bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptional Profiling of Resistant and Susceptible Cultivars of Grapevine (Vitis L.) Reveals Hypersensitive Responses to Plasmopara viticola
Authors: Gong Peijie , Kang Jun , Sadeghnezhad Ehsan , Bao Ruoxuan , Ge Mengqing , Zhuge Yaxian , Shangguan Lingfei , Fang Jinggui
Published: April 2022

Grapevine downy mildew is the most serious disease of grapevine cultivars that affects the rate of resistance/susceptibility to Plasmopara viticola. In this study, we used the susceptible cultivar “Zitian Seedless” and the resistant cultivar “Kober 5BB” as materials to determine the transcriptome differences and phenotypes of the leaves after inoculation with downy mildew. The differences in microstructures and molecular levels were compared and analyzed. Fluorescence staining and microscopic observations confirmed that hypersensitive cell death occurred around the stomata in “Kober 5BB” infected by downy mildew zoospores. Meanwhile, transcriptomic profiling indicated that there were 11,713 and 6,997 gene expression differences between the resistant and susceptible cultivars at 72 h after inoculation when compared to control (0 h), respectively. The differentially expressed genes of the two cultivars are significantly enriched in different pathways, including response to plant-pathogen interaction, mitogen-activated protein kinase (MAPK) signaling pathway, plant hormone signal transduction, phenylpropanoid, and flavonoid biosynthesis. Furthermore, the results of functional enrichment analysis showed that H2O2 metabolism, cell death, reactive oxygen response, and carbohydrate metabolism are also involved in the defense response of “Kober 5BB,” wherein a total of 322 key genes have been identified. The protein interaction network showed that metacaspases (MCAs), vacuolar processing enzymes (VPEs), and Papain-like cysteine proteases (PLCPs) play an important role in the execution of hypersensitive responses (HR). In conclusion, we demonstrated that HR cell death is the key strategy in the process of grape defense against downy mildew, which may be mediated or activated by Caspase-like proteases.
Differences in the Plastispheres of Biodegradable and Non-biodegradable Plastics: A Mini Review
Authors: Peng Chu , Wang Jiao , Liu Xianhua , Wang Lei
Published: April 2022

There has been a steady rise in the production and disposal of biodegradable plastics. Unlike the microorganisms present in the biofilms on non-biodegradable plastic surfaces (the “plastisphere”), the plastisphere of biodegradable plastic has not been well-characterized. As the polymer structure of biodegradable plastic has a higher microbial affinity than that of non-biodegradable plastic, their plastispheres are assumed to be different. This review summarizes the reported differences in microbial communities on the surface of biodegradable and non-biodegradable plastics, discusses the driving forces behind these differences, and discusses the potential environmental risks. Overall, the plastisphere biomass on the surface of non-biodegradable plastic was observed to be lower than that of biodegradable plastic. The community structure of microbes in both plastispheres was diverse, mainly due to the properties of the plastic surface, such as surface charge, hydrophilicity/hydrophobicity, roughness, and bioavailability of polymer components for microbes. Further research should focus on developing biodegradable plastic that degrade faster in the environment, revealing the mechanism of enrichment of ARGs and potential pathogens on plastics, and understanding the potential influence of plastispheres on the evolution and selection of plastic-degrading microbial potential.
Isolation and Characterization of Two Lytic Phages Efficient Against Phytopathogenic Bacteria From Pseudomonas and Xanthomonas Genera
Authors: Korniienko Nataliia , Kharina Alla , Zrelovs Nikita , Jindřichová Barbora , Moravec Tomaš , Budzanivska Iryna , Burketová Lenka , Kalachova Tetiana
Published: April 2022

Pseudomonas syringae is a bacterial pathogen that causes yield losses in various economically important plant species. At the same time, P. syringae pv. tomato (Pst) is one of the best-studied bacterial phytopathogens and a popular model organism. In this study, we report on the isolation of two phages from the market-bought pepper fruit showing symptoms of bacterial speck. These Pseudomonas phages were named Eir4 and Eisa9 and characterized using traditional microbiological methods and whole-genome sequencing followed by various bioinformatics approaches. Both of the isolated phages were capable only of the lytic life cycle and were efficient against several pathovars from Pseudomonas and Xanthomonas genera. With the combination of transmission electron microscopy (TEM) virion morphology inspection and comparative genomics analyses, both of the phages were classified as members of the Autographiviridae family with different degrees of novelty within the known phage diversity. Eir4, but not Eisa9, phage application significantly decreased the propagation of Pst in the leaf tissues of Arabidopsis thaliana plants. The biological properties of Eir4 phage allow us to propose it as a potential biocontrol agent for use in the prevention of Pst-associated bacterioses and also as a model organism for the future research of mechanisms of phage–host interactions in different plant systems.
Links Among Crop Diversification, Microbial Diversity, and Soil Organic Carbon: Mini Review and Case Studies
Authors: Wooliver Rachel , Kivlin Stephanie N. , Jagadamma Sindhu
Published: April 2022

Interactions between species above- and belowground are among the top factors that govern ecosystem functioning including soil organic carbon (SOC) storage. In agroecosystems, understanding how crop diversification affects soil biodiversity and SOC storage at the local scale remains a key challenge for addressing soil degradation and biodiversity loss that plague these systems. Yet, outcomes of crop diversification for soil microbial diversity and SOC storage, which are key indicators of soil health, are not always positive but rather they are highly idiosyncratic to agroecosystems. Using five case studies, we highlight the importance of selecting ideal crop functional types (as opposed to focusing on plant diversity) when considering diversification options for maximizing SOC accumulation. Some crop functional types and crop diversification approaches are better suited for enhancing SOC at particular sites, though SOC responses to crop diversification can vary annually and with duration of crop cover. We also highlight how SOC responses to crop diversification are more easily interpretable through changes in microbial community composition (as opposed to microbial diversity). We then develop suggestions for future crop diversification experiment standardization including (1) optimizing sampling effort and sequencing depth for soil microbial communities and (2) understanding the mechanisms guiding responses of SOC functional pools with varying stability to crop diversification. We expect that these suggestions will move knowledge forward about biodiversity and ecosystem functioning in agroecosystems, and ultimately be of use to producers for optimizing soil health in their croplands.
Bacteriophage Cocktail and Microcin-Producing Probiotic Escherichia coli Protect Mice Against Gut Colonization With Multidrug-Resistant Escherichia coli Sequence Type 131
Authors: Porter Stephen B. , Johnston Brian D. , Kisiela Dagmara , Clabots Connie , Sokurenko Evgeni V. , Johnson James R.
Published: April 2022

Non-antibiotic measures are needed to reduce the rate of infections due to multidrug-resistant organisms (MDROs), including by eliminating the commensal reservoir that underlies such strains’ dissemination and leads to recurrent infections. Here, we tested a cocktail of pre-selected bacteriophages and an engineered microcin C7-producing probiotic Escherichia coli Nissle-1917 strain for their ability to reduce gut colonization by an E. coli strain from sequence type 131 (ST131)-H30R, which is the major clonal group of MDROs among extraintestinal clinical E. coli isolates. Although the bacteriophage cocktail was highly effective against ST131-H30R strains both in vitro and in a murine model of subcutaneous sepsis, it was only weakly and transiently effective against gut colonization by the target ST131-H30R strain (0.5 log10 decrease on d + 1: p < 0.001; no significant effect on d + 4 and beyond). The probiotic strain, while also highly active against ST131-H30R in vitro, was ineffective against ST131-H30R gut colonization despite its abundant presence in feces. Nonetheless, despite failing as decolonizing agents when administered separately, when co-administered the bacteriophage cocktail and probiotic strain exhibited striking synergy against ST131-H30R gut colonization. This combinatory effect was most pronounced on d + 1 (3.3 log10 target strain decrease: p < 0.001), and persisted until d + 7 (0.5 log10 decrease; p < 0.02.). Although by d + 10 the ST131-H30R load was fully restored, these findings provide proof of concept for combined bacteriophage-plus-probiotic administration to reduce or, possibly, to prevent gut colonization with MDROs in high-risk individuals.
The Value of H2BC12 for Predicting Poor Survival Outcomes in Patients With WHO Grade II and III Gliomas
Authors: Zhou Jie , Xing Zhaoquan , Xiao Yilei , Li Mengyou , Li Xin , Wang Ding , Dong Zhaogang
Published: April 2022

Purpose: Glioma is a common primary malignant brain tumor. Grade II (GII) gliomas are prone to develop into anaplastic grade III (GIII) gliomas, which indicate a higher malignancy and poorer survival outcome. This study aimed to satisfy the increasing demand for novel sensitive biomarkers and potential therapeutic targets in the treatment of GII and GIII gliomas.

Methods: A TCGA dataset was used to investigate the expression of H2BC12 mRNA in GII and GIII gliomas and its relation to clinical pathologic characteristics. Glioma tissues were collected to verify results from the TCGA dataset, and H2BC12 mRNA was detected by RT-qPCR. ROC analysis was employed to evaluate the classification power for GII and GIII. The significance of H2BC12 mRNA GII and GIII gliomas was also investigated. In addition, H2BC12 expression-related pathways were enriched by gene set enrichment analysis (GSEA). DNA methylation level and mutation of H2BC12 were analyzed by the UALCAN and CBioPortal databases, respectively.

Results: Based on the sample data from multiple databases and RT-qPCR, higher expression of H2BC12 mRNA was found in GII and GIII glioma tissue compared to normal tissue, which was consistent with a trend with our clinical specimen. H2BC12 mRNA had a better power in distinguishing between GII and GIII and yielded an AUC of 0.706 with a sensitivity of 76.9% and specificity of 81.8%. Meanwhile, high H2BC12 levels were associated with IDH status, 1p/19q codeletion, primary therapy outcome, and the histological type of gliomas. Moreover, the overall survival (OS), disease-specific survival (DSS), and progress-free interval (PFI) of GII glioma patients with higher levels of H2BC12 were shorter than those of patients with lower levels as well as GIII patients. In the multivariate analysis, a high H2BC12 level was an independent predictor for poor survival outcomes of gliomas. The Wnt or PI3K-AKT signaling pathways, DNA repair, cellular senescence, and DNA double-strand break repair were differentially activated in phenotypes that were positively associated with H2BC12. H2BC12 DNA methylation was high in TP53 nonmutant patients, and no H2BC12 mutation was observed in gliomas patients.

Conclusion: H2BC12 is a promising biomarker for the diagnosis and prognosis of patients with WHO grade II and III gliomas.
Roles of Negatively Charged Histone Lysine Acylations in Regulating Nucleosome Structure and Dynamics
Authors: Jing Yihang , Li Xin , Liu Zheng , Li Xiang David
Published: April 2022

The nucleosome, the basic repeating unit of chromatin, is a dynamic structure that consists of DNA and histones. Insights derived from biochemical and biophysical approaches have revealed that histones posttranslational modifications (PTMs) are key regulators of nucleosome structure and dynamics. Mounting evidence suggests that the newly identified negatively charged histone lysine acylations play significant roles in altering nucleosome and chromatin dynamics, subsequently affecting downstream DNA-templated processes including gene transcription and DNA damage repair. Here, we present an overview of the dynamic changes of nucleosome and chromatin structures in response to negatively charged histone lysine acylations, including lysine malonylation, lysine succinylation, and lysine glutarylation.
The Key Factors Predicting Dementia in Individuals With Alzheimer’s Disease-Type Pathology
Authors: McCorkindale Andrew N. , Patrick Ellis , Duce James A. , Guennewig Boris , Sutherland Greg T.
Published: April 2022

Dementia affects millions of individuals worldwide, yet there are no effective treatments. Alzheimer’s disease, the most common form of dementia, is characterized by amyloid and tau pathology with amyloid accumulation thought to precipitate tau pathology, neurodegeneration, and dementia. The Religious Orders Study and Memory and Aging Project (ROSMAP) cohort is a unique resource with quantitative pathology from multiple brain regions, RNA sequencing, and longitudinal cognitive data. Our previous work applying machine learning to the RNA sequencing data identified lactoferrin (LTF) as the gene most predictive of amyloid accumulation with a potential amyloidogenic mechanism identified in vitro and with cell-culture models. In the present study, we examined which pathologies and genes were related to cognitive status (dementia, mild impairment, and no cognitive impairment) and rate of cognitive decline. Tau load in the anterior cingulate and ADAMTS2, encoding a metallopeptidase, were the respective regional pathology and gene most associated with cognitive decline, while PRTN3, encoding a serine protease, was the key protective feature. ADAMTS2, but not PRTN3, was related to amyloid and tau load in the previous study while LTF was not related to cognitive decline here. These findings confirm a general relationship between tau pathology and dementia, show the specific importance of tau pathology in the anterior cingulate cortex and identify ADAMTS2 as a potential target for slowing cognitive decline.
Statistical Parametric Mapping in Amyloid Positron Emission Tomography
Authors: Smith Natasha M. , Ford Jeremy N. , Haghdel Arsalan , Glodzik Lidia , Li Yi , D’Angelo Debra , RoyChoudhury Arindam , Wang Xiuyuan , Blennow Kaj , de Leon Mony J. , Ivanidze Jana
Published: April 2022

Alzheimer’s disease (AD), the most common cause of dementia, has limited treatment options. Emerging disease modifying therapies are targeted at clearing amyloid-β (Aβ) aggregates and slowing the rate of amyloid deposition. However, amyloid burden is not routinely evaluated quantitatively for purposes of disease progression and treatment response assessment. Statistical Parametric Mapping (SPM) is a technique comparing single-subject Positron Emission Tomography (PET) to a healthy cohort that may improve quantification of amyloid burden and diagnostic performance. While primarily used in 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-PET, SPM’s utility in amyloid PET for AD diagnosis is less established and uncertainty remains regarding optimal normal database construction. Using commercially available SPM software, we created a database of 34 non-APOE ε4 carriers with normal cognitive testing (MMSE > 25) and negative cerebrospinal fluid (CSF) AD biomarkers. We compared this database to 115 cognitively normal subjects with variable AD risk factors. We hypothesized that SPM based on our database would identify more positive scans in the test cohort than the qualitatively rated [11C]-PiB PET (QR-PiB), that SPM-based interpretation would correlate better with CSF Aβ42 levels than QR-PiB, and that regional z-scores of specific brain regions known to be involved early in AD would be predictive of CSF Aβ42 levels. Fisher’s exact test and the kappa coefficient assessed the agreement between SPM, QR-PiB PET, and CSF biomarkers. Logistic regression determined if the regional z-scores predicted CSF Aβ42 levels. An optimal z-score cutoff was calculated using Youden’s index. We found SPM identified more positive scans than QR-PiB PET (19.1 vs. 9.6%) and that SPM correlated more closely with CSF Aβ42 levels than QR-PiB PET (kappa 0.13 vs. 0.06) indicating that SPM may have higher sensitivity than standard QR-PiB PET images. Regional analysis demonstrated the z-scores of the precuneus, anterior cingulate and posterior cingulate were predictive of CSF Aβ42 levels [OR (95% CI) 2.4 (1.1, 5.1) p = 0.024; 1.8 (1.1, 2.8) p = 0.020; 1.6 (1.1, 2.5) p = 0.026]. This study demonstrates the utility of using SPM with a “true normal” database and suggests that SPM enhances diagnostic performance in AD in the clinical setting through its quantitative approach, which will be increasingly important with future disease-modifying therapies.
Integrating Lipidomics and Transcriptomics Reveals the Crosstalk Between Oxidative Stress and Neuroinflammation in Central Nervous System Demyelination
Authors: Zhao Zhi-jie , Zheng Rui-zhe , Wang Xiao-jing , Li Tong-qi , Dong Xiao-hua , Zhao Chang-yi , Li Xin-yuan
Published: April 2022

Multiple sclerosis (MS) is an incurable and progressive neurodegenerative disease that affects more than 2.5 million people worldwide and brings tremendous economic pressures to society. However, the pathophysiology of MS is still not fully elucidated, and there is no effective treatment. Demyelination is thought to be the primary pathophysiological alteration in MS, and our previous study found abnormal lipid metabolism in the demyelinated corpus callosum. Growing evidence indicates that central nervous system (CNS) demyelinating diseases never result from one independent factor, and the simultaneous participation of abnormal lipid metabolism, oxidative stress, and neuroinflammation could potentiate each other in the pathogenesis of MS. Therefore, a single omics analysis cannot provide a full description of any neurodegenerative disease. It has been demonstrated that oxidative stress and neuroinflammation are two reciprocal causative reasons for the progression of MS disease. However, the potential crosstalk between oxidative stress and neuroinflammation remains elusive so far. With an integrated analysis of targeted lipidomics and transcriptomics, our research presents the potential interaction between abnormalities of lipid metabolism, mitochondrial dysfunction, oxidative stress, and neuroinflammation in CNS demyelinating diseases. The findings of this paper may be used to identify possible targets for the therapy of CNS demyelinating diseases.
The Use of Real-Time Quaking-Induced Conversion for the Diagnosis of Human Prion Diseases
Authors: Poleggi Anna , Baiardi Simone , Ladogana Anna , Parchi Piero
Published: April 2022

Prion diseases are rapidly progressive, invariably fatal, transmissible neurodegenerative disorders associated with the accumulation of the amyloidogenic form of the prion protein in the central nervous system (CNS). In humans, prion diseases are highly heterogeneous both clinically and neuropathologically. Prion diseases are challenging to diagnose as many other neurologic disorders share the same symptoms, especially at clinical onset. Definitive diagnosis requires brain autopsy to identify the accumulation of the pathological prion protein, which is the only specific disease biomarker. Although brain post-mortem investigation remains the gold standard for diagnosis, antemortem clinical, instrumental, and laboratory tests showing variable sensitivities and specificity, being surrogate disease biomarkers, have been progressively introduced in clinical practice to reach a diagnosis. More recently, the ultrasensitive Real-Time Quaking-Induced Conversion (RT-QuIC) assay, exploiting, for the first time, the detection of misfolded prion protein through an amplification strategy, has highly improved the “in-vitam” diagnostic process, reaching in cerebrospinal fluid (CSF) and olfactory mucosa (OM) around 96% sensitivity and close to 100% specificity. RT-QuIC also improved the detection of the pathologic prion protein in several peripheral tissues, possibly even before the clinical onset of the disease. The latter aspect is of great interest for the early and even preclinical diagnosis in subjects at genetic risk of developing the disease, who will likely be the main target population in future clinical trials. This review presents an overview of the current knowledge and future perspectives on using RT-QuIC to diagnose human prion diseases.
Methyltransferase-Like 3 Rescues the Amyloid-beta protein-Induced Reduction of Activity-Regulated Cytoskeleton Associated Protein Expression via YTHDF1-Dependent N6-Methyladenosine Modification
Authors: Xu Chenhaoyi , Huang Huanghuang , Zhang Min , Zhang Pei , Li Zezhi , Liu Xueyuan , Fang Min
Published: April 2022

Activity-regulated cytoskeleton-associated protein (ARC) is activated by the induction of long-term potentiation and plays an important role in the synaptic plasticity of memory consolidation. Previous studies have shown that abnormal expression of ARC in the brains of patients with Alzheimer’s Disease (AD) leads to the disturbance of synaptic plasticity. ARC expression is mainly regulated by transcriptional and post-translational modification. However, it is unclear whether N6-methyladenosine (m6A) engages in the epigenetic modification of ARC. The AlzData database was used to analyze the brain of AD patients, and Aβ-induced cell models were used. We revealed that ARC expression was reduced in AD patients and Aβ-induced cell models. There were five m6A modification sites of ARC mRNA that were predicted by the SRAMP database, and ARC mRNA was confirmed as the target gene of methyltransferase-like 3 (METTL3) by MeRIP. Amyloid-beta protein (Aβ) repressed the m6A modification. Knockdown of METTL3 decreased ARC mRNA m6A modification and reduced ARC protein expression, while overexpression of METTL3 rescued ARC expression after Aβ treatment. Knockdown of YTH domain family, member 1 (YTHDF1) decreased ARC protein expression, while the overexpression of YTHDF1 could not rescue the loss of ARC protein expression after 3-deazaadenosine treatment or knockdown of METTL3. Our findings identify that METTL3 rescues the Aβ-induced reduction of ARC expression via YTHDF1-Dependent m6A modification, which suggests an important mechanism of epigenetic alteration in AD.
The Intriguing Contribution of Hippocampal Long-Term Depression to Spatial Learning and Long-Term Memory
Authors: Stacho Martin , Manahan-Vaughan Denise
Published: April 2022

Long-term potentiation (LTP) and long-term depression (LTD) comprise the principal cellular mechanisms that fulfill established criteria for the physiological correlates of learning and memory. Traditionally LTP, that increases synaptic weights, has been ascribed a prominent role in learning and memory whereas LTD, that decreases them, has often been relegated to the category of “counterpart to LTP” that serves to prevent saturation of synapses. In contradiction of these assumptions, studies over the last several years have provided functional evidence for distinct roles of LTD in specific aspects of hippocampus-dependent associative learning and information encoding. Furthermore, evidence of the experience-dependent “pruning” of excitatory synapses, the majority of which are located on dendritic spines, by means of LTD has been provided. In addition, reports exist of the temporal and physical restriction of LTP in dendritic compartments by means of LTD. Here, we discuss the role of LTD and LTP in experience-dependent information encoding based on empirical evidence derived from conjoint behavioral and electrophysiological studies conducted in behaving rodents. We pinpoint the close interrelation between structural modifications of dendritic spines and the occurrence of LTP and LTD. We report on findings that support that whereas LTP serves to acquire the general scheme of a spatial representation, LTD enables retention of content details. We argue that LTD contributes to learning by engaging in a functional interplay with LTP, rather than serving as its simple counterpart, or negator. We propose that similar spatial experiences that share elements of neuronal representations can be modified by means of LTD to enable pattern separation. Therewith, LTD plays a crucial role in the disambiguation of similar spatial representations and the prevention of generalization.
Error-Related Negativity-Based Robot-Assisted Stroke Rehabilitation System: Design and Proof-of-Concept
Authors: Kumar Akshay , Gao Lin , Li Jiaming , Ma Jiaxin , Fu Jianming , Gu Xudong , Mahmoud Seedahmed S. , Fang Qiang
Published: April 2022

Conventional rehabilitation systems typically execute a fixed set of programs that most motor-impaired stroke patients undergo. In these systems, the brain, which is embodied in the body, is often left out. Including the brains of stroke patients in the control loop of a rehabilitation system can be worthwhile as the system can be tailored to each participant and, thus, be more effective. Here, we propose a novel brain-computer interface (BCI)-based robot-assisted stroke rehabilitation system (RASRS), which takes inputs from the patient's intrinsic feedback mechanism to adapt the assistance level of the RASRS. The proposed system will utilize the patients' consciousness about their performance decoded through their error-related negativity signals. As a proof-of-concept, we experimented on 12 healthy people in which we recorded their electroencephalogram (EEG) signals while performing a standard rehabilitation exercise. We set the performance requirements beforehand and observed participants' neural responses when they failed/met the set requirements and found a statistically significant (p < 0.05) difference in their neural responses in the two conditions. The feasibility of the proposed BCI-based RASRS was demonstrated through a use-case description with a timing diagram and meeting the crucial requirements for developing the proposed rehabilitation system. The use of a patient's intrinsic feedback mechanism will have significant implications for the development of human-in-the-loop stroke rehabilitation systems.
Dynamic Video Image Segmentation Based on Dual Channel Convolutional Kernel and Multi-Frame Feature Fusion
Authors: Chen Zuguo , Chen Chaoyang , Lu Ming
Published: April 2022

The color image of the fire hole is key for the working condition identification of the aluminum electrolysis cell (AEC). However, the image of the fire hole is difficult for image segmentation due to the nonuniform distributed illuminated background and oblique beam radiation. Thus, a joint dual channel convolution kernel (DCCK) and multi-frame feature fusion (MFF) method is developed to achieve dynamic fire hole video image segmentation. Considering the invalid or extra texture disturbances in the edge feature images, the DCCK is used to select the effective edge features. Since the obtained edge features of the fire hole are not completely closed, the MFF algorithm is further applied to complement the missing portion of the edge. This method can assist to obtain the complete fire hole image of the AEC. The experiment results demonstrate that the proposed method has higher precision, recall rate, and lower boundary redundancy rate with well segmented image edge for the aid of working condition identification of the AEC.
Not Only COVID-19: Involvement of Multiple Chemosensory Systems in Human Diseases
Authors: Caretta Antonio , Mucignat-Caretta Carla
Published: April 2022

Chemosensory systems are deemed marginal in human pathology. In appraising their role, we aim at suggesting a paradigm shift based on the available clinical and experimental data that will be discussed. Taste and olfaction are polymodal sensory systems, providing inputs to many brain structures that regulate crucial visceral functions, including metabolism but also endocrine, cardiovascular, respiratory, and immune systems. Moreover, other visceral chemosensory systems monitor different essential chemical parameters of “milieu intérieur,” transmitting their data to the brain areas receiving taste and olfactory inputs; hence, they participate in regulating the same vital functions. These chemosensory cells share many molecular features with olfactory or taste receptor cells, thus they may be affected by the same pathological events. In most COVID-19 patients, taste and olfaction are disturbed. This may represent only a small portion of a broadly diffuse chemosensory incapacitation. Indeed, many COVID-19 peculiar symptoms may be explained by the impairment of visceral chemosensory systems, for example, silent hypoxia, diarrhea, and the “cytokine storm”. Dysregulation of chemosensory systems may underlie the much higher mortality rate of COVID-19 Acute Respiratory Distress Syndrome (ARDS) compared to ARDSs of different origins. In chronic non-infectious diseases like hypertension, diabetes, or cancer, the impairment of taste and/or olfaction has been consistently reported. This may signal diffuse chemosensory failure, possibly worsening the prognosis of these patients. Incapacitation of one or few chemosensory systems has negligible effects on survival under ordinary life conditions but, under stress, like metabolic imbalance or COVID-19 pneumonia, the impairment of multiple chemosensory systems may lead to dire consequences during the course of the disease.
Simulating Multi-Scale Pulmonary Vascular Function by Coupling Computational Fluid Dynamics With an Anatomic Network Model
Authors: Ebrahimi Behdad Shaarbaf , Kumar Haribalan , Tawhai Merryn H. , Burrowes Kelly S. , Hoffman Eric A. , Clark Alys R.
Published: April 2022

The function of the pulmonary circulation is truly multi-scale, with blood transported through vessels from centimeter to micron scale. There are scale-dependent mechanisms that govern the flow in the pulmonary vascular system. However, very few computational models of pulmonary hemodynamics capture the physics of pulmonary perfusion across the spatial scales of functional importance in the lung. Here we present a multi-scale model that incorporates the 3-dimensional (3D) complexities of pulmonary blood flow in the major vessels, coupled to an anatomically-based vascular network model incorporating the multiple contributing factors to capillary perfusion, including gravity. Using the model we demonstrate how we can predict the impact of vascular remodeling and occlusion on both macro-scale functional drivers (flow distribution between lungs, and wall shear stress) and micro-scale contributors to gas exchange. The model predicts interactions between 3D and 1D models that lead to a redistribution of blood between postures, both on a macro- and a micro-scale. This allows us to estimate the effect of posture on left and right pulmonary artery wall shear stress, with predictions varying by 0.75–1.35 dyne/cm2 between postures.
Post-stroke Dysphagia: Prognosis and Treatment–A Systematic Review of RCT on Interventional Treatments for Dysphagia Following Subacute Stroke
Authors: Balcerak Philipp , Corbiere Sydney , Zubal Richard , Kägi Georg
Published: April 2022

Purpose

Post-stroke dysphagia is an underdiagnosed but relevant complication, associated with worse outcome, dependency and quality of life of stroke survivors. Detailed mechanisms of post-stroke dysphagia are not very well understood, but established therapeutic concepts are needed. Different interventional studies have been published dealing with post-stroke dysphagia. This systematic review wants to collect and give an overview over the published evidence.

Methods

PubMed, Embase, Cochrane, CINAHL were searched for relevant interventional studies on post-stroke dysphagia in the (sub-)acute setting (within 3 months of stroke onset). The search has been filtered for randomized trials with an inactive control and the relevant data extracted.

Results

After initially finding 2,863 trials, finally 41 trials have been included. Seven different therapeutic concepts have been evaluated (Acupuncture, behavioral/physical therapy, drug therapy, neuromuscular electrical stimulation, pharyngeal electrical stimulation, transcranial direct current stimulation and repetitive transcranial magnetic stimulation). Studies of all modalities have shown some effect on post-stroke dysphagia with several studies raising concerns about the potential bias.

Conclusion

The amount and quality of studies are not enough to suggest certain therapies. Some therapeutical concepts (intensive physical therapy, transcranial magnetic stimulation, drug therapy) seem to be good potential therapeutic options, but further research is needed.
Long-Term Outcome of Temporal Lobe Epilepsy Surgery in 621 Patients With Hippocampal Sclerosis: Clinical and Surgical Prognostic Factors
Authors: Pereira Dalio Marina Teixeira Ramalho , Velasco Tonicarlo Rodrigues , Feitosa Izabela Dayany Franca , Assirati Junior João Alberto , Carlotti Junior Carlos Gilberto , Leite João Pereira , dos Santos Antonio Carlos , Alexandre Veriano , Nakano Frederico Nakane , Saute Ricardo Lutzky , Wichert-Ana Lauro , Sakamoto Americo Ceiki
Published: April 2022

Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy and is frequently drug-resistant (DR) to antiseizure medication (ASM), corresponding to approximately one-third of the cases. When left inadequately treated, it can worsen the quality of life, cognitive deficits, and risk of death. The standard treatment for drug-resistant TLE is the surgical removal of the structures involved, with good long-term outcome rates of 60–70 % and a low rate of adverse effects. The goal of successful treatment is sustained seizure freedom. In our study, we evaluated sustained long-term (up to 23 years) surgical outcomes in 621 patients with DR-TLE associated with hippocampal sclerosis, who underwent a temporal lobectomy. We analyzed the main predictive factors that influence the surgical outcome related to seizure control, through a longitudinal and retrospective study, using a multivariable regression model. We found that 73.6% of the patients were free from disabling seizures (Engel Class I), maintained over time in 65% of patients followed up to 23 years after surgery. We found that four independent variables predicted seizure outcomes. The presence of dysmnesic and olfactory aura predicted a less favorable outcome. The history of febrile seizure and the surgical technique predicted a good outcome. Regarding the type of surgical technique, the standard anteromesial temporal lobectomy (ATL) led to significantly better outcomes (78.6% Engel Class I) when compared to the selective amygdalohippocampectomy via subtemporal approach (67.2% Engel Class I; p = 0.002), suggesting that the neuronal networks involved in the epileptogenic zone may be beyond mesial temporal structures. The multivariable regression model with the above-mentioned predictor variables revealed an ExpB = 3.627 (N = 621, p < 0.001), indicating that the model was able to distinguish between patients with a seizure-free. We conclude that epilepsy surgery is a safe procedure, with low rates of postoperative complications and good long-term results.
Relevance of Cognition and Emotion for Patient-Reported Quality of Life After Stroke in Working Age: An Observational Cohort Study
Authors: Pinter Daniela , Fandler-Höfler Simon , Fruhwirth Viktoria , Berger Lisa , Bachmaier Gerhard , Horner Susanna , Eppinger Sebastian , Kneihsl Markus , Enzinger Christian , Gattringer Thomas
Published: April 2022

Background

Patient-reported quality of life (QoL) may help to capture sequela of stroke more comprehensively. We aimed to investigate QoL in working age persons with ischemic stroke regarding impaired domains and identify factors associated with better QoL.

Methods

We invited persons with stroke aged 18–55 years to participate in this prospective observational study. We assessed QoL and self-rated health using the EuroQol 5 Dimension questionnaire (EQ-5D) during hospital stay (baseline) and at 3-months follow-up (FU). Additionally, the National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), cognition (Montreal Cognitive assessment, MOCA), emotion (Hospital Anxiety and Depression Scale), and return to work were evaluated. We used hierarchical regression to identify predictors of QoL (self-rated health and QoL Index score) at FU.

Results

We included 138 persons with stroke (mean age = 43.6 ± 10 years; 41% female; median admission NIHSS = 2), of whom 99 participated at FU. QoL Index and self-rated health were correlated with NIHSS, mRS, anxiety, and depression at both timepoints. Although 80% had favorable functional outcome at FU (mRS < 2), high proportions of these persons reported problems in the “Pain and/or Discomfort” (25.3%) and “Anxiety/Depression” (22.8%) dimensions. Only discharge NIHSS and baseline MOCA independently predicted self-rated health at FU. Female sex, higher discharge NIHSS, and higher baseline depression scores predicted worse QoL Index scores at FU.

Conclusions

Three months post-stroke, working age persons with stroke frequently reported problems in dimensions not assessed by the routinely used mRS. Despite correlations between clinical scales and QoL, patient-reported outcomes and screening for cognition and emotion ensure a more comprehensive assessment of post-stroke consequences relevant for QoL.
Case Report: Interferon-Alpha-Induced Neuromyelitis Optica Spectrum Disorder
Authors: Rao Jie , Xu Na , Sun Jing , Li Yan , Fu Fangwang
Published: April 2022

Background and Objectives

To describe a new case of neuromyelitis optica spectrum disorder (NMOSD) induced by the administration of interferon-alpha (IFNα) and to raise awareness of this rare drug-induced disease of IFNα treatment.

Methods

A single case study and comprehensive literature review of eight cases.

Results

A 24-year-old man was diagnosed with cerebral venous thrombosis and essential thrombocythemia. He had been undergoing IFNα treatment (IFNα-2b, 3 million IU per day) without any side effects for 18 months, at which point the patient developed persistent hiccups, nausea, urinary retention, and numbness. Spinal magnetic resonance imaging revealed a longitudinal abnormality extending from the medulla to the entire spinal cord. The patient was positive for anti-aquaporin-4 antibody (AQP4-IgG) in both the serum and cerebrospinal fluid (CSF), which confirmed the diagnosis of NMOSD. Thus, recombinant IFNα-2b was suspended immediately. Because his condition did not improve after 6-day treatment of methylprednisolone pulse therapy (1,000 mg for 3 days, then 500 mg for 3 days), intravenous immunoglobulin (0.4 g/kg/day for 5 days) was administered. The patient gradually improved. Low-dose prednisolone and mycophenolate mofetil were subsequently administered as a long-term treatment. The patient was discharged with subtle limb numbness and their expanded disability status score (EDSS) was 1. At the 1-year follow-up, the patient had not relapsed and tested negative for AQP4-IgG. We further identified the eight patients with IFNα-induced NMOSD. The median onset age was 59 years, and the median time of IFNα exposure was 18 months. Optic neuritis was the most common initial symptom (five, 55.6%), followed by myelitis in three patients and area postrema syndrome in one patient. More than half (five, 55.6%) of the patients were monophasic. After IFNα discontinuation and immunotherapy, most (seven, 77.8%) patients remained relapse-free. However, only one patient was free of sequelae.

Conclusion

This study highlights the potential pathogenic risk of NMOSD of IFNα treatment. Given the high disability rates of this rare drug-induced disease, it is crucial to monitor the early manifestations of NMOSD during IFNα treatment.
Self-reported Tinnitus and Vertigo or Dizziness in a Cohort of Adult Long COVID Patients
Authors: Degen Chantal Vanessa , Mikuteit Marie , Niewolik Jacqueline , Schröder Dominik , Vahldiek Kai , Mücke Urs , Heinemann Stephanie , Müller Frank , Behrens Georg Martin Norbert , Klawonn Frank , Dopfer-Jablonka Alexandra , Steffens Sandra
Published: April 2022

Tinnitus, vertigo and dizziness are symptoms commonly reported among Long and Post COVID patients, however the severity of these symptoms has not been assessed in large trials. Therefore, in this study a large cohort of Long COVID patients was surveyed about the presence and severity of tinnitus and vertigo or dizziness symptoms. The online survey was completed by a German cohort of 1,082 adult Long COVID patients after a mean period of 43.2 weeks ± 23.4 weeks after infection. Eighty percent were not fully vaccinated (at least two vaccinations) at the time of their first COVID symptoms and 9.8% were hospitalized in the course of their acute SARS-CoV-2 infection. At the time of the survey, 60% of patients reported the presence of vertigo or dizziness with a mean severity of 4.6 ± 2.7 on a scale of 1 (least severe) to 10 (most severe) and 30% complained of tinnitus with a mean severity of 4.8 ± 3.0. Approximately one fifth of the participants with tinnitus and vertigo or dizziness, rated their symptoms to be severe. The data shown in this study confirms that tinnitus and vertigo or dizziness are common symptoms in Long COVID patients and demonstrates, that a compelling number of patients rate their symptoms as severe. The self-reported severity highlights the need for Long COVID clinics to address these symptoms effectively. We suggest a multidisciplinary diagnostic and therapeutic approach to prevent further morbidity and socioeconomic burden for Long COVID patients suffering from severe vertigo, dizziness or tinnitus.
A Color-Picture Version of Boston Naming Test Outperformed the Black-and-White Version in Discriminating Amnestic Mild Cognitive Impairment and Mild Alzheimer's Disease
Authors: Li Dan , Yu Yue-Yi , Hu Nan , Zhang Min , Liu Li , Fan Li-Mei , Ruan Shi-Shuang , Wang Fen
Published: April 2022

Despite the ubiquity of the Boston naming test (BNT) in clinical practice and research, concerns have been expressed about its poor quality pictures, insufficient psychometric properties, and cultural bias in non-English language backgrounds. We modified the black-and-white BNT with a set of color pictures since color effects have been suggested to improve naming accuracy in the visual naming test. This study aimed to examine and compare the reliability and validity of the color-picture version of BNT (CP-BNT) and the black-and-white version of BNT (BW-BNT) to differentiate amnestic mild cognitive impairment (aMCI) or mild Alzheimer's disease (AD) from the cognitive normals. This study included two subgroups, and each subgroup had 101 normal controls, 51 aMCI, and 52 mild AD. One subgroup undertook BW-BNT and the other conducted CP-BNT. The reliability, convergent and discriminant validity, and the diagnostic accuracy of two versions of BNT were evaluated. The CP-BNT showed a greater area under the curve (AUC) than the BW-BNT for aMCI (80.3 vs.s 69.4%) and mild AD (93.5 vs. 77.6%). The CP-BNT also demonstrated better convergent validity with CDR global scores and better reliability (Cronbach's coefficient 0.66 for the CP-BNT vs. 0.55 for the BW-BNT). At the optimal cutoff value of spontaneous naming, the CP-BNT demonstrated improved sensitivity and specificity for differentiating mild AD from NC with a higher positive predictive value, negative predictive value, and lower false-positive rate. Compared with BW-BNT, CP-BNT is a more reliable and valid test to assess cognitive and naming impairment.
Intermittent Visual Occlusions Increase Balance Training Effectiveness
Authors: Symeonidou Evangelia-Regkina , Ferris Daniel P.
Published: April 2022

Improving dynamic balance can prevent falls in humans with neurological and mechanical deficits. Dynamic balance requires the neural integration of multisensory information to constantly assess the state of body mechanics. Prior research found that intermittent visual rotations improved balance training during walking on a narrow beam, but limitations from the immersive virtual reality headset hindered balance training effectiveness overall. We theorized that intermittent visual occlusions with electrically controlled liquid crystal glasses would overcome the previous limitations of the immersive virtual reality headset and provide a means to enhance dynamic balance training efficacy. Forty healthy young individuals walked on a treadmill-mounted balance beam for 30 min (20 subjects with intermittent visual occlusions and 20 subjects with unperturbed vision). Balance performance, in number of step-offs of the beam, improved by 78% for the visual occlusions group on the same day of the training, a near fourfold improvement compared to the 21% improvement for the unperturbed vision group (t(38) = –5.2, p < 0.001). The difference between groups was also apparent 2 weeks later testing for retention (60% improvement for the visual occlusions group, 5% for the unperturbed vision group; t(38) = –4.2, p < 0.001). Intermittent visual occlusions are likely a simple method for enhancing balance training in dynamic motor tasks.
Rectangularity Is Stronger Than Symmetry in Interpreting 2D Pictures as 3D Objects
Authors: Sugihara Kokichi , Pinna Baingio
Published: April 2022

It is known that the human brain has a strong preference for rectangularity in interpreting pictures as 3D shapes. Symmetry is also considered to be a factor that the human vision system places high priority on when perceiving 3D objects. Thus, a question is raised: which is more basic, the rectangularity preference or the symmetry preference? To answer this question, we carried out experiments using pictures that have at least two interpretations as 3D objects, one of which was rectangular but not symmetric, and the other of which was symmetric but not rectangular. We found that the preference for rectangularity is stronger than that for symmetry. This observation will help us to understand various 3D optical illusions, including the room-size illusion and the ambiguous object illusion.