bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of dietary tryptophan on the antioxidant capacity and immune response associated with TOR and TLRs/MyD88/NF-κB signaling pathways in northern snakehead, Channa argus (Cantor, 1842)
Authors: Zhang Xin , Wang Anran , Chang Enhui , Han Bei , Xu Jie , Fu Yu , Dong Xiaojing , Miao Shuyan 
Published: April 2023

IntroductionDietary tryptophan (Trp) has been shown to influence fish feed intake, growth, immunity and inflammatory responses. The purpose of this study was to investigate the effect and mechanism of Trp on immune system of juvenile northern snakehead (Channa argus Cantor, 1842).MethodsA total of 540 fish (10.21 ± 0.11 g) were fed six experimental diets containing graded levels of Trp at 1.9, 3.0, 3.9, 4.8, 5.9 and 6.8 g/kg diet for 70 days, respectively.Results and DiscussionThe results showed that supplementation of 1.9-4.8 g/kg Trp in diets had no effect on the hepatosomatic index (HSI) and renal index (RI), while dietary 3.9 and 4.8 g/kg Trp significantly increased spleen index (SI) of fish. Dietary 3.9, 4.8, 5.9 and 6.8 g/kg Trp enhanced the total hemocyte count (THC), the activities of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD). Malondinaldehyde (MDA) levels in the blood were significantly decreased by consuming 3.9 and 4.8 g/kg Trp. Fish fed with 3.0 and 3.9 g/kg Trp diets up-regulated interleukin 6 (il-6) and interleukin 8 (il-8) mRNA levels. The expression of tumor necrosis factor α (tnf-α) was highest in fish fed with 3.0 g/kg Trp diet, and the expression of interleukin 1β (il-1β) was highest in fish fed with 3.9 g/kg Trp diet. Dietary 4.8, 5.9 and 6.8 g/kg Trp significantly decreased il-6 and tnf-α mRNA levels in the intestine. Moreover, Trp supplementation was also beneficial to the mRNA expression of interleukin 22 (il-22). Additionally, the mRNA expression levels of target of rapamycin (tor), toll-like receptor-2 (tlr2), toll-like receptor-4 (tlr4), toll-like receptor-5 (tlr5) and myeloid differentiation primary response 88 (myd88) of intestine were significantly up-regulated in fish fed 1.9, 3.0 and 3.9 g/kg Trp diets, and down-regulated in fish fed 4.8, 5.9 and 6.8 g/kg Trp diets. Dietary 4.8 and 5.9 g/kg Trp significantly increased the expression of inhibitor of nuclear factor kappa B kinase beta subunit (ikkβ) and decreased the expression of inhibitor of kappa B (iκbα), but inhibited nuclear transcription factor kappa B (nf-κb) mRNA level. Collectively, these results indicated that dietary 4.8 g/kg Trp could improve antioxidant capacity and alleviate intestinal inflammation associated with TOR and TLRs/MyD88/NF-κB signaling pathways.
A cross-sectional study of retinal vessel changes based on optical coherence tomography angiography in Alzheimer’s disease and mild cognitive impairment
Authors: Ma Xiaoyu , Xie Zengmai , Wang Huan , Tian Zhongping , Bi Yanlong , Li Yunxia , Zhang Li 
Published: April 2023

BackgroundThe involvement of retina and its vasculature has been recently described in Alzheimer’s disease (AD). Optical coherence tomography angiography (OCTA) is noninvasively used to assess the retinal blood flow.ObjectiveThis study was to compare vessel density (VD) and blood perfusion density (PD) of the macular in AD patients, mild cognitive impairment (MCI) patients and healthy controls by OCTA, which may provide new ideas for diagnosis of AD or MCI.MethodsAD patients, MCI patients and healthy controls underwent a comprehensive ophthalmic and neurological evaluations, including cognitive function assessments as well as visual acuity, intraocular pressure (IOP), slit lamp examinations, and OCTA. General demographic data, cognitive function, retinal VD and PD were compared among three groups. The correlations among retinal VD, PD and cognitive function, amyloid-beta (Aβ) protein and phosphorylated Tau (p-Tau) protein were further evaluated. The correlations between retinal superficial capillary plexus and cognitive function, Aβ protein and p-Tau protein were also explored.ResultsA total of 139 participants were recruited into this study, including 43 AD patients, 62 MCI patients, and 34 healthy controls. After adjusting for sex, age, history of smoking, history of alcohol intake, hypertension, hyperlipidemia, best corrected visual acuity, and IOP, VD and PD in the nasal and inferior regions of the inner ring, superior and inferior regions of outer ring in the AD group were significantly lower than in the control group (p &lt; 0.05). PD in nasal region of outer ring also significantly decreased in the AD group. VD and PD in superior and inferior regions of inner ring, superior and temporal regions of outer ring in the MCI group were markedly lower than in the control group (p &lt; 0.05). After adjusting for sex and age, VD and PD were correlated with Montreal Cognitive Assessment Basic score, Mini-mental State Examination score, visuospatial function and executive function (p &lt; 0.05), while Aβ protein and p-Tau protein had no relationship with VD and PD.ConclusionOur findings suggest that superficial retinal VD and PD in macula may be potential non-invasive biomarkers for AD and MCI, and these vascular parameters correlate with cognitive function.
Association of candidate genetic variants and circulating levels of ApoE/ApoJ with common neuroimaging features of cerebral amyloid angiopathy
Authors: Bonaterra-Pastra Anna , Benítez Sònia , Pancorbo Olalla , Rodríguez-Luna David , Vert Carla , Rovira Alex , Freijo M. Mar , Tur Silvia , Martínez-Zabaleta Maite , Cardona Portela Pere , Vera Rocío , Lebrato-Hernández Lucia , Arenillas Juan F. , Pérez-Sánchez Soledad , Domínguez-Mayoral Ana , Fàbregas Joan Martí , Mauri Gerard , Montaner Joan , Sánchez-Quesada Jose Luis , Hernández-Guillamon Mar 
Published: April 2023

IntroductionCerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid-β (Aβ) in brain vessels and is a main cause of lobar intracerebral hemorrhage (ICH) in the elderly. CAA is associated with magnetic resonance imaging (MRI) markers of small vessel disease (SVD). Since Aβ is also accumulated in Alzheimer’s disease (AD) in the brain parenchyma, we aimed to study if several single nucleotide polymorphisms (SNPs) previously associated with AD were also associated with CAA pathology. Furthermore, we also studied the influence of APOE and CLU genetic variants in apolipoprotein E (ApoE) and clusterin/apolipoprotein J (ApoJ) circulating levels and their distribution among lipoproteins.MethodsThe study was carried out in a multicentric cohort of 126 patients with lobar ICH and clinical suspicion of CAA.ResultsWe observed several SNPs associated with CAA neuroimaging MRI markers [cortical superficial siderosis (cSS), enlarged perivascular spaces in the centrum semiovale (CSO-EPVS), lobar cerebral microbleeds (CMB), white matter hyperintensities (WMH), corticosubcortical atrophy and CAA-SVD burden score]. Concretely, ABCA7 (rs3764650), CLU (rs9331896 and rs933188), EPHA1 (rs11767557), and TREML2 (rs3747742) were significantly associated with a CAA-SVD burden score. Regarding circulating levels of apolipoproteins, protective AD SNPs of CLU [rs11136000 (T) and rs9331896 (C)] were significantly associated with higher HDL ApoJ content in the lobar ICH cohort. APOEε2 carriers presented higher plasma and LDL-associated ApoE levels whereas APOEε4 carriers presented lower plasma ApoE levels. Additionally, we observed that lower circulating ApoJ and ApoE levels were significantly associated with CAA-related MRI markers. More specifically, lower LDL-associated ApoJ and plasma and HDL-associated ApoE levels were significantly associated with CSO-EPVS, lower ApoJ content in HDL with brain atrophy and lower ApoE content in LDL with the extent of cSS.DiscussionThis study reinforces the relevance of lipid metabolism in CAA and cerebrovascular functionality. We propose that ApoJ and ApoE distribution among lipoproteins may be associated with pathological features related to CAA with higher ApoE and ApoJ levels in HDL possibly enhancing atheroprotective, antioxidative, and anti-inflammatory responses in cerebral β-amyloidosis.
Spatiotemporal dynamics of the development of mouse olfactory system from prenatal to postnatal period
Authors: Kim Bo-Ra , Rha Min-Seok , Cho Hyung-Ju , Yoon Joo-Heon , Kim Chang-Hoon 
Published: April 2023

IntroductionThe olfactory epithelium (OE) and olfactory bulb (OB) are the major components of the olfactory system and play critical roles in olfactory perception. However, the embryonic development of OE and OB by using the olfactory specific genes has not been comprehensively investigated yet. Most previous studies were limited to a specific embryonic stage, and very little is known, till date, about the development of OE.MethodsThe current study aimed to explore the development of mouse olfactory system by spatiotemporal analysis of the histological features by using the olfactory specific genes of olfactory system from the prenatal to postnatal period.ResultsWe found that OE is divided into endo-turbinate, ecto-turbinate, and vomeronasal organs, and that putative OB with putative main and accessory OB is formed in the early developmental stage. The OE and OB became multilayered in the later developmental stages, accompanied by the differentiation of olfactory neurons. Remarkably, we found the development of layers of olfactory cilia and differentiation of OE to progress dramatically after birth, suggesting that the exposure to air may facilitate the final development of OE.DiscussionOverall, the present study laid the groundwork for a better understanding of the spatial and temporal developmental events of the olfactory system.
Pausing before verb production is associated with mild cognitive impairment in Parkinson’s disease
Authors: Andrade Eduardo Inacio Nascimento , Manxhari Christina , Smith Kara M. 
Published: April 2023

BackgroundCognitive dysfunction and communication impairment are common and disabling symptoms in Parkinson’s Disease (PD). Action verb deficits occur in PD, but it remains unclear if these impairments are related to motor system dysfunction and/or cognitive decline. The objective of our study was to evaluate relative contributions of cognitive and motor dysfunction to action verb production in naturalistic speech of patients with PD. We proposed that pausing before action-related language is associated with cognitive dysfunction and may serve as a marker of mild cognitive impairment in PD.MethodParticipants with PD (n = 92) were asked to describe the Cookie Theft picture. Speech files were transcribed, segmented into utterances, and verbs classified as action or non-action (auxiliary). We measured silent pauses before verbs and before utterances containing verbs of different classes. Cognitive assessment included Montreal Cognitive Assessment (MoCA) and neuropsychological tests to categorize PD participants as normal cognition (PD-NC) or mild cognitive impairment (PD-MCI) based on Movement Disorders Society (MDS) Task Force Tier II criteria. Motor symptoms were assessed using MDS-UPDRS. We performed Wilcoxon rank sum tests to identify differences in pausing between PD-NC and PD-MCI. Logistic regression models using PD-MCI as dependent variables were used to evaluate the association between pause variables and cognitive status.ResultsParticipants with PD-MCI demonstrated more pausing before and within utterances compared to PD-NC, and the duration of these pauses were correlated with MoCA but not motor severity (MDS-UPDRS). Logistic regression models demonstrated that pauses before action utterances were associated with PD-MCI status, whereas pauses before non-action utterances were not significantly associated with cognitive diagnosis.ConclusionWe characterized pausing patterns in spontaneous speech in PD-MCI, including analysis of pause location with respect to verb class. We identified associations between cognitive status and pausing before utterances containing action verbs. Evaluation of verb-related pauses may be developed into a potentially powerful speech marker tool to detect early cognitive decline in PD and better understand linguistic dysfunction in PD.
Steady electrocorticogram characteristics predict specific stress-induced behavioral phenotypes
Authors: Desnouveaux Laura , Poly Betty , Edmond Mathilde , Aphezberro Cathy , Coulon David , Boutet Francis , Le Coz Christine , Fargeau Francisca , Linard Cyril , Caillol Pierre , Duffaud Anaïs M. , Servonnet Aurélie , Ferhani Ouamar , Trousselard Marion , Taudon Nicolas , Canini Frédéric , Claverie Damien 
Published: April 2023

IntroductionDepending on the individual, exposure to an intense stressor may, or may not, lead to a stress-induced pathology. Predicting the physiopathological evolution in an individual is therefore an important challenge, at least for prevention. In this context, we developed an ethological model of simulated predator exposure in rats: we call this the multisensorial stress model (MSS). We hypothesized that: (i) MSS exposure can induce stress-induced phenotypes, and (ii) an electrocorticogram (ECoG) recorded before stress exposure can predict phenotypes observed after stress.MethodsForty-five Sprague Dawley rats were equipped with ECoG telemetry and divided into two groups. The Stress group (n = 23) was exposed to an MSS that combined synthetic fox feces odor deposited on filter paper, synthetic blood odor, and 22 kHz rodent distress calls; the Sham group (n = 22) was not exposed to any sensorial stimulus. Fifteen days after initial exposure, the two groups were re-exposed to a context that included a filter paper soaked with water as a traumatic object (TO) reminder. During this re-exposure, freezing behavior and avoidance of the filter paper were measured.ResultsThree behaviors were observed in the Stress group: 39% developed a fear memory phenotype (freezing, avoidance, and hyperreactivity); 26% developed avoidance and anhedonia; and 35% made a full recovery. We also identified pre-stress ECoG biomarkers that accurately predicted cluster membership. Decreased chronic 24 h frontal Low θ relative power was associated with resilience; increased frontal Low θ relative power was associated with fear memory; and decreased parietal β2 frequency was associated with the avoidant-anhedonic phenotype.DiscussionThese predictive biomarkers open the way to preventive medicine for stress-induced diseases.
Evidence for a protective effect of the loss of α4-containing nicotinic acetylcholine receptors on Aβ-related neuropathology in Tg2576 mice
Authors: Vilella Antonietta , Romoli Benedetto , Bodria Martina , Pons Stéphanie , Maskos Uwe , Zoli Michele 
Published: April 2023

IntroductionLoss of cholinergic neurons as well as α4β2* (* = containing) nicotinic acetylcholine receptors (nAChRs) is a prominent feature of Alzheimer’s disease (AD). Specifically, amyloid β (Aβ), the principal pathogenic factor of AD, is a high affinity ligand for nAChRs. Yet, the pathophysiological role of nAChRs in AD is not well established.MethodsIn the present study, we have investigated the effects of the loss of α4* nAChRs on the histological alterations of the Tg2576 mouse model of AD (APPswe) crossing hemizygous APPswe mice with mice carrying the genetic inactivation of α4 nAChR subunit (α4KO).ResultsA global decrease in Aβ plaque load was observed in the forebrain of APPswe/α4KO mice in comparison with APPswe mice, that was particularly marked in neocortex of 15 month-old mice. At the same age, several alterations in synaptophysin immunoreactivity were observed in cortico-hippocampal regions of APPswe mice that were partially counteracted by α4KO. The analysis of the immunoreactivity of specific astroglia (glial fibrillary acidic protein, GFAP) and microglia (ionized calcium-binding adapter molecule, Iba1) markers showed an increase in the number as well as in the area occupied by these cells in APPswe mice that were partially counteracted by α4KO.ConclusionOverall, the present histological study points to a detrimental role of α4* nAChRs that may be specific for Aβ-related neuropathology.
Alterations of peripheral cytokines, BDNF, and surface-based morphometry indices in T2DM patients without cognitive impairment
Authors: Lyu Wenjiao , Chen Yuna , Zhao Kui , Tan Xin , Wu Ye , Qiu Shijun 
Published: April 2023

PurposeThis study aimed to investigate potential biological mechanisms underlying cognitive function alterations in Type 2 diabetes mellitus (T2DM) patients by integrating cortical morphology with peripheral cytokine levels and brain-derived neurotrophic factor (BDNF) levels, and to offer potential insights for the early detection of T2DM-related cognitive impairment.MethodsThis study included 16 T2DM patients with a Montreal Cognitive Assessment (MoCA) score of at least 26 points, as well as 16 healthy controls with normal cognitive function. The participants also completed the digit span test and digit symbol substitution test. Participants’ serum levels of Interleukin 4 (IL-4), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and BDNF were also examined. Each subject underwent a high-resolution 3T structural brain MRI scan. Based on the aparc. a2009s atlas, we calculated the cortical thickness, sulcus depth, gyrification index, and fractal dimension for each participant using surface-based morphometry (SBM). Correlation analysis between cognitive measures, serum levels of cytokines and BDNF, and SBM indices were further performed.ResultsThe levels of IL-4 and BDNF showed significant group differences. In the T2DM group, the sulcus depth exhibited a significant decrease in the left transverse frontopolar gyri and sulci, as well as in the right pole-occipital; the fractal dimension showed a significant increase in the right posterior-dorsal part of the cingulate gyrus; and the gyrification index significantly increased in the left inferior part of the precentral sulcus and right triangular part of the inferior frontal gyrus. Correlation analysis revealed a significant positive correlation between IL-10 levels and the sulcus depth of left transverse frontopolar gyri and sulci; a significant positive correlation between the sulcus depth of the right pole-occipital and the digit span test-forward scores, and a significant negative correlation between the gyrification index of the left inferior part of the precentral sulcus and the digit span test-backward scores among T2DM participants.ConclusionT2DM patients without cognitive impairment displayed reductions in IL 4 and BDNF levels, as well as significant alterations in their SBM indices, indicating that prior to the emergence of cognitive impairment, the SBM indices, peripheral cytokines, and BDNF may have altered in T2DM patients. IL-10 may lessen inflammation-related brain edema and preserve sulcus depth in T2DM patients through its anti-inflammatory activity.
Vertebrobasilar artery cooling infusion in acute ischemic stroke for posterior circulation following thrombectomy: Rationale, design and protocol for a prospective randomized controlled trial
Authors: Cheng Zhe , Ding Yuchuan , Rajah Gary B. , Gao Jie , Li Fenghai , Ma Linlin , Geng Xiaokun 
Published: April 2023

BackgroundAlthough endovascular mechanical thrombectomy demonstrates clinical efficacy in posterior circulation acute ischemic stroke (AIS), only one third of these patients attain functional independence with a third of patients’ expiring despite vascular recanalization. Neuroprotection strategies, such as therapeutic hypothermia (TH) have been considered a promising adjunctive treatment in AIS. We propose the following rationale, design and protocol for a prospective randomized controlled trial (RCT) aimed to determine whether Vertebrobasilar Artery Cooling Infusion (VACI) improves functional outcomes in posterior circulation AIS patients post mechanical thrombectomy.MethodsSubjects in the study will be assigned randomly to either the cooling infusion or the control group in a 1:1 ratio (n = 40). Patients allocated to the cooling infusion group will receive 300 ml cool saline at 4C through the catheter (30 ml/min) into vertebral artery after thrombectomy. The control group will receive the same volume of 37C saline. All patients enrolled will receive standard care according to current guidelines for stroke management. The primary outcome is symptomatic intracranial hemorrhage (ICH), whereas the secondary outcomes include functional outcome score, infarction volume, mortality, ICH, fatal ICH, cerebral vasospasm, coagulation abnormality, pneumonia and urinary infection.DiscussionsThis study will determine the preliminary safety, feasibility, and neuroprotective benefits of VACI in posterior circulation AIS patients with reperfusion therapy. The results of this study may provide evidence for VACI as a new therapy in posterior circulation AIS.Clinical Trial Registration:www.chictr.org.cn, ChiCTR2200065806, registered on November 15, 2022.
Preoperative prediction of sonic hedgehog and group 4 molecular subtypes of pediatric medulloblastoma based on radiomics of multiparametric MRI combined with clinical parameters
Authors: Wang Yuanlin , Wang Longlun , Qin Bin , Hu Xihong , Xiao Wenjiao , Tong Zanyong , Li Shuang , Jing Yang , Li Lusheng , Zhang Yuting 
Published: April 2023

PurposeTo construct a machine learning model based on radiomics of multiparametric magnetic resonance imaging (MRI) combined with clinical parameters for predicting Sonic Hedgehog (SHH) and Group 4 (G4) molecular subtypes of pediatric medulloblastoma (MB).MethodsThe preoperative MRI images and clinical data of 95 patients with MB were retrospectively analyzed, including 47 cases of SHH subtype and 48 cases of G4 subtype. Radiomic features were extracted from T1-weighted imaging (T1), contrast-enhanced T1 weighted imaging (T1c), T2-weighted imaging (T2), T2 fluid-attenuated inversion recovery imaging (T2FLAIR), and apparent diffusion coefficient (ADC) maps, using variance thresholding, SelectKBest, and Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithms. The optimal features were filtered using LASSO regression, and a logistic regression (LR) algorithm was used to build a machine learning model. The receiver operator characteristic (ROC) curve was plotted to evaluate the prediction accuracy, and verified by its calibration, decision and nomogram. The Delong test was used to compare the differences between different models.ResultsA total of 17 optimal features, with non-redundancy and high correlation, were selected from 7,045 radiomics features, and used to build an LR model. The model showed a classification accuracy with an under the curve (AUC) of 0.960 (95% CI: 0.871−1.000) in the training cohort and 0.751 (95% CI: 0.587−0.915) in the testing cohort, respectively. The location of the tumor, pathological type, and hydrocephalus status of the two subtypes of patients differed significantly (p &lt; 0.05). When combining radiomics features and clinical parameters to construct the combined prediction model, the AUC improved to 0.965 (95% CI: 0.898−1.000) in the training cohort and 0.849 (95% CI: 0.695−1.000) in the testing cohort, respectively. There was a significant difference in the prediction accuracy, as measured by AUC, between the testing cohorts of the two prediction models, which was confirmed by Delong’s test (p = 0.0144). Decision curves and nomogram further validate that the combined model can achieve net benefits in clinical work.ConclusionThe combined prediction model, constructed based on radiomics of multiparametric MRI and clinical parameters can potentially provide a non-invasive clinical approach to predict SHH and G4 molecular subtypes of MB preoperatively.