bluuebunny/crossref_metadata_2025_split huggingface dataset:
4,4′-methylenediphenol reduces Aβ-induced toxicity in a Caenorhabditis elegans model of Alzheimer’s disease
Authors: Yu Xingzhi , Tao Jie , Xiao Tian , Duan Xiaohua 
Published: May 2024

IntroductionGastrodia elata Blume is a widely used medicinal and edible herb with a rich chemical composition. Moreover, prescriptions containing Gastrodia elata are commonly used for the prevention and treatment of cardiovascular, cerebrovascular, and aging-related diseases. Recent pharmacological studies have confirmed the antioxidant and neuroprotective effects of Gastrodia elata, and, in recent years, this herb has also been used in the treatment of Alzheimer’s disease (AD) and other neurodegenerative disorders. We have previously shown that 4,4′-methylenediphenol, a key active ingredient of Gastrodia elata, can mitigate amyloid-β (Aβ)-induced paralysis in AD model worms as well as prolong the lifespan of the animals, thus displaying potential as a treatment of AD.MethodsWe investigated the effects of 4,4′-methylenediphenol on AD and aging through paralysis, lifespan, and behavioral assays. In addition, we determined the anti-AD effects of 4,4′-methylenediphenol by reactive oxygen species (ROS) assay, lipofuscin analysis, thioflavin S staining, metabolomics analysis, GFP reporter gene worm assay, and RNA interference assay and conducted in-depth studies on its mechanism of action.Results4,4′-Methylenediphenol not only delayed paralysis onset and senescence in the AD model worms but also enhanced their motility and stress tolerance. Meanwhile, 4,4′-methylenediphenol treatment also reduced the contents of reactive oxygen species (ROS) and lipofuscin, and decreased Aβ protein deposition in the worms. Broad-spectrum targeted metabolomic analysis showed that 4,4′-methylenediphenol administration had a positive effect on the metabolite profile of the worms. In addition, 4,4′-methylenediphenol promoted the nuclear translocation of DAF-16 and upregulated the expression of SKN-1, SOD-3, and GST-4 in the respective GFP reporter lines, accompanied by an enhancement of antioxidant activity and a reduction in Aβ toxicity; importantly, our results suggested that these effects of 4,4′-methylenediphenol were mediated, at least partly, via the activation of DAF-16.ConclusionWe have demonstrated that 4,4′-methylenediphenol can reduce Aβ-induced toxicity in AD model worms, suggesting that it has potential for development as an anti-AD drug. Our findings provide ideas and references for further research into the anti-AD effects of Gastrodia elata and its active ingredients.
Cathepsin-mediated regulation of alpha-synuclein in Parkinson’s disease: a Mendelian randomization study
Authors: Lin Liyu , Wu Zilun , Luo Haocheng , Huang Yunxuan 
Published: May 2024

ObjectiveThe observational association between cathepsin and Parkinson’s disease (PD) has been partially explored in previous research. However, the causal relationship remains unclear. In this study, our objective is to investigate the causal link between cathepsin and PD using Mendelian randomization (MR) analysis and elucidate the underlying mechanisms governing their interaction.MethodsUtilizing bidirectional two-sample MR and multivariable MR, we systematically investigates the causal relationship between nine cathepsins and PD. The data pertaining to cathepsins were obtained from the Integrative Epidemiology Unit (IEU) Open GWAS Project, while data related to PD were sourced from versions R9 and R10 of the FinnGen database. The primary analytical method utilized was the inverse variance weighted (IVW), with MR analysis initially conducted using PD data from R9, complemented by a series of sensitivity analyses. Subsequently, replication analysis was performed on the R10 dataset, and meta-analysis were employed to merge the findings from both datasets. To explore potential mechanisms by which Cathepsins may impact PD, MR analyses were performed on significant Cathepsins with alpha-synuclein. MR analysis and colocalization analysis were conducted on expression quantitative trait loci (eQTL) data of gene related to alpha-synuclein with PD data.ResultForward MR analyses revealed more cathepsin B (CTSB) associated with less PD risk (OR = 0.898, 95%CI: 0.834–0.966, p = 0.004), while more cathepsin H (CTSH) (OR = 1.076, 95%CI: 1.007–1.149, p = 0.029) and more cathepsin S (CTSS) (OR = 1.076, 95%CI: 1.007–1.150, p = 0.030) associated with increasing PD risk. Meta-analyses validated these associations. Multivariate MR Results were consistent with those before adjustment. No significant results were observed in bidirectional MR analysis. In the investigation of the underlying mechanism, our findings demonstrate that CTSB significantly reduces the levels of alpha-synuclein (OR = 0.909, 95%CI: 0.841–0.983, p = 0.017). Concurrently, a genetically determined positive correlation between alpha-synuclein and PD is illuminated by both eQTL MR and colocalization analysis.ConclusionIn conclusion, this MR study yields robust evidence suggesting an association between elevated levels of CTSB and reduced PD risk, mediated by the downregulation of alpha-synuclein levels. Conversely, higher levels of CTSH and CTSS are associated with an increased risk of PD. These findings offer novel insights into the pathophysiological mechanisms of PD and identify potential drug targets for disease prevention and treatment warranting further clinical investigations.
Coordinated reset stimulation of plastic neural networks with spatially dependent synaptic connections
Authors: Kromer Justus A. , Tass Peter A. 
Published: May 2024

BackgroundAbnormal neuronal synchrony is associated with several neurological disorders, including Parkinson’s disease (PD), essential tremor, dystonia, and epilepsy. Coordinated reset (CR) stimulation was developed computationally to counteract abnormal neuronal synchrony. During CR stimulation, phase-shifted stimuli are delivered to multiple stimulation sites. Computational studies in plastic neural networks reported that CR stimulation drove the networks into an attractor of a stable desynchronized state by down-regulating synaptic connections, which led to long-lasting desynchronization effects that outlasted stimulation. Later, corresponding long-lasting desynchronization and therapeutic effects were found in animal models of PD and PD patients. To date, it is unclear how spatially dependent synaptic connections, as typically observed in the brain, shape CR-induced synaptic downregulation and long-lasting effects.MethodsWe performed numerical simulations of networks of leaky integrate-and-fire neurons with spike-timing-dependent plasticity and spatially dependent synaptic connections to study and further improve acute and long-term responses to CR stimulation.ResultsThe characteristic length scale of synaptic connections relative to the distance between stimulation sites plays a key role in CR parameter adjustment. In networks with short synaptic length scales, a substantial synaptic downregulation can be achieved by selecting appropriate stimulus-related parameters, such as the stimulus amplitude and shape, regardless of the employed spatiotemporal pattern of stimulus deliveries. Complex stimulus shapes can induce local connectivity patterns in the vicinity of the stimulation sites. In contrast, in networks with longer synaptic length scales, the spatiotemporal sequence of stimulus deliveries is of major importance for synaptic downregulation. In particular, rapid shuffling of the stimulus sequence is advantageous for synaptic downregulation.ConclusionOur results suggest that CR stimulation parameters can be adjusted to synaptic connectivity to further improve the long-lasting effects. Furthermore, shuffling of CR sequences is advantageous for long-lasting desynchronization effects. Our work provides important hypotheses on CR parameter selection for future preclinical and clinical studies.
MRI-based radiomics models predict cystic brain radionecrosis of nasopharyngeal carcinoma after intensity modulated radiotherapy
Authors: Hou Jing , He Yun , Li Handong , Lu Qiang , Lin Huashan , Zeng Biao , Xie Chuanmiao , Yu Xiaoping 
Published: May 2024

ObjectiveTo construct radiomics models based on MRI at different time points for the early prediction of cystic brain radionecrosis (CBRN) for nasopharyngeal carcinoma (NPC).MethodsA total of 202 injured temporal lobes from 155 NPC patients with radiotherapy-induced temporal lobe injury (RTLI) after intensity modulated radiotherapy (IMRT) were included in the study. All the injured lobes were randomly divided into the training (n = 143) and validation (n = 59) sets. Radiomics models were constructed by using features extracted from T2WI at two different time points: at the end of IMRT (post-IMRT) and the first-detected RTLI (first-RTLI). A delta-radiomics feature was defined as the percentage change in a radiomics feature from post-IMRT to first-RTLI. The radiomics nomogram was constructed by combining clinical risk factors and radiomics signatures using multivariate logistic regression analysis. Predictive performance was evaluated using area under the curve (AUC) from receiver operating characteristic analysis and decision curve analysis (DCA).ResultsThe post-IMRT, first-RTLI, and delta-radiomics models yielded AUC values of 0.84 (95% CI: 0.76–0.92), 0.86 (95% CI: 0.78–0.94), and 0.77 (95% CI: 0.67–0.87), respectively. The nomogram exhibited the highest AUC of 0.91 (95% CI: 0.85–0.97) and sensitivity of 0.82 compared to any single radiomics model. From the DCA, the nomogram model provided more clinical benefit than the radiomics models or clinical model.ConclusionThe radiomics nomogram model combining clinical factors and radiomics signatures based on MRI at different time points after radiotherapy showed excellent prediction potential for CBRN in patients with NPC.
Elevated lipopolysaccharide binding protein in Alzheimer’s disease patients with APOE3/E3 but not APOE3/E4 genotype
Authors: Romo Eduardo Z. , Hong Brian V. , Patel Rishi Y. , Agus Joanne K. , Harvey Danielle J. , Maezawa Izumi , Jin Lee-Way , Lebrilla Carlito B. , Zivkovic Angela M. 
Published: May 2024

IntroductionThe role of lipopolysaccharide binding protein (LBP), an inflammation marker of bacterial translocation from the gastrointestinal tract, in Alzheimer’s disease (AD) is not clearly understood.MethodsIn this study the concentrations of LBP were measured in n = 79 individuals: 20 apolipoprotein E (APOE)3/E3 carriers with and 20 without AD dementia, and 19 APOE3/E4 carriers with and 20 without AD dementia. LBP was found to be enriched in the 1.21–1.25 g/mL density fraction of plasma, which has previously been shown to be enriched in intestinally derived high-density lipoproteins (HDL). LBP concentrations were measured by ELISA.ResultsLBP was significantly increased within the 1.21–1.25 g/mL density fraction of plasma in APOE3/E3 AD patients compared to controls, but not APOE3/E4 patients. LBP was positively correlated with Clinical Dementia Rating (CDR) and exhibited an inverse relationship with Verbal Memory Score (VMS).DiscussionThese results underscore the potential contribution of gut permeability to bacterial toxins, measured as LBP, as an inflammatory mediator in the development of AD, particularly in individuals with the APOE3/E3 genotype, who are genetically at 4-12-fold lower risk of AD than individuals who express APOE4.
The effect of new e-commerce platform’s OSC promotion on consumer cognition: from cognitive legitimacy and cognitive psychology perspective
Authors: Yu Deng , Wei Han , Xuefeng Zhang , Zhongxuan Huang , Yijun Zhang 
Published: May 2024

IntroductionIn the realm of emerging e-commerce platforms, the influence of online shopping events, specifically online carnival promotions (OSC), on consumer behavior is a significant area of interest.This paper delves into the effects of such promotions on consumer perceptions, a topic that has not been extensively explored in academic research.MethodsTo investigate this phenomenon, two distinct studies were conducted. The first study employed a questionnaire-based experiment involving 220 participants, divided into two groups. The first study examined the mediating role of cognitive legitimacy in the relationship between OSC events organized by new e-commerce platforms and the perceptions of consumers. The second study utilized an event-related potentials (ERPs) experiment with 33 participants to explore the differences in consumer perceptions between OSC promotions and general promotions by new e-commerce platforms. This study measured the brain’s response to promotional stimuli to gain insights into the cognitive processes involved.ResultsThe first study yielded results that suggest OSC activities can facilitate the establishment of cognitive legitimacy for new e-commerce platforms. This, in turn, was found to be associated with an increase in positive purchase intentions among consumers. In the second study, the ERPs data indicated that exposure to OSC promotional materials elicited larger P2 and N2 ERP components when participants were presented with the logo of a new e-commerce platform. This was in contrast to the response to general promotional materials, suggesting a heightened cognitive and perceptual engagement with OSC promotions.DiscussionThe findings from both studies collectively imply that OSC promotions have a distinct impact on consumer perceptions and cognitive processes. The implicit memory triggered by these promotions appears to influence the identification of new platforms and the mechanisms of cognitive control during online shopping. This, in turn, may have implications for explicit consumer behavior, suggesting that OSC promotions could be a powerful tool for shaping consumer attitudes and behaviors in the e-commerce space. The results underscore the importance of understanding the nuances of consumer engagement with new e-commerce platforms and the role of promotional strategies in fostering a positive brand image and consumer loyalty.
Consistent spectro-spatial features of human ECoG successfully decode naturalistic behavioral states
Authors: Alasfour Abdulwahab , Gilja Vikash 
Published: May 2024

ObjectiveUnderstanding the neural correlates of naturalistic behavior is critical for extending and confirming the results obtained from trial-based experiments and designing generalizable brain-computer interfaces that can operate outside laboratory environments. In this study, we aimed to pinpoint consistent spectro-spatial features of neural activity in humans that can discriminate between naturalistic behavioral states.ApproachWe analyzed data from five participants using electrocorticography (ECoG) with broad spatial coverage. Spontaneous and naturalistic behaviors such as “Talking” and “Watching TV” were labeled from manually annotated videos. Linear discriminant analysis (LDA) was used to classify the two behavioral states. The parameters learned from the LDA were then used to determine whether the neural signatures driving classification performance are consistent across the participants.Main resultsSpectro-spatial feature values were consistently discriminative between the two labeled behavioral states across participants. Mainly, θ, α, and low and high γ in the postcentral gyrus, precentral gyrus, and temporal lobe showed significant classification performance and feature consistency across participants. Subject-specific performance exceeded 70%. Combining neural activity from multiple cortical regions generally does not improve decoding performance, suggesting that information regarding the behavioral state is non-additive as a function of the cortical region.SignificanceTo the best of our knowledge, this is the first attempt to identify specific spectro-spatial neural correlates that consistently decode naturalistic and active behavioral states. The aim of this work is to serve as an initial starting point for developing brain-computer interfaces that can be generalized in a realistic setting and to further our understanding of the neural correlates of naturalistic behavior in humans.
Riemannian transfer learning based on log-Euclidean metric for EEG classification
Authors: Zhuo Fanbo , Zhang Xiaocheng , Tang Fengzhen , Yu Yaobo , Liu Lianqing 
Published: May 2024

IntroductionBrain computer interfaces (BCI), which establish a direct interaction between the brain and the external device bypassing peripheral nerves, is one of the hot research areas. How to effectively convert brain intentions into instructions for controlling external devices in real-time remains a key issue that needs to be addressed in brain computer interfaces. The Riemannian geometry-based methods have achieved competitive results in decoding EEG signals. However, current Riemannian classifiers tend to overlook changes in data distribution, resulting in degenerated classification performance in cross-session and/or cross subject scenarios.MethodsThis paper proposes a brain signal decoding method based on Riemannian transfer learning, fully considering the drift of the data distribution. Two Riemannian transfer learning methods based log-Euclidean metric are developed, such that historical data (source domain) can be used to aid the training of the Riemannian decoder for the current task, or data from other subjects can be used to boost the training of the decoder for the target subject.ResultsThe proposed methods were verified on BCI competition III, IIIa, and IV 2a datasets. Compared with the baseline that without transfer learning, the proposed algorithm demonstrates superior classification performance. In contrast to the Riemann transfer learning method based on the affine invariant Riemannian metric, the proposed method obtained comparable classification performance, but is much more computationally efficient.DiscussionWith the help of proposed transfer learning method, the Riemannian classifier obtained competitive performance to existing methods in the literature. More importantly, the transfer learning process is unsupervised and time-efficient, possessing potential for online learning scenarios.
Lacticaseibacillus paracasei LC86 mitigates age-related muscle wasting and cognitive impairment in SAMP8 mice through gut microbiota modulation and the regulation of serum inflammatory factors
Authors: Cai Yihui , Dong Yao , Han Mei , Jin Manfei , Liu Huan , Gai Zhonghui , Zou Kang 
Published: May 2024

PurposeChronic inflammation contributes to the decline in muscle strength and cognitive abilities associated with aging. This study aims to clarify the effects of oral administration of Lacticaseibacillus paracasei LC86 on these age-related declines, as well as its impact on the composition of gut microbiota.MethodsSenescence-accelerated mouse prone 8 (SAMP8) mice received a 12 week regimen of LC86 (1 × 109 CFU/day). Muscle strength was assessed through forelimb grip strength and four-limb hanging tests. Cognitive function was evaluated through behavioral performance tests, and changes in gut microbiota were analyzed.ResultsAdministration of LC86 significantly enhanced muscle strength, demonstrated by increased grip strength and higher glycogen content in the gastrocnemius muscle (p = 0.041, p = 0.017, and p = 0.000, respectively). Behavioral tests suggested that LC86 mitigated age-related cognitive decline. Furthermore, there was a significant decrease in serum pro-inflammatory cytokines, such as IL-6, TNF-α, and MCP-1 (p = 0.002, p = 0.000, and p = 0.005, respectively), and an elevation in the anti-inflammatory cytokine IL-10 level (p = 0.000). An increase in hepatic antioxidant capacity was observed. Significant changes in the gut microbiota composition were noted, including increased populations of Bifidobacterium and Lactobacillus and decreased levels of Escherichia/Shigella and Bacteroides.ConclusionThe findings suggest that LC86 supplementation mitigates muscle weakness and cognitive impairment in aging SAMP8 mice, potentially through the modulation of inflammation and gut microbiota composition. LC86 emerges as a promising candidate for ameliorating the decline of muscular and cognitive functions associated with aging.
Does chili pepper consumption affect BMI and obesity risk? A cross-sectional analysis
Authors: Liu Mengxue , Zhu Yihao , Wang Fei 
Published: May 2024

BackgroundThe effects of chili intake on overweight and obesity have attracted significant interest in recent years. This study aimed to investigate the correlation between chili consumption frequency, body mass index (BMI), and obesity prevalence in the American population.MethodsData from participants in National Health and Nutrition Examination Survey (NHANES) 2003–2006 were collected. We enrolled 6,138 participants with complete information on chili intake and BMI in this cross-sectional study. Multivariate logistic regression and sensitivity analyses were conducted to explore the relationship between chili intake frequency and BMI and obesity. Subgroup analyses and interaction tests were employed to assess the stability of the observed correlation.ResultsIncreased chili consumption frequency was linked to higher BMI values and a greater prevalence of obesity. Compared to the non-consumption group, the highest frequency group had a multivariate-adjusted β of 0.71 (95% CI: 0.05, 1.38) for BMI and an OR of 1.55 (95% CI: 1.22, 1.97) for obesity in the fully adjusted model. This positive association between chili intake frequency and obesity was more pronounced in females and older adults (≥ 60 years old).ConclusionOur findings suggest a positive association between chili intake frequency and BMI and obesity in United States adults, suggesting that controlling chili intake frequency could potentially contribute to improved weight management in the general population.
A novel mutation in GAS8 gene associated with chronic rhinosinusitis with nasal polyposis in a case of primary ciliary dyskinesia: a case report
Authors: Artesani Maria Cristina , Santarsiero Sara , Sitzia Emanuela , Lepri Francesca Romana , Magliozzi Monia , Majo Fabio , Ullmann Nicola , Stracuzzi Alessandra , Novelli Antonio , Cristalli Giovanni , Fiocchi Alessandro 
Published: May 2024

BackgroundPrimary ciliary dyskinesia (PCD) is considered a rare cause of chronic rhinosinusitis with nasal polyposis (CRSwNP), which is reported in 6% of children with PCD. The forms of PCD associated with the variants of the GAS8 gene identified so far seem to be linked to recurrent respiratory infections (sinusitis, otitis, and bronchiectasis) without situs inversus.Case presentationWe report a case of an 11-year-old girl with recurrent otitis media, productive cough, and chronic rhinosinusitis with nasal polyposis with homozygosity for a novel nonsense mutation in the GAS8.ConclusionChildren with CRSwNP should be treated in a multidisciplinary manner (ENT, pulmonologist, allergist, pathologist, pediatrician, and geneticist) because nasal polyposis often hides etiologies that must be recognized.