bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors contributing to sleep disturbances and excessive daytime sleepiness in patients with Parkinson's disease
Authors: Ogaki Keitaro , Fujita Hiroaki , Nozawa Narihiro , Shiina Tomohiko , Sakuramoto Hirotaka , Suzuki Keisuke 
Published: March 2023

BackgroundSleep disturbances and excessive daytime sleepiness (EDS) are common non-motor symptoms in patients with Parkinson's disease (PD). The purpose of this study was to identify the contributors to sleep disturbances, including insomnia, restless legs syndrome, rapid eye movement sleep behavior disorder (RBD), sleep-disordered breathing, nocturnal akinesia and EDS, in patients with PD.MethodsWe conducted a cross-sectional study including 128 consecutive Japanese patients with PD. Sleep disturbances and EDS were defined as a PD Sleep Scale-2 (PDSS-2) total score ≥15 and an Epworth Sleepiness Scale (ESS) score &gt;10, respectively. The patients were divided into four groups according to the presence or absence of sleep disturbances and EDS. We evaluated the disease severity, motor symptoms, cognition, olfactory test, the Scales for Outcomes in PD-Autonomic dysfunction (SCOPA-AUT), the Beck Depression Inventory-II (BDI-II), and the RBD Screening Questionnaire Japanese version (RBDSQ-J).ResultsOf 128 patients, 64 had neither EDS nor sleep disturbances, 29 had sleep disturbances without EDS, 14 had EDS without sleep disturbances, and 21 had both EDS and sleep disturbances. Patients with sleep disturbances had higher BDI-II scores than those without sleep disturbances. Probable RBD was more frequent in patients with both sleep disturbances and EDS than in those with neither EDS nor sleep disturbances. The SCOPA-AUT score was lower in patients with neither EDS nor sleep disturbances than in patients in the other three groups. Using multivariable logistic regression analysis with neither sleep disturbances nor EDS as a reference group, that the SCOPA-AUT score was an independent contributor to sleep disturbances (adjusted OR, 1.192; 95% CI, 1.065–1.333; P = 0.002) or EDS (OR, 1.245; 95% CI, 1.087–1.424; P = 0.001) and that the BDI-II (OR, 1.121; 95% CI, 1.021–1.230; P = 0.016) and RBDSQ-J scores (OR, 1.235; 95% CI, 1.007–1.516; P = 0.043) as well as the SCOPA-AUT score (OR, 1.137; 95% CI, 1.006–1.285; P = 0.040) were independent contributors to both sleep disturbances and EDS.ConclusionsAutonomic symptoms were associated with patients with sleep disturbances or EDS, and depressive and RBD symptoms in addition to autonomic symptoms were associated with patients with both sleep disturbances and EDS.
Genetic variants and phenotype analysis in a five-generation Chinese pedigree with PCDH19 female-limited epilepsy
Authors: Zhou Wenjuan , Ouyang Yuzhen , Ji Yuqiao , Xi Qiong , Zhao Lingling 
Published: March 2023

ObjectiveAlbeit the gene of PCDH19-FE was ascertained, the correlation of gene mutation, PCDH19 protein structure, and phenotype heterogeneity remained obscure. This study aimed to report a five-generation pedigree of seven female patients of PCDH19-FE and tried to explore whether two variants were correlated with PCDH19 protein structure and function alteration, and PCDH19-FE phenotype.MethodsWe analyzed the clinical data and genetic variants of a PCDH19-FE pedigree, to explore the phenotype heterogeneity of PCDH19-FE and underlying mechanisms. In addition to the clinical information of family members, next-generation sequencing was adopted to detect the variant sites of probands with validation by sanger sequencing. And the sanger sequencing was conducted in other patients in this pedigree. The biological conservation analysis and population polymorphism analysis of variants were also performed subsequently. The structure alteration of mutated PCDH19 protein was predicted by AlphaFold2.ResultsBased on a five-generation pedigree of PCDH19-FE, missense variants of c.695A&gt;G and c.2760T&gt;A in the PCDH19 gene were found in the heterozygous proband (V:1), which resulted in the change of amino acid 232 from Asn to Ser (p.Asn232Ser) and amino acid 920 from Asp to Glu (p.Asp920Glu) influencing PCDH19 function. The other six females in the pedigree (II:6, II:8, IV:3, IV:4, IV:5, IV:11) exhibited different clinical phenotypes but shared the same variant. Two males with the same variant have no clinical manifestations (III:3, III:10). The biological conservation analysis and population polymorphism analysis demonstrated the highly conservative characteristics of these two variants. AlphaFold2 predicted that the variant, p.Asp920Glu, led to the disappearance of the hydrogen bond between Asp at position 920 and His at position 919. Furthermore, the hydrogen bond between Asp920 and His919 also disappeared when the Asn amino acid mutated to Ser at position 232.ConclusionA strong genotype-phenotype heterogeneity was observed among female patients with the same genotype in our PCDH19-FE pedigree. And two missense variants, c.695A &gt; G and c.2760T&gt;A in the PCDH19 gene, have been identified in our pedigree. The c.2760T&gt;A variant was a novel variant site probably related to the PCDH19-FE.
Factors affecting variability in vestibulo-ocular reflex gain in the Video Head Impulse Test in individuals without vestibulopathy: A systematic review of literature
Authors: Money-Nolan Laurel Elise , Flagge Ashley Gaal 
Published: March 2023

IntroductionThe purpose of this systematic review was to summarize and synthesize published evidence examining variations in vestibulo-ocular reflex (VOR) gain outcomes for the Video Head Impulse Test (vHIT) in healthy individuals without vestibulopathy in order to describe factors that may influence test outcomes.MethodsComputerized literature searches were performed from four search engines. The studies were selected based on relevant inclusion and exclusion criteria, and were required to examine VOR gain in healthy adults without vestibulopathy. The studies were screened using Covidence (Cochrane tool) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards (PRISMA-2020).ResultsA total of 404 studies were initially retrieved, of which a total of 32 studies met inclusion criteria. Four major categories were identified which lead to significant variation in VOR gain outcomes: participant-based factors, tester/examiner-based factors, protocol-based factors, and equipment-based factors.DiscussionVarious subcategories are identified within each of these classifications and are discussed, including recommendations for decreasing VOR gain variability in clinical practice.
Causal relationship between human blood omega-3 fatty acids and the risk of epilepsy: A two-sample Mendelian randomization study
Authors: Liang Zhen , Lou Yingyue , Li Zijian , Liu Songyan 
Published: March 2023

BackgroundThough omega-3 fatty acids reduce seizures in several animal models, considerable controversy exists regarding the association between omega-3 fatty acids and epilepsy in human.ObjectiveTo assess whether genetically determined human blood omega-3 fatty acids are causally associated with the risk of epilepsy outcomes.MethodsWe conducted a two-sample Mendelian randomization (MR) analysis by applying summary statistics of genome-wide association study datasets of both exposure and outcomes. Single nucleotide polymorphisms significantly associated with blood omega-3 fatty acids levels were selected as instrumental variables to estimate the causal effects on epilepsy. Five MR analysis methods were conducted to analyze the final results. The inverse-variance weighted (IVW) method was used as the primary outcome. The other MR analysis methods (MR-Egger, weighted median, simple mode, and weighted mode) were conducted as the complement to IVW. Sensitivity analyses were also conducted to evaluate heterogeneity and pleiotropy.ResultsGenetically predicted the increase of human blood omega-3 fatty acids levels was associated with a higher risk of epilepsy (OR = 1.160, 95%CI = 1.051–1.279, P = 0.003).ConclusionsThis study revealed a causal relationship between blood omega-3 fatty acids and the risk of epilepsy, thus providing novel insights into the development mechanism of epilepsy.
Combined effect of transcutaneous auricular vagus nerve stimulation and 0.1 Hz slow-paced breathing on working memory
Authors: Tian Qian-Qian , Cheng Chen , Liu Peng-Hui , Yin Zi-Xin , Zhang Meng-Kai , Cui Ya-Peng , Zhao Rui , Deng Hui , Lu Li-Ming , Tang Chun-Zhi , Xu Neng-Gui , Yang Xue-Juan , Sun Jin-Bo , Qin Wei 
Published: March 2023

BackgroundPrevious research has found that transcutaneous auricular vagus nerve stimulation (taVNS) can improve working memory (WM) performance. It has also been shown that 0.1 Hz slow-paced breathing (SPB, i.e., breathing at a rate of approximately 6 breaths/min) can significantly influence physical state and cognitive function via changes in autonomic afferent activity. In the present study, we investigated the synergistic effects of taVNS and SPB on WM performance.MethodsA total of 96 healthy people participated in this within-subjects experiment involving four conditions, namely taVNS, SPB, combined taVNS with SPB (taVNS + SPB), and sham. Each participant underwent each intervention for 30 min and WM was compared pre- and post-intervention using the spatial and digit n-back tasks in a random order four times. Permutation-based analysis of variance was used to assess the interaction between time and intervention.ResultsFor the spatial 3-back task, a significant interaction between time and intervention was found for the accuracy rate of matching trials (mACC, p = 0.03). Post hoc analysis suggested that both taVNS and taVNS + SPB improved WM performance, however, no significant difference was found in the SPB or sham groups.ConclusionThis study has replicated the effects of taVNS on WM performance reported in previous studies. However, the synergistic effects of combined taVNS and SPB warrant further research.
EARDS: EfficientNet and attention-based residual depth-wise separable convolution for joint OD and OC segmentation
Authors: Zhou Wei , Ji Jianhang , Jiang Yan , Wang Jing , Qi Qi , Yi Yugen 
Published: March 2023

BackgroundGlaucoma is the leading cause of irreversible vision loss. Accurate Optic Disc (OD) and Optic Cup (OC) segmentation is beneficial for glaucoma diagnosis. In recent years, deep learning has achieved remarkable performance in OD and OC segmentation. However, OC segmentation is more challenging than OD segmentation due to its large shape variability and cryptic boundaries that leads to performance degradation when applying the deep learning models to segment OC. Moreover, the OD and OC are segmented independently, or pre-requirement is necessary to extract the OD centered region with pre-processing procedures.MethodsIn this paper, we suggest a one-stage network named EfficientNet and Attention-based Residual Depth-wise Separable Convolution (EARDS) for joint OD and OC segmentation. In EARDS, EfficientNet-b0 is regarded as an encoder to capture more effective boundary representations. To suppress irrelevant regions and highlight features of fine OD and OC regions, Attention Gate (AG) is incorporated into the skip connection. Also, Residual Depth-wise Separable Convolution (RDSC) block is developed to improve the segmentation performance and computational efficiency. Further, a novel decoder network is proposed by combining AG, RDSC block and Batch Normalization (BN) layer, which is utilized to eliminate the vanishing gradient problem and accelerate the convergence speed. Finally, the focal loss and dice loss as a weighted combination is designed to guide the network for accurate OD and OC segmentation.Results and discussionExtensive experimental results on the Drishti-GS and REFUGE datasets indicate that the proposed EARDS outperforms the state-of-the-art approaches. The code is available at https://github.com/M4cheal/EARDS.
Demonstrating a link between diet, gut microbiota and brain: 14C radioactivity identified in the brain following gut microbial fermentation of 14C-radiolabeled tyrosine in a pig model
Authors: Murray Margaret , Barlow Christopher K. , Blundell Scott , Buecking Mark , Gibbon Anne , Goeckener Bernd , Kaminskas Lisa M. , Leitner Patricia , Selby-Pham Sophie , Sinclair Andrew , Waktola Habtewold D. , Williamson Gary , Bennett Louise E. 
Published: March 2023

BackgroundThere is a need to better understand the relationship between the diet, the gut microbiota and mental health. Metabolites produced when the human gut microbiota metabolize amino acids may enter the bloodstream and have systemic effects. We hypothesize that fermentation of amino acids by a resistant protein-primed gut microbiota could yield potentially toxic metabolites and disturb the availability of neurotransmitter precursors to the brain. However, these mechanisms are challenging to investigate via typical in vitro and clinical methods.MethodsWe developed a novel workflow using 14C radiolabeling to investigate complex nutrient-disease relationships. The first three steps of the workflow are reported here. α-Linolenic acid (ALA) was used as a model nutrient to confirm the efficacy of the workflow, and tyrosine (Tyr) was the test nutrient. 14C-Tyr was administered to male weanling pigs fed a high resistant protein diet, which primed the gut microbiota for fermenting protein. The hypotheses were; (1) that expected biodistribution of 14C-ALA would be observed, and (2) that radioactivity from 14C-Tyr, representing Tyr and other amino acids released from resistant protein following gut microbial fermentation, would be bioavailable to the brain.ResultsRadioactivity from the 14C-ALA was detected in tissues reflecting normal utilization of this essential fatty acid. Radioactivity from the 14C-Tyr was detected in the brain (0.15% of original dose).ConclusionMetabolites of gut-fermented protein and specifically amino acid precursors to neurotransmitters such as tyrosine, are potentially able to affect brain function. By extension, resistant proteins in the diet reaching the gut microbiota, also have potential to release metabolites that can potentially affect brain function. The high specificity of detection of 14C radioactivity demonstrates that the proposed workflow can similarly be applied to understand other key diet and health paradigms.
Cannabidiol treatment improves metabolic profile and decreases hypothalamic inflammation caused by maternal obesity
Authors: Rodrigues Fernanda da Silva , Jantsch Jeferson , Fraga Gabriel de Farias , Dias Victor Silva , Eller Sarah , De Oliveira Tiago Franco , Giovenardi Márcia , Guedes Renata Padilha 
Published: March 2023

IntroductionThe implications of maternal overnutrition on offspring metabolic and neuroimmune development are well-known. Increasing evidence now suggests that maternal obesity and poor dietary habits during pregnancy and lactation can increase the risk of central and peripheral metabolic dysregulation in the offspring, but the mechanisms are not sufficiently established. Furthermore, despite many studies addressing preventive measures targeted at the mother, very few propose practical approaches to treat the damages when they are already installed.MethodsHere we investigated the potential of cannabidiol (CBD) treatment to attenuate the effects of maternal obesity induced by a cafeteria diet on hypothalamic inflammation and the peripheral metabolic profile of the offspring in Wistar rats.ResultsWe have observed that maternal obesity induced a range of metabolic imbalances in the offspring in a sex-dependant manner, with higher deposition of visceral white adipose tissue, increased plasma fasting glucose and lipopolysaccharides (LPS) levels in both sexes, but the increase in serum cholesterol and triglycerides only occurred in females, while the increase in plasma insulin and the homeostatic model assessment index (HOMA-IR) was only observed in male offspring. We also found an overexpression of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNFα), interleukin (IL) 6, and interleukin (IL) 1β in the hypothalamus, a trademark of neuroinflammation. Interestingly, the expression of GFAP, a marker for astrogliosis, was reduced in the offspring of obese mothers, indicating an adaptive mechanism to in utero neuroinflammation. Treatment with 50 mg/kg CBD oil by oral gavage was able to reduce white adipose tissue and revert insulin resistance in males, reduce plasma triglycerides in females, and attenuate plasma LPS levels and overexpression of TNFα and IL6 in the hypothalamus of both sexes.DiscussionTogether, these results indicate an intricate interplay between peripheral and central counterparts in both the pathogenicity of maternal obesity and the therapeutic effects of CBD. In this context, the impairment of internal hypothalamic circuitry caused by neuroinflammation runs in tandem with the disruptions of important metabolic processes, which can be attenuated by CBD treatment in both ends.
Online educational interventions in pediatric intensive care medicine
Authors: Daniel Dennis , Wolbrink Traci A. 
Published: March 2023

BackgroundOnline education has experienced explosive growth, particularly in the wake of the COVID-19 pandemic. We explored the current state of the evidence base for online education targeted towards healthcare professionals working in pediatric intensive care units (PICUs), to report how we are using online education in our field.Materials and MethodsWe performed a literature review by systematically generating a list of publications indexed in PubMed describing online educational interventions in the PICU, using Medical Subject Header (MeSH)-based search terms and the following inclusion criteria: studies published after 2005 that describe online educational interventions aimed at healthcare professional working in the PICU. We reviewed the full text of all included articles, and summarized the study aims, design, and results.ResultsOur initial search yielded 1,071 unique articles. After screening abstracts and titles, then full texts, eight articles were included in the review. Many online learning modalities are represented, including websites, self-study modules, videos, videoconferencing, online self-assessment with feedback, virtual patient cases, screen-based simulation, and podcasts. Three studies focused on residents, two studies on nurses, two studies on a multidisciplinary team, and one study on transport nurses and paramedics. Most studies utilized participant surveys to assess satisfaction, and half included pre- and post-intervention multiple-choice question tests. Only one study included a patient-related outcome measure.ConclusionsDespite growth in online medical educational intervention research, there are relatively few published studies in pediatric critical care, and only one study evaluated the impact of online learning on patient outcomes. There remain significant opportunities for PICU educators to assess the impact of online educational interventions, especially related to clinician behaviors and patient outcomes.
Bioinformatics-based construction of prognosis-related methylation prediction model for pancreatic cancer patients and its application value
Authors: Cao Tiansheng , Wu Hongsheng , Ji Tengfei 
Published: March 2023

Objective: Pancreatic adenocarcinoma (PAAD) is a highly malignant gastrointestinal tumor with almost similar morbidity and mortality. In this study, based on bioinformatics, we investigated the role of gene methylation in PAAD, evaluated relevant factors affecting patient prognosis, screened potential anti-cancer small molecule drugs, and constructed a prediction model to assess the prognosis of PAAD.Methods: Clinical and genomic data of PAAD were collected from the Tumor Genome Atlas Project (TCGA) database and gene expression profiles were obtained from the GTEX database. Analysis of differentially methylated genes (DMGs) and significantly differentially expressed genes (DEGs) was performed on tumorous samples with KRAS wild-type and normal samples using the “limma” package and combined analysis. We selected factors significantly associated with survival from the significantly differentially methylated and expressed genes (DMEGs), and their fitting into a relatively streamlined prognostic model was validated separately from the internal training and test sets and the external ICGC database to show the robustness of the model.Results: In the TCGA database, 2,630 DMGs were identified, with the largest gap between DMGs in the gene body and TSS200 region. 318 DEGs were screened, and the enrichment analysis of DMGs and DEGs was taken to intersect DMEGs, showing that the DMEGs were mainly related to Olfactory transduction, natural killer cell mediated cytotoxicity pathway, and Cytokine -cytokine receptor interaction. DMEGs were able to distinguish well between PAAD and paraneoplastic tissues. Through techniques such as drug database and molecular docking, we screened a total of 10 potential oncogenic small molecule compounds, among which felbamate was the most likely target drug for PAAD. We constructed a risk model through combining three DMEGs (S100P, LY6D, and WFDC13) with clinical factors significantly associated with prognosis, and confirmed the model robustness using external and internal validation.Conclusion: The classification model based on DMEGs was able to accurately separate normal samples from tumor samples and find potential anti-PAAD drugs by performing gene-drug interactions on DrugBank.
Identification of Camellia oleifera WRKY transcription factor genes and functional characterization of CoWRKY78
Authors: Li Jingbin , Xiong Chaowei , Ruan Dong , Du Wei , Li He , Ruan Chengjiang 
Published: March 2023

Camellia oleifera Abel is a highly valued woody edible oil tree, which is endemic to China. It has great economic value because C. oleifera seed oil contains a high proportion of polyunsaturated fatty acids. C. oleifera anthracnose caused by Colletotrichum fructicola, poses a serious threat to C. oleifera growth and yield and causes the benefit of the C. oleifera industry to suffer directly. The WRKY transcription factor family members have been widely characterized as vital regulators in plant response to pathogen infection. Until now, the number, type and biological function of C. oleifera WRKY genes are remains unknown. Here, we identified 90 C. oleifera WRKY members, which were distributed across 15 chromosomes. C. oleifera WRKY gene expansion was mainly attributed to segmental duplication. We performed transcriptomic analyses to verify the expression patterns of CoWRKYs between anthracnose-resistant and -susceptible cultivars of C. oleifera. These results demonstrated that multiple candidate CoWRKYs can be induced by anthracnose and provide useful clues for their functional studies. CoWRKY78, an anthracnose-induced WRKY gene, was isolated from C. oleifera. It was significantly down-regulated in anthracnose-resistant cultivars. Overexpression of CoWRKY78 in tobacco markedly reduced resistance to anthracnose than WT plants, as evidenced by more cell death, higher malonaldehyde content and reactive oxygen species (ROS), but lower activities of superoxide dismutase (SOD), peroxidase (POD), as well as phenylalanine ammonia-lyase (PAL). Furthermore, the expression of multiple stress-related genes, which are associated with ROS-homeostasis (NtSOD and NtPOD), pathogen challenge (NtPAL), and pathogen defense (NtPR1, NtNPR1, and NtPDF1.2) were altered in the CoWRKY78-overexpressing plants. These findings increase our understanding of the CoWRKY genes and lay the foundation for the exploration of anthracnose resistance mechanisms and expedite the breeding of anthracnose-resistant C. oleifera cultivars.