bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative assessment of Alzheimer’s disease-related biomarkers in plasma and neuron-derived extracellular vesicles: a nested case-control study
Authors: Manolopoulos Apostolos , Delgado-Peraza Francheska , Mustapic Maja , Pucha Krishna Ananthu , Nogueras-Ortiz Carlos , Daskalopoulos Alexander , Knight De’Larrian DeAnté , Leoutsakos Jeannie-Marie , Oh Esther S. , Lyketsos Constantine G. , Kapogiannis Dimitrios 
Published: September 2023

Introduction: Alzheimer’s disease (AD) is currently defined according to biomarkers reflecting the core underlying neuropathological processes: Aβ deposition, Tau, and neurodegeneration (ATN). The soluble phase of plasma and plasma neuron-derived extracellular vesicles (NDEVs) are increasingly being investigated as sources of biomarkers. The aim of this study was to examine the comparative biomarker potential of these two biofluids, as well as the association between respective biomarkers.Methods: We retrospectively identified three distinct diagnostic groups of 44 individuals who provided samples at baseline and at a mean of 3.1 years later; 14 were cognitively unimpaired at baseline and remained so (NRM-NRM), 13 had amnestic MCI that progressed to AD dementia (MCI-DEM) and 17 had AD dementia at both timepoints (DEM-DEM). Plasma NDEVs were isolated by immunoaffinity capture targeting the neuronal markers L1CAM, GAP43, and NLGN3. In both plasma and NDEVs, we assessed ATN biomarkers (Aβ42, Aβ40, total Tau, P181-Tau) alongside several other exploratory markers.Results: The Aβ42/Aβ40 ratio in plasma and NDEVs was lower in MCI-DEM than NRM-NRM at baseline and its levels in NDEVs decreased over time in all three groups. Similarly, plasma and NDEV-associated Aβ42 was lower in MCI-DEM compared to NRM-NRM at baseline and its levels in plasma decreased over time in DEM-DEM. For NDEV-associated proBDNF, compared to NRM-NRM, its levels were lower in MCI-DEM and DEM-DEM at baseline, and they decreased over time in the latter group. No group differences were found for other exploratory markers. NDEV-associated Aβ42/Aβ40 ratio and proBDNF achieved the highest areas under the curve (AUCs) for discriminating between diagnostic groups, while proBDNF was positively associated with Mini-Mental State Examination (MMSE) score. No associations were found between the two biofluids for any assessed marker.Discussion: The soluble phase of plasma and plasma NDEVs demonstrate distinct biomarker profiles both at a single time point and longitudinally. The lack of association between plasma and NDEV measures indicates that the two types of biofluids demonstrate distinct biomarker signatures that may be attributable to being derived through different biological processes. NDEV-associated proBDNF may be a useful biomarker for AD diagnosis and monitoring.
Testing the effect of high-definition transcranial direct current stimulation of the insular cortex to modulate decision-making and executive control
Authors: Gorrino Irene , Canessa Nicola , Mattavelli Giulia 
Published: September 2023

IntroductionPrevious neuroimaging evidence highlighted the role of the insular and dorsal anterior cingulate cortex (dACC) in conflict monitoring and decision-making, thus supporting the translational implications of targeting these regions in neuro-stimulation treatments for clinical purposes. Recent advancements of targeting and modeling procedures for high-definition tDCS (HD-tDCS) provided methodological support for the stimulation of otherwise challenging targets, and a previous study confirmed that cathodal HD-tDCS of the dACC modulates executive control and decision-making metrics in healthy individuals. On the other hand, evidence on the effect of stimulating the insula is still needed.MethodsWe used a modeling/targeting procedure to investigate the effect of stimulating the posterior insula on Flanker and gambling tasks assessing, respectively, executive control and both loss and risk aversion in decision-making. HD-tDCS was applied through 6 small electrodes delivering anodal, cathodal or sham stimulation for 20 min in a within-subject offline design with three separate sessions.ResultsBayesian statistical analyses on Flanker conflict effect, as well as loss and risk aversion, provided moderate evidence for the null model (i.e., absence of HD-tDCS modulation).DiscussionThese findings suggest that further research on the effect of HD-tDCS on different regions is required to define reliable targets for clinical applications. While modeling and targeting procedures for neuromodulation in clinical research could lead to innovative protocols for stand-alone treatment, or possibly in combination with cognitive training, assessing the effectiveness of insula stimulation might require sensitive metrics other than those investigated here.
Association between glycated hemoglobin and functional outcomes in patients with intracranial large artery atherosclerotic disease-related acute ischemic stroke: identifying the magic number
Authors: Zafar Azra , Albakr Aishah , Shahid Rizwana , Alkhamis Fahd , Alabdali Majed , Aljaafari Danah , Nazish Saima , AlShamrani Foziah Jabbar Gossab , Shariff Erum , Zeeshan Mohammad , AlSulaiman Abdulla , AlAmri Abdullah Saleh , Aldehailan Anas Salman , Al-Jehani Hosam 
Published: September 2023

ObjectiveThis study aimed to investigate the effect of the glycated hemoglobin A1c (HbA1c) level on the functional outcome (FOC) in patients with intracranial large artery atherosclerotic disease (ICLAD)-related acute ischemic stroke (AIS).MethodsThis retrospective study enrolled patients with ICLAD-related AIS who were admitted to King Fahd University Hospital between January 2017 and September 2021. Patients were divided into two groups based on the optimal cutoff HbA1c level determined using receiver operating characteristic curve analysis—those with HbA1c ≤6.9% and those with HbA1c &gt;6.9%. Demographic and other clinical characteristics were compared between the two groups using chi-square tests. The association between HbA1c and 90-day FOC was assessed using the chi-square test and odds ratios (ORs). Multivariate analysis was performed to adjust for confounding factors.ResultsA total of 140 patients were included in the analysis. A significant association was observed between the HbA1c level and FOC. Compared to patients with HbA1c ≤6.9%, patients with HbA1c &gt;6.9% were more likely to have an unfavorable FOC [p = &lt;0.001, OR = 2.05, 95% confidence interval (CI) = 1.33–3.14]. The association between HbA1c &gt;6.9% and unfavorable FOC was sustained even after adjusting for confounding factors (p = 0.008) and atherosclerosis risk factors (p = 0.01). HbA1c &gt;6.9% was also associated with higher ORs for in-hospital complications (p = 0.06, OR = 1.34, 95% CI = 1.02–1.77) and mortality (p = 0.07, OR = 1.42, 95% CI = 1.06–1.92) although these associations did not attain significant p-values.ConclusionHbA1c &gt;6.9% was significantly associated with unfavorable FOC in ICLAD-related AIS. However, further studies with larger sample sizes are required to verify whether HbA1c is an independent predictor of poor FOC. Nevertheless, targeting HbA1c &lt;7% should be the goal of physicians when managing patients at high risk of ICLAD.
The thalamus and basal ganglia are smaller in children with epilepsy after perinatal stroke
Authors: Vaher Ulvi , Ilves Norman , Ilves Nigul , Laugesaar Rael , Männamaa Mairi , Loorits Dagmar , Kool Pille , Ilves Pilvi 
Published: September 2023

BackgroundEpilepsy is one of the most serious consequences of perinatal stroke. Epilepsy itself has been proposed as a risk factor for impaired cognitive, language, and behavioral functioning. It is still unclear which children develop epilepsy after perinatal stroke. The current study aimed to evaluate the volume of the thalamus and the basal ganglia in children after perinatal stroke in relation to poststroke epilepsy.MethodsThe follow-up study included 29 children with perinatal arterial ischemic stroke (AIS), 33 children with presumed periventricular venous infarction (PVI), and 46 age- and sex-matched healthy controls. Magnetic resonance imaging was performed in children between the ages of 4 and 18 years, and volumetric analysis by segmentation was used to evaluate the size of the thalamus, caudate nucleus, putamen, globus pallidus, hippocampus, amygdala, and nucleus accumbens.ResultsDuring a median follow-up time of 12.8 years [interquartile range (IQR): 10.8–17.3] in the AIS group and 12.5 years (IQR: 9.3–14.8) in the PVI group (p = 0.32), epilepsy developed in 10 children (34.5%) with AIS and in 4 (12.1%) children with PVI, p = 0.036 [odds ratio (OR) = 3.8, 95%, confidence interval (CI): 1.04–14]. Epilepsy and interictal epileptiform discharges (IEDs) without clinical seizures were more often expressed in children with AIS (n = 16, 55%) than in children with PVI (n = 7, 21.2%), p = 0.0057 (OR = 3.8 95% CI: 1.04–14). In the AIS group, the ipsilesional and contralesional thalamus, ipsilesional caudate nucleus, and nucleus accumbens were significantly smaller in children with epilepsy compared to children without epilepsy. In the PVI group, the ipsilesional thalamus, caudate nucleus, and nucleus accumbens were smaller in the pooled group of epilepsy plus IED alone compared to children without epilepsy.ConclusionIn children with AIS, epilepsy or IED occurred more often compared to children with PVI. Both patients with AIS and PVI with severe damage to the basal ganglia and the thalamus have a higher risk of developing poststroke epilepsy and should be monitored more closely throughout childhood to initiate timely antiseizure medication and rehabilitation.
Association between miR-365 polymorphism and ischemic stroke in a Chinese population
Authors: Weng Yin-Hua , Yu Wen-Tao , Luo Yan-Ping , Liu Chao , Gu Xi-Xi , Chen Huo-Ying , Liu Hong-Bo 
Published: September 2023

BackgroundIschemic stroke (IS) represents a major cause of morbidity and mortality across the globe. The aberrant expression of miR-365 has been found to be implicated in a wide array of human diseases, including atherosclerosis and cancer. Studies on single-nucleotide polymorphisms (SNPs) in miRNA genes can help gain insight into the susceptibility to the condition. This study aimed to examine the relationship between miR-365 SNPs and the risk of IS.MethodsThe study recruited 215 IS patients and 220 controls. The SNPscans genotyping was employed to genotype three polymorphic loci (rs121224, rs30230, and rs178553) of miR-365. The relative expression of miR-365 in peripheral blood mononuclear cells of the patients and controls was determined by using real-time quantitative PCR.ResultsThe miR-365 rs30230 polymorphism exhibited a significant association with the risk of developing IS (TC vs. CC: adjusted OR = 0.55, 95% CI: 0.33-0.92, P = 0.022; TT vs. CC: adjusted OR = 0.34, 95% CI: 0.14–0.85, P = 0.021; TC +TT vs. CC: adjusted OR = 0.51, 95% CI: 0.31–0.83, P = 0.007; T vs. C: adjusted OR = 0.57, 95% CI: 0.39–0.83, P = 0.004). Haplotype analysis revealed that the C-T-G haplotype was associated with a decreased risk of IS (OR = 0.68, 95% CI: 0.46–1.00, P = 0.047). Furthermore, miR-365 expression was significantly higher in IS patients than in controls (P &lt; 0.001). Interestingly, patients with rs30230 TC or TT genotypes had lower miR-365 levels compared to their counterparts with CC genotypes (P &lt; 0.001).ConclusionsThe miR-365 rs30230 polymorphism might bear an association with IS susceptibility in the Chinese population, and the rs30230 TC/TT genotype might be a protective factor against IS.
Predicting acute ischemic stroke using the revised Framingham stroke risk profile and multimodal magnetic resonance imaging
Authors: Sun Jiali , Sui Ying , Chen Yue , Lian Jianxiu , Wang Wei 
Published: September 2023

Background and purposePatients with transient ischemic attacks (TIA) have a significant risk of developing acute ischemic strokes (AIS), emphasizing the critical need for hierarchical management. This study aims to develop a clinical-imaging model utilizing multimodal magnetic resonance imaging (mMRI) and the revised Framingham Stroke Risk Profile (FSRP) to predict AIS and achieve early secondary prevention.MethodsmMRI scans were conducted on patients with symptomatic intracranial atherosclerotic disease (ICAD) to assess vascular wall features and cerebral perfusion parameters. Based on diffusion-weighted imaging (DWI), patients were divided into two groups: TIA and AIS. Clinical data were evaluated to calculate the FSRP score. Differences in clinical and imaging characteristics between the groups were analyzed, and a predictive model for AIS probability in patients with ICAD was established.ResultsA total of 112 TIA and AIS patients were included in the study. The results showed that the AIS group had higher proportions of FSRP-high risk, hyperhomocysteinemia, and higher value of low-density lipoprotein (LDL), standardized plaque index (SQI), and enhancement rate (ER) compared to the TIA group (p &lt; 0.05). Mean transit time (MTT) and time to peak (TTP) in the lesion area were significantly longer in the AIS group (p &lt; 0.05). Multivariate analysis identified FSRP-high risk (p = 0.027) and high ER (p = 0.046) as independent risk factors for AIS. The combined clinical and mMRI model produced an area under the curve (AUC) of 0.791 in receiver operating characteristic (ROC) analysis. The constructed nomogram model combining clinical and mMRI features demonstrated favorable clinical net benefits.ConclusionFSRP-high risk and high ER were confirmed as independent risk factors for AIS. The combined prediction model utilizing clinical and imaging markers effectively predicts stroke risk in symptomatic ICAD patients.
Transient ischemic attacks in patients with active and occult cancer
Authors: Beyeler Morin , Castigliego Pasquale , Baumann Joel , Ziegler Victor , Kielkopf Moritz , Mueller Madlaine , Bauer-Gambelli Stefan A. , Mujanovic Adnan , Meinel Thomas Raphael , Horvath Thomas , Fischer Urs , Kaesmacher Johannes , Heldner Mirjam R. , Seiffge David , Arnold Marcel , Pabst Thomas , Berger Martin D. , Navi Babak B. , Jung Simon , Bücke Philipp 
Published: September 2023

Background and aimParaneoplastic coagulopathy can present as stroke and is associated with specific biomarker changes. Identifying paraneoplastic coagulopathy can help guide secondary prevention in stroke patients, and early cancer detection might improve outcomes. However, unlike ischemic stroke, it remains unclear whether paraneoplastic coagulopathy is associated with transient ischemic attacks (TIA). This study assessed the presence of cancer-related biomarkers in TIA patients and evaluated long-term mortality rates in patients with and without active cancer.MethodsActive cancer was retrospectively identified in consecutive TIA patients treated at a comprehensive stroke center between 2015 and 2019. An association between the presence of cancer and cancer-related biomarkers was assessed using multivariable logistic regression. Long-term mortality after TIA was analyzed using multivariable Cox regression.ResultsAmong 1436 TIA patients, 72 had active cancer (5%), of which 17 were occult (1.2%). Cancer-related TIA was associated with male gender (adjusted odds ratio [aOR] 2.29, 95% CI 1.12–4.68), history of smoking (aOR 2.77, 95% CI 1.34–5.7), elevated D-dimer (aOR 1.77, 95% CI 1.26–2.49), lactate dehydrogenase (aOR 1.003, 95% CI 1.00–1.005), lower leukocyte count (aOR 1.20, 95% CI 1.04–1.38), and lower hemoglobin (aOR 1.02, 95% CI 1.00–1.04). Long-term mortality was associated with both active cancer (adjusted hazard ratios [aHR] 2.47, 95% CI 1.58–3.88) and occult cancer (aHR 3.08, 95% CI 1.30–7.32).ConclusionCancer-related TIA is not uncommon. Biomarkers known to be associated with cancer-related stroke also seem to be present in TIA patients. Early identification would enable targeted treatment strategies and could improve outcomes in this patient population.
Tract- and gray matter- based spatial statistics show white matter and gray matter microstructural differences in autistic males
Authors: DiPiero Marissa , Cordash Hassan , Prigge Molly B. , King Carolyn K. , Morgan Jubel , Guerrero-Gonzalez Jose , Adluru Nagesh , King Jace B. , Lange Nicholas , Bigler Erin D. , Zielinski Brandon A. , Alexander Andrew L. , Lainhart Janet E. , Dean Douglas C. 
Published: September 2023

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental condition commonly studied in the context of early childhood. As ASD is a life-long condition, understanding the characteristics of brain microstructure from adolescence into adulthood and associations to clinical features is critical for improving outcomes across the lifespan. In the current work, we utilized Tract Based Spatial Statistics (TBSS) and Gray Matter Based Spatial Statistics (GBSS) to examine the white matter (WM) and gray matter (GM) microstructure in neurotypical (NT) and autistic males.MethodsMulti-shell diffusion MRI was acquired from 78 autistic and 81 NT males (12-to-46-years) and fit to the DTI and NODDI diffusion models. TBSS and GBSS were performed to analyze WM and GM microstructure, respectively. General linear models were used to investigate group and age-related group differences. Within the ASD group, relationships between WM and GM microstructure and measures of autistic symptoms were investigated.ResultsAll dMRI measures were significantly associated with age across WM and GM. Significant group differences were observed across WM and GM. No significant age-by-group interactions were detected. Within the ASD group, positive relationships with WM microstructure were observed with ADOS-2 Calibrated Severity Scores.ConclusionUsing TBSS and GBSS our findings provide new insights into group differences of WM and GM microstructure in autistic males from adolescence into adulthood. Detection of microstructural differences across the lifespan as well as their relationship to the level of autistic symptoms will deepen to our understanding of brain-behavior relationships of ASD and may aid in the improvement of intervention options for autistic adults.
Ketogenic effects of medium chain triglycerides containing formula and its correlation to breath acetone in healthy volunteers: a randomized, double-blinded, placebo-controlled, single dose-response study
Authors: Nakamura Kentaro , Hagihara Keisuke , Nagai Naoko , Egashira Ryuichiro , Takeuchi Mariko , Nakano Mai , Saito Hitomi , Moriguchi Misaki , Tonari Satoko , Fujii Hisako , Miyake Akimitsu , Omae Yusuke , Ashida Kinya 
Published: September 2023

The efficacy of low-carbohydrate, high-fat diets, such as ketogenic diets, for cancer patients is of research interest. We previously demonstrated the efficacy of the ketogenic diet in a case study in which medium-chain triglycerides (MCTs) or MCT-containing formula (ketogenic formula) was used as a supplement to increase blood ketone bodies. However, little is known about the amounts needed to induce ketogenic effects and about the usefulness of monitoring of breath acetone. To investigate the pharmacokinetics of MCTs and their metabolites, blood ketone bodies and breath acetone, 24 healthy subjects received one of four single oral doses of the ketogenic formula (equivalent to 0, 10, 20, and 30 g of MCTs) under fasting conditions. Total blood ketone bodies, β-hydroxybutyrate, octanoic acid, and decanoic acid were increased in a dose-dependent manner. The ketogenic effect was considered to depend on octanoic and decanoic acids, because a positive correlation was observed between them. A strong positive correlation was also observed between total serum ketone bodies and breath acetone at each time points. Therefore, monitoring breath acetone levels seems a less invasive method to predict blood concentrations of ketone bodies during ketogenic diet therapy.Clinical trial registration:https://rctportal.niph.go.jp/en/detail?trial_id=UMIN000032634, UMIN-CTR UMIN000032634.
Long non-coding RNA H19 enhances the pro-apoptotic activity of ITF2357 (a histone deacetylase inhibitor) in colorectal cancer cells
Authors: Zichittella Chiara , Loria Marco , Celesia Adriana , Di Liberto Diana , Corrado Chiara , Alessandro Riccardo , Emanuele Sonia , Conigliaro Alice 
Published: September 2023

Introduction: Long non-coding RNA H19 (lncH19) is highly expressed in colorectal cancer (CRC) and plays critical roles in tumor development, proliferation, metastasis, and drug resistance. Indeed, the expression of lncH19 usually affects the outcomes of chemo-, endocrine, and targeted therapies. ITF2357 (givinostat) is a histone deacetylase inhibitor (HDACi) that revealed a significant anti-tumor action by inducing apoptosis in different tumor models, including leukemia, melanoma, and glioblastoma. However, no data are present in the literature regarding the use of this compound for CRC treatment. Here, we investigate the role of lncH19 in ITF2357-induced apoptosis in CRC cells.Methods: The HCT-116 CRC cell line was stably silenced for H19 to investigate the role of this lncRNA in ITF2357-induced cell death. Cell viability assays and flow cytometric analyses were performed to assess the anti-proliferative and pro-apoptotic effects of ITF2357 in CRC cell lines that are silenced or not for lncH19. RT-PCR and Western blot were used to study the effects of ITF2357 on autophagy and apoptosis markers. Finally, bioinformatics analyses were used to identify miRNAs targeting pro-apoptotic factors that can be sponged by lncH19.Results: ITF2357 increased the expression levels of H19 and reduced HCT-116 cell viability, inducing apoptosis, as demonstrated by the increase in annexin-V positivity, caspase 3 cleavage, and poly (ADP-ribose) polymerase (PARP-1) degradation. Interestingly, the apoptotic effect of ITF2357 was much less evident in lncH19-silenced cells. We showed that lncH19 plays a functional role in the pro-apoptotic activity of the drug by stabilizing TP53 and its transcriptional targets, NOXA and PUMA. ITF2357 also induced autophagy in CRC cells, which was interpreted as a pro-survival response not correlated with lncH19 expression. Furthermore, ITF2357 induced apoptosis in 5-fluorouracil-resistant HCT-116 cells that express high levels of lncH19.Conclusion: This study shows that lncH19 expression contributes to ITF2357-induced apoptosis by stabilizing TP53. Overall, we suggest that lncH19 expression may be exploited to favor HDACi-induced cell death and overcome 5-fluorouracil chemoresistance.