bluuebunny/crossref_metadata_2025_split huggingface dataset:
NMR Metabolite Profiles of the Bivalve Mollusc Mytilus galloprovincialis Before and After Immune Stimulation With Vibrio splendidus
Authors: Frizzo Riccardo , Bortoletto Enrico , Riello Tobia , Leanza Luigi , Schievano Elisabetta , Venier Paola , Mammi Stefano 
Published: September 2021

The hemolymph metabolome of Mytilus galloprovincialis injected with live Vibrio splendidus bacteria was analyzed by 1H-NMR spectrometry. Changes in spectral hemolymph profiles were already detected after mussel acclimation (3 days at 18 or 25 °C). A significant decrease of succinic acid was accompanied by an increase of most free amino acids, mytilitol, and, to a smaller degree, osmolytes. These metabolic changes are consistent with effective osmoregulation, and the restart of aerobic respiration after the functional anaerobiosis occurred during transport. The injection of Vibrio splendidus in mussels acclimated at 18°C caused a significant decrease of several amino acids, sugars, and unassigned chemical species, more pronounced at 24 than at 12 h postinjection. Correlation heatmaps indicated dynamic metabolic adjustments and the relevance of protein turnover in maintaining the homeostasis during the response to stressful stimuli. This study confirms NMR-based metabolomics as a feasible analytical approach complementary to other omics techniques in the investigation of the functional mussel responses to environmental challenges.
CD74 Correlated With Malignancies and Immune Microenvironment in Gliomas
Authors: Xu Shengchao , Li Xizhe , Tang Lu , Liu Zhixiong , Yang Kui , Cheng Quan 
Published: September 2021

Background: Cluster of differentiation 74 (CD74) is found to be highly involved in the development of various types of cancers and could affect the activities of infiltrated cells in the tumor microenvironment. However, these studies only focus on a few types of immune cells. Our study aims to comprehensively explore the role of CD74 in glioma prognosis and immune microenvironment.Methods: A total of 40 glioma specimens were collected in this study. We extracted data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene-Expression Omnibus (GEO) databases to explore the expression pattern of CD74 in gliomas. gene sets enrichment analysis and gene set variation analysis analyses were conducted to characterize the immune features of CD74. ESTIMATE, ssGSEA, Tumor IMmune Estimation Resource, and CIBERSORT algorithms were applied to assess the immune infiltration. Kaplan-Meier analysis was used for survival analysis. Receiver operating characteristic analysis was used to evaluate the predictive accuracy of CD74 in glioma diagnosis and prognosis.Results: A total of 2,399 glioma patients were included in our study. CD74 was highly expressed in glioma tissue compared to normal brain tissue and its expression was significantly higher in the high-grade glioma compared to the lower grade glioma at transcriptional and translational levels. Besides, CD74 was positively associated with immune checkpoints and inflammatory cytokines as well as immune processes including cytokine secretion and leukocyte activation. The high expression of CD74 indicated a high infiltration of immune cells such as macrophages, dendritic cells, and neutrophils. Moreover, patients with high expression of CD74 had poor prognoses. CD74 had moderate predictive accuracy in the diagnosis of glioblastoma and prediction of survival.Conclusions: In conclusion, our study revealed that the high expression of CD74 was associated with poor prognosis and high immune infiltration. CD74 could be used as a potential target for glioma treatment and as a biomarker to predict the prognosis of glioma patients.
Dissecting Monomer-Dimer Equilibrium of an RNase P Protein Provides Insight Into the Synergistic Flexibility of 5’ Leader Pre-tRNA Recognition
Authors: Zeng Danyun , Abzhanova Ainur , Brown Benjamin P. , Reiter Nicholas J. 
Published: September 2021

Ribonuclease P (RNase P) is a universal RNA-protein endonuclease that catalyzes 5’ precursor-tRNA (ptRNA) processing. The RNase P RNA plays the catalytic role in ptRNA processing; however, the RNase P protein is required for catalysis in vivo and interacts with the 5’ leader sequence. A single P RNA and a P protein form the functional RNase P holoenzyme yet dimeric forms of bacterial RNase P can interact with non-tRNA substrates and influence bacterial cell growth. Oligomeric forms of the P protein can also occur in vitro and occlude the 5’ leader ptRNA binding interface, presenting a challenge in accurately defining the substrate recognition properties. To overcome this, concentration and temperature dependent NMR studies were performed on a thermostable RNase P protein from Thermatoga maritima. NMR relaxation (R1, R2), heteronuclear NOE, and diffusion ordered spectroscopy (DOSY) experiments were analyzed, identifying a monomeric species through the determination of the diffusion coefficients (D) and rotational correlation times (τc). Experimental diffusion coefficients and τc values for the predominant monomer (2.17 ± 0.36 * 10−10 m2/s, τc = 5.3 ns) or dimer (1.87 ± 0.40* 10−10 m2/s, τc = 9.7 ns) protein assemblies at 45°C correlate well with calculated diffusion coefficients derived from the crystallographic P protein structure (PDB 1NZ0). The identification of a monomeric P protein conformer from relaxation data and chemical shift information enabled us to gain novel insight into the structure of the P protein, highlighting a lack of structural convergence of the N-terminus (residues 1–14) in solution. We propose that the N-terminus of the bacterial P protein is partially disordered and adopts a stable conformation in the presence of RNA. In addition, we have determined the location of the 5’ leader RNA in solution and measured the affinity of the 5’ leader RNA–P protein interaction. We show that the monomer P protein interacts with RNA at the 5’ leader binding cleft that was previously identified using X-ray crystallography. Data support a model where N-terminal protein flexibility is stabilized by holoenzyme formation and helps to accommodate the 5’ leader region of ptRNA. Taken together, local structural changes of the P protein and the 5’ leader RNA provide a means to obtain optimal substrate alignment and activation of the RNase P holoenzyme.
Rebleeding of Ruptured Intracranial Aneurysm After Admission: A Multidimensional Nomogram Model to Risk Assessment
Authors: Liu Qingyuan , Yang Yi , Yang Junhua , Li Maogui , Yang Shuzhe , Wang Nuochuan , Wu Jun , Jiang Pengjun , Wang Shuo 
Published: September 2021

ObjectiveRebleeding is recognized as the main cause of mortality after intracranial aneurysm rupture. Though timely intervention can prevent poor prognosis, there is no agreement on the surgical priority and choosing medical treatment for a short period after rupture. The aim of this study was to investigate the risk factors related to the rebleeding after admission and establish predicting models for better clinical decision-making.MethodsThe patients with ruptured intracranial aneurysms (RIAs) between January 2018 and September 2020 were reviewed. All patients fell to the primary and the validation cohort by January 2020. The hemodynamic parameters were determined through the computational fluid dynamics simulation. Cox regression analysis was conducted to identify the risk factors of rebleeding. Based on the independent risk factors, nomogram models were built, and their predicting accuracy was assessed by using the area under the curves (AUCs).ResultA total of 577 patients with RIAs were enrolled in this present study, 86 patients of them were identified as undergoing rebleeding after admission. Thirteen parameters were identified as significantly different between stable and rebleeding aneurysms in the primary cohort. Cox regression analysis demonstrated that six parameters, including hypertension [hazard ratio (HR), 2.54; P = 0.044], bifurcation site (HR, 1.95; P = 0.013), irregular shape (HR, 4.22; P = 0.002), aspect ratio (HR, 12.91; P &lt; 0.001), normalized wall shear stress average (HR, 0.16; P = 0.002), and oscillatory stress index (HR, 1.14; P &lt; 0.001) were independent risk factors related to the rebleeding after admission. Two nomograms were established, the nomogram including clinical, morphological, and hemodynamic features (CMH nomogram) had the highest predicting accuracy (AUC, 0.92), followed by the nomogram including clinical and morphological features (CM nomogram; AUC, 0.83), ELAPSS score (AUC, 0.61), and PHASES score (AUC, 0.54). The calibration curve for the probability of rebleeding showed good agreement between prediction by nomograms and actual observation. In the validation cohort, the discrimination of the CMH nomogram was superior to the other models (AUC, 0.93 vs. 0.86, 0.71 and 0.48).ConclusionWe presented two nomogram models, named CMH nomogram and CM nomogram, which could assist in identifying the RIAs with high risk of rebleeding.
Reduced Risk of Atrial Fibrillation Following Cholecystectomy: A Nationwide Population-Based Study
Authors: Ho Tung Ching , Chen Yu-Ching , Lin Che-Chen , Tai Hsu-Chih , Wei Cheng-Yu , Yeh Yung-Hsiang , Hsu Chung Y. 
Published: September 2021

Background: Gallstone disease (GD) is associated with a high risk of cardiovascular disease. However, it is unknown whether GD contributes to atrial fibrillation (AF). We aimed to investigate the association between GD and AF.Methods: We performed a population-based cohort study using data from the Taiwan National Health Insurance Research Database between 2001 and 2011. A GD cohort of 230,076 patients was compared with a control cohort consisting of an equal number of patients matched for age, sex, cardiovascular and gastrointestinal comorbidities.Results: In total, 5,992 (49.8/10,000 person-years) patients with GD and 5,804 (44.5/10,000 person-years) controls developed AF. GD increased AF risk with a hazard ratio (HR) of 1.20 [95% confidence interval (CI), 1.16–1.25]. In patients with GD but without cholecystectomy, the HR of AF reached 1.57 (95% CI = 1.50–1.63). After cholecystectomy, the HR of AF significantly decreased to 0.85 (95% CI = 0.81–0.90). Among the three age groups with GD (&lt;45, 45–64, and ≥65 years), the adjusted HRs of AF were 1.59 (95% CI = 1.08–2.33), 1.31 (95% CI = 1.18–1.45), and 1.18 (95% CI = 1.13–1.22), respectively. Compared with patients with a CHA2DS2-VASc score equal to 0, the HRs of AF risk among total cohort patients and a score equal to 1, 2, 3, and ≥ 4 were 1.28 (95% CI = 1.15–1.43), 2.26 (95% CI = 2.00–2.56), 3.81 (95% CI = 3.35–4.34), and 5.09 (95% CI = 4.42–5.87), respectively.Conclusion: This population-based longitudinal follow-up study showed that patients with GD had an increased AF risk. Moreover, cholecystectomy was related to reduced AF risk. Cardiovascular checkups may be necessary for patients with GD, especially those who are young and have other typical risk factors.
Secular Trends in the Incidence of and Mortality Due to Alzheimer’s Disease and Other Forms of Dementia in China From 1990 to 2019: An Age-Period-Cohort Study and Joinpoint Analysis
Authors: Gao Yongliang , Liu Xiaonan 
Published: September 2021

BackgroundThe number of individuals with dementia is increasing, which negatively affects families, communities, and health care systems worldwide. The changes in the incidence of and mortality due to Alzheimer’s disease and other forms of dementia at the national level in China have remained unknown over the past three decades.MethodsFollowing the general analytical strategy used in the Global Burden of Disease Study (GBD) 2019, the age- and sex-specific incidence and mortality rates for dementia in China were analyzed. Trends in the incidence of and mortality due to dementia from 1990 to 2019 were assessed by joinpoint regression analysis. The effects of age, period and cohort on the incidence of and mortality due to dementia were estimated by an age-period-cohort model.ResultsThe age-standardized incidence and mortality rates per 100,000 population were 103.83 (95% UI, 87.93–118.87) and 23.32 (95% UI, 5.66–61.31), respectively, for dementia in 2019. From 1990 to 2019, a significant average annual percentage change (AAPC) in the age-standardized incidence rate was observed in both males [0.49% (95% CI, 0.43–0.55%)] and females [0.31% (95% CI, 0.24–0.38%)], and the age-standardized mortality rate significantly increased in males [0.42% (95% CI, 0.31–0.53%)]. The population aged 55–59 years had the highest AAPC in the incidence of dementia [0.87% (95% CI, 0.81–0.93%)]. The age effect showed that the relative risks (RRs) of incident dementia and dementia-associated mortality increased with age among males and females, and individuals aged 60 years and older had significantly higher RRs. The RR of incident dementia increased with time, and the RR started to substantially increase in 2009. The cohort effect showed that the incidence decreased in successive birth cohorts.ConclusionAlzheimer’s disease and other forms of dementia continue to become more common among males and females in China, and the associated mortality rate in males significantly increased from 1990 to 2019. Early interventions should be implemented to reduce the burden of dementia on individuals at high risk in China.
Investigating Associations Between Inflammatory Biomarkers, Gray Matter, Neurofilament Light and Cognitive Performance in Healthy Older Adults
Authors: Karoly Hollis C. , Skrzynski Carillon J. , Moe Erin , Bryan Angela D. , Hutchison Kent E. 
Published: September 2021

Background: Exploring biological variables that may serve as indicators of the development and progression of cognitive decline is currently a high-priority research area. Recent studies have demonstrated that during normal aging, individuals experience increased inflammation throughout the brain and body, which may be linked to cognitive impairment and reduced gray matter volume in the brain. Neurofilament light polypeptide (NfL), which is released into the circulation following neuronal damage, has been proposed as a biomarker for neurodegenerative diseases, and may also have utility in the context of normal aging. The present study tested associations between age, peripheral levels of the pro-inflammatory cytokine IL-6, peripheral NfL, brain volume, and cognitive performance in a sample of healthy adults over 60 years old.Methods: Of the 273 individuals who participated in this study, 173 had useable neuroimaging data, a subset of whom had useable blood data (used for quantifying IL-6 and NfL) and completed a cognitive task. Gray matter (GM) thickness values were extracted from brain areas of interest using Freesurfer. Regression models were used to test relationships between IL-6, NfL, GM, and cognitive performance. To test putative functional relationships between these variables, exploratory path analytic models were estimated, in which the relationship between age, IL-6, and working memory performance were linked via four different operationalizations of brain health: (1) a latent GM variable composed of several regions linked to cognitive impairment, (2) NfL alone, (3) NfL combined with the GM latent variable, and (4) the hippocampus alone.Results: Regression models showed that IL-6 and NfL were significantly negatively associated with GM volume and that GM was positively associated with cognitive performance. The path analytic models indicated that age and cognitive performance are linked by GM in the hippocampus as well as several other regions previously associated with cognitive impairment, but not by NfL alone. Peripheral IL-6 was not associated with age in any of the path models.Conclusions: Results suggest that among healthy older adults, there are several GM regions that link age and cognitive performance. Notably, NfL alone is not a sufficient marker of brain changes associated with aging, inflammation, and cognitive performance.
Polygenic Hazard Score Associated Multimodal Brain Networks Along the Alzheimer’s Disease Continuum
Authors: Li Kaicheng , Fu Zening , Qi Shile , Luo Xiao , Zeng Qingze , Xu Xiaopei , Huang Peiyu , Zhang Minming , Calhoun Vince D. 
Published: September 2021

BackgroundLate-onset Alzheimer’s disease (AD) is a polygenic neurodegenerative disease. Identifying the neuroimaging phenotypes behind the genetic predisposition of AD is critical to the understanding of AD pathogenesis. Two major questions which previous studies have led to are: (1) should the general “polygenic hazard score” (PHS) be a good choice to identify the individual genetic risk for AD; and (2) should researchers also include inter-modality relationships in the analyses considering these may provide complementary information about the AD etiology.MethodsWe collected 88 healthy controls, 77 patients with mild cognitive impairment (MCI), and 22 AD patients to simulate the AD continuum included from the ADNI database. PHS-guided multimodal fusion was used to investigate the impact of PHS on multimodal brain networks in AD-continuum by maximizing both inter-modality association and reference-modality correlation. Fractional amplitude of low frequency fluctuations, gray matter (GM) volume, and amyloid standard uptake value ratios were included as neuroimaging features. Eventually, the changes in neuroimaging features along AD continuum were investigated, and relationships between cognitive performance and identified PHS associated multimodal components were established.ResultsWe found that PHS was associated with multimodal brain networks, which showed different functional and structural impairments under increased amyloid deposits. Notably, along with AD progression, functional impairment occurred before GM atrophy, amyloid deposition started from the MCI stage and progressively increased throughout the disease continuum.ConclusionPHS is associated with multi-facets of brain impairments along the AD continuum, including cognitive dysfunction, pathological deposition, which might underpin the AD pathogenesis.
Effects of an Oroxylum indicum Extract (Sabroxy®) on Cognitive Function in Adults With Self-reported Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Study
Authors: Lopresti Adrian L. , Smith Stephen J. , Majeed Muhammed , Drummond Peter D. 
Published: September 2021

Background: Oroxylum indicum has been used in traditional Ayurvedic medicine for the prevention and treatment of several diseases and may have neuroprotective effects.Purpose: Examine the effects of Oroxylum indicum on cognitive function in older adults with self-reported cognitive complaints.Study Design: Two-arm, parallel-group, 12-week, randomized, double-blind, placebo-controlled trial.Methods: Eighty-two volunteers received either 500 mg, twice daily of a standardized Oroxylum indicum extract or placebo. Outcome measures included several computer-based cognitive tasks, the Control, Autonomy, Self-Realization, and Pleasure scale (CASP-19), Cognitive Failures Questionnaire (CFQ), and the Montreal Cognitive Assessment (MoCA). Changes in the concentration of brain-derived neurotrophic factor (BDNF) were also examined.Results: Compared to the placebo, Oroxylum indicum was associated with greater improvements in episodic memory, and on several computer-based cognitive tasks such as immediate word recall and numeric working memory, and a faster rate of learning on the location learning task. However, there were no other significant differences in performance on the other assessed cognitive tests, the MoCA total score, or other self-report questionnaires. BDNF concentrations increased significantly in both groups, with no statistically-significant between-group differences. Oroxylum indicum was well tolerated except for an increased tendency for mild digestive complaints and headaches.Conclusion: The results of this first human trial on the cognitive-enhancing effects of Oroxylum indicum suggest that it is a promising herbal candidate for the improvement of cognitive function in older adults with self-reported cognitive complaints.
Assessing Fatty Infiltration of Paraspinal Muscles in Patients With Lumbar Spinal Stenosis: Goutallier Classification and Quantitative MRI Measurements
Authors: Mandelli Filippo , Nüesch Corina , Zhang Yuancheng , Halbeisen Florian , Schären Stefan , Mündermann Annegret , Netzer Cordula 
Published: September 2021

Objective: Fatty infiltration of paraspinal muscle is associated with spinal disorders. It can be assessed qualitatively (i.e., Goutallier classification) and quantitatively using image processing software. The aims of this study were to compare paraspinal muscle fatty infiltration as assessed using the Goutallier classification vs. quantitative magnetic resonance images (MRI) measurements and to investigate the association between anthropometric parameters and paraspinal muscle morphology and fatty infiltration in patients with symptomatic lumbar spinal stenosis (LSS).Methods: Patients affected by symptomatic LSS scheduled for surgery with available MRI of the lumbar spine were included in this retrospective cross-sectional study. Fatty infiltration at each lumbar level was rated qualitatively according to the Goutallier classification and quantified based on the cross-sectional area (CSA) of the paraspinal muscle, of its lean fraction (LeanCSA), and the ratio between LeanCSA and CSA and the CSA relative to the CSA of vertebral body (RCSA). Considering the muscle as a single unit, overall fatty infiltration according to Goutallier, overall CSA, LeanCSA, LeanCSA/CSA, and RCSA were computed as averages (aGoutallier, aCSA, aLeanCSA, aLeanCSA/aCSA, and aRCSA). Associations among parameters were assessed using Spearman's respective Pearson's correlation coefficients.Results: Eighteen patients, with a mean age of 71.3 years, were included. aGoutallier correlated strongly with aLeanCSA and aLeanCSA/aCSA (R = −0.673 and R = −0.754, both P &lt; 0.001). There was a very strong correlation between values of the left and right sides for CSA (R = 0.956, P &lt; 0.001), LeanCSA (R = 0.900, P &lt; 0.001), and LeanCSA/CSA (R = 0.827, P &lt; 0.001) at all levels. Among all anthropometric measurements, paraspinal muscle CSA correlated the most with height (left: R = 0.737, P &lt; 0.001; right: R = 0.700, P &lt; 0.001), while there was a moderate correlation between vertebral body CSA and paraspinal muscle CSA (left: R = 0.448, P &lt; 0.001; right: R = 0.454, P &lt; 0.001). Paraspinal muscle CSA correlated moderately with body mass index (BMI; left: R = 0.423, P &lt; 0.001; right: R = 0.436, P &lt; 0.001), and there was no significant correlation between aLeanCSA or aLeanCSA/CSA and BMI.Conclusions: The Goutallier classification is a reliable yet efficient tool for assessing fatty infiltration of paraspinal muscles in patients with symptomatic LSS. We suggest taking body height as a reference for normalization in future studies assessing paraspinal muscle atrophy and fatty infiltration.