateral occipital regions. Demyelination mapped ~6 months post-injury is significantly more severe than that observed in typical aging (p < 0.05), with temporal, cingulate, and insular regions losing more myelin (30%, 20%, and 16%, respectively) than most other areas, although occipital regions experience 22% less demyelination. Thus, occipital regions may be more susceptible to primary injury, whereas temporal, cingulate and insular regions may be more susceptible to later manifestations of injury sequelae. The spatial profiles of aging- and mTBI-related chronic demyelination overlap substantially; exceptions include primary motor and somatosensory cortices, where myelin is relatively spared post-mTBI. These features resemble those of white matter demyelination and cortical thinning during Alzheimer's disease, whose risk increases after mTBI.
Health-Related Quality of Life in Cervical Dystonia Using EQ-5D-5L: A Large Cross-Sectional Study in China
Authors: Liang Yan , Lin Junyu , Hou Yanbing , Zhang Lingyu , Ou Ruwei , Li Chunyu , Wei Qianqian , Cao Bei , Liu Kuncheng , Jiang Zheng , Yang Tianmi , Yang Jing , Zhang Meng , Kang Simin , Xiao Yi , Jiang Qirui , Yang Jing , Song Wei , Chen Xueping , Zhao Bi , Wu Ying , Shang Huifang
Published: June 2022

Purpose

The study aimed to evaluate the health-related quality of life (HRQoL) measured by the five-level EuroQol-5 dimensions (EQ-5D-5L) in patients with cervical dystonia, and to explore the determinants of HRQoL in patients with cervical dystonia.

Methods

EQ-5D-5L health state profiles were converted into a single aggregated “health utility” score. A calibrated visual analog scale (EQ VAS) was used for self-rating of current health status. Multiple linear regression analysis was used to explore the factors associated with HRQoL in cervical dystonia.

Results

A total of 333 patients with cervical dystonia were enrolled in the analysis, with an average age of 44.3 years old. The most common impaired dimension of health was anxiety/depression (73.6%), followed by pain/discomfort (68.2%) and usual activities (48%). The median health utility score was 0.80, and the median EQ VAS score was 70.2. Multivariate linear regression analysis indicated that disease duration and the scores of the Hamilton Depression Rating Scale (HDRS), Pittsburgh sleep quality index (PSQI), Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Part I, and TWSTRS Part III were associated with the health utility scores. After adjusting other parameters, the TWSTRS Part III score and the HDRS score were significantly associated with the EQ VAS scores (p < 0.05).

Conclusion

This study evaluated HRQoL in patients with cervical dystonia using the Chinese version of the EQ-5D-5L scale. We found that, besides motor symptoms, non-motor symptoms, including depression, pain, and sleep quality, could be greater determinants of HRQoL in patients with cervical dystonia. Management of non-motor symptoms, therefore, may help improve HRQoL in patients with cervical dystonia.
Frequency of Neurological Diseases After COVID-19, Influenza A/B and Bacterial Pneumonia
Authors: Zarifkar Pardis , Peinkhofer Costanza , Benros Michael E. , Kondziella Daniel
Published: June 2022

Introduction

COVID-19 might affect the incidence of specific neurological diseases, but it is unknown if this differs from the risk following other infections. Here, we characterized the frequency of neurodegenerative, cerebrovascular, and immune-mediated neurological diseases after COVID-19 compared to individuals without COVID-19 and those with other respiratory tract infections.

Methods

This population-based cohort study utilized electronic health records covering ~50% of Denmark's population (n = 2,972,192). Between 02/2020 and 11/2021, we included individuals tested for COVID-19 or diagnosed with community-acquired bacterial pneumonia in hospital-based facilities. Additionally, we included individuals tested for influenza in the corresponding pre-pandemic period between 02/ 2018 and 11/2019. We stratified cohorts for in- and outpatient status, age, sex, and comorbidities.

Results

In total, 919,731 individuals were tested for COVID-19, of whom 43,375 tested positive (35,362 outpatients, 8,013 inpatients). Compared to COVID-negative outpatients, COVID-19 positive outpatients had an increased RR of Alzheimer's disease (RR = 3.5; 95%CI: 2.2–5.5) and Parkinson's disease (RR = 2.6; 95%CI: 1.7–4.0), ischemic stroke (RR = 2.7; 95%CI: 2.3–3.2) and intracerebral hemorrhage (RR = 4.8; 95%CI: 1.8–12.9). However, when comparing to other respiratory tract infections, only the RR for ischemic stroke was increased among inpatients with COVID-19 when comparing to inpatients with influenza (RR = 1.7; 95%CI: 1.2–2.4) and only for those >80 years of age when comparing to inpatients with bacterial pneumonia (RR = 2.7; 95%CI: 1.2–6.2). Frequencies of multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome and narcolepsy did not differ after COVID-19, influenza and bacterial pneumonia.

Conclusion

The risk of neurodegenerative and cerebrovascular, but not neuroimmune, disorders was increased among COVID-19 positive outpatients compared to COVID-negative outpatients. However, except for ischemic stroke, most neurological disorders were not more frequent after COVID-19 than after other respiratory infections.
Altered Intrinsic Brain Activity in Patients With Toothache Using the Percent Amplitude of a Fluctuation Method: A Resting-State fMRI Study
Authors: Yang Jun , Shao Yi , Shen Yan-Kun , Zhu Hong-Shui , Li Bin , Yu Qiu-Yue , Kang Min , Xu San-Hua , Ying Ping , Ling Qian , Zou Jie , Wei Hong , He Yu-Lin
Published: June 2022

Objective

The percent amplitude of fluctuation (PerAF) technique was utilized to evaluate the neural functions of specific cerebrum areas in patients with toothache (TA).

Patients and Methods

An aggregation of 18 patients with TA (eight males and 10 females) were included in the study. We also recruited 18 healthy controls (HCs; eight men and 10 women) aligned for sex and age. Resting functional magnetic resonance imaging (rs-fMRI) scans were obtained. Then, we utilized the PerAF method and a support vector machine (SVM) to analyze the image data and measure neural abnormalities in related cerebrum areas. Receiver operating characteristic (ROC) curve analysis was utilized to appraise the two data sets.

Results

The PerAF signals in the right dorsolateral superior frontal gyrus (RDSFG) and the right posterior central gyrus (RPCG) of TA sufferers were lower than HC signals. These results may reveal neural dysfunctions in relevant cerebrum regions. The AUC values of PerAF in the two areas were 0.979 in the RDSFG and 0.979 in the RPCG. The SVM results suggested that PerAF could be utilized to distinguish the TA group from HCs with a sensitivity of 75.00%, a specificity of 66.67%, and an accuracy of 70.83%.

Conclusion

Patients with TA had marked differences in PerAF values in some regions of the cerebrum. Changes in PerAF values represented distinctions in blood oxygen level dependent semaphore intensity, which reflected the overactivity or inactivation of some cerebrum areas in those suffering from TA. At the same time, we analyzed the PerAF values of TAs with ROC curve, which can be helpful for the diagnosis of TA severity and subsequent treatment. Our results may help to elucidate the pathological mechanism of TA.
Transcutaneous Auricular Vagus Nerve Stimulation Differently Modifies Functional Brain Networks of Subjects With Different Epilepsy Types
Authors: von Wrede Randi , Rings Thorsten , Bröhl Timo , Pukropski Jan , Schach Sophia , Helmstaedter Christoph , Lehnertz Klaus
Published: June 2022

Epilepsy types differ by pathophysiology and prognosis. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive treatment option in epilepsy. Nevertheless, its mode of action and impact on different types of epilepsy are still unknown. We investigated whether short-term taVNS differently affects local and global characteristics of EEG-derived functional brain networks in different types of epilepsy. Thirty subjects (nine with focal epilepsy, 11 with generalized epilepsy, and 10 without epilepsy or seizures) underwent a 3-h continuous EEG-recording (1 h pre-stimulation, 1 h taVNS stimulation, 1 h post-stimulation) from which we derived evolving functional brain networks. We assessed—in a time-resolved manner—important global (topological, robustness, and stability properties) and local (centralities of vertices and edges) network characteristics. Compared to the subjects with focal epilepsies and without epilepsy, those with generalized epilepsies clearly presented with different topological properties of their functional brain network already at rest. Furthermore, subjects with focal and generalized epilepsies reacted differently to the stimulation, expressed as different taVNS-induced immediate and enduring reorganization of global network characteristics. On the local network scale, no discernible spatial pattern could be detected, which points to a rather unspecific and generalized modification of brain activity. Assessing functional brain network characteristics can provide additional information for differentiating between focal and generalized epilepsy. TaVNS-related modifications of global network characteristics clearly differ between epilepsy types. Impact of such a non–pharmaceutical intervention on clinical decision-making in the treatment of different epilepsy types needs to be assessed in future studies.
TNF-α Orchestrates Experience-Dependent Plasticity of Excitatory and Inhibitory Synapses in the Anterior Piriform Cortex
Authors: Guo Anni , Lau Chunyue Geoffrey
Published: June 2022

Homeostatic synaptic plasticity, which induces compensatory modulation of synapses, plays a critical role in maintaining neuronal circuit function in response to changing activity patterns. Activity in the anterior piriform cortex (APC) is largely driven by ipsilateral neural activity from the olfactory bulb and is a suitable system for examining the effects of sensory experience on cortical circuits. Pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) can modulate excitatory and inhibitory synapses, but its role in APC is unexplored. Here we examined the role of TNF-α in adjusting synapses in the mouse APC after experience deprivation via unilateral naris occlusion. Immunofluorescent staining revealed that activity deprivation increased excitatory, and decreased inhibitory, synaptic density in wild-type mice, consistent with homeostatic regulation. Quantitative RT-PCR showed that naris occlusion increased the expression of Tnf mRNA in APC. Critically, occlusion-induced plasticity of excitatory and inhibitory synapses was completely blocked in the Tnf knockout mouse. Together, these results show that TNF-α is an important orchestrator of experience-dependent plasticity in the APC.
Machine Learning-Based Prediction of the Outcomes of Cochlear Implantation in Patients With Cochlear Nerve Deficiency and Normal Cochlea: A 2-Year Follow-Up of 70 Children
Authors: Lu Simeng , Xie Jin , Wei Xingmei , Kong Ying , Chen Biao , Chen Jingyuan , Zhang Lifang , Yang Mengge , Xue Shujin , Shi Ying , Liu Sha , Xu Tianqiu , Dong Ruijuan , Chen Xueqing , Li Yongxin , Wang Haihui
Published: June 2022

Cochlear nerve deficiency (CND) is often associated with variable outcomes of cochlear implantation (CI). We assessed previous investigations aiming to identify the main factors that determine CI outcomes, which would enable us to develop predictive models. Seventy patients with CND and normal cochlea who underwent CI surgery were retrospectively examined. First, using a data-driven approach, we collected demographic information, radiographic measurements, audiological findings, and audition and speech assessments. Next, CI outcomes were evaluated based on the scores obtained after 2 years of CI from the Categories of Auditory Performance index, Speech Intelligibility Rating, Infant/Toddler Meaningful Auditory Integration Scale or Meaningful Auditory Integration Scale, and Meaningful Use of Speech Scale. Then, we measured and averaged the audiological and radiographic characteristics of the patients to form feature vectors, adopting a multivariate feature selection method, called stability selection, to select the features that were consistent within a certain range of model parameters. Stability selection analysis identified two out of six characteristics, namely the vestibulocochlear nerve (VCN) area and the number of nerve bundles, which played an important role in predicting the hearing and speech rehabilitation results of CND patients. Finally, we used a parameter-optimized support vector machine (SVM) as a classifier to study the postoperative hearing and speech rehabilitation of the patients. For hearing rehabilitation, the accuracy rate was 71% for both the SVM classification and the area under the curve (AUC), whereas for speech rehabilitation, the accuracy rate for SVM classification and AUC was 93% and 94%, respectively. Our results identified that a greater number of nerve bundles and a larger VCN area were associated with better CI outcomes. The number of nerve bundles and VCN area can predict CI outcomes in patients with CND. These findings can help surgeons in selecting the side for CI and provide reasonable expectations for the outcomes of CI surgery.
Compromised Cortical-Hippocampal Network Function From Transient Hypertension: Linking Mid-Life Hypertension to Late Life Dementia Risk
Authors: Lai Aaron Y. , Bazzigaluppi Paolo , Morrone Christopher D. , Hill Mary E. , Stefanovic Bojana , McLaurin JoAnne
Published: June 2022

Mid-life hypertension is a major risk factor for developing dementia later in life. While anti-hypertensive drugs restore normotension, dementia risk remains above baseline suggesting that brain damage sustained during transient hypertension is irreversible. The current study characterized a rat model of transient hypertension with an extended period of normotensive recovery: F344 rats were treated with L-NG-Nitroarginine methyl ester (L-NAME) for 1 month to induce hypertension then allowed up to 4 months of recovery. With respect to cognitive deficits, comparison between 1 month and 4 months of recovery identified initial deficits in spatial memory that resolved by 4 months post-hypertension; contrastingly, loss of cognitive flexibility did not. The specific cells and brain regions underlying these cognitive deficits were investigated. Irreversible structural damage to the brain was observed in both the prefrontal cortex and the hippocampus, with decreased blood vessel density, myelin and neuronal loss. We then measured theta-gamma phase amplitude coupling as a readout for network function, a potential link between the observed cognitive and pathological deficits. Four months after hypertension, we detected decreased theta-gamma phase amplitude coupling within each brain region and a concurrent increase in baseline connectivity between the two regions reflecting an attempt to maintain function that may account for the improvement in spatial memory. Our results demonstrate that connectivity between prefrontal cortex and hippocampus is a vulnerable network affected by transient hypertension which is not rescued over time; thus demonstrating for the first time a mechanistic link between the long-term effects of transient hypertension and dementia risk.
Evaluating the Safety of Simultaneous Intracranial Electroencephalography and Functional Magnetic Resonance Imaging Acquisition Using a 3 Tesla Magnetic Resonance Imaging Scanner
Authors: Fujita Yuya , Khoo Hui Ming , Hirayama Miki , Kawahara Masaaki , Koyama Yoshihiro , Tarewaki Hiroyuki , Arisawa Atsuko , Yanagisawa Takufumi , Tani Naoki , Oshino Satoru , Lemieux Louis , Kishima Haruhiko
Published: June 2022

Background

The unsurpassed sensitivity of intracranial electroencephalography (icEEG) and the growing interest in understanding human brain networks and ongoing activities in health and disease have make the simultaneous icEEG and functional magnetic resonance imaging acquisition (icEEG-fMRI) an attractive investigation tool. However, safety remains a crucial consideration, particularly due to the impact of the specific characteristics of icEEG and MRI technologies that were safe when used separately but may risk health when combined. Using a clinical 3-T scanner with body transmit and head-receive coils, we assessed the safety and feasibility of our icEEG-fMRI protocol.

Methods

Using platinum and platinum-iridium grid and depth electrodes implanted in a custom-made acrylic-gel phantom, we assessed safety by focusing on three factors. First, we measured radio frequency (RF)-induced heating of the electrodes during fast spin echo (FSE, as a control) and the three sequences in our icEEG-fMRI protocol. Heating was evaluated with electrodes placed orthogonal or parallel to the static magnetic field. Using the configuration with the greatest heating observed, we then measured the total heating induced in our protocol, which is a continuous 70-min icEEG-fMRI session comprising localizer, echo-planar imaging (EPI), and magnetization-prepared rapid gradient-echo sequences. Second, we measured the gradient switching-induced voltage using configurations mimicking electrode implantation in the frontal and temporal lobes. Third, we assessed the gradient switching-induced electrode movement by direct visual detection and image analyses.

Results

On average, RF-induced local heating on the icEEG electrode contacts tested were greater in the orthogonal than parallel configuration, with a maximum increase of 0.2°C during EPI and 1.9°C during FSE. The total local heating was below the 1°C safety limit across all contacts tested during the 70-min icEEG-fMRI session. The induced voltage was within the 100-mV safety limit regardless of the configuration. No gradient switching-induced electrode displacement was observed.

Conclusion

We provide evidence that the additional health risks associated with heating, neuronal stimulation, or device movement are low when acquiring fMRI at 3 T in the presence of clinical icEEG electrodes under the conditions reported in this study. High specific absorption ratio sequences such as FSE should be avoided to prevent potential inadvertent tissue heating.