bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal Tracking of Immune Responses in COVID-19 Convalescents Reveals Absence of Neutralization Activity Against Omicron and Staggered Impairment to Other SARS-CoV-2 Variants of Concern
Authors: Odak Ivan , Schultze-Florey Christian R. , Hammerschmidt Swantje I. , Ritter Christiane , Willenzon Stefanie , Friedrichsen Michaela , Ravens Inga , Sikora Ruth , Bayir Lâle M. , Gutierrez Jauregui Rodrigo , Bernhardt Günter , Stankov Metodi V. , Cossmann Anne , Hansen Guido , Krey Thomas , Cornberg Markus , Koenecke Christian , Behrens Georg M. N. , Bošnjak Berislav , Förster Reinhold
Published: March 2022

Evaluating long-term protection against SARS-CoV-2 variants of concern in convalescing individuals is of high clinical relevance. In this prospective study of a cohort of 46 SARS-CoV-2 patients infected with the Wuhan strain of SARS-CoV-2 we longitudinally analyzed changes in humoral and cellular immunity upon early and late convalescence. Antibody neutralization capacity was measured by surrogate virus neutralization test and cellular responses were investigated with 31-colour spectral flow cytometry. Spike-specific, isotype-switched B cells developed already during the disease phase, showed a memory phenotype and did not decrease in numbers even during late convalescence. Otherwise, no long-lasting perturbations of the immune compartment following COVID-19 clearance were observed. During convalescence anti-Spike (S1) IgG antibodies strongly decreased in all patients. We detected neutralizing antibodies against the Wuhan strain as well as the Alpha and Delta but not against the Beta, Gamma or Omicron variants for up to 7 months post COVID-19. Furthermore, correlation analysis revealed a strong association between sera anti-S1 IgG titers and their neutralization capacity against the Wuhan strain as well as Alpha and Delta. Overall, our data suggest that even 7 month after the clearance of COVID-19 many patients possess a protective layer of immunity, indicated by the persistence of Spike-specific memory B cells and by the presence of neutralizing antibodies against the Alpha and Delta variants. However, lack of neutralizing antibodies against the Beta, Gamma and Omicron variants even during the peak response is of major concern as this indicates viral evasion of the humoral immune response.
B-Lymphocytes in the Pathophysiology of Pancreatic Adenocarcinoma
Authors: Minici Claudia , Testoni Sabrina , Della-Torre Emanuel
Published: March 2022

Pancreatic adenocarcinoma is highly infiltrated by B lymphocytes but the relevance of these immune cells in tumor development has been surprisingly overlooked until recently. Based on available evidence from other solid tumors, interaction between B lymphocytes and neoplastic cells is probably not uniformly stimulatory or inhibitory. Although presentation of tumor antigens to T cells and production of antitumor immunoglobulins might intuitively suggest a prominent tumor suppressive activity, specific subsets of B lymphocytes can secrete growth factors for neoplastic cells and immunosuppressive cytokines thus promoting escape from immunosurveillance and cancer progression. Because many of these mechanisms might also be implicated in the development of PDAC, and immune-modulation of B-cell activity is nowadays possible at different levels, determining the role of B-lymphocytes in this lethal cancer becomes of utmost importance to design novel therapeutic strategies. This review aims to discuss the emerging role of B cells in PDAC tumorigenesis, progression, and associated stromal reaction.
Effects of Lower Fishmeal With Hydrolyzed Fish Protein Powder on the Growth Performance and Intestinal Development of Juvenile Pearl Gentian Grouper (Epinephelus fuscoguttatus ♀ and Epinephelus lanceolatus ♂)
Authors: Hlordzi Vivian , Wang Junqing , Li Tianbi , Cui Zhiying , Tan Beiping , Liu Hongyu , Yang Qihui , Dong Xiaohui , Zhang Shuang , Chi Shuyan
Published: March 2022

The effect of hydrolyzed fish protein powder (HFP) on the growth, intestinal development, gene mRNA expression, and enzyme activity in the intestine and liver of juvenile hybrid grouper (Epinephelus fuscoguttatus ♀ and Epinephelus lanceolatus ♂) was assessed after an 8-week feeding trial. Seven isonitrogenous (50%) and isolipidic (9%) diets were fed to hybrid grouper with 0% (CT), 1% (H1), 1.5% (H2), 2% (H3), 2.5% (H4), 3% (H5), and 4% (H6) HFP. No significant difference (p > 0.05) in weight gain rate (WGR), specific growth rate (SGR), feed conversion ratio (FCR), and survival rate (SR) was observed in all the groups. The crude protein content in the H6 group was significantly higher than in the other groups (p < 0.05). Intestinal lipase and trypsin activity were significantly higher in H3 and H5 groups (p < 0.05). In the serum, superoxide dismutase (SOD) activity was significantly higher in H5 and H6 groups, while malondialdehyde (MDA) activity was lower (p < 0.05) compared to other treatments. Insulin-like growth factor (IGF-I) and target of rapamycin (TOR) mRNA expression levels in the intestine and muscle were significantly higher in the H2 group and H1 group (p < 0.05), respectively. The most abundant intestinal bacteria found at the genus level are Acinetobacter, Vibrio, and Flavobacteriaceae. The villus was significantly longer in hybrid grouper fed with different levels of HFP compared to the control, and fish in the H2 group had thicker intestinal muscle compared to the other groups (p < 0.05). In conclusion, the addition of HFP to the low fishmeal (FM) diets of juvenile grouper improved the intestinal development and increased the levels of intestinal digestive enzymes.
CMR Measures of Left Atrial Volume Index and Right Ventricular Function Have Prognostic Value in Chronic Thromboembolic Pulmonary Hypertension
Authors: Shahin Yousef , Alabed Samer , Rehan Quadery Syed , Lewis Robert A. , Johns Christopher , Alkhanfar Dheyaa , Sukhanenko Maria , Alandejani Faisal , Garg Pankaj , Elliot Charlie A. , Hameed Abdul , Charalampopoulos Athaniosis , Wild James M. , Condliffe Robin , Swift Andrew J. , Kiely David G.
Published: March 2022

Providing prognostic information is important when counseling patients and planning treatment strategies in chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to assess the prognostic value of gold standard imaging of cardiac structure and function using cardiac magnetic resonance imaging (CMR) in CTEPH. Consecutive treatment-naive patients with CTEPH who underwent right heart catheterization and CMR between 2011 and 2017 were identified from the ASPIRE (Assessing-the-Specturm-of-Pulmonary-hypertensIon-at-a-REferral-center) registry. CMR metrics were corrected for age and sex where appropriate. Univariate and multivariate regression models were generated to assess the prognostic ability of CMR metrics in CTEPH. Three hundred and seventy-five patients (mean+/-standard deviation: age 64+/-14 years, 49% female) were identified and 181 (48%) had pulmonary endarterectomy (PEA). For all patients with CTEPH, left-ventricular-stroke-volume-index-%predicted (LVSVI%predicted) (p = 0.040), left-atrial-volume-index (LAVI) (p = 0.030), the presence of comorbidities, incremental shuttle walking test distance (ISWD), mixed venous oxygen saturation and undergoing PEA were independent predictors of mortality at multivariate analysis. In patients undergoing PEA, LAVI (p < 0.010), ISWD and comorbidities and in patients not undergoing surgery, right-ventricular-ejection-fraction-%predicted (RVEF%pred) (p = 0.040), age and ISWD were independent predictors of mortality. CMR metrics reflecting cardiac function and left heart disease have prognostic value in CTEPH. In those undergoing PEA, LAVI predicts outcome whereas in patients not undergoing PEA RVEF%pred predicts outcome. This study highlights the prognostic value of imaging cardiac structure and function in CTEPH and the importance of considering left heart disease in patients considered for PEA.
The Association Between Onset of Staphylococcal Non-menstrual Toxic Shock Syndrome With Inducibility of Toxic Shock Syndrome Toxin-1 Production
Authors: Taki Yusuke , Watanabe Shinya , Sato’o Yusuke , Tan Xin-Ee , Ono Hisaya K. , Kiga Kotaro , Aiba Yoshifumi , Sasahara Teppei , Azam Aa Haeruman , Thitiananpakorn Kanate , Veeranarayanan Srivani , Li Feng-Yu , Zhang Yuancheng , Kawaguchi Tomofumi , Hossain Sarah , Maniruzzaman  , Hu Dong-Liang , Cui Longzhu
Published: March 2022

Non-menstrual toxic shock syndrome (non-mTSS) is a life-threatening disease caused by Staphylococcus aureus strains producing superantigens, such as staphylococcal enterotoxins A, B, C, and toxic shock syndrome toxin-1 (TSST-1). However, little is known about why the TSS cases are rare, although S. aureus strains frequently carry a tst gene, which encodes TSST-1. To answer this question, the amount of TSST-1 produced by 541 clinical isolates was measured in both the presence and absence of serum supplementation to growth media. Then a set of S. aureus strains with similar genetic backgrounds isolated from patients presenting with non-mTSS and those with clinical manifestations other than non-mTSS was compared for their TSST-1 inducibility by human serum, and their whole-genome sequences were determined. Subsequently, the association of mutations identified in the tst promoter of non-mTSS strains with TSST-1 inducibility by human serum was evaluated by constructing promoter replacement mutants and green fluorescent protein (GFP) reporter recombinants. Results showed that 39 out of 541 clinical isolates (7.2%), including strains isolated from non-mTSS patients, had enhanced production of TSST-1 in the presence of serum. TSST-1 inducibility by human serum was more clearly seen in non-mTSS strains of clonal complex (CC)-5. Moreover, the whole-genome sequence analysis identified a set of sequence variations at a putative SarA-binding site of the tst promoter. This sequence variation was proven to be partially responsible for the induction of TSST-1 production by human serum. We conclude that the onset of staphylococcal toxic shock syndrome caused by TSST-1-producing CC-5 strains seem at least partially initiated by serum induction of TSST-1, which is regulated by the mutation of putative SarA-binding site at the tst promoter.
A Newly Isolated Strain Lysobacter brunescens YQ20 and Its Performance on Wool Waste Biodegradation
Authors: Ma Qinyuan , Zhang Ya`ning , Zheng Xue , Luan Fang , Han Ping , Zhang Xianghe , Yin Yanmiao , Wang Xiaoxiao , Gao Xiuzhen
Published: March 2022

Wool keratin is difficult to degrade as comparing to feathers because of its tough secondary structure. In order to develop an approach for high-value utilization of wool fiber waste by keratinolytic microorganisms, which is produced from shearing, weaving, and industrial processing of wool, screening of wool-degrading bacterium with high degradation efficiency were performed in this study. To this end, Lysobacter brunescens YQ20 was identified and characterized. The optimized conditions for wool degradation were pH 9.0 and 37°C with 20% liquid volume of Erlenmeyer flask. After fermentation, 15 essential amino acids were detected when wool fiber waste was fermented. The total amino acids produced from 1% wool per hour were 13.7 mg/L. The concentration was 8.6-fold higher than that produced by the strain Stenotrophomonas maltophilia BBE11-1, which had previously been reported to have the highest wool-degrading capacity. Our study reports the first Lysobacter strain that exhibits efficient wool degradation and yields higher concentrations of amino acids than previously reported strains. Whole-genome sequencing indicated that there were 18 keratinase-like genes in the genome of YQ20, which exhibited a long evolutionary distance from those of Bacillus. Therefore, L. brunescens YQ20 may have applications in the environmentally friendly management of wool waste as fertilizer in agriculture.
E-Test or Agar Dilution for Metronidazole Susceptibility Testing of Helicobacter pylori: Importance of the Prevalence of Metronidazole Resistance
Authors: Chen Jinnan , Huang Yu , Ding Zhaohui , Liang Xiao , Lu Hong
Published: March 2022

Background

A number of studies have shown that E-test overestimated the presence of Helicobacter pylori resistance compared to agar dilution.

Objective

The purpose of this study was to explore whether E-test could be an alternative for agar dilution to detect the metronidazole susceptibility of H. pylori.

Method

E-test and agar dilution were used to assess the susceptibility of H. pylori to metronidazole, clarithromycin, and levofloxacin in 281 clinical isolates obtained from China where the resistance was high. Cohen’s kappa analysis, McNemar’s test, and essential and categorical agreement analysis were performed for these two methods.

Results

Overall, the result of the E-test showed a similar prevalence of resistance rate to all antibiotics compared with agar dilution. The essential agreement of the E-test method and agar dilution in the evaluation susceptibility of H. pylori to clarithromycin and levofloxacin was moderate at 89.0 and 79.7%, respectively, but only 45.9% for metronidazole. The results shown by a categorical agreement (CA) between the E-test and agar dilution were 100% for both clarithromycin and levofloxacin. As for metronidazole, the CA was 98.7%, no major error was identified, and the rate of a very major error was 1.8%.

Conclusion

E-test can be an alternative method to detect the metronidazole susceptibility of H. pylori.
Machine Learning and Deep Learning Applications in Metagenomic Taxonomy and Functional Annotation
Authors: Mathieu Alban , Leclercq Mickael , Sanabria Melissa , Perin Olivier , Droit Arnaud
Published: March 2022

Shotgun sequencing of environmental DNA (i.e., metagenomics) has revolutionized the field of environmental microbiology, allowing the characterization of all microorganisms in a sequencing experiment. To identify the microbes in terms of taxonomy and biological activity, the sequenced reads must necessarily be aligned on known microbial genomes/genes. However, current alignment methods are limited in terms of speed and can produce a significant number of false positives when detecting bacterial species or false negatives in specific cases (virus, plasmids, and gene detection). Moreover, recent advances in metagenomics have enabled the reconstruction of new genomes using de novo binning strategies, but these genomes, not yet fully characterized, are not used in classic approaches, whereas machine and deep learning methods can use them as models. In this article, we attempted to review the different methods and their efficiency to improve the annotation of metagenomic sequences. Deep learning models have reached the performance of the widely used k-mer alignment-based tools, with better accuracy in certain cases; however, they still must demonstrate their robustness across the variety of environmental samples and across the rapid expansion of accessible genomes in databases.
Genetic Diversity, Distribution, and Genomic Characterization of Antibiotic Resistance and Virulence of Clinical Pseudomonas aeruginosa Strains in Kenya
Authors: Kiyaga Shahiid , Kyany'a Cecilia , Muraya Angela W. , Smith Hunter J. , Mills Emma G. , Kibet Caleb , Mboowa Gerald , Musila Lillian
Published: March 2022

Pseudomonas aeruginosa is a leading cause of nosocomial infections worldwide. It can produce a range of debilitating infections, have a propensity for developing antimicrobial resistance, and present with a variety of potent virulence factors. This study investigated the sequence types (ST), phenotypic antimicrobial susceptibility profiles, and resistance and virulence genes among clinical isolates from urinary tract and skin and soft tissue infections. Fifty-six P. aeruginosa clinical isolates were obtained from six medical centers across five counties in Kenya between 2015 and 2020. Whole-genome sequencing (WGS) was performed to conduct genomic characterization, sequence typing, and phylogenetic analysis of the isolates. Results showed the presence of globally distributed high-risk clones (ST244 and ST357), local high-risk clones (ST2025, ST455, and ST233), and a novel multidrug-resistant (MDR) clone carrying virulence genes (ST3674). Furthermore, 31% of the study isolates were found to be MDR with phenotypic resistance to a variety of antibiotics, including piperacillin (79%), ticarcillin-clavulanic acid (57%), meropenem (34%), levofloxacin (70%), and cefepime (32%). Several resistance genes were identified, including carbapenemases VIM-6 (ST1203) and NDM-1 (ST357), fluoroquinolone genes, crpP, and qnrVCi, while 14 and 22 different chromosomal mutations were detected in the gyrA and parC genes, respectively. All isolates contained at least three virulence genes. Among the virulence genes identified, phzB1 was the most abundant (50/56, 89%). About 21% (12/56) of the isolates had the exoU+/exoS- genotype, while 73% (41/56) of the isolates had the exoS+/exoU- genotype. This study also discovered 12 novel lineages of P. aeruginosa, of which one (ST3674) demonstrated both extensive antimicrobial resistance and the highest number of virulence genes (236/242, 98%). Although most high-risk clones were detected in Nairobi County, high-risk and clones of interest were found throughout the country, indicating the local spread of global epidemic clones and the emergence of new strains. Thus, this study illustrates the urgent need for coordinated local, regional, and international antimicrobial resistance surveillance efforts.
Virulence of Emerging Arthrotropic Avian Reoviruses Correlates With Their Ability to Activate and Traffic Interferon-γ Producing Cytotoxic CD8+ T Cells Into Gastrocnemius Tendon
Authors: Ayalew Lisanework E. , Ahmed Khawaja Ashfaque , Popowich Shelly , Lockerbie Betty-Chow , Gupta Ashish , Tikoo Suresh K. , Ojkic Davor , Gomis Susantha
Published: March 2022

Newly emerging arthrotropic avian reoviruses (ARVs) are genetically divergent, antigenically heterogeneous, and economically costly. Nevertheless, the mechanism of emerging ARV-induced disease pathogenesis and potential differences in virulence between virus genotypes have not been adequately addressed. In this study, the life cycle of ARV, including the formation of cytoplasmic ARV neo-organelles, paracrystalline structures, and virus release mechanisms, were characterized in the infected host cell by transmission electron microscopy (TEM). In addition, progressive changes in the structure of infected cells were investigated by time-lapse and field emission scanning electron (FE-SE) microscopy. ARVs from the four genotypic cluster groups included in the study caused gross and microscopic lesions in the infected birds. Marked infiltration of γδT cells, CD4+ and CD8+ T lymphocytes were observed in ARV infected tendon tissues starting day 3 post-infection. The ARV variant from genotype cluster-2 triggered significantly high trafficking of IFN-γ producing CD8+ T lymphocytes in tendon tissues and concomitantly showed high morbidity and severe disease manifestations. In contrast, the ARV variant from genotype cluster-4 was less virulent, caused milder disease, and accompanied less infiltration of IFN-γ producing CD8+ T cells. Interestingly, when we blunted antiviral immune responses using clodronate liposomes (which depletes antigen-presenting cells) or cyclosporin (which inhibits cytokine production that regulates T-cell proliferation), significantly lower IFN-γ producing CD8+ T cells infiltrated into tendon tissues, resulting in reduced tendon tissues apoptosis and milder disease manifestations. In summary, these data suggest that the degree of ARV virulence and tenosynovitis/arthritis are potentially directly associated with the ability of the virus to traffic massive infiltration of cytotoxic CD8+ T cells into the infected tissues. Moreover, the ability to traffic cytotoxic CD8+ T cells into infected tendon tissues and the severity of tenosynovitis differ between variants from different ARV genotype cluster groups. However, more than one virus isolate per genotype group needs to be tested to further confirm the association of pathogenicity with genotype. These findings can be used to further examine the interaction of viral and cellular pathways which are essential for the pathogenesis of the disease at the molecular level and to develop effective disease control strategies.
VAMP2 Expression and Genotype Are Possible Discriminators in Different Forms of Dementia
Authors: Costa Andrea Saul , Ferri Evelyn , Guerini Franca Rosa , Rossi Paolo Dionigi , Arosio Beatrice , Clerici Mario
Published: March 2022

Vascular alterations often overlap with neurodegeneration, resulting in mixed forms of dementia (MD) that are hard to differentiate from Alzheimer’s Disease (AD). The 26 bp intergenic polymorphism of VAMP2, a key component of SNARE complex, as well as its mRNA and protein levels are associated with neurological diseases. We evaluated ApoE4 and VAMP2 26 bp Ins/Del genotype distribution in 177 AD, 132 MD, 115 Mild Cognitive Impairment (MCI) and 250 individuals without cognitive decline (CT), as well as VAMP2 gene expression in a subset of 73 AD, 122 MD, 103 MCI and 140 CT. Forty-two MCI evolved to AD (22 MCI-AD) or MD (20 MCI-MD) over time. VAMP2 mRNA was higher in MD compared to AD (p = 0.0013) and CT (p = 0.0017), and in MCI-MD compared to MCI-AD (p < 0.001) after correcting for age, gender, MMSE and ApoE4 +/− covariates (pc = 0.004). A higher VAMP2 expression was observed in subjects carrying the minor allele Del compared to those carrying the Ins/Ins genotype (p = 0.012). Finally, Del/Del genotype was more frequently carried by MD/MCI-MD compared to CT (pc = 0.036). These results suggest that VAMP2 mRNA expression can discriminate mixed form of dementia from AD, possibly being a biomarker of AD evolution in MCI patients.
Early Life Exposure to Tumor Necrosis Factor Induces Precocious Sensorimotor Reflexes Acquisition and Increases Locomotor Activity During Mouse Postnatal Development
Authors: Paraschivescu Cristina , Barbosa Susana , Van Steenwinckel Juliette , Gressens Pierre , Glaichenhaus Nicolas , Davidovic Laetitia
Published: March 2022

Inflammation appears as a cardinal mediator of the deleterious effect of early life stress exposure on neurodevelopment. More generally, immune activation during the perinatal period, and most importantly elevations of pro-inflammatory cytokines levels could contribute to psychopathology and neurological deficits later in life. Cytokines are also required for normal brain function in homeostatic conditions and play a role in neurodevelopmental processes. Despite these latter studies, whether pro-inflammatory cytokines such as Tumor Necrosis Factor (TNF) impact neurodevelopmental trajectories and behavior during the immediate postnatal period remains to be elucidated. To address this issue, we have injected mouse pups daily with recombinant TNF from postnatal day (P)1 to P5. This yielded a robust increase in peripheral and central TNF at P5, and also an increase of additional pro-inflammatory cytokines. Compared to control pups injected with saline, mice injected with TNF acquired the righting and the acoustic startle reflexes more rapidly and exhibited increased locomotor activity 2 weeks after birth. Our results extend previous work restricted to adult behaviors and support the notion that cytokines, and notably TNF, modulate early neurodevelopmental trajectories.
Integrative Functional Transcriptomic Analyses Implicate Shared Molecular Circuits in Sensorineural Hearing Loss
Authors: Chen Peng , Hao Jun-Jun , Li Meng-Wen , Bai Jing , Guo Yuan-Ting , Liu Zhen , Shi Peng
Published: March 2022

Sensorineural hearing loss (SNHL) is referred to as the most common type of hearing loss and typically occurs when the inner ear or the auditory nerve is damaged. Aging, noise exposure, and ototoxic drugs represent three main causes of SNHL, leading to substantial similarities in pathophysiological characteristics of cochlear degeneration. Although the common molecular mechanisms are widely assumed to underlie these similarities, its validity lacks systematic examination. To address this question, we generated three SNHL mouse models from aging, noise exposure, and cisplatin ototoxicity, respectively. Through constructing gene co-expression networks for the cochlear transcriptome data across different hearing-damaged stages, the three models are found to significantly correlate with each other in multiple gene co-expression modules that implicate distinct biological functions, including apoptosis, immune, inflammation, and ion transport. Bioinformatics analyses reveal several potential hub regulators, such as IL1B and CCL2, both of which are verified to contribute to apoptosis accompanied by the increase of (ROS) in in vitro model system. Our findings disentangle the shared molecular circuits across different types of SNHL, providing potential targets for the broad effective therapeutic agents in SNHL.
Abnormal White Matter Microstructure in the Limbic System Is Associated With Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders
Authors: Sato Akemi , Tominaga Koji , Iwatani Yoshiko , Kato Yoko , Wataya-Kaneda Mari , Makita Kai , Nemoto Kiyotaka , Taniike Masako , Kagitani-Shimono Kuriko
Published: March 2022

Objective

Tuberous sclerosis complex (TSC) is a genetic disease that arises from TSC1 or TSC2 abnormalities and induces the overactivation of the mammalian/mechanistic target of rapamycin pathways. The neurological symptoms of TSC include epilepsy and tuberous sclerosis complex-associated neuropsychiatric disorders (TAND). Although TAND affects TSC patients' quality of life, the specific region in the brain associated with TAND remains unknown. We examined the association between white matter microstructural abnormalities and TAND, using diffusion tensor imaging (DTI).

Methods

A total of 19 subjects with TSC and 24 age-matched control subjects were enrolled. Tract-based spatial statistics (TBSS) were performed to assess group differences in fractional anisotropy (FA) between the TSC and control groups. Atlas-based association analysis was performed to reveal TAND-related white matter in subjects with TSC. Multiple linear regression was performed to evaluate the association between TAND and the DTI parameters; FA and mean diffusivity in seven target regions and projection fibers.

Results

The TBSS showed significantly reduced FA in the right hemisphere and particularly in the inferior frontal occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), uncinate fasciculus (UF), and genu of corpus callosum (CC) in the TSC group relative to the control group. In the association analysis, intellectual disability was widely associated with all target regions. In contrast, behavioral problems and autistic features were associated with the limbic system white matter and anterior limb of the internal capsule (ALIC) and CC.

Conclusion

The disruption of white matter integrity may induce underconnectivity between cortical and subcortical regions. These findings suggest that TANDs are not the result of an abnormality in a specific brain region, but rather caused by connectivity dysfunction as a network disorder. This study indicates that abnormal white matter connectivity including the limbic system is relevant to TAND. The analysis of brain and behavior relationship is a feasible approach to reveal TAND related white matter and neural networks. TAND should be carefully assessed and treated at an early stage.
Secondary Prevention in Radiologically Isolated Syndromes and Prodromal Stages of Multiple Sclerosis
Authors: Amato Maria Pia , De Stefano Nicola , Inglese Matilde , Morena Emanuele , Ristori Giovanni , Salvetti Marco , Trojano Maria
Published: March 2022

Following the extraordinary progress in the treatment of multiple sclerosis (MS), two major unmet needs remain: understanding the etiology of the disease and, hence, designing definitive cures (this perspective is neither at hand, nor it can be taken for granted that the etiologic targets will be readily treatable); the prevention of an overt and disabling disease, which seems to be a more realistic and pragmatic perspective, as the integration of genetic data with endophenotypes, MRI, and other biomarkers ameliorates our ability to identify early neuroinflammation. Radiologically isolated syndrome (RIS; diagnosed when the unanticipated MRI finding of brain spatial dissemination of focal white matter lesions highly suggestive of MS occurs in subjects without symptoms of MS, and with normal neurological examinations) and the recently focused “prodromal MS” are conditions at risk of conversion toward overt disease. Here, we explore the possibility of secondary prevention approaches in these early stages of neuroinflammation. RIS and prodromal MS are rare conditions, which suggest the importance of Study Groups and Disease Registry to implement informative clinical trials. We summarize ongoing preventive approaches in the early stages of the demyelinating process, especially in RIS conditions. Moreover, we highlight the importance of the biomarkers and the predictors of evolution to overt disease, which may be useful to select the individuals at risk of conversion to clinically isolated syndrome (CIS) and/or clinically definite MS. Finally, we illustrate the importance of the endophenotypes to test the frontline immunomodulatory approach for preventive strategies. Future investigations, especially in relatives of patients, based on MRI techniques and biological studies (better with integrated approaches) may provide opportunities to understand the MS early causal cascade and may help to identify a “therapeutic window” to potentially reverse early disease processes.
Abnormal Brain MRI Findings in Anti-N-Methyl-D-Aspartate Receptor Encephalitis and Correlation With Outcomes
Authors: Lei Chunyan , Chang Xiaolong , Li Haijiang , Zhong Lianmei
Published: March 2022

Purpose

The reported prevalence of abnormal findings by brain MRI varies from 11 to 83% among patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Here, we investigated the prevalence of abnormal MRI findings in Chinese patients and explored whether such findings are correlated with clinical outcomes.

Methods

This retrospective study analyzed a consecutive series of 52 patients with anti-NMDAR encephalitis admitted to our hospital. The patients were assigned to the “MRI-normal” or the “MRI-abnormal” group based on brain MRI after admission. The groups were compared in terms of clinicodemographic characteristics and scores on the Mini-Mental State Examination (MMSE) and modified Rankin Scale (mRS) 3 and 12 months after admission.

Results

Thirty-seven (71.15%) of the patients showed abnormalities on brain MRI; these patients were more likely to be men and showed abnormalities on electroencephalography. Patients who showed normal or abnormal MRI findings did not differ significantly in terms of clinical symptoms, rates of mortality or relapse, or mRS scores after 3 and 12 months. However, patients with abnormal MRI showed significantly lower MMSE scores than those with normal MRI after 3 and 12 months.

Conclusions

We found high prevalence of abnormal MRI findings in our sample of Chinese patients with anti-NMDAR encephalitis. We also found that the abnormal findings were associated with cognitive decline but not necessarily with mortality or functional outcomes in the short or long term.
Case Report: Anti-NF186+ CIDP After Receiving the Inactivated Vaccine for Coronavirus Disease (COVID-19)
Authors: Wen Shirui , Huang Kailing , Zhu Haoyue , Li Peihong , Zhou Luo , Feng Li
Published: March 2022

Corona Virus Disease 2019 (COVID-19), the novel coronavirus disease, is now a global pandemic. Vaccination can significantly reduce the mortality rate caused by the severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2). There are currently several effective vaccines that have been introduced. Inactivated COVID-19 vaccine is one of these options and is generally considered safe. Neurofascin (NF) plays an important role in keeping the functionality of the node of Ranvier. We report here a rare case of anti-NF186+ chronic inflammatory demyelinating polyneuropathy (CIDP) in a 23-year-old male patient who was vaccinated with inactivated COVID-19 vaccine prior to the onset. This report adds a new possible rare side effect of a COVID-19 vaccine and provides a case for the clinical effectiveness of rituximab (RTX) in patients with anti-NF186+ CIDP.
Efficacy and Safety of Diet Therapies in Children With Autism Spectrum Disorder: A Systematic Literature Review and Meta-Analysis
Authors: Yu Yuping , Huang Jinyue , Chen Xiaofang , Fu Jia , Wang Xinhui , Pu Linjie , Gu Chunyu , Cai Chunquan
Published: March 2022

Objective

Autism Spectrum Disorder is a neurodevelopmental disorder, with a rapid increase in recognition over the past decade. Interest in alternative therapies is growing annually, such as dietary therapies including gluten-free and/or casein-free diet, and the ketogenic diet. However, there is no consensus on the efficacy and safety of dietary therapy in children with ASD up to now. This study aimed to assess the efficacy and safety of these diet interventions for children with ASD based on a meta-analysis of global data.

Methods

Seven databases (Cochrane Library, PubMed, EMBASE, Web of Science, VIP, CNKI, and Wanfang) were searched according to the established inclusion criteria, from the inception of the databases to August 18, 2021. The Cochrane Bias risk assessment tool was intended to assess the quality of the included studies. Review Manager 5.4 software was used as an efficacy analysis tool of the included studies, taking the core autistic symptoms and scales of ASD as therapeutic efficacy evaluations.

Results

In total, 7 RCTs with 338 participants were finally obtained. All studies assessed the association between core autistic symptoms and therapeutic diet, showing a statistically significant effect (standard mean difference (SMD) of −0.51, 95% confidence interval (Cl): −0.81 to −0.21), in which two studies which followed the GFD diet reported significant reductions in social behaviors (SMD of−0.41, 95% Cl: −0.75 to −0.06), showing no correlation with the length of the interventions (P < 0.05). Two studies were performed in KD diet suggested a significant effect in core symptoms (SMD of −0.67, 95% Cl: −1.04 to −0.31). No statistically significant changes were observed in the GFCF diet, GFD diet, cognition, communication, and stereotypical behaviors subgroups (all P > 0.05).

Conclusion

The results of a meta-analysis suggest that diet therapies can significantly ameliorate core symptoms of ASD, and GFD diets are conducive to improving social behaviors. Although the results suggest the effectiveness of dietary therapy for ASD, limited by the small sample size of RCTs, more well-designed, and high-quality clinical trials are needed to validate the above conclusions.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021277565.
Aneurysm Location Affects Clinical Course and Mortality in Patients With Subarachnoid Hemorrhage
Authors: Göttsche Jennifer , Piffko Andras , Pantel Tobias F. , Westphal Manfred , Dührsen Lasse , Czorlich Patrick , Sauvigny Thomas
Published: March 2022

Objective

The influence of preexisting factors on the clinical course of patients with subarachnoid hemorrhage (SAH), such as patient age, arterial hypertension, and aneurysm characteristics, is still a matter of debate. However, the specific impact of the exact aneurysm location has not received adequate attention. Therefore, the aim of this study was to investigate the influence of aneurysm location as a preexisting factor on the clinical course and mortality.

Methods

The data of consecutive patients with aneurysmal SAH who were treated from October 2010 to July 2020 were retrospectively analyzed. We distinguished four aneurysm locations: the anterior complex, internal carotid artery (ICA), middle cerebral artery (MCA), and posterior circulation. Logistic regression analysis and receiver operating characteristics were used to investigate the influence of aneurysm location on the occurrence of acute hydrocephalus, Delayed Cerebral Ischemia (DCI), neurological outcome, and in-hospital mortality. Neurological outcome was assessed 3 months after discharge using the Glasgow Outcome Scale.

Results

A total of 603 patients were included in this study. Patients with MCA aneurysms were 2.52 times less likely to develop acute hydrocephalus compared to patients with anterior complex aneurysms (p = 0.001). Delayed cerebral ischemia occurred most frequently in patients with an anterior complex aneurysm and least frequently in MCA aneurysms (p = 0.014). In ICA aneurysms, mortality was 2.56-fold higher than in patients with aneurysms of the anterior complex (p = 0.006). An additional ROC analysis showed a good prediction for in-hospital mortality when taking the aneurysm's location into account [AUC.855 (CI.817 −0.893)].

Conclusions

The aneurysm's location proved to be a significant predictor of acute hydrocephalus, DCI, and in-hospital mortality, demonstrating the impact of this preexisting biological factor on the course of SAH.
Research Progress on Intracranial Lymphatic Circulation and Its Involvement in Disorders
Authors: Chen Fan , Xie Xuan , Wang Liang
Published: March 2022

The lymphatic system is an important part of the circulatory system, as an auxiliary system of the vein, which has the functions of immune defense, maintaining the stability of the internal environment, and regulating the pressure of the tissue. It has long been thought that there are no typical lymphatic vessels consisting of endothelial cells in the central nervous system (CNS). In recent years, studies have confirmed the presence of lymphatic vessels lined with endothelial cells in the meninges. The periventricular meninges of the CNS host different populations of immune cells that affect the immune response associated with the CNS, and the continuous drainage of interstitial and cerebrospinal fluid produced in the CNS also proceeds mainly by the lymphatic system. This fluid process mobilizes to a large extent the transfer of antigens produced by the CNS to the meningeal immune cells and subsequently to the peripheral immune system through the lymphatic network, with clinically important implications for infectious diseases, autoimmunity, and tumor immunology. In our review, we discussed recent research advances in intracranial lymphatic circulation and the pathogenesis of its associated diseases, especially the discovery of meningeal lymphatic vessels, which has led to new therapeutic targets for the treatment of diseases associated with the intracranial lymphatic system.
Case Report: Dysfunction of the Paraventricular Hypothalamic Nucleus Area Induces Hypersomnia in Patients
Authors: Wang Zan , Zhong Yu-Heng , Jiang Shan , Qu Wei-Min , Huang Zhi-Li , Chen Chang-Rui
Published: March 2022

Background

Hypersomnia is a common and highly impairing symptom marked by pathological excessive sleepiness, which induces suboptimal functioning and poor quality of life. Hypersomnia can be both a primary (e.g., hypersomnolence disorder) and secondary (e.g., tumors, and head trauma) symptom of disorders. However, its underlying mechanisms remain largely unknown.

Case Presentation

We report that three clinical cases with lesions around the paraventricular nucleus of the hypothalamus (PVH) area showed excessive daytime sleepiness and a prolonged nocturnal sleep lasting more than 20 h per day. Sleep architecture and subjective daytime sleepiness were examined by polysomnography. These cases were presented with stroke, myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders and neuromyelitis optical spectrum disorder (NMOSD), respectively. Magnetic resonance imaging (MRI) showed lesions around the PVH area in all these three patients. After treatment of their primary disorders, their excessive sleep decreased as the PVH area recovered.

Conclusion

Our findings suggest that the PVH may play an essential role in the occurrence of hypersomnia.
Preoperative Collateral Perfusion Using Arterial Spin Labeling: A Predictor of Surgical Collaterals in Moyamoya Angiopathy
Authors: Wang Maoxue , Wang Yi , Zhang Wen , Zhao Xiance , Yang Yongbo , Zhang Bing
Published: March 2022

Objectives

Various degrees of surgical collateral circulation are often found in moyamoya angiopathy (MMA) patients after revascularization. Little is known about arterial spin labeling (ASL) that affects surgical collateral circulation. This study aimed to investigate the effect of ASL on surgical collaterals in patients with MMA after combined bypass surgery.

Methods

MMA patients with complete radiological and clinical information, who had undergone combined bypass, were enrolled in this study. Surgical collaterals were classified as good or poor based on the Matsushima standard. Cerebral perfusion on ASL was quantitatively analyzed as relative cerebral blood flow (rCBF). The qualitative collateral score was calculated using a four-grade scale. Univariable and multivariable logistic regressions were performed to identify the predictors for surgical collaterals after combined bypass.

Results

In total, 66 hemispheres of 61 patients (47 years old ± 8.66) were prospectively included (29 and 37 hemispheres with good and poor surgical collaterals, respectively). The presurgical collateral score was significantly lower in patients with good surgical collaterals (13.72 scores ± 7.83) than in those with poor surgical collaterals (19.16 scores ± 6.65, P = 0.005). The presurgical rCBF and modified Rankin scale (mRS) scores were not significantly different between the two groups (PrCBF = 0.639, PmRS = 0.590). The collateral score was significantly elevated (good: 13.72 scores ± 7.83 vs. 20.79 scores ± 6.65, P < 0.001; poor: 19.16 scores ± 6.65 vs. 22.84 scores ± 5.06, P < 0.001), and the mRS was reduced (good: 1.66 scores ± 1.14 vs. 0.52 scores ± 0.83, P < 0.001; poor: 1.49 scores ± 0.90 vs. 0.62 scores ± 0.76, P < 0.001) in patients after revascularization. Multivariable logistic regression showed that preoperative collateral scores [odds ratio (OR): 0.791; 95% confidence interval (CI): 0.695, 0.900; P < 0.001], age (OR: 0.181; 95% CI: 0.039, 0.854; P = 0.031), sex (OR: 0.154; 95% CI: 0.035, 0.676; P = 0.013), and hypertension (OR: 0.167; 95% CI: 0.038, 0.736; P = 0.018) were predictors of surgical collaterals after combined revascularization.

Conclusion

The preoperative collateral score based on ASL could be a predictor for surgical collaterals in patients with MMA after combined bypass surgery. Combined with age, sex, and hypertension, it may have a better predictive effect.
Targeted Lipidomics Reveal the Effect of Perchlorate on Lipid Profiles in Liver of High-Fat Diet Mice
Authors: Wang Qiao , Song Wanying , Tian Yimei , Hu Peihao , Liu Xin , Xu Lin , Gong Zhiyong
Published: March 2022

Perchlorate, commonly available in drinking water and food, acts on the iodine uptake by the thyroid affecting lipid metabolism. High-fat diets leading to various health problems continually raise public concern. In the present study, liver lipid metabolism profiles and metabolic pathways were investigated in C57BL/6J mice chronically exposed to perchlorate using targeted metabolomics. Mice were fed a high-fat diet and treated orally with perchlorate at 0.1 mg/kg bw (body weight), 1 mg/kg bw and 10 mg/kg bw daily for 12 weeks. Perchlorate induced disorders of lipid metabolism in vivo and hepatic lipid accumulation confirmed by serum biochemical parameters and histopathological examination. There were 34 kinds of lipid in liver detected by UHPLC-MS/MS and key metabolites were identified by multivariate statistical analysis evaluated with VIP > 1, p-value < 0.05, fold change > 1.2 or < 0.8. Perchlorate low, medium and high dose groups were identified with 11, 7 and 8 significantly altered lipid metabolites compared to the control group, respectively. The results of the metabolic pathway analysis revealed that the differential metabolites classified into different experimental groups contribute to the glycerophospholipid metabolic pathway. These findings provide insights into the effects of perchlorate on lipid metabolism during long-term exposure to high-fat diets and contribute to the evaluation of perchlorate liver toxic mechanisms and health effects.
Carnitine and Depression
Authors: Liu Ting , Deng Kunhong , Xue Ying , Yang Rui , Yang Rong , Gong Zhicheng , Tang Mimi
Published: March 2022

Depression has become one of the most common mental diseases in the world, but the understanding of its pathogenesis, diagnosis and treatments remains insufficient. Carnitine is a natural substance that exists in organisms, which can be synthesized in vivo or supplemented by intake. Relationships of carnitine with depression, bipolar disorder and other mental diseases have been reported in different studies. Several studies show that the level of acylcarnitines (ACs) changes significantly in patients with depression compared with healthy controls while the supplementation of acetyl-L-carnitine is beneficial to the treatment of depression. In this review, we aimed to clarify the effects of ACs in depressive patients and to explore whether ACs might be the biomarkers for the diagnosis of depression and provide new ideas to treat depression.
An MRI-Based Radiomic Model for Individualized Prediction of Hepatocellular Carcinoma in Patients With Hepatitis B Virus-Related Cirrhosis
Authors: Wei Yichen , Gong Jie , He Xin , Liu Bo , Liu Tiejun , Yang Shuohui , Zhou Zhipeng , Liang Lingyan , Zhan Songhua , Xia Ziqiang , Duan Gaoxiong , Lin Bin , Han Qiuli , Li Shasha , Qin Wei , Pickhardt Perry J. , Deng Demao
Published: March 2022

Objective

To develop and validate a radiomic nomogram for individualized prediction of hepatocellular carcinoma (HCC) in HBV cirrhosis patients based on baseline magnetic resonance imaging examinations and clinical data.

Methods

364 patients with HBV cirrhosis from five hospitals were assigned to the training, internal validation, external validation-1 or external validation-2 cohort. All patients underwent baseline magnetic resonance image (MRI) scans and clinical follow-up within three-year time. Clinical risk factors and MRI-based features were extracted and analyzed. The radiomic signatures were built using the radiomics-score (Rad-score) that calculated for each patient as a linear weighted combination of selected MRI-based features. Prognostic performances of the clinical and radiomic nomograms were evaluated with Cox modeling in the training and validation cohorts.

Results

Eighteen features were selected for inclusion in the Rad-score prognostic model. The radiomic signature from multi-sequence MRI yielded a concordance index (C-index) of 0.710, 0.681, 0.632 and 0.658 in the training, internal validation, external validation-1, external validation-2 cohorts, respectively. Sex and Child-Turcotte-Pugh (CTP) class were the most prognostic clinical risk factors in univariate Cox proportional hazards analyses. The radiomic combined nomogram that integrated the radiomic signature with the clinical factors yielded a C-index of 0.746, 0.710, and 0.641 in the training, internal validation, and external validation-1 cohorts, respectively, which was an improvement over either the clinical nomogram or radiomic signature alone.

Conclusion

We developed an MRI-based radiomic combined nomogram with good discrimination ability for the individualized prediction of HCC in HBV cirrhosis patients within three-year time.