bluuebunny/crossref_metadata_2025 huggingface dataset:
Destination and Specific Impact of Different Bile Acids in the Intestinal Pathogen Clostridioides difficile
Authors: Metzendorf Nicole G. , Lange Lena Melanie , Lainer Nina , Schlüter Rabea , Dittmann Silvia , Paul Lena-Sophie , Troitzsch Daniel , Sievers Susanne
Published: March 2022

The anaerobic bacterium Clostridioides difficile represents one of the most problematic pathogens, especially in hospitals. Dysbiosis has been proven to largely reduce colonization resistance against this intestinal pathogen. The beneficial effect of the microbiota is closely associated with the metabolic activity of intestinal microbes such as the ability to transform primary bile acids into secondary ones. However, the basis and the molecular action of bile acids (BAs) on the pathogen are not well understood. We stressed the pathogen with the four most abundant human bile acids: cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA) and lithocholic acid (LCA). Thin layer chromatography (TLC), confocal laser scanning microscopy (CLSM), and electron microscopy (EM) were employed to track the enrichment and destination of bile acids in the bacterial cell. TLC not only revealed a strong accumulation of LCA in C. difficile, but also indicated changes in the composition of membrane lipids in BA-treated cells. Furthermore, morphological changes induced by BAs were determined, most pronounced in the virtually complete loss of flagella in LCA-stressed cells and a flagella reduction after DCA and CDCA challenge. Quantification of both, protein and RNA of the main flagella component FliC proved the decrease in flagella to originate from a change in gene expression on transcriptional level. Notably, the loss of flagella provoked by LCA did not reduce adhesion ability of C. difficile to Caco-2 cells. Most remarkably, extracellular toxin A levels in the presence of BAs showed a similar pattern as flagella expression. That is, CA did not affect toxin expression, whereas lower secretion of toxin A was determined in cells stressed with LCA, DCA or CDCA. In summary, the various BAs were shown to differentially modify virulence determinants, such as flagella expression, host cell adhesion and toxin synthesis. Our results indicate differences of BAs in cellular localization and impact on membrane composition, which could be a reason of their diverse effects. This study is a starting point in the elucidation of the molecular mechanisms underlying the differences in BA action, which in turn can be vital regarding the outcome of a C. difficile infection.
Analysis of Key Control Points of Microbial Contamination Risk in Pork Production Processes Using a Quantitative Exposure Assessment Model
Authors: Yang Tengteng , Zhao Ge , Liu Yunzhe , Wang Lin , Gao Yubin , Zhao Jianmei , Liu Na , Huang Xiumei , Zhang Qingqing , Liu Junhui , Zhang Xiyue , Wang Junwei , Xu Ying
Published: March 2022

Pork is one of the most common foods causing microbial foodborne diseases. Since pork directly enters the market after slaughtering, the control of microbial contamination in the slaughtering processes is the key to ensuring the quality and safety of pork. The contamination level of Escherichia coli, a health-indicator bacterium, can reflect the risk level of potential pathogens. In order to assess the E. coli exposure risk of pork during slaughtering and to identify the key control points, we established an E. coli quantitative exposure assessment model for swine-slaughtering processes in slaughterhouses of different sizes. The model simulation data indicated the E. coli contamination pattern on the surfaces of swine carcasses during slaughtering. The changes in E. coli contamination were analyzed according to the simulation data of each slaughtering process. It was found that the number of E. coli after trimming in big and small slaughterhouses increased to the maximum values for the whole processes, which were 3.63 and 3.52 log10 CFU/100 cm2, respectively. The risk contribution of each slaughtering process to the E. coli contamination on the surface of terminal swine carcasses can be determined by correlation analysis. Because the absolute value of correlation coefficient during the trimming process was maximum (0.49), it was regarded as the most important key control point. This result can be further proved via the multilocus sequence typing of E. coli. The dominant sequence type before trimming processes was ST10. ST1434 began to appear in the trimming process and then became the dominant sequence type in the trimming and pre-cooling processes. The model can provide a theoretical basis for microbial hygiene supervision and risk control in swine-slaughtering processes.
Genetic Regulation of Alginate Production in Azotobacter vinelandii a Bacterium of Biotechnological Interest: A Mini-Review
Authors: Núñez Cinthia , López-Pliego Liliana , Ahumada-Manuel Carlos Leonel , Castañeda Miguel
Published: March 2022

Alginates are a family of polymers composed of guluronate and mannuronate monomers joined by β (1–4) links. The different types of alginates have variations in their monomer content and molecular weight, which determine the rheological properties and their applications. In industry, alginates are commonly used as additives capable of viscosifying, stabilizing, emulsifying, and gelling aqueous solutions. Recently, additional specialized biomedical uses have been reported for this polymer. Currently, the production of alginates is based on the harvesting of seaweeds; however, the composition and structure of the extracts are highly variable. The production of alginates for specialized applications requires a precise composition of monomers and molecular weight, which could be achieved using bacterial production systems such as those based on Azotobacter vinelandii, a free-living, non-pathogenic bacterium. In this mini-review, we analyze the latest advances in the regulation of alginate synthesis in this model.
Diagnosis and Surveillance of Neonatal Infections by Metagenomic Next-Generation Sequencing
Authors: Zhang Rong , Zhuang Yan , Xiao Zheng-hui , Li Cai-yun , Zhang Fan , Huang Wei-qing , Zhang Min , Peng Xiao-Ming , Liu Chao
Published: March 2022

Microbial infections cause significant morbidity and mortality in neonates. Metagenomic next-generation sequencing is a hypothesis-free and culture-free test that enables broad identification of pathogens and antimicrobial resistance genes directly from clinical samples within 24 h. In this study, we used mNGS for etiological diagnosis and monitoring the efficacy of antibiotic treatment in a cohort of neonatal patients with severe infections. The median age was 19.5 (3–52) days, median gestational age was 37.96 (31–40+3) weeks, and the median birth weight was 3,261 (1,300–4,300) g. The types of infectious diseases included pneumonia, sepsis, and meningitis. mNGS reported microbial findings in all cases, which led to changes in antibiotic treatment. These included cases of Mycobacterium tuberculosis, Legionella pneumophila, and Bacillus cereus. Eight of ten infants recovered after antibiotic adjustment and showed normal development during follow-up. On the other hand, neurological retardation was seen in two infants with meningitis. mNGS enabled etiological diagnosis and guided antibiotic therapy when all conventional methods failed to discover the culprit. It has the potential to cut down the overall cost and burden of disease management in neonatal infections.
The Immunity Protection of Central Nervous System Induced by Pseudorabies Virus DelgI/gE/TK in Mice
Authors: Xu Lei , Wei Jian-feng , Zhao Jun , Xu Si-yao , Lee Feng-qin , Nie Min-cai , Xu Zhi-wen , Zhou Yuan-cheng , Zhu Ling
Published: March 2022

Based on a variant strain, we constructed a gE/gI/TK-deleted pseudorabies virus (PRV). A total of 18 female mice were randomized to a vaccination group to receive PRV XJ delgE/gI/TK, a vehicle group to receive Dulbecco’s modified Eagle’s medium, and a mock group to confirm the protection of PRV delgE/gI/TK on the central nervous system in mice. Subsequently, the vaccination and vehicle groups were infected with PRV XJ. The mice in the vehicle group showed more severe neurological symptoms and higher viral loads than those in the vaccination group. The exudation of Evans blue and the expression of tight junction protein showed no difference in all groups. HE staining showed vacuolar neuronal degeneration in the vehicle group brain, but no tissue lesions were observed in the vaccination group. TNF-α, IL-6, and synuclein were upregulated in the brain of mice in the vehicle group, while those were inhibited among mice in the vaccination group. IFN-β, IFN-γ, ISG15, Mx1, and OAS1 showed no difference in the brain between the vaccination and vehicle groups. In addition, TNF-α and IL-6 were inhibited, and antiviral factors were increased in the intestine of the mice in the vaccination group compared to those in the vehicle group. Our study showed that PRV XJ delgE/gI/TK inhibited neurological damage and the inflammation of the intestine and brain induced by PRV and activated the innate immunity of the intestine.
Genome-Wide Approaches to Unravel the Host Factors Involved in Chikungunya Virus Replication
Authors: Tanaka Atsushi , Suzuki Youichi
Published: March 2022

Chikungunya virus (CHIKV), the causative agent of Chikungunya fever (CHIKVF) that is often characterized by fever, headache, rash, and arthralgia, is transmitted to humans by Aedes mosquito bites. Although the mortality rate associated with CHIKV infection is not very high, CHIKVF has been confirmed in more than 40 countries, not only in tropical but also in temperate areas. Therefore, CHIKV is a growing major threat to the public health of the world. However, a specific drug is not available for CHIKV infection. As demonstrated by many studies, the processes completing the replication of CHIKV are assisted by many host factors, whereas it has become clear that the host cell possesses some factors limiting the virus replication. This evidence will provide us with an important clue for the development of pharmacological treatment against CHIKVF. In this review, we briefly summarize cellular molecules participating in the CHIKV infection, particularly focusing on introducing recent genome-wide screen studies that enabled illuminating the virus-host interactions.
Extracellular Matrix-Based Gene Expression Signature Defines Two Prognostic Subtypes of Hepatocellular Carcinoma With Different Immune Microenvironment Characteristics
Authors: Tang Hui , You Tingting , Sun Zhao , Bai Chunmei , Wang Yingyi
Published: March 2022

Background: Accumulating evidence has suggested that the extracellular matrix (ECM) plays a vital role in the development and progression of cancer, and could be recognized as a biomarker of the response to immunotherapy. However, the effect of the ECM signature in hepatocellular carcinoma (HCC) is not well understood.

Methods: HCC patients derived from the TCGA-LIHC dataset were clustered according to the ECM signature. The differences in prognosis, functional enrichment, immune infiltration, and mutation characteristics between distinct molecular clusters were examined, and its predictive value on the sensitivities to chemotherapy and immunotherapy was further analyzed. Then, a prognostic model was built based on the ECM-related gene expression pattern.

Results: HCC patients were assigned into two molecular subtypes. Approximately 80% of HCC patients were classified into cluster A with poor prognosis, more frequent TP53 mutation, and lower response rate to immunotherapy. In contrast, patients in cluster B had better survival outcomes and higher infiltration levels of dendritic cells, macrophages, and regulatory T cells. The prognostic risk score model based on the expression profiles of six ECM-related genes (SPP1, ADAMTS5, MMP1, BSG, LAMA2, and CDH1) demonstrated a significant association with higher histologic grade and advanced TNM stage. Moreover, the prognostic risk score showed good performance in both the training dataset and validation dataset, as well as improved prognostic capacity compared with TNM stage.

Conclusions: We characterized two HCC subtypes with distinct clinical outcomes, immune infiltration, and mutation characteristics. A novel prognostic model based on the ECM signature was further developed, which may contribute to individualized prognostic prediction and aid in clinical decision-making.
Cortical Short-Range Fiber Connectivity and Its Association With Deep Brain White Matter Hyperintensities in Older Diabetic People With Low Serum Vitamin B12
Authors: Liu Kai , Wang Xiaopeng , Zhang Teng , Wang Wei , Li Ruohan , Lu Li , Deng Yanjia , Xu Kai , Kwok Timothy
Published: March 2022

Although previous studies have indicated that older people with diabetes mellitus (DM) had an approximately two times larger white matter hyperintensity (WMH) load than those without DM, the influence of WMHs on cognition is uncertain and inconsistent in the literature. It is unclear whether the short-range fibers in the juxtacortical region, traditionally considered to be spared from WMH pathology, are enhanced as an adaptive response to deep WM degeneration in older diabetic people with normal cognition. Moreover, the specific effect of vitamin B12 deficiency, commonly accompanied by DM, remains to be investigated. This study implemented a specialized analysis of the superficial cortical short-range fiber connectivity density (SFiCD) based on a data-driven framework in 70 older individuals with DM and low serum vitamin B12. Moreover, the effects of time and vitamin B12 supplementation were assessed based on a randomized placebo-controlled trial in 59 individuals. The results demonstrated a higher SFiCD in diabetic individuals with a higher deep WMH load. Additionally, a significant interaction between DWMH load and homocysteine on SFiCD was found. During the 27-month follow-up period, a longitudinal increase in the SFiCD was observed in the bilateral frontal cortices. However, the observed longitudinal SFiCD change was not dependent on vitamin B12 supplementation; thus, the specific reason for the longitudinal cortical short fiber densification may need further study. Overall, these findings may help us better understand the neurobiology of brain plasticity in older patients with DM, as well as the interplay among DM, WMH, and vitamin B12 deficiency.
Musicianship-Related Structural and Functional Cortical Features Are Preserved in Elderly Musicians
Authors: Rus-Oswald Oana G. , Benner Jan , Reinhardt Julia , Bürki Céline , Christiner Markus , Hofmann Elke , Schneider Peter , Stippich Christoph , Kressig Reto W. , Blatow Maria
Published: March 2022

Background

Professional musicians are a model population for exploring basic auditory function, sensorimotor and multisensory integration, and training-induced neuroplasticity. The brain of musicians exhibits distinct structural and functional cortical features; however, little is known about how these features evolve during aging. This multiparametric study aimed to examine the functional and structural neural correlates of lifelong musical practice in elderly professional musicians.

Methods

Sixteen young musicians, 16 elderly musicians (age >70), and 15 elderly non-musicians participated in the study. We assessed gray matter metrics at the whole-brain and region of interest (ROI) levels using high-resolution magnetic resonance imaging (MRI) with the Freesurfer automatic segmentation and reconstruction pipeline. We used BrainVoyager semiautomated segmentation to explore individual auditory cortex morphotypes. Furthermore, we evaluated functional blood oxygenation level-dependent (BOLD) activations in auditory and non-auditory regions by functional MRI (fMRI) with an attentive tone-listening task. Finally, we performed discriminant function analyses based on structural and functional ROIs.

Results

A general reduction of gray matter metrics distinguished the elderly from the young subjects at the whole-brain level, corresponding to widespread natural brain atrophy. Age- and musicianship-dependent structural correlations revealed group-specific differences in several clusters including superior, middle, and inferior frontal as well as perirolandic areas. In addition, the elderly musicians exhibited increased gyrification of auditory cortex like the young musicians. During fMRI, the elderly non-musicians activated predominantly auditory regions, whereas the elderly musicians co-activated a much broader network of auditory association areas, primary and secondary motor areas, and prefrontal and parietal regions like, albeit weaker, the young musicians. Also, group-specific age- and musicianship-dependent functional correlations were observed in the frontal and parietal regions. Moreover, discriminant function analysis could separate groups with high accuracy based on a set of specific structural and functional, mainly temporal and occipital, ROIs.

Conclusion

In conclusion, despite naturally occurring senescence, the elderly musicians maintained musicianship-specific structural and functional cortical features. The identified structural and functional brain regions, discriminating elderly musicians from non-musicians, might be of relevance for the aging musicians’ brain. To what extent lifelong musical activity may have a neuroprotective impact needs to be addressed further in larger longitudinal studies.
Reelin Alterations, Behavioral Phenotypes, and Brain Anomalies in Schizophrenia: A Systematic Review of Insights From Rodent Models
Authors: Sánchez-Hidalgo Ana C. , Martín-Cuevas Celia , Crespo-Facorro Benedicto , Garrido-Torres Nathalia
Published: March 2022

Reelin is an extracellular matrix glycoprotein reduced in brain regions (the prefrontal cortex and the hippocampus) of patients with schizophrenia. There are diverse rodent models of schizophrenia that mimic patient symptoms based on various causal theories; however, likely shared reelin alterations have not yet been systematically assessed in those models. A systematic review of the literature was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model. Articles focused on psychotic disorders or schizophrenia and their relationship with reelin in rodent models were selected. Data (first author, publication year, results, both open field and prepulse inhibition test results, and type of reelin alteration) were extracted in duplicate by two independent reviewers. The 37 reviewed articles reported about various schizophrenia models and their reelin alterations, brain morphology, and behavioral defects. We conclude that reelin is an altered preclinical biomarker common to all models included, mainly prenatal or genetic models, and a key protein in schizophrenia disease, making the reelin signaling pathway in prenatal stages a target of special interest for future preclinical and clinical studies. All models presented at least one of the four described reelin alteration types.

Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021210568], identifier [CRD42021210568].
Accuracy of Robotic and Frame-Based Stereotactic Neurosurgery in a Phantom Model
Authors: Spyrantis Andrea , Woebbecke Tirza , Rueß Daniel , Constantinescu Anne , Gierich Andreas , Luyken Klaus , Visser-Vandewalle Veerle , Herrmann Eva , Gessler Florian , Czabanka Marcus , Treuer Harald , Ruge Maximilian , Freiman Thomas M.
Published: March 2022

Background

The development of robotic systems has provided an alternative to frame-based stereotactic procedures. The aim of this experimental phantom study was to compare the mechanical accuracy of the Robotic Surgery Assistant (ROSA) and the Leksell stereotactic frame by reducing clinical and procedural factors to a minimum.

Methods

To precisely compare mechanical accuracy, a stereotactic system was chosen as reference for both methods. A thin layer CT scan with an acrylic phantom fixed to the frame and a localizer enabling the software to recognize the coordinate system was performed. For each of the five phantom targets, two different trajectories were planned, resulting in 10 trajectories. A series of five repetitions was performed, each time based on a new CT scan. Hence, 50 trajectories were analyzed for each method. X-rays of the final cannula position were fused with the planning data. The coordinates of the target point and the endpoint of the robot- or frame-guided probe were visually determined using the robotic software. The target point error (TPE) was calculated applying the Euclidian distance. The depth deviation along the trajectory and the lateral deviation were separately calculated.

Results

Robotics was significantly more accurate, with an arithmetic TPE mean of 0.53 mm (95% CI 0.41–0.55 mm) compared to 0.72 mm (95% CI 0.63–0.8 mm) in stereotaxy (p < 0.05). In robotics, the mean depth deviation along the trajectory was −0.22 mm (95% CI −0.25 to −0.14 mm). The mean lateral deviation was 0.43 mm (95% CI 0.32–0.49 mm). In frame-based stereotaxy, the mean depth deviation amounted to −0.20 mm (95% CI −0.26 to −0.14 mm), the mean lateral deviation to 0.65 mm (95% CI 0.55–0.74 mm).

Conclusion

Both the robotic and frame-based approach proved accurate. The robotic procedure showed significantly higher accuracy. For both methods, procedural factors occurring during surgery might have a more relevant impact on overall accuracy.
Altered Brain Criticality in Schizophrenia: New Insights From Magnetoencephalography
Authors: Alamian Golnoush , Lajnef Tarek , Pascarella Annalisa , Lina Jean-Marc , Knight Laura , Walters James , Singh Krish D. , Jerbi Karim
Published: March 2022

Schizophrenia has a complex etiology and symptomatology that is difficult to untangle. After decades of research, important advancements toward a central biomarker are still lacking. One of the missing pieces is a better understanding of how non-linear neural dynamics are altered in this patient population. In this study, the resting-state neuromagnetic signals of schizophrenia patients and healthy controls were analyzed in the framework of criticality. When biological systems like the brain are in a state of criticality, they are thought to be functioning at maximum efficiency (e.g., optimal communication and storage of information) and with maximum adaptability to incoming information. Here, we assessed the self-similarity and multifractality of resting-state brain signals recorded with magnetoencephalography in patients with schizophrenia patients and in matched controls. Schizophrenia patients had similar, although attenuated, patterns of self-similarity and multifractality values. Statistical tests showed that patients had higher values of self-similarity than controls in fronto-temporal regions, indicative of more regularity and memory in the signal. In contrast, patients had less multifractality than controls in the parietal and occipital regions, indicative of less diverse singularities and reduced variability in the signal. In addition, supervised machine-learning, based on logistic regression, successfully discriminated the two groups using measures of self-similarity and multifractality as features. Our results provide new insights into the baseline cognitive functioning of schizophrenia patients by identifying key alterations of criticality properties in their resting-state brain data.
The Fractal Tapestry of Life: II Entailment of Fractional Oncology by Physiology Networks
Authors: West Bruce J.
Published: March 2022

This is an essay advocating the efficacy of using the (noninteger) fractional calculus (FC) for the modeling of complex dynamical systems, specifically those pertaining to biomedical phenomena in general and oncological phenomena in particular. Herein we describe how the integer calculus (IC) is often incapable of describing what were historically thought to be simple linear phenomena such as Newton’s law of cooling and Brownian motion. We demonstrate that even linear dynamical systems may be more accurately described by fractional rate equations (FREs) when the experimental datasets are inconsistent with models based on the IC. The Network Effect is introduced to explain how the collective dynamics of a complex network can transform a many-body noninear dynamical system modeled using the IC into a set of independent single-body fractional stochastic rate equations (FSREs). Note that this is not a mathematics paper, but rather a discussion focusing on the kinds of phenomena that have historically been approximately and improperly modeled using the IC and how a FC replacement of the model better explains the experimental results. This may be due to hidden effects that were not anticapated in the IC model, or to an effect that was acknowledged as possibly significant, but beyond the mathematical skills of the investigator to Incorporate into the original model. Whatever the reason we introduce the FRE used to describe mathematical oncology (MO) and review the quality of fit of such models to tumor growth data. The analytic results entailed in MO using ordinary diffusion as well as fractional diffusion are also briefly discussed. A connection is made between a time-dependent fractional-order derivative, technically called a distributed-order parameter, and the multifractality of time series, such that an observed multifractal time series can be modeled using a FRE with a distributed fractional-order derivative. This equivalence between multifractality and distributed fractional derivatives has not received the recognition in the applications literature we believe it warrants.
Applied Bayesian Approaches for Research in Motor Neuron Disease
Authors: Temp Anna G. M. , Naumann Marcel , Hermann Andreas , Glaß Hannes
Published: March 2022

Statistical evaluation of empirical data is the basis of the modern scientific method. Available tools include various hypothesis tests for specific data structures, as well as methods that are used to quantify the uncertainty of an obtained result. Statistics are pivotal, but many misconceptions arise due to their complexity and difficult-to-acquire mathematical background. Even though most studies rely on a frequentist interpretation of statistical readouts, the application of Bayesian statistics has increased due to the availability of easy-to-use software suites and an increased outreach favouring this topic in the scientific community. Bayesian statistics take our prior knowledge together with the obtained data to express a degree of belief how likely a certain event is. Bayes factor hypothesis testing (BFHT) provides a straightforward method to evaluate multiple hypotheses at the same time and provides evidence that favors the null hypothesis or alternative hypothesis. In the present perspective, we show the merits of BFHT for three different use cases, including a clinical trial, basic research as well as a single case study. Here we show that Bayesian statistics is a viable addition of a scientist's statistical toolset, which can help to interpret data.
Low EEG Gamma Entropy and Glucose Hypometabolism After Corpus Callosotomy Predicts Seizure Outcome After Subsequent Surgery
Authors: Kosugi Kenzo , Iijima Keiya , Yokosako Suguru , Takayama Yutaro , Kimura Yuiko , Kaneko Yuu , Sumitomo Noriko , Saito Takashi , Nakagawa Eiji , Sato Noriko , Iwasaki Masaki
Published: March 2022

Background

Patients with generalized epilepsy who had lateralized EEG abnormalities after corpus callosotomy (CC) occasionally undergo subsequent surgeries to control intractable epilepsy.

Objectives

This study evaluated retrospectively the combination of EEG multiscale entropy (MSE) and FDG-PET for identifying lateralization of the epileptogenic zone after CC.

Methods

This study included 14 patients with pharmacoresistant epilepsy who underwent curative epilepsy surgery after CC. Interictal scalp EEG and FDG-PET obtained after CC were investigated to determine (1) whether the MSE calculated from the EEG and FDG-PET findings was lateralized to the surgical side, and (2) whether the lateralization was associated with seizure outcomes.

Results

Seizure reduction rate was higher in patients with lateralized findings to the surgical side than those without (MSE: p < 0.05, FDG-PET: p < 0.05, both: p < 0.01). Seizure free rate was higher in patients with lateralized findings in both MSE and FDG-PET than in those without (p < 0.05).

Conclusions

This study demonstrated that patients with lateralization of MSE and FDG-PET to the surgical side had better seizure outcomes. The combination of MSE and conventional FDG-PET may help to select surgical candidates for additional surgery after CC with good postoperative seizure outcomes.
Lobar Cerebral Microbleeds Are Associated With Cognitive Decline in Patients With Type 2 Diabetes Mellitus
Authors: Shao Pengfei , Xu Hengheng , Sheng Xiaoning , Qin Ruomeng , Ma Junyi , Luo Yishan , Lee Allan , Shi Lin , Huang Lili , Cheng Yue , Zhao Hui , Xu Yun
Published: March 2022

Purpose

Combined the number, volume, and location of cerebral microbleeds (CMBs), this study aimed to explore the different features of CMBs and their correlation with cognitive ability in patients with type 2 diabetes mellitus (T2DM).

Methods

This study recruited 95 patients with T2DM and 80 healthy control (HC) individuals. AccuBrain®, an automated tool, was used to obtain the number and volume of CMBs. The scores on global cognition and five cognitive domains were derived from a battery of cognitive tests. The logistic regression and multivariate linear regression were conducted to determine the relationship between the CMBs (number, volume, and location) and cognitive ability in patients with T2DM.

Results

After adjusting for several variables, the total volume of CMBs (OR = 0.332, 95%CI: 0.133–0.825, and p = 0.018) was independent risk factor for cognitive impairment, whereas the total number of CMBs was not (OR = 0933, 95%CI: 0.794–1.097, and p = 0.400). Furthermore, the volume of CMBs in lobar regions was independently associated with working memory (β = −0.239, 95%CI: −0.565 to −0.035, and p = 0.027). However, no significant correlation between the number of CMBs (both lobar and deep/infratentorium) and any cognitive domains was observed.

Conclusions

Lobar CMBs was related with cognitive impairment in patients with T2DM and might be a potential early warning signal. Compared with the counting analysis, the quantitative method offered a more sensitive and objective measurement for studying imaging features of CMBs.
Headache in the Neurological Emergency Department—High Degree of Inadequate Documentation Calls for Structured Assessments
Authors: Rimmele Florian , Janke Josephine , Kropp Peter , Kasch Ramon , Walter Uwe , Jürgens Tim P.
Published: March 2022

Headaches are a frequent reason for presentation to the emergency department (ED) and can pose a great challenge for the attending physicians. First and foremost, the distinction between a primary and secondary headache with potentially life-threatening implications can be difficult. Moreover, it often occurs that no specific headache diagnosis is made at discharge from the ED. Therefore, in this present retrospective cross-sectional study, all patients who presented to the emergency department of the Department of Neurology at Rostock University Medical Centre with the main symptom of headache between November 2013 and November 2016 underwent a neurological examination and the extent to which warning symptoms (“red flags”) for a secondary headache as well as symptoms necessary for a correct headache diagnosis according to the ICHD-3 classification were recorded and documented. We could show that documentation of red flags and clinical characteristics is inadequate and does not allow proper diagnostic categorization. To facilitate concise documentation and rapid decision making we suggest a structured and standardized form for documenting the headache history and red flags in the ED.
Evaluation of the Psychometric Properties of the Health Assessment Questionnaire (HAQ) in a Population of Individuals With Multiple Sclerosis
Authors: Berardi Anna , Conte Antonella , Cimmino Lucilla , Cimmino Carlotta , Baione Viola , Crisafulli Sebastiano Giuseppe , Tofani Marco , Tartaglia Matteo , Fabbrini Giovanni , Galeoto Giovanni
Published: March 2022

Introduction

The Health Assessment Questionnaire (HAQ) has been translated into many languages and it has been classified as the predictor of disability and medical costs, however, the psychometric properties of the HAQ have never been studied in a population with neurological disease. The purpose of this study was the evaluation of the psychometric properties of HAQ in a population of individuals with multiple sclerosis (MS).

Materials and Methods

This cross-sectional study was conducted with patients diagnosed with MS. The evaluation tools administered were the 36-item short form health survey (SF–36) to evaluate the health state of the patients and HAQ and to evaluate the limitations of the activities of daily living (ADL).

Results

A total of 34 patients were included in this study. Cronbach's alpha assessed the internal consistency of the HAQ, and it is equal to 0.94. The study revealed some significant correlations between the dimensions of the SF-36 and the sub-categories of the HAQ using Pearson's Correlation Coefficient. Significant correlations emerged between the demographic and clinical characteristics of patients and the subcategories of HAQ.

Discussion

The HAQ is a valid and reliable tool to assess the limitations of the activities of daily living, and it could provide for the healthcare and rehabilitation sector with an additional evaluation tool.
Subthalamic Deep Brain Stimulation Lead Asymmetry Impacts the Parkinsonian Gait Disorder
Authors: Schott Frederik P. , Gulberti Alessandro , Pinnschmidt Hans O. , Gerloff Christian , Moll Christian K. E. , Schaper Miriam , Koeppen Johannes A. , Hamel Wolfgang , Pötter-Nerger Monika
Published: March 2022

Background

The preferable position of Deep Brain Stimulation (DBS) electrodes is proposed to be located in the dorsolateral subthalamic nucleus (STN) to improve general motor performance. The optimal DBS electrode localization for the post-operative improvement of balance and gait is unknown.

Methods

In this single-center, retrospective analyses, 66 Parkinson’s disease (PD) patients (24 female, age 63 ± 7 years) were assessed pre- and post-operatively (8.45 ± 4.2 months after surgery) by using MDS-UPDRS, freezing of gait (FoG) score, Giladi’s gait and falls questionnaire and Berg balance scale. The clinical outcome was related to the DBS electrode coordinates in x, y, z plane as revealed by image-based reconstruction (SureTune™). Binomial generalized linear mixed models with fixed-effect variables electrode asymmetry, parkinsonian subtype, medication, age class and clinical DBS induced changes were analyzed.

Results

Subthalamic nucleus-deep brain stimulation improved all motor, balance and FoG scores in MED OFF condition, however there were heterogeneous results in MED ON condition. DBS electrode reconstructed coordinates impacted the responsiveness of axial symptoms. FoG and balance responders showed slightly more medially located STN electrode coordinates and less medio-lateral asymmetry of the electrode reconstructed coordinates across hemispheres compared to non-responders.

Conclusion

Deep brain stimulation electrode reconstructed coordinates, particularly electrode asymmetry on the medio-lateral axis affected the post-operative responsiveness of balance and FoG symptoms in PD patients.
Applying Dimensionality Reduction Techniques in Source-Space Electroencephalography via Template and Magnetic Resonance Imaging-Derived Head Models to Continuously Decode Hand Trajectories
Authors: Srisrisawang Nitikorn , Müller-Putz Gernot R.
Published: March 2022

Several studies showed evidence supporting the possibility of hand trajectory decoding from low-frequency electroencephalography (EEG). However, the decoding in the source space via source localization is scarcely investigated. In this study, we tried to tackle the problem of collinearity due to the higher number of signals in the source space by two folds: first, we selected signals in predefined regions of interest (ROIs); second, we applied dimensionality reduction techniques to each ROI. The dimensionality reduction techniques were computing the mean (Mean), principal component analysis (PCA), and locality preserving projections (LPP). We also investigated the effect of decoding between utilizing a template head model and a subject-specific head model during the source localization. The results indicated that applying source-space decoding with PCA yielded slightly higher correlations and signal-to-noise (SNR) ratios than the sensor-space approach. We also observed slightly higher correlations and SNRs when applying the subject-specific head model than the template head model. However, the statistical tests revealed no significant differences between the source-space and sensor-space approaches and no significant differences between subject-specific and template head models. The decoder with Mean and PCA utilizes information mainly from precuneus and cuneus to decode the velocity kinematics similarly in the subject-specific and template head models.
Mixed Neuropathologies, Neural Motor Resilience and Target Discovery for Therapies of Late-Life Motor Impairment
Authors: Buchman Aron S. , Bennett David A.
Published: March 2022

By age 85, most adults manifest some degree of motor impairment. However, in most individuals a specific etiology for motor decline and treatment to modify its inexorable progression cannot be identified. Recent clinical-pathologic studies provide evidence that mixed-brain pathologies are commonly associated with late-life motor impairment. Yet, while nearly all older adults show some degree of accumulation of Alzheimer’s disease and related dementias (ADRD) pathologies, the extent to which these pathologies contribute to motor decline varies widely from person to person. Slower or faster than expected motor decline in the presence of brain injury and/or pathology has been conceptualized as more or less “resilience” relative to the average person This suggests that other factors, such as lifestyles or other neurobiologic indices may offset or exacerbate the negative effects of pathologies via other molecular pathways. The mechanisms underlying neural motor resilience are just beginning to be illuminated. Unlike its cousin, cognitive resilience which is restricted to neural mechanisms above the neck, the motor system extends the total length of the CNS and beyond the CNS to reach muscle and musculoskeletal structures, all of which are crucial for motor function. Building on prior work, we propose that by isolating motor decline unrelated to neuropathologies and degeneration, investigators can identify genes and proteins that may provide neural motor resilience. Elucidating these molecular mechanisms will advance our understanding of the heterogeneity of late-life motor impairment. This approach will also provide high value therapeutic targets for drug discovery of therapies that may offset the negative motor consequences of CNS pathologies that are currently untreatable.
Upward Shifts in the Internal Representation of Frequency Can Persist Over a 3-Year Period for Cochlear Implant Patients Fit With a Relatively Short Electrode Array
Authors: Dorman Michael F. , Natale Sarah C. , Noble Jack H. , Zeitler Daniel M.
Published: March 2022

Patients fit with cochlear implants (CIs) commonly indicate at the time of device fitting and for some time after, that the speech signal sounds abnormal. A high pitch or timbre is one component of the abnormal percept. In this project, our aim was to determine whether a number of years of CI use reduced perceived upshifts in frequency spectrum and/or voice fundamental frequency. The participants were five individuals who were deaf in one ear and who had normal hearing in the other ear. The deafened ears had been implanted with a 18.5 mm electrode array which resulted in signal input frequencies being directed to locations in the spiral ganglion (SG) that were between one and two octaves higher than the input frequencies. The patients judged the similarity of a clean signal (a male-voice sentence) presented to their implanted ear and candidate, implant-like, signals presented to their normal-hearing (NH) ear. Matches to implant sound quality were obtained, on average, at 8 months after device activation (see section “Time 1”) and at 35 months after activation (see section “Time 2”). At Time 1, the matches to CI sound quality were characterized, most generally, by upshifts in the frequency spectrum and in voice pitch. At Time 2, for four of the five patients, frequency spectrum values remained elevated. For all five patients F0 values remained elevated. Overall, the data offer little support for the proposition that, for patients fit with shorter electrode arrays, cortical plasticity nudges the cortical representation of the CI voice toward more normal, or less upshifted, frequency values between 8 and 35 months after device activation. Cortical plasticity may be limited when there are large differences between frequencies in the input signal and the locations in the SG stimulated by those frequencies.
Research on Voxel-Based Features Detection and Analysis of Alzheimer’s Disease Using Random Survey Support Vector Machine
Authors: Meng Xianglian , Wu Yue , Liu Wenjie , Wang Ying , Xu Zhe , Jiao Zhuqing
Published: March 2022

Alzheimer’s disease (AD) is a degenerative disease of the central nervous system characterized by memory and cognitive dysfunction, as well as abnormal changes in behavior and personality. The research focused on how machine learning classified AD became a recent hotspot. In this study, we proposed a novel voxel-based feature detection framework for AD. Specifically, using 649 voxel-based morphometry (VBM) methods obtained from MRI in Alzheimer’s Disease Neuroimaging Initiative (ADNI), we proposed a feature detection method according to the Random Survey Support Vector Machines (RS-SVM) and combined the research process based on image-, gene-, and pathway-level analysis for AD prediction. Particularly, we constructed 136, 141, and 113 novel voxel-based features for EMCI (early mild cognitive impairment)-HC (healthy control), LMCI (late mild cognitive impairment)-HC, and AD-HC groups, respectively. We applied linear regression model, least absolute shrinkage and selection operator (Lasso), partial least squares (PLS), SVM, and RS-SVM five methods to test and compare the accuracy of these features in these three groups. The prediction accuracy of the AD-HC group using the RS-SVM method was higher than 90%. In addition, we performed functional analysis of the features to explain the biological significance. The experimental results using five machine learning indicate that the identified features are effective for AD and HC classification, the RS-SVM framework has the best classification accuracy, and our strategy can identify important brain regions for AD.
Decoding Bilateral Hindlimb Kinematics From Cat Spinal Signals Using Three-Dimensional Convolutional Neural Network
Authors: Fathi Yaser , Erfanian Abbas
Published: March 2022

To date, decoding limb kinematic information mostly relies on neural signals recorded from the peripheral nerve, dorsal root ganglia (DRG), ventral roots, spinal cord gray matter, and the sensorimotor cortex. In the current study, we demonstrated that the neural signals recorded from the lateral and dorsal columns within the spinal cord have the potential to decode hindlimb kinematics during locomotion. Experiments were conducted using intact cats. The cats were trained to walk on a moving belt in a hindlimb-only condition, while their forelimbs were kept on the front body of the treadmill. The bilateral hindlimb joint angles were decoded using local field potential signals recorded using a microelectrode array implanted in the dorsal and lateral columns of both the left and right sides of the cat spinal cord. The results show that contralateral hindlimb kinematics can be decoded as accurately as ipsilateral kinematics. Interestingly, hindlimb kinematics of both legs can be accurately decoded from the lateral columns within one side of the spinal cord during hindlimb-only locomotion. The results indicated that there was no significant difference between the decoding performances obtained using neural signals recorded from the dorsal and lateral columns. The results of the time-frequency analysis show that event-related synchronization (ERS) and event-related desynchronization (ERD) patterns in all frequency bands could reveal the dynamics of the neural signals during movement. The onset and offset of the movement can be clearly identified by the ERD/ERS patterns. The results of the mutual information (MI) analysis showed that the theta frequency band contained significantly more limb kinematics information than the other frequency bands. Moreover, the theta power increased with a higher locomotion speed.
Restricted Proliferation During Neurogenesis Contributes to Regionalisation of the Amphioxus Nervous System
Authors: Gattoni Giacomo , Andrews Toby G. R. , Benito-Gutiérrez Èlia
Published: March 2022

The central nervous system of the cephalochordate amphioxus consists of a dorsal neural tube with an anterior brain. Two decades of gene expression analyses in developing amphioxus embryos have shown that, despite apparent morphological simplicity, the amphioxus neural tube is highly regionalised at the molecular level. However, little is known about the morphogenetic mechanisms regulating the spatiotemporal emergence of cell types at distinct sites of the neural axis and how their arrangements contribute to the overall neural architecture. In vertebrates, proliferation is key to provide appropriate cell numbers of specific types to particular areas of the nervous system as development proceeds, but in amphioxus proliferation has never been studied at this level of detail, nor in the specific context of neurogenesis. Here, we describe the dynamics of cell division during the formation of the central nervous system in amphioxus embryos, and identify specific regions of the nervous system that depend on proliferation of neuronal precursors at precise time-points for their maturation. By labelling proliferating cells in vivo at specific time points in development, and inhibiting cell division during neurulation, we demonstrate that localised proliferation in the anterior cerebral vesicle is required to establish the full cell type repertoire of the frontal eye complex and the putative hypothalamic region of the amphioxus brain, while posterior proliferating progenitors, which were found here to derive from the dorsal lip of the blastopore, contribute to elongation of the caudal floor plate. Between these proliferative domains, we find that trunk nervous system differentiation is independent from cell division, in which proliferation decreases during neurulation and resumes at the early larval stage. Taken together, our results highlight the importance of proliferation as a tightly controlled mechanism for shaping and regionalising the amphioxus neural axis during development, by addition of new cells fated to particular types, or by influencing tissue geometry.