bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor NLRP3-Derived IL-1β Drives the IL-6/STAT3 Axis Resulting in Sustained MDSC-Mediated Immunosuppression
Authors: Tengesdal Isak W. , Dinarello Alberto , Powers Nicholas E. , Burchill Matthew A. , Joosten Leo A. B. , Marchetti Carlo , Dinarello Charles A. 
Published: September 2021

Tumors evade the immune system by inducing inflammation. In melanoma, tumor-derived IL-1β drives inflammation and the expansion of highly immunosuppressive myeloid-derived suppressor cells (MDSCs). Similar in many tumors, melanoma is also linked to the downstream IL‐6/STAT3 axis. In this study, we observed that both recombinant and tumor-derived IL-1β specifically induce pSTAT3(Y705), creating a tumor-autoinflammatory loop, which amplifies IL-6 signaling in the human melanoma cell line 1205Lu. To disrupt IL-1β/IL-6/STAT3 axis, we suppressed IL-1β-mediated inflammation by inhibiting the NOD-like receptor protein 3 (NLRP3) using OLT1177, a safe-in-humans specific NLRP3 oral inhibitor.In vivo, using B16F10 melanoma, OLT1177 effectively reduced tumor progression (p&lt; 0.01); in primary tumors, OLT1177 decreased pSTAT3(Y705) by 82% (p&lt;0.01) andII6expression by 53% (p&lt;0.05). Disruption of tumor-derived NLRP3, either pharmacologically or genetically, reduced STAT3 signaling in bone marrow cells. In PMN-MDSCs isolated from tumor-bearing mice treated with OLT1177, we observed significant reductions in immunosuppressive genes such asPdcd1l1,Arg1,Il10andTgfb1. In conclusion, the data presented here show that the inhibition of NLRP3 reduces IL-1β induction of pSTAT3(Y705) preventing expression of immunosuppressive genes as well as activity in PMN-MDSCs.
Partially Hydrolysed Whey Has Superior Allergy Preventive Capacity Compared to Intact Whey Regardless of Amoxicillin Administration in Brown Norway Rats
Authors: Graversen Katrine Bækby , Larsen Jeppe Madura , Pedersen Signe Schultz , Sørensen Laila Vestergaard , Christoffersen Heidi Frahm , Jacobsen Lotte Neergaard , Halken Susanne , Licht Tine Rask , Bahl Martin Iain , Bøgh Katrine Lindholm 
Published: September 2021

BackgroundIt remains largely unknown how physicochemical properties of hydrolysed infant formulas influence their allergy preventive capacity, and results from clinical and animal studies comparing the preventive capacity of hydrolysed infant formula with conventional infant formula are inconclusive. Thus, the use of hydrolysed infant formula for allergy prevention in atopy-prone infants is highly debated. Furthermore, knowledge on how gut microbiota influences allergy prevention remains scarce.ObjectiveTo gain knowledge on (1) how physicochemical properties of hydrolysed whey products influence the allergy preventive capacity, (2) whether host microbiota disturbance influences allergy prevention, and (3) to what extent hydrolysed whey products influence gut microbiota composition.MethodsThe preventive capacity of four different ad libitum administered whey products was investigated in Brown Norway rats with either a conventional or an amoxicillin-disturbed gut microbiota. The preventive capacity of products was evaluated as the capacity to reduce whey-specific sensitisation and allergic reactions to intact whey after intraperitoneal post-immunisations with intact whey. Additionally, the direct effect of the whey products on the growth of gut bacteria derived from healthy human infant donors was evaluated by in vitro incubation.ResultsTwo partially hydrolysed whey products with different physicochemical characteristics were found to be superior in preventing whey-specific sensitisation compared to intact and extensively hydrolysed whey products. Daily oral amoxicillin administration, initiated one week prior to intervention with whey products, disturbed the gut microbiota but did not impair the prevention of whey-specific sensitisation. The in vitro incubation of infant faecal samples with whey products indicated that partially hydrolysed whey products might confer a selective advantage to enterococci.ConclusionsOur results support the use of partially hydrolysed whey products for prevention of cow’s milk allergy in atopy-predisposed infants regardless of their microbiota status. However, possible direct effects of partially hydrolysed whey products on gut microbiota composition warrants further investigation.
Prediction of Radiation Pneumonitis Using Genome-Scale Flux Analysis of RNA-Seq Derived From Peripheral Blood
Authors: Yang Siqi , Yao Yi , Dong Yi , Liu Junqi , Li Yingge , Yi Lina , Huang Yani , Gao Yanjun , Yin Junping , Li Qingqing , Ye Dafu , Gong Hongyun , Xu Bin , Li Jian , Song Qibin 
Published: September 2021

Purpose: Radiation pneumonitis (RP) frequently occurs during a treatment course of chest radiotherapy, which significantly reduces the clinical outcome and efficacy of radiotherapy. The ability to easily predict RP before radiotherapy would allow this disease to be avoided.Methods and Materials: This study recruited 48 lung cancer patients requiring chest radiotherapy. For each participant, RNA sequencing (RNA-Seq) was performed on a peripheral blood sample before radiotherapy. The RNA-Seq data was then integrated into a genome-scale flux analysis to develop an RP scoring system for predicting the probability of occurrence of RP. Meanwhile, the clinical information and radiation dosimetric parameters of this cohort were collected for analysis of any statistical associations between these parameters and RP. A non-parametric rank sum test showed no significant difference between the predicted results from the RP score system and the clinically observed occurrence of RP in this cohort.Results: The results of the univariant analysis suggested that the tumor stage, exposure dose, and bilateral lung dose of V5 and V20 were significantly associated with the occurrence of RP. The results of the multivariant analysis suggested that the exposure doses of V5 and V20 were independent risk factors associated with RP and a level of RP ≥ 2, respectively. Thus, our results indicate that our RP scoring system could be applied to accurately predict the risk of RP before radiotherapy because the scores were highly consistent with the clinically observed occurrence of RP.Conclusion: Compared with the standard statistical methods, this genome-scale flux-based scoring system is more accurate, straightforward, and economical, and could therefore be of great significance when making clinical decisions for chest radiotherapy.
Associations of IRAK1 Gene Polymorphisms and mRNA Expression With NMOSD Risk in the Northern Chinese Han Population
Authors: Yan Hongjing , Guo Ruoyi , Chen Weifeng , Xi Xutao , Wang Lianchang , Ma Jianxun , Li Bin 
Published: September 2021

Objectives:Interleukin (IL)-1 receptor-associated kinase 1 (IRAK1) is a very important immunomodulatory gene for autoimmune diseases located on the X chromosome. However, there was little study about the correlation of IRAK1 functional single nucleotide polymorphisms with mRNA expression in neuromyelitis optica spectrum disorder (NMOSD) patients. In this study, we aimed to investigate the plausible association of IRAK1 polymorphism, IRAK1 mRNA expression, and NMOSD risk in the northern Chinese Han population.Methods:Four loci of IRAK1 gene (rs1059702, rs7061789, rs1059703, and rs3027898) were genotyped using multiplex SNaPshot technique in 102 NMOSD patients and 213 healthy subjects. Allele, genotype, and haplotype frequencies were compared. Stratified analyses were conducted by age, sex, AQP4 status, and age of onset. IRAK1 mRNA levels in the peripheral blood mononuclear cells of 30 NMOSD patients (of active phase) and 15 healthy control subjects were detected using qPCR. The correlations between the SNP polymorphisms and mRNA expression levels of genes were tested using non-parametric tests.Results:The minor allele frequencies (MAF) of these four locis were significantly lower in NMOSD cases than that of the controls. The frequencies of rs1059703G/G genotype, rs1059702A/A genotype, rs3027898 C/C genotype, and rs7061789G/G genotype were higher in the case group than that of the control group. Haplotype analysis revealed that the major haplotype “G-A-C-G” (alleles in the order of SNPs rs1059703, rs1059702, rs3027898, and rs7061789), containing the risk alleles, conferred an adverse effect on NMOSD. The level of IRAK1mRNA was markedly higher in NMOSD when compared to the healthy control groups. The IRAK1mRNA levels of female patients with the major haplotype were significantly higher compared to those with other haplotypes and to the male patients with the same genotype.Conclusion:IRAK1 polymorphisms were highly correlated with NMOSD susceptibility. Its haplotype G-A-C-G (rs1059703-rs1059702-rs3027898-rs7061789) confers increasing the risk of NMOSD in female patients. The IRAK1 risk haplotype G-A-C-G upregulated IRAK1 mRNA expression in female NMOSD patients. Our study provides a novel insight into the molecular mechanism of the pathogenesis of NMOSD and reveals that IRAK1 is the potential mechanism-specific druggable target in NMOSD disease.
Case Report: Minimal Neurological Deficit of Two Adult Patients With Weston–Hurst Syndrome Due to Early Craniectomy: Case Series and Review of Literature on Craniectomy
Authors: Loesch-Biffar Anna Mira , Junker Andreas , Linn Jennifer , Thon Niklas , Heck Suzette , Ottomeyer Caroline , Straube Andreas , Pfister Hans Walter 
Published: September 2021

Objectives:We describe two new cases of acute hemorrhagic leucoencephalitis (AHLE), who survived with minimal sequelae due to early measures against increased intracranial pressure, particularly craniotomy. The recently published literature review on treatment and outcome of AHLE was further examined for the effect of craniotomy.Methods:We present two cases from our institution. The outcome of 44 cases from the literature was defined either as good (no deficit, minimal deficit/no daily help) or poor outcome (severe deficit/disabled, death). Patients with purely infratentorial lesions (n= 9) were excluded. Fisher's exact test was applied.Results:Two cases are presented: A 43-year-old woman with rapidly progressive aphasia and right hemiparesis due to a huge left frontal white matter lesion with rim contrast enhancement. Pathology was consistent with AHLE. The second case was a 56-year-old woman with rapidly progressive aphasia and right hemiparesis. Cranial MRI showed a huge left temporo-occipital white matter lesion with typical morphology for AHLE. Both patients received craniotomy within the first 24 h and consequent immunosuppressive-immunomodulatory treatment and survived with minimal deficits. Out of 35 supratentorial reported AHLE cases, seven patients received decompressive craniotomy. Comparing all supratentorial cases, patients who received craniotomy were more likely to have a good outcome (71 vs. 29%).Conclusion:Due to early control of the intracranial pressure, particularly due to early craniotomy; diagnosis per biopsy; and immediate start of immunosuppressive-immunomodulatory therapies (cortisone pulse, plasma exchanges), both patients survived with minimal sequelae. Craniotomy plays an important role and should be considered early on in patients with probable AHLE.
Short-Latency Covert Saccades - The Explanation for Good Dynamic Visual Performance After Unilateral Vestibular Loss?
Authors: Sjögren Julia , Karlberg Mikael , Hickson Craig , Magnusson Måns , Fransson Per-Anders , Tjernström Fredrik 
Published: September 2021

Background: Functional head impulse test (fHIT) tests the ability of the vestibulo-ocular reflex (VOR) to allow visual perception during head movements. Our previous study showed that active head movements to the side with a vestibular lesion generated a dynamic visual performance that were as good as during movements to the intact side.Objective: To examine the differences in eye position during the head impulse test when performed with active and passive head movements, in order to better understand the role of the different saccade properties in improving visual performance.Method: We recruited 8 subjects with complete unilateral vestibular loss (4 men and 4 women, mean age 47 years) and tested them with video Head Impulse Test (vHIT) and Functional Head Impulse Test (fHIT) during passive and active movements while looking at a target. We assessed the mean absolute position error of the eye during different time frames of the head movement, the peak latency and the peak velocity of the first saccade, as well as the visual performance during the head movement.Results: Active head impulses to the lesioned side generated dynamic visual performances that were as good as when testing the intact side. Active head impulses resulted in smaller position errors during the visual perception task (p = 0.006) compared to passive head-impulses and the position error during the visual perception time frame correlated with shorter latencies of the first saccade (p &lt; 0.001).Conclusion: Actively generated head impulses toward the side with a complete vestibular loss resulted in a position error within or close to the margin necessary to obtain visual perception for a brief period of time in patients with chronic unilateral vestibular loss. This seems to be attributed to the appearance of short-latency covert saccades, which position the eyes in a more favorable position during head movements.
Brain Network Integrity Changes in Subjective Cognitive Decline: A Possible Physiological Biomarker of Dementia
Authors: Fogel Hilla , Levy-Lamdan Ofri , Zifman Noa , Hiller Tal , Efrati Shai , Suzin Gil , Hack Dallas C. , Dolev Iftach , Tanne David 
Published: September 2021

Objective: The current study seeks to illustrate potential early and objective neurophysiological biomarkers of neurodegenerative cognitive decline by evaluating features of brain network physiological performance and structure utilizing different modalities.Methods: This study included 17 clinically healthy individuals with self-reported cognitive decline (Subjective Cognitive Decline group, SCD, no objective finding of cognitive decline), 12 individuals diagnosed with amnestic Mild Cognitive Impairment (aMCI), 11 individuals diagnosed with Dementia, and 15 healthy subjects. All subjects underwent computerized cognitive performance testing, MRI scans including T1 for gray matter (GM) volume quantification, DTI for quantification of white matter (WM) microstructure fractional anisotropy (FA) and mean diffusivity (MD), and brain network function evaluation using DELPHI (TMS-EEG) measures of connectivity, excitability, and plasticity.Results: Both DELPHI analysis of network function and DTI analysis detected a significant decrease in connectivity, excitability, and WM integrity in the SCD group compared to healthy control (HC) subjects; a significant decrease was also noted for aMCI and Dementia groups compared to HC. In contrast, no significant decrease was observed in GM volume in the SCD group compared to healthy norms, a significant GM volume decrease was observed only in objectively cognitively impaired aMCI subjects and in dementia subjects.Conclusions: This study results suggest that objective direct measures of brain network physiology and WM integrity may provide early-stage biomarkers of neurodegenerative-related changes in subjects that have not yet displayed any other objective measurable cognitive or GM volume deficits which may facilitate early preventive care for neurodegenerative decline and dementia.
Evaluation of Thiol Homeostasis in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders
Authors: Arslan Burak , Arslan Gökçe Ayhan , Tuncer Aslı , Karabudak Rana , Dinçel Aylin Sepici 
Published: September 2021

Objectives: The aim of this pilot study was to evaluate dynamic thiol-disulfide homeostasis as a novel oxidative stress parameter in multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) to better understand the role of thiol homeostasis in neuroimmunological diseases.Methods: A total of 85 participants were included in this study, consisting of 18 healthy controls, 52 patients diagnosed with MS, seven with NMOSD, and eight with MOGAD. We measured total thiol (–SH+-S–S–) and native thiol (–SH) levels in the serum of all the participants, and in a subset of patients (n = 11), these parameters were investigated in paired cerebrospinal fluid (CSF) and serum samples. Dynamic disulfide concentrations were calculated separately. Finally, we determined if there was any relationship between clinical features and dynamic thiol homeostasis.Results: There was a statistically significant difference between serum and CSF levels of biomarkers of thiol homeostasis. Serum total thiol (317.88 ± 66.04) and native thiol (211.61 ± 44.15) levels were significantly lower in relapsed patients compared to those in remission (368.84 ± 150.36 vs. 222.52 ± 70.59, respectively).Conclusions: Oxidative stress plays a crucial role in the physiopathology of neuroimmunological diseases. Thiol homeostasis may be useful for monitoring disease activity.
MMP-9 as a Biomarker for Predicting Hemorrhagic Strokes in Moyamoya Disease
Authors: Lu Junlin , Wang Jingyi , Lin Zhidong , Shi Guangchao , Wang Rong , Zhao Yahui , Zhao Yuanli , Zhao Jizong 
Published: September 2021

Objective: This study was conducted in order to investigate the association of matrix metalloproteinase (MMP)-9 levels with phenotypes of moyamoya disease (MMD).Methods: This study included plasma samples from 84 MMD patients. The clinical variables of these patients were reviewed from the medical record. The serum concentration of tight junction, adherens junction proteins, and MMPs (MMP-2 and MMP-9) was determined using the ELISA method. Patients with hemorrhagic-onset MMD were compared with those with ischemic-onset MMD.Results: Compared with pediatric patients, the expression of MMP-9 was significantly higher, while the MMP-2 and vascular endothelial-cadherin were lower in adult patients. In adult subgroup analysis, hemorrhagic MMD patients exhibited significantly higher serum concentrations of MMP-9 compared with ischemic MMD patients. The ROC curve identified that a baseline serum MMP-9 level &gt;1,011 ng/ml may be associated with spontaneous hemorrhage in adult MMD patients with 70.37% sensitivity and 71.88% specificity [area under curve (AUC), 0.73; 95% CI 0.597–0.864; P = 0.003]. A late Suzuki stage (&gt;4) (OR 4.565, 95% CI 1.028–20.280, P = 0.046) and serum concentrations of MMP-9 &gt;1,011 ng/ml (OR 7.218, 95% CI 1.826–28.533, P = 0.005) are risk predictors of hemorrhages in MMD patients. Hemorrhagic-type MMD patients had higher serum levels of MMP-9 and BBB permeability compared with ischemic-type MMD patients. Adult MMD patients had higher serum levels of MMP-9 and BBB permeability compared with pediatric patients.Conclusions: MMP-9 might serve as a biomarker for hemorrhage prediction in MMD. Serum MMP-9 level &gt;1,011 ng/ml is an independent risk factor of MMD hemorrhagic strokes.
Use of F-18 FDG PET/CT Through Delayed Diuretic Imaging for Preoperative Evaluation of Upper Urinary Tract-Occupying Lesions
Authors: Wang Jun , Zhang Liang , Wu Jian Guo , Chen Ruohua , Shen Jia lin 
Published: September 2021

PurposeTo evaluate the value of F-18 FDG PET/CT in the differentiation of malignant and benign upper urinary tract-occupying lesions.Patients and Methods64 patients with upper urinary tract-occupying lesions underwent F-18 FDG PET/CT at RenJi Hospital from January 2015 to February 2019 in this retrospective study. Of the 64 patients, 50 patients received nephroureterectomy or partial ureterectomy; 14 patients received ureteroscopy and biopsy. The comparisons of PET/CT parameters and clinical characteristics between malignant and benign upper urinary tract-occupying lesions were investigated.ResultsOf the 64 patients, 49 were found to have malignant tumors. Receiver operating characteristic analysis determined the lesion SUVmax value of 6.75 as the threshold for predicting malignant tumors. There were significant associations between malignant and benign upper urinary tract-occupying lesions and SUVmax of lesion (P&lt;0.001), lesion size (P&lt;0.001), and patient age (P=0.011). Multivariate analysis showed that SUVmax of lesion (P=0.042) and patient age (P=0.009) as independent predictors for differentiation of malignant from benign upper urinary tract-occupying lesions. There was a significant difference in tumor size between the positive (SUVmax &gt;6.75) and negative (SUVmax ≤6.75) PET groups in 38 of the 49 patients with malignant tumors.ConclusionThe SUVmax of lesion and patient age is associated with the nature of upper urinary tract-occupying lesions. F-18 FDG PET/CT may be useful to distinguish between malignant and benign upper urinary tract-occupying lesions and determine a suitable therapeutic strategy.
Glioma Stem-Like Cells and Metabolism: Potential for Novel Therapeutic Strategies
Authors: Harland Abigail , Liu Xia , Ghirardello Mattia , Galan M. Carmen , Perks Claire M. , Kurian Kathreena M. 
Published: September 2021

Glioma stem-like cells (GSCs) were first described as a population which may in part be resistant to traditional chemotherapeutic therapies and responsible for tumour regrowth. Knowledge of the underlying metabolic complexity governing GSC growth and function may point to potential differences between GSCs and the tumour bulk which could be harnessed clinically. There is an increasing interest in the direct/indirect targeting or reprogramming of GSC metabolism as a potential novel therapeutic approach in the adjuvant or recurrent setting to help overcome resistance which may be mediated by GSCs. In this review we will discuss stem-like models, interaction between metabolism and GSCs, and potential current and future strategies for overcoming GSC resistance.