bluuebunny/crossref_metadata_2025 huggingface dataset:
CD8+ T Cells Involved in Metabolic Inflammation in Visceral Adipose Tissue and Liver of Transgenic Pigs
Authors: Zhang Kaiyi , Tao Cong , Xu Jianping , Ruan Jinxue , Xia Jihan , Zhu Wenjuan , Xin Leilei , Ye Huaqiong , Xie Ning , Xia Boce , Li Chenxiao , Wu Tianwen , Wang Yanfang , Schroyen Martine , Xiao Xinhua , Fan Jiangao , Yang Shulin
Published: July 2021

Anti-inflammatory therapies have the potential to become an effective treatment for obesity-related diseases. However, the huge gap of immune system between human and rodent leads to limitations of drug discovery. This work aims at constructing a transgenic pig model with higher risk of metabolic diseases and outlining the immune responses at the early stage of metaflammation by transcriptomic strategy. We used CRISPR/Cas9 techniques to targeted knock-in three humanized disease risk genes, GIPRdn, hIAPP and PNPLA3I148M. Transgenic effect increased the risk of metabolic disorders. Triple-transgenic pigs with short-term diet intervention showed early symptoms of type 2 diabetes, including glucose intolerance, pancreatic lipid infiltration, islet hypertrophy, hepatic lobular inflammation and adipose tissue inflammation. Molecular pathways related to CD8+ T cell function were significantly activated in the liver and visceral adipose samples from triple-transgenic pigs, including antigen processing and presentation, T-cell receptor signaling, co-stimulation, cytotoxicity, and cytokine and chemokine secretion. The similar pro-inflammatory signaling in liver and visceral adipose tissue indicated that there might be a potential immune crosstalk between the two tissues. Moreover, genes that functionally related to liver antioxidant activity, mitochondrial function and extracellular matrix showed distinct expression between the two groups, indicating metabolic stress in transgenic pigs’ liver samples. We confirmed that triple-transgenic pigs had high coincidence with human metabolic diseases, especially in the scope of inflammatory signaling at early stage metaflammation. Taken together, this study provides a valuable large animal model for the clinical study of metaflammation and metabolic diseases.
The Role of Toll-Like Receptor-2 in Clostridioides difficile Infection: Evidence From a Mouse Model and Clinical Patients
Authors: Lai Yi-Hsin , Tsai Bo-Yang , Hsu Chih-Yu , Chen Yi-Hsuan , Chou Po-Han , Chen Yueh-Lin , Liu Hsiao-Chieh , Ko Wen-Chien , Tsai Pei-Jane , Hung Yuan-Pin
Published: July 2021

Background

Clostridioides difficile is the leading cause of nosocomial infectious diarrhea. Toll-like receptors (TLRs) are the major components of innate immunity that sense pathogens. The relationship between TLRs and C. difficile infection (CDI) was analyzed in clinical patients and a mouse model.

Materials and Methods

A prospective investigation was conducted in medical wards of Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan, from January 2011 to January 2013. Adult patients were followed up for the development of CDI. Single nucleotide polymorphisms (SNPs) of TLR2 and TLR4 were analyzed to assess the relationship between genetic polymorphisms and the development of CDI. A mouse model of CDI was used to investigate the pathogenic role of TLRs in CDI, TLR2 and TLR4 knockout (Tlr2-/- and Tlr4-/-) mice.

Results

In the prospective study, 556 patients were enrolled, and 6.5% (36) of patients, accounting for 3.59 episodes per 1000 patient-days, developed CDI. Of 539 patients with available blood samples, the TLR2 rs3804099 polymorphism was more often noted in those with CDI than in those without CDI (64.5% vs. 46.1%; P = 0.046) but was not significant in multivariate analysis. Because the TLR2 rs3804099 polymorphism was moderately associated with CDI, the role of TLR2 and TLR4 was further evaluated in a mouse model. Both Tlr2-/- and Tlr4-/- mice showed more severe CDI disease than wild-type mice in terms of body weight change and fecal content five days after oral challenge with C. difficile. Furthermore, Tlr2-/- mice suffered from more severe disease than Tlr4-/- mice, as evidenced by stool consistency, cecum weight, and survival rate.

Conclusion

The TLR2 rs3804099 polymorphism is marginally associated with the development of CDI, and the pathogenic role of TLR2 is further supported by a mouse model.
A Single-Cell Atlas of Lymphocyte Adaptive Immune Repertoires and Transcriptomes Reveals Age-Related Differences in Convalescent COVID-19 Patients
Authors: Bieberich Florian , Vazquez-Lombardi Rodrigo , Yermanos Alexander , Ehling Roy A. , Mason Derek M. , Wagner Bastian , Kapetanovic Edo , Di Roberto Raphael Brisset , Weber Cédric R. , Savic Miodrag , Rudolf Fabian , Reddy Sai T.
Published: July 2021

COVID-19 disease outcome is highly dependent on adaptive immunity from T and B lymphocytes, which play a critical role in the control, clearance and long-term protection against SARS-CoV-2. To date, there is limited knowledge on the composition of the T and B cell immune receptor repertoires [T cell receptors (TCRs) and B cell receptors (BCRs)] and transcriptomes in convalescent COVID-19 patients of different age groups. Here, we utilize single-cell sequencing (scSeq) of lymphocyte immune repertoires and transcriptomes to quantitatively profile the adaptive immune response in COVID-19 patients of varying age. We discovered highly expanded T and B cells in multiple patients, with the most expanded clonotypes coming from the effector CD8+T cell population. Highly expanded CD8+and CD4+T cell clones show elevated markers of cytotoxicity (CD8: PRF1, GZMH, GNLY; CD4: GZMA), whereas clonally expanded B cells show markers of transition into the plasma cell state and activation across patients. By comparing young and old convalescent COVID-19 patients (mean ages = 31 and 66.8 years, respectively), we found that clonally expanded B cells in young patients were predominantly of the IgA isotype and their BCRs had incurred higher levels of somatic hypermutation than elderly patients. In conclusion, our scSeq analysis defines the adaptive immune repertoire and transcriptome in convalescent COVID-19 patients and shows important age-related differences implicated in immunity against SARS-CoV-2.
Immune Signature Linked to COVID-19 Severity: A SARS-Score for Personalized Medicine
Authors: Russick Jules , Foy Pierre-Emmanuel , Josseaume Nathalie , Meylan Maxime , Hamouda Nadine Ben , Kirilovsky Amos , Sissy Carine El , Tartour Eric , Smadja David M. , Karras Alexandre , Hulot Jean-Sébastien , Livrozet Marine , Fayol Antoine , Arlet Jean-Benoit , Diehl Jean-Luc , Dragon-Durey Marie-Agnès , Pagès Franck , Cremer Isabelle
Published: July 2021

SARS-CoV-2 infection leads to a highly variable clinical evolution, ranging from asymptomatic to severe disease with acute respiratory distress syndrome, requiring intensive care units (ICU) admission. The optimal management of hospitalized patients has become a worldwide concern and identification of immune biomarkers predictive of the clinical outcome for hospitalized patients remains a major challenge. Immunophenotyping and transcriptomic analysis of hospitalized COVID-19 patients at admission allow identifying the two categories of patients. Inflammation, high neutrophil activation, dysfunctional monocytic response and a strongly impaired adaptive immune response was observed in patients who will experience the more severe form of the disease. This observation was validated in an independent cohort of patients. Using in silico analysis on drug signature database, we identify differential therapeutics that specifically correspond to each group of patients. From this signature, we propose a score—the SARS-Score—composed of easily quantifiable biomarkers, to classify hospitalized patients upon arrival to adapt treatment according to their immune profile.
Anti-Microbiota Vaccines Modulate the Tick Microbiome in a Taxon-Specific Manner
Authors: Mateos-Hernández Lourdes , Obregón Dasiel , Wu-Chuang Alejandra , Maye Jennifer , Bornères Jeremie , Versillé Nicolas , de la Fuente José , Díaz-Sánchez Sandra , Bermúdez-Humarán Luis G. , Torres-Maravilla Edgar , Estrada-Peña Agustín , Hodžić Adnan , Šimo Ladislav , Cabezas-Cruz Alejandro
Published: July 2021

The lack of tools for the precise manipulation of the tick microbiome is currently a major limitation to achieve mechanistic insights into the tick microbiome. Anti-tick microbiota vaccines targeting keystone bacteria of the tick microbiota alter tick feeding, but their impact on the taxonomic and functional profiles of the tick microbiome has not been tested. In this study, we immunized a vertebrate host model (Mus musculus) with live bacteria vaccines targeting keystone (i.e., Escherichia-Shigella) or non-keystone (i.e., Leuconostoc) taxa of tick microbiota and tested the impact of bacterial-specific antibodies (Abs) on the structure and function of tick microbiota. We also investigated the effect of these anti-microbiota vaccines on mice gut microbiota composition. Our results showed that the tick microbiota of ticks fed on Escherichia coli-immunized mice had reduced Escherichia-Shigella abundance and lower species diversity compared to ticks fed on control mice immunized with a mock vaccine. Immunization against keystone bacteria restructured the hierarchy of nodes in co-occurrence networks and reduced the resistance of the bacterial network to taxa removal. High levels of E. coli-specific IgM and IgG were negatively correlated with the abundance of Escherichia-Shigella in tick microbiota. These effects were not observed when Leuconostoc was targeted with vaccination against Leuconostoc mesenteroides. Prediction of functional pathways in the tick microbiome using PICRUSt2 revealed that E. coli vaccination reduced the abundance of lysine degradation pathway in tick microbiome, a result validated by qPCR. In contrast, the gut microbiome of immunized mice showed no significant alterations in the diversity, composition and abundance of bacterial taxa. Our results demonstrated that anti-tick microbiota vaccines are a safe, specific and an easy-to-use tool for manipulation of vector microbiome. These results guide interventions for the control of tick infestations and pathogen infection/transmission.
Prostanoids and Resolution of Inflammation – Beyond the Lipid-Mediator Class Switch
Authors: Schmid Tobias , Brüne Bernhard
Published: July 2021

Bioactive lipid mediators play a major role in regulating inflammatory processes. Herein, early pro-inflammatory phases are characterized and regulated by prostanoids and leukotrienes, whereas specialized pro-resolving mediators (SPM), including lipoxins, resolvins, protectins, and maresins, dominate during the resolution phase. While pro-inflammatory properties of prostanoids have been studied extensively, their impact on later phases of the inflammatory process has been attributed mainly to their ability to initiate the lipid-mediator class switch towards SPM. Yet, there is accumulating evidence that prostanoids directly contribute to the resolution of inflammation and return to homeostasis. In this mini review, we summarize the current knowledge of the resolution-regulatory properties of prostanoids and discuss potential implications for anti-inflammatory, prostanoid-targeted therapeutic interventions.
Mobile Genetic Elements of Vibrio cholerae and the Evolution of Its Antimicrobial Resistance
Authors: De Rituparna
Published: July 2021

Vibrio cholerae (VC) is the causative agent of the severe dehydrating diarrheal disease cholera. The primary treatment for cholera is oral rehydration therapy (ORT). However, in case of moderate to severe dehydration, antibiotics are administered to reduce morbidity. Due to the emergence of multidrug resistant (MDR) strains of VC routinely used antibiotics fail to be effective in cholera patients. Antimicrobial resistance (AMR) is encoded in the genome of bacteria and is usually acquired from other organisms cohabiting in the environment or in the gut with which it interacts in the gut or environmental niche. The antimicrobial resistance genes (ARGs) are usually borne on mobile genetic elements (MGEs) like plasmids, transposons, integrons and SXT constin. Horizontal gene transfer (HGT) helps in the exchange of ARGs among bacteria leading to dissemination of AMR. In VC the acquisition and loss of AMR to many antibiotics have been found to be a dynamic process. This review describes the different AMR determinants and mechanisms of resistance that have been discovered in VC. These ARGs borne usually on MGEs have been recovered from isolates associated with past and present epidemics worldwide. These are responsible for resistance of VC to common antibiotics and are periodically lost and gained contributing to its genetic evolution. These resistance markers can be routinely used for AMR surveillance in VC. The review also presents a precise perspective on the importance of the gut microbiome in the emergence of MDR VC and concludes that the gut microbiome is a potential source of molecular markers and networks which can be manipulated for the interception of AMR in the future.
Far-Field Effects of Impulsive Noise on Coastal Bottlenose Dolphins
Authors: Fernandez-Betelu Oihane , Graham Isla M. , Brookes Kate L. , Cheney Barbara J. , Barton Tim R. , Thompson Paul M.
Published: July 2021

Increasing levels of anthropogenic underwater noise have caused concern over their potential impacts on marine life. Offshore renewable energy developments and seismic exploration can produce impulsive noise which is especially hazardous for marine mammals because it can induce auditory damage at shorter distances and behavioral disturbance at longer distances. However, far-field effects of impulsive noise remain poorly understood, causing a high level of uncertainty when predicting the impacts of offshore energy developments on marine mammal populations. Here we used a 10-year dataset on the occurrence of coastal bottlenose dolphins over the period 2009–2019 to investigate far-field effects of impulsive noise from offshore activities undertaken in three different years. Activities included a 2D seismic survey and the pile installation at two offshore wind farms, 20–75 km from coastal waters known to be frequented by dolphins. We collected passive acoustic data in key coastal areas and used a Before-After Control-Impact design to investigate variation in dolphin detections in areas exposed to different levels of impulsive noise from these offshore activities. We compared dolphin detections at two temporal scales, comparing years and days with and without impulsive noise. Passive acoustic data confirmed that dolphins continued to use the impact area throughout each offshore activity period, but also provided evidence of short-term behavioral responses in this area. Unexpectedly, and only at the smallest temporal scale, a consistent increase in dolphin detections was observed at the impact sites during activities generating impulsive noise. We suggest that this increase in dolphin detections could be explained by changes in vocalization behavior. Marine mammal protection policies focus on the near-field effects of impulsive noise; however, our results emphasize the importance of investigating the far-field effects of anthropogenic disturbances to better understand the impacts of human activities on marine mammal populations.
Lipidomics of Environmental Microbial Communities. II: Characterization Using Molecular Networking and Information Theory
Authors: Ding Su , Bale Nicole J. , Hopmans Ellen C. , Villanueva Laura , Arts Milou G. I. , Schouten Stefan , Sinninghe Damsté Jaap S.
Published: July 2021

Structurally diverse, specialized lipids are crucial components of microbial membranes and other organelles and play essential roles in ecological functioning. The detection of such lipids in the environment can reveal not only the occurrence of specific microbes but also the physicochemical conditions to which they are adapted to. Traditionally, liquid chromatography coupled with mass spectrometry allowed for the detection of lipids based on chromatographic separation and individual peak identification, resulting in a limited data acquisition and targeting of certain lipid groups. Here, we explored a comprehensive profiling of microbial lipids throughout the water column of a marine euxinic basin (Black Sea) using ultra high-pressure liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMS/MS). An information theory framework combined with molecular networking based on the similarity of the mass spectra of lipids enabled us to capture lipidomic diversity and specificity in the environment, identify novel lipids, differentiate microbial sources within a lipid group, and discover potential biomarkers for biogeochemical processes. The workflow presented here allows microbial ecologists and biogeochemists to process quickly and efficiently vast amounts of lipidome data to understand microbial lipids characteristics in ecosystems.
How Do Shipworms Eat Wood? Screening Shipworm Gill Symbiont Genomes for Lignin-Modifying Enzymes
Authors: Stravoravdis Stefanos , Shipway J. Reuben , Goodell Barry
Published: July 2021

Shipworms are ecologically and economically important mollusks that feed on woody plant material (lignocellulosic biomass) in marine environments. Digestion occurs in a specialized cecum, reported to be virtually sterile and lacking resident gut microbiota. Wood-degrading CAZymes are produced both endogenously and by gill endosymbiotic bacteria, with extracellular enzymes from the latter being transported to the gut. Previous research has predominantly focused on how these animals process the cellulose component of woody plant material, neglecting the breakdown of lignin – a tough, aromatic polymer which blocks access to the holocellulose components of wood. Enzymatic or non-enzymatic modification and depolymerization of lignin has been shown to be required in other wood-degrading biological systems as a precursor to cellulose deconstruction. We investigated the genomes of five shipworm gill bacterial symbionts obtained from the Joint Genome Institute Integrated Microbial Genomes and Microbiomes Expert Review for the production of lignin-modifying enzymes, or ligninases. The genomes were searched for putative ligninases using the Joint Genome Institute’s Function Profile tool and blastp analyses. The resulting proteins were then modeled using SWISS-MODEL. Although each bacterial genome possessed at least four predicted ligninases, the percent identities and protein models were of low quality and were unreliable. Prior research demonstrates limited endogenous ability of shipworms to modify lignin at the chemical/molecular level. Similarly, our results reveal that shipworm bacterial gill-symbiont enzymes are unlikely to play a role in lignin modification during lignocellulose digestion in the shipworm gut. This suggests that our understanding of how these keystone organisms digest and process lignocellulose is incomplete, and further research into non-enzymatic and/or other unknown mechanisms for lignin modification is required.
Nutrient-Limited Enrichments of Nitrifiers From Soil Yield Consortia of Nitrosocosmicus-Affiliated AOA and Nitrospira-Affiliated NOB
Authors: Rodriguez Jonathan , Chakrabarti Seemanti , Choi Eunkyung , Shehadeh Nisreen , Sierra-Martinez Samantha , Zhao Jun , Martens-Habbena Willm
Published: July 2021

The discovery of ammonia-oxidizing archaea (AOA) and complete ammonia-oxidizing (comammox) bacteria widespread in terrestrial ecosystems indicates an important role of these organisms in terrestrial nitrification. Recent evidence indicated a higher ammonia affinity of comammox bacteria than of terrestrial AOA and ammonia-oxidizing bacteria (AOB), suggesting that comammox bacteria could potentially represent the most low-nutrient adapted nitrifiers in terrestrial systems. We hypothesized that a nutrient-limited enrichment strategy could exploit the differences in cellular kinetic properties and yield enrichments dominated by high affinity and high yield comammox bacteria. Using soil with a mixed community of AOA, AOB, and comammox Nitrospira, we compared performance of nutrient-limited chemostat enrichment with or without batch culture pre-enrichment in two different growth media without inhibitors or antibiotics. Monitoring of microbial community composition via 16S rRNA and amoA gene sequencing showed that batch enrichments were dominated by AOB, accompanied by low numbers of AOA and comammox Nitrospira. In contrast, nutrient-limited enrichment directly from soil, and nutrient-limited sub-cultivation of batch enrichments consistently yielded high enrichments of Nitrosocosmicus-affiliated AOA associated with multiple canonical nitrite-oxidizing Nitrospira strains, whereas AOB numbers dropped below 0.1% and comammox Nitrospira were lost completely. Our results reveal competitiveness of Nitrosocosmicus sp. under nutrient limitation, and a likely more complex or demanding ecological niche of soil comammox Nitrospira than simulated in our nutrient-limited chemostat experiments.
The abaI/abaR Quorum Sensing System Effects on Pathogenicity in Acinetobacter baumannii
Authors: Sun Xiaoyu , Ni Zhaohui , Tang Jie , Ding Yue , Wang Xinlei , Li Fan
Published: July 2021

Acinetobacter baumannii is a Gram-negative pathogen that has emerged as one of the most troublesome pathogens for healthcare institutions globally. Bacterial quorum sensing (QS) is a process of cell-to-cell communication that relies on the production, secretion, and detection of autoinducer (AI) signals to share information about cell density and regulate gene expression accordingly. The molecular and genetic bases of A. baumannii virulence remains poorly understood. Therefore, the contribution of the abaI/abaR QS system to growth characteristics, morphology, biofilm formation, resistance, motility, and virulence of A. baumannii was studied in detail. RNA sequencing (RNA-seq) analysis indicated that genes involved in various aspects of energy production and conversion; valine, leucine, and isoleucine degradation; and lipid transport and metabolism are associated with bacterial pathogenicity. Our work provides a new insight into the abaI/abaR QS system effects on pathogenicity in A. baumannii. We propose that targeting the acyl homoserine lactone (AHL) synthase enzyme abaI could provide an effective strategy for attenuating virulence. On the contrary, interdicting the AI synthase receptor abaR elicits unpredictable consequences, which may lead to enhanced bacterial virulence.
Antimicrobial Properties of Food Nanopackaging: A New Focus on Foodborne Pathogens
Authors: Anvar Amir Ali , Ahari Hamed , Ataee Maryam
Published: July 2021

Food products contaminated by foodborne pathogens (bacteria, parasites, and viruses) cause foodborne diseases. Today, great efforts are being allocated to the development of novel and effective agents against food pathogenic microorganisms. These efforts even might have a possible future effect in coronavirus disease 2019 (COVID-19) pandemic. Nanotechnology introduces a novel food packaging technology that creates and uses nanomaterials with novel physiochemical and antimicrobial properties. It could utilize preservatives and antimicrobials to extend the food shelf life within the package. Utilizing the antimicrobial nanomaterials into food packaging compounds typically involves incorporation of antimicrobial inorganic nanoparticles such as metals [Silver (Ag), Copper (Cu), Gold (Au)], and metal oxides [Titanium dioxide (TiO2), Silicon oxide (SiO2), Zinc oxide (ZnO)]. Alternatively, intelligent food packaging has been explored for recognition of spoilage and pathogenic microorganisms. This review paper focused on antimicrobial aspects of nanopackaging and presented an overview of antibacterial properties of inorganic nanoparticles. This article also provides information on food safety during COVID-19 pandemic.
Developing Bioprospecting Strategies for Bioplastics Through the Large-Scale Mining of Microbial Genomes
Authors: Vuong Paton , Lim Daniel J. , Murphy Daniel V. , Wise Michael J. , Whiteley Andrew S. , Kaur Parwinder
Published: July 2021

The accumulation of petroleum-based plastic waste has become a major issue for the environment. A sustainable and biodegradable solution can be found in Polyhydroxyalkanoates (PHAs), a microbially produced biopolymer. An analysis of the global phylogenetic and ecological distribution of potential PHA producing bacteria and archaea was carried out by mining a global genome repository for PHA synthase (PhaC), a key enzyme involved in PHA biosynthesis. Bacteria from the phylum Actinobacteria were found to contain the PhaC Class II genotype which produces medium-chain length PHAs, a physiology until now only found within a few Pseudomonas species. Further, several PhaC genotypes were discovered within Thaumarchaeota, an archaeal phylum with poly-extremophiles and the ability to efficiently use CO2 as a carbon source, a significant ecological group which have thus far been little studied for PHA production. Bacterial and archaeal PhaC genotypes were also observed in high salinity and alkalinity conditions, as well as high-temperature geothermal ecosystems. These genome mining efforts uncovered previously unknown candidate taxa for biopolymer production, as well as microbes from environmental niches with properties that could potentially improve PHA production. This in silico study provides valuable insights into unique PHA producing candidates, supporting future bioprospecting efforts toward better targeted and relevant taxa to further enhance the diversity of exploitable PHA production systems.
Higher Total Cerebral Small Vessel Disease Burden Was Associated With Mild Cognitive Impairment and Overall Cognitive Dysfunction: A Propensity Score-Matched Case–Control Study
Authors: Li Xuanting , Yuan Junliang , Qin Wei , Yang Lei , Yang Shuna , Li Yue , Hu Wenli
Published: July 2021

Background and Objective

The combination of neuroimaging and cognition characteristics may provide complementary information for early identification of mild cognitive impairment (MCI). This study aimed to establish the clinical relevance between cerebral small vessel disease (CSVD) burden and MCI and further explored the cognitive characteristics linked to CSVD applying a propensity score matching (PSM) approach.

Methods

The study was designed as a case–control study. All the subjects underwent the standard clinical assessments, neuropsychological testing battery (including global cognition, memory, executive function, and speed and motor control domains), and brain magnetic resonance imaging (MRI). A 1:2 nearest-neighbor matching approach without replacement was employed with a caliper of 0.15 in the PSM approach.

Results

A total of 84 MCI patients and 186 cognitively normal controls were included in this study. After PSM, 74 MCI patients and 129 controls were successfully matched, and the covariate imbalance was well eliminated. Compared with controls, the MCI group had more severe CSVD burden. In the binary logistic regression analysis, CSVD was associated with MCI after adjusting for all confounders. The results of multivariate linear regression analyses showed that higher total MRI CSVD burden was related to the deficit of cognitive performance in global cognition and three important cognitive domains after adjusting for all confounders.

Conclusion

Cerebral small vessel disease was an independent risk factor of MCI. Moreover, higher total MRI CSVD burden was associated with the overall cognitive impairment among middle-aged and elderly Chinese adults.
The Expanding Role of Quantitative Pupillometry in the Evaluation and Management of Traumatic Brain Injury
Authors: Boulter Jason H. , Shields Margaret M. , Meister Melissa R. , Murtha Gregory , Curry Brian P. , Dengler Bradley A.
Published: July 2021

Traumatic brain injury is a rapidly increasing source of morbidity and mortality across the world. As such, the evaluation and management of traumatic brain injuries ranging from mild to severe are under active investigation. Over the last two decades, quantitative pupillometry has been increasingly found to be useful in both the immediate evaluation and ongoing management of traumatic brain injured patients. Given these findings and the portability and ease of use of modern pupillometers, further adoption and deployment of quantitative pupillometers into the preclinical and hospital settings of both resource rich and medically austere environments.
Multi-Dimensional Diffusion Tensor Imaging Biomarkers for Cognitive Decline From the Preclinical Stage: A Study of Post-stroke Small Vessel Disease
Authors: Du Jing , Zhu Hong , Yu Ling , Lu Peiwen , Qiu Yage , Zhou Yan , Cao Wenwei , Lu Dong , Zhao Wei , Yang Jie , Sun Junfeng , Xu Qun
Published: July 2021

Objectives: We aim to investigate whether multi-dimensional diffusion tensor imaging (DTI) measures can sensitively identify different cognitive status of cerebral small vessel disease (CSVD) and to explore the underlying pattern of white matter disruption in CSVD.

Methods: Two hundred and two participants were recruited, composed of 99 CSVD patients with mild cognitive impairment (VaMCI) and 60 with no cognitive impairment (NCI) and 43 healthy subjects as normal controls (NC). Full domain neuropsychological tests and diffusion-weighted imaging were performed on each subject. DTI metrics such as fractional anisotropy (FA), mean diffusivity (MD), the skeletonized mean diffusivity (PSMD), and structural brain network measures including network strength, global efficiency (EGlobal), and local efficiency (ELocal) were calculated. Region of interest (ROI) analysis of 42 white matter tracts was performed to examine the regional anatomical white matter disruption for each group.

Results: Significant differences of multiple cognitive test scores across all cognitive domains especially processing and executive function existed among the three groups. DTI measures (FA, MD, and PSMD) showed significant group difference with the cognitive status changing. FA and EGlobal showed significant correlation with processing speed, executive function, and memory. ROI analysis found that white matter integrity impairment occurred from the preclinical stage of vascular cognitive impairment (VCI) due to CSVD. These lesions in the NCI group mainly involved some longitudinal fibers such as right superior longitudinal fasciculus (SLF-R), right superior fronto-occipital fasciculus (SFO-R), and right uncinate fasciculus (UNC-R), which might be more vulnerable to the cerebrovascular aging and disease process.

Conclusions: DTI measures are sensitive neuroimaging markers in detecting the early cognitive impairment and able to differentiate the different cognitive status due to CSVD. Subtle changes of some vulnerable white matter tracts may be observed from the preclinical stage of VCI and have a local to general spreading pattern during the disease progression.
Diagnosis of Acute Central Dizziness With Simple Clinical Information Using Machine Learning
Authors: Kim Bum Joon , Jang Su-Kyeong , Kim Yong-Hwan , Lee Eun-Jae , Chang Jun Young , Kwon Sun U. , Kim Jong S. , Kang Dong-Wha
Published: July 2021

Background: Acute dizziness is a common symptom among patients visiting emergency medical centers. Extensive neurological examinations aimed at delineating the cause of dizziness often require experience and specialized training. We tried to diagnose central dizziness by machine learning using only basic clinical information.

Methods: Patients were enrolled who had visited an emergency medical center with acute dizziness and underwent diffusion-weighted imaging. The enrolled patients were dichotomized as either having central (with a corresponding central lesion) or non-central dizziness. We obtained patient demographics, risk factors, vital signs, and presentation (non-whirling type dizziness or vertigo). Various machine learning algorithms were used to predict central dizziness. The area under the receiver operating characteristic curve (AUROC) was measured to evaluate diagnostic accuracy. The SHapley Additive exPlanations (SHAP) value was used to explain the importance of each factor.

Results: Of the 4,481 visits, 414 (9.2%) were determined as central dizziness. Central dizziness patients were more often older and male and had more risk factors and higher systolic blood pressure. They also presented more frequently with non-whirling type dizziness (79 vs. 54.4%) than non-central dizziness. Catboost model showed the highest AUROC (0.738) with a 94.4% sensitivity and 31.9% specificity in the test set (n = 1,317). The SHAP value was highest for previous stroke presence (mean; 0.74), followed by male (0.33), presentation as non-whirling type dizziness (0.30), and age (0.25).

Conclusions: Machine learning is feasible for classifying central dizziness using demographics, risk factors, vital signs, and clinical dizziness presentation, which are obtainable at the triage.
Case Report: Dexmedetomidine for Intractable Clusters of Myoclonic Jerks and Paroxysmal Sympathetic Hyperactivity in Progressive Encephalomyelitis With Rigidity and Myoclonus
Authors: Fujino Yuzo , Shiga Kensuke , Hori Masatoshi , Tamura Aiko , Iizuka Takahiro
Published: July 2021

Introduction: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a severe form of stiff-person spectrum disorder characterized by painful spasms, myoclonic jerks, hyperekplexia, brainstem dysfunction, and dysautonomia, which is sometimes resistant to γ-amino-butyric acid (GABA)-ergic agents. The response to immunotherapy varies depending on identified autoantibodies. We report a dramatic response to dexmedetomidine in a patient with glycine receptor (GlyR) antibody-positive PERM who developed intractable clusters of myoclonic jerks and paroxysmal sympathetic hyperactivity (PSH) that was highly refractory to conventional symptomatic treatment with GABAergic drugs and immunotherapy.

Case Presentation: A 62-year-old Japanese man was transferred to our center for intermittent painful spasms that progressed in severity over the preceding 7 weeks. On admission, he had gaze-evoked nystagmus, and paroxysmal painful spasms/myoclonic jerks triggered by sound or touch. The myoclonic jerks rapidly worsened, along with the development of hyperekplexia, opisthotonus, and PSH, leading to prolonged apnea requiring mechanical ventilation. Brain and spinal cord magnetic resonance imaging was unremarkable. Cerebrospinal fluid (CSF) examination revealed mild pleocytosis and oligoclonal bands. Surface electromyography confirmed simultaneous agonist-antagonist continuous motor unit activity. Based on the clinico-electrophysiological features, PERM was suspected. He was initially treated with intravenous steroids, immunoglobulin, benzodiazepines, and propofol, but the symptoms persisted. On day 9, he received a continuous infusion of dexmedetomidine, which resulted in dramatic reduction in the frequency of clusters of myoclonic jerks and PSH. The effect of dexmedetomidine was confirmed by surface electromyography. The addition of plasma exchange resulted in further clinical improvement. GlyR antibodies were identified in the CSF but not the serum, leading to the diagnosis of GlyR antibody-positive PERM.

Conclusions: PERM is an immune-mediated disorder, but dexmedetomidine, a highly selective α2-adrenergic agonist, may alleviate paroxysmal symptoms by decreasing noradrenergic neuronal activity, resulting in attenuation of antibody-mediated disinhibited increased motor and sympathetic activity. Dexmedetomidine may be useful as an adjunctive symptomatic therapy in PERM and related disorders.
Germ Cell Drivers: Transmission of Preconception Stress Across Generations
Authors: Duffy Korrina A. , Bale Tracy L. , Epperson C. Neill
Published: July 2021

Exposure to stress can accelerate maturation and hasten reproduction. Although potentially adaptive, the trade-off is higher risk for morbidity and mortality. In humans, the intergenerational effects of stress have been demonstrated, but the precise mechanisms are unknown. Strikingly, even if parental stress occurs prior to conception, as adults, their offspring show worse mental and physical health. Emerging evidence primarily from preclinical models suggests that epigenetic programming may encode preconception stress exposures in germ cells, potentially impacting the phenotype of the offspring. In this narrative review, we evaluate the strength of the evidence for this mechanism across animals and humans in both males and females. The strongest evidence comes from studies of male mice, in which paternal preconception stress is associated with a host of phenotypic changes in the offspring and stress-induced changes in the small non-coding RNA content in sperm have been implicated. Two recent studies in men provide evidence that some small non-coding RNAs in sperm are responsive to past and current stress, including some of the same ones identified in mice. Although preliminary evidence suggests that findings from mice may map onto men, the next steps will be (1) considering whether stress type, severity, duration, and developmental timing affect germ cell epigenetic markers, (2) determining whether germ cell epigenetic markers contribute to disease risk in the offspring of stress-exposed parents, and (3) overcoming methodological challenges in order to extend this research to females.
Analysis-rcs-data: Open-Source Toolbox for the Ingestion, Time-Alignment, and Visualization of Sense and Stimulation Data From the Medtronic Summit RC+S System
Authors: Sellers Kristin K. , Gilron Ro’ee , Anso Juan , Louie Kenneth H. , Shirvalkar Prasad R. , Chang Edward F. , Little Simon J. , Starr Philip A.
Published: July 2021

Closed-loop neurostimulation is a promising therapy being tested and clinically implemented in a growing number of neurological and psychiatric indications. This therapy is enabled by chronically implanted, bidirectional devices including the Medtronic Summit RC+S system. In order to successfully optimize therapy for patients implanted with these devices, analyses must be conducted offline on the recorded neural data, in order to inform optimal sense and stimulation parameters. The file format, volume, and complexity of raw data from these devices necessitate conversion, parsing, and time reconstruction ahead of time-frequency analyses and modeling common to standard neuroscientific analyses. Here, we provide an open-source toolbox written in Matlab which takes raw files from the Summit RC+S and transforms these data into a standardized format amenable to conventional analyses. Furthermore, we provide a plotting tool which can aid in the visualization of multiple data streams and sense, stimulation, and therapy settings. Finally, we describe an analysis module which replicates RC+S on-board power computations, a functionality which can accelerate biomarker discovery. This toolbox aims to accelerate the research and clinical advances made possible by longitudinal neural recordings and adaptive neurostimulation in people with neurological and psychiatric illnesses.
EOGNET: A Novel Deep Learning Model for Sleep Stage Classification Based on Single-Channel EOG Signal
Authors: Fan Jiahao , Sun Chenglu , Long Meng , Chen Chen , Chen Wei
Published: July 2021

In recent years, automatic sleep staging methods have achieved competitive performance using electroencephalography (EEG) signals. However, the acquisition of EEG signals is cumbersome and inconvenient. Therefore, we propose a novel sleep staging approach using electrooculogram (EOG) signals, which are more convenient to acquire than the EEG. A two-scale convolutional neural network first extracts epoch-wise temporary-equivalent features from raw EOG signals. A recurrent neural network then captures the long-term sequential information. The proposed method was validated on 101 full-night sleep data from two open-access databases, the montreal archive of sleep studies and Sleep-EDF, achieving an overall accuracy of 81.2 and 76.3%, respectively. The results are comparable to those models trained with EEG signals. In addition, comparisons with six state-of-the-art methods further demonstrate the effectiveness of the proposed approach. Overall, this study provides a new avenue for sleep monitoring.
Infant and Child MRI: A Review of Scanning Procedures
Authors: Copeland Anni , Silver Eero , Korja Riikka , Lehtola Satu J. , Merisaari Harri , Saukko Ekaterina , Sinisalo Susanne , Saunavaara Jani , Lähdesmäki Tuire , Parkkola Riitta , Nolvi Saara , Karlsson Linnea , Karlsson Hasse , Tuulari Jetro J.
Published: July 2021

Magnetic resonance imaging (MRI) is a safe method to examine human brain. However, a typical MR scan is very sensitive to motion, and it requires the subject to lie still during the acquisition, which is a major challenge for pediatric scans. Consequently, in a clinical setting, sedation or general anesthesia is often used. In the research setting including healthy subjects anesthetics are not recommended for ethical reasons and potential longer-term harm. Here we review the methods used to prepare a child for an MRI scan, but also on the techniques and tools used during the scanning to enable a successful scan. Additionally, we critically evaluate how studies have reported the scanning procedure and success of scanning. We searched articles based on special subject headings from PubMed and identified 86 studies using brain MRI in healthy subjects between 0 and 6 years of age. Scan preparations expectedly depended on subject’s age; infants and young children were scanned asleep after feeding and swaddling and older children were scanned awake. Comparing the efficiency of different procedures was difficult because of the heterogeneous reporting of the used methods and the success rates. Based on this review, we recommend more detailed reporting of scanning procedure to help find out which are the factors affecting the success of scanning. In the long term, this could help the research field to get high quality data, but also the clinical field to reduce the use of anesthetics. Finally, we introduce the protocol used in scanning 2 to 5-week-old infants in the FinnBrain Birth Cohort Study, and tips for calming neonates during the scans.
Age Influences Loss Aversion Through Effects on Posterior Cingulate Cortical Thickness
Authors: Guttman Zoe R. , Ghahremani Dara G. , Pochon Jean-Baptiste , Dean Andy C. , London Edythe D.
Published: July 2021

Decision-making strategies shift during normal aging and can profoundly affect wellbeing. Although overweighing losses compared to gains, termed “loss aversion,” plays an important role in choice selection, the age trajectory of this effect and how it may be influenced by associated changes in brain structure remain unclear. We therefore investigated the relationship between age and loss aversion, and tested for its mediation by cortical thinning in brain regions that are susceptible to age-related declines and are implicated in loss aversion — the insular, orbitofrontal, and anterior and posterior cingulate cortices. Healthy participants (n= 106, 17–54 years) performed the Loss Aversion Task. A subgroup (n= 78) provided structural magnetic resonance imaging scans. Loss aversion followed a curvilinear trajectory, declining in young adulthood and increasing in middle-age, and thinning of the posterior cingulate cortex mediated this trajectory. The findings suggest that beyond a threshold in middle adulthood, atrophy of the posterior cingulate cortex influences loss aversion.
Dairy-Derived and Egg White Proteins in Enhancing Immune System Against COVID-19
Authors: Batiha Gaber El-Saber , Alqarni Mohammed , Awad Dina A. B. , Algammal Abdelazeem M. , Nyamota Richard , Wahed Mir I. I. , Shah Muhammad Ajmal , Amin Mohammad N. , Adetuyi Babatunde O. , Hetta Helal F. , Cruz-Martins Natália , Koirala Niranjan , Ghosh Arabinda , Echeverría Javier , Pagnossa Jorge Pamplona , Sabatier Jean-Marc
Published: July 2021

Coronavirus disease (COVID-19) is a global health challenge, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) triggers a plethora of respiratory disturbances and even multiple organs failure that can be fatal. Nutritional intervention is one of the key components toward to a proper management of COVID-19 patients, especially in those requiring medication, and should thus be considered the first-line treatment. Immuno-modulation and -stimulation are currently being explored in COVID-19 management and are gaining interest by food and pharmaceutical industries. Various dietary combinations, bioactive components, nutrients and fortified foods have been reported to modulate inflammation during disease progression. Dietary combinations of dairy-derived products and eggs are gaining an increasing attention given the huge immunomodulatory and anti-inflammatory properties attributed to some of their chemical constituents. Eggs are complex dietary components containing many essential nutrients and bioactive compounds as well as a high-quality proteins. Similarly, yogurts can replenish beneficial bacteria and contains macronutrients capable of stimulating immunity by enhancing cell immunity, reducing oxidative stress, neutralizing inflammation and regulating the intestinal barriers and gut microbiome. Thus, this review highlights the impact of nutritional intervention on COVID-19 management, focusing on the immunomodulatory and inflammatory effects of immune-enhancing nutrients.
A Clinical Perspective of Low Carbohydrate Ketogenic Diets: A Narrative Review
Authors: Sukkar Samir Giuseppe , Muscaritoli Maurizio
Published: July 2021

Low carbohydrates diets (LCDs), which provide 20–120 g of carbohydrates per day, have long been used as therapeutic options in the treatment of severe obesity, type 2 diabetes mellitus and other morbid conditions, with good results in terms of weight loss and control of the main metabolic parameters, at least in the short and medium term. According to the caloric content and the macronutrient composition, we can classify LCDs in hypocaloric, normoproteic diets [such as the Very Low-Calorie Ketogenic Diet (VLCKD) or the protein-sparing modified fasting (PSMF)], hypocaloric, hyperproteic and hyperlipidic diets (e.g., Atkins, Paleo diets…) and normocaloric, normo-/hyperproteic diets (eucaloric KD), the latter mainly used in patients with brain tumors (gliomas) and refractory epilepsy. In addition to LCD diets, another interesting dietary approach which gained attention in the last few decades is fasting and its beneficial effects in terms of modulation of metabolic pathways, cellular processes and hormonal secretions. Due to the impossibility of using fasting regimens for long periods of time, several alternative strategies have been proposed that can mimic the effects, including calorie restriction, intermittent or alternating fasting, and the so-called fasting mimicking diets (FMDs). Recent preclinical studies have shown positive effects of FMDs in various experimental models of tumors, diabetes, Alzheimer Disease, and other morbid conditions, but to date, the scientific evidence in humans is limited to some opens studies and case reports. The purpose of our narrative review is to offer an overview of the characteristics of the main dietary regimens applied in the treatment of different clinical conditions as well as of the scientific evidence that justifies their use, focusing on low and zero-carb diets and on the different types of fasting.