bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mRNA panel for differentiation between acute exacerbation or pneumonia in COPD patients
Authors: Bertrams Wilhelm , Wilhelm Jochen , Veeger Pia-Marie , Hanko Carolina , Brinke Kristina auf dem , Klabunde Björn , Pott Hendrik , Weckler Barbara , Greulich Timm , Vogelmeier Claus F. , Schmeck Bernd 
Published: March 2024

IntroductionPatients suffering from chronic obstructive pulmonary disease (COPD) are prone to acute exacerbations (AECOPD) or community acquired pneumonia (CAP), both posing severe risk of morbidity and mortality. There is no available biomarker that correctly separates AECOPD from COPD. However, because CAP and AECOPD differ in aetiology, treatment and prognosis, their discrimination would be important.MethodsThis study analysed the ability of selected candidate transcripts from peripheral blood mononuclear cells (PBMCs) to differentiate between patients with AECOPD, COPD &amp; CAP, and CAP without pre-existing COPD.ResultsIn a previous study, we identified differentially regulated genes between CAP and AECOPD in PBMCs. In the present new cohort, we tested the potential of selected candidate PBMC transcripts to differentiate at early time points AECOPD, CAP+COPD, and CAP without pre-existing COPD. Expression of YWHAG, E2F1 and TDRD9 held predictive power: This gene set predicted diseases markedly better (model accuracy up to 100%) than classical clinical markers like CRP, lymphocyte count and neutrophil count (model accuracy up to 82%).DiscussionIn summary, in our cohort expression levels of YWHAG, E2F1 and TDRD9 differentiated with high accuracy between COPD patients suffering from acute exacerbation or CAP.
Mepolizumab and benralizumab in patients with severe asthma and a history of eosinophilic granulomatosis with polyangiitis
Authors: Desaintjean Charlene , Ahmad Kaïs , Traclet Julie , Gerfaud-Valentin Mathieu , Durel Cecile-Audrey , Glerant Jean-Charles , Hot Arnaud , Lestelle François , Mainbourg Sabine , Nasser Mouhamad , Seve Pascal , Turquier Ségolène , Devouassoux Gilles , Cottin Vincent 
Published: March 2024

IntroductionAsthma associated with eosinophilic granulomatosis with polyangiitis (EGPA) is often severe and corticosteroid-dependent, leading to significant morbidity. Mepolizumab and benralizumab are humanized monoclonal antibodies targeting interleukin 5 (IL-5) and its receptor, respectively. They have been shown to be effective in steroid-sparing in patients with severe eosinophilic asthma.ObjectiveOur aim was to evaluate the efficacy and safety of mepolizumab and benralizumab prescribed for severe asthma in patients with EGPA under “real-world” conditions.MethodsThis was a retrospective analysis of patients with EGPA and persistent asthma who received either mepolizumab 100 or 300 mg administered every 4 weeks, or benralizumab 30 mg administered every 4 weeks for the initial 3 injections and followed by an injection every 8 weeks thereafter, whilst combined with oral glucocorticoids. The follow-up every 6 ± 3 months included an assessment of clinical manifestations, pulmonary function tests and eosinophil cell count. The primary outcome was the proportion of patients at 12 months receiving a daily oral dose of prednisone or equivalent of 4 mg or less with a BVAS of 0.ResultsTwenty-six patients were included. After 12 months of treatment with mepolizumab or benralizumab, 32% of patients met the primary outcome and were receiving less than 4 mg of prednisone per day with a BVAS of 0. The median dose of prednisone was 10 mg per day at baseline, 9 mg at 6 months, and 5 mg at 12 months (p ≤ 0.01). At 12 months, 23% of patients were weaned off corticosteroids, while an increase or no change in dose was observed in 27% of patients. The median eosinophil count was significantly reduced from 365 cells/mm3 to 55 cells/mm3 at 6 months and 70 cells/mm3 at 12 months, respectively. No significant change was observed in FEV1. After 12 months of treatment, 14% of patients had had an average of 1 exacerbation of asthma, compared with 52% of patients before baseline. The tolerability profile was favorable.ConclusionIn this real-world study in patients with severe asthma and a history of EGPA asthma, mepolizumab and benralizumab had a significant steroid-sparing effect and reduced asthma exacerbation, but no significant effect on lung function.
Causal associations of genetically predicted gut microbiota and blood metabolites with inflammatory states and risk of infections: a Mendelian randomization analysis
Authors: Liu Yingjian , Zhu Qian , Guo Gongjie , Xie Zhipeng , Li Senlin , Lai Chengyang , Wu Yonglin , Wang Liansheng , Zhong Shilong 
Published: March 2024

BackgroundInflammation serves as a key pathologic mediator in the progression of infections and various diseases, involving significant alterations in the gut microbiome and metabolism. This study aims to probe into the potential causal relationships between gut microbial taxa and human blood metabolites with various serum inflammatory markers (CRP, SAA1, IL-6, TNF-α, WBC, and GlycA) and the risks of seven common infections (gastrointestinal infections, dysentery, pneumonia, bacterial pneumonia, bronchopneumonia and lung abscess, pneumococcal pneumonia, and urinary tract infections).MethodsTwo-sample Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW), maximum likelihood, MR-Egger, weighted median, and MR-PRESSO.ResultsAfter adding other MR models and sensitivity analyses, genus Roseburia was simultaneously associated adversely with CRP (Beta IVW = −0.040) and SAA1 (Beta IVW = −0.280), and family Bifidobacteriaceae was negatively associated with both CRP (Beta IVW = −0.034) and pneumonia risk (Beta IVW = −0.391). After correction by FDR, only glutaroyl carnitine remained significantly associated with elevated CRP levels (Beta IVW = 0.112). Additionally, threonine (Beta IVW = 0.200) and 1-heptadecanoylglycerophosphocholine (Beta IVW = −0.246) were found to be significantly associated with WBC levels. Three metabolites showed similar causal effects on different inflammatory markers or infectious phenotypes, stearidonate (18:4n3) was negatively related to SAA1 and urinary tract infections, and 5-oxoproline contributed to elevated IL-6 and SAA1 levels. In addition, 7-methylguanine showed a positive correlation with dysentery and bacterial pneumonia.ConclusionThis study provides novel evidence confirming the causal effects of the gut microbiome and the plasma metabolite profile on inflammation and the risk of infection. These potential molecular alterations may aid in the development of new targets for the intervention and management of disorders associated with inflammation and infections.
A Mendelian randomization investigation of the causal association between the gut microbiota and sleep disorders
Authors: Yan Wei , Zhuang Zhenzhen , Gao Yuhao , Wang Yuntao , He Daikun 
Published: March 2024

BackgroundIncreasing numbers of people are suffering from sleep disorders. The gut microbiota of these individuals differs significantly. However, no reports are available on the causal associations between specific gut microbiota and sleep disorders.MethodsData on gut genera were obtained from the MiBioGen consortium. Twenty-four cohorts with 18,340 individuals of European origin were included. Sleep disorder data, which included 216,454 European individuals, were retrieved from the FinnGen Biobank. Subsequently, two-sample Mendelian randomization was performed to analyze associations between sleep disorders and specific components of the gut microbiota.ResultsInverse variance weighting (IVW) revealed a negative correlation between Coprobacter and sleep disorders (OR = 0.797, 95% CI = 0.66–0.96, and p = 0.016), a positive correlation between Lachnospiraceae and sleep disorders (OR = 1.429, 95% CI = 1.03–1.98, and p = 0.032), a negative association between Oscillospira and sleep disorders (OR = 0.745, 95% CI = 0.56–0.98, and p = 0.038), and a negative association between Peptococcus and sleep disorders (OR = 0.858, 95% CI = 0.74–0.99, p = 0.039).ConclusionA significant causal relationship was found between four specific gut microbiota and sleep disorders. One family, Lachnospiraceae, was observed to increase the risk of sleep disorders, while three genera, namely, Coprobacter, Oscillospira, and Peptococcus, could reduce the risk of sleep disorders. However, further investigations are needed to confirm the specific mechanisms by which the gut microbiota affects sleep.
Associative role of HLA-DRB1 as a protective factor for susceptibility and progression of Parkinson’s disease: a Chinese cross-sectional and longitudinal study
Authors: He Raoli , Zeng Yuqi , Wang Chaodong , Chen Lina , Cai Guoen , Chen Ying , Wang Yingqing , Ye Qinyong , Chen Xiaochun 
Published: March 2024

BackgroundPrevious genome-wide association studies investigating the relationship between the HLA-DRB1 and the risk of Parkinson’s disease (PD) have shown limited racial diversity and have not explored clinical heterogeneity extensively.MethodsThe study consisted of three parts: a case–control study, a cross-sectional study, and a longitudinal cohort study. The case–control study included 477 PD patients and 477 healthy controls to explore the relationship between rs660895 and PD susceptibility. The cross-sectional study utilized baseline data from 429 PD patients to examine the correlation between rs660895 and PD features. The longitudinal study included 388 PD patients who completed a 3-year follow-up to investigate the effects of rs660895 on PD progression.ResultsIn the case–control study, HLA-DRB1 rs660895-G allele was associated with a decreased risk of PD in allele model (adjusted OR=0.72, p = 0.003) and dominant model (AG + GG vs. AA: adjusted OR = 0.67, p = 0.003). In the cross-sectional analysis, there was no association between rs660895 and the onset age, motor phenotype, or initial motor symptoms. In the longitudinal analysis, PD patients with the G allele exhibited a slower progression of motor symptoms (MDS-UPDRS-III total score: β = −5.42, p &lt; 0.001, interaction ptime × genotype &lt; 0.001) and non-motor symptoms (NMSS score: β = −4.78, p = 0.030, interaction ptime × genotype &lt; 0.001).ConclusionOur findings support HLA-DRB1 rs660895-G allele is a protective genetic factor for PD risk in Chinese population. Furthermore, we also provide new evidence for the protective effect of rs660895-G allele in PD progression.
Causal role of immune cells on risk of Parkinson’s disease: a Mendelian randomization study
Authors: Gu Jian , Qiao Yue , Cong Shuyan 
Published: March 2024

BackgroundPrevious observational studies have suggested a correlation between immune cells and Parkinson’s disease (PD), yet specific investigations into the causal relationship between the two remain limited. This study aims to explore this potential causal relationship.MethodsWe utilized genome-wide association study (GWAS) data on immune cells and Parkinson’s Disease, conducting a two-sample Mendelian randomization (MR) analysis using single nucleotide polymorphisms (SNPs). To estimate causality, we employed inverse variance weighting (IVW), MR-Egger, and weighted median (WM) methods. For sensitivity analysis, we used Cochran’s Q-test, MR-Egger intercept, leave-one-out analysis, and funnel plots.ResultsAfter false discovery rate (FDR) correction, the effects of PD on immune cells, and vice versa, were not statistically significant. These include CX3CR1 on CD14+ CD16-monocyte (OR = 0.91, 95% CI = 0.86–0.96, p = 0.0003 PFDR = 0.152), CD62L-CD86+ myeloid DC AC (OR = 0.93, 95% CI = 0.89–0.97, p = 0.0005, PFDR = 0.152),CD11b on Mo (OR = 1.08, 95% CI = 1.03–1.13, p = 0.001, PFDR = 0.152), CD38 on igd+ cd24− (OR = 1.14, 95% CI = 1.06–1.23, p = 0.001, PFDR = 0.152), D14+ cd16+ monocyte %monocyte (OR = 1.10, 95% CI = 1.04–1.17, p = 0.001, PFDR = 0.159). Additionally, PD may be causally related to the immune phenotype of CM CD8br %T cell (beta = 0.10, 95% CI = 1.14–1.16, p = 0.0004, PFDR = 0.151), SSC-A on monocyte (beta = 0.11, 95% CI = 1.15–1.18, p = 0.0004, PFDR = 0.1 SSC-A on monocyte). No pleiotropy was determined.ConclusionThis study suggested a potential causal link between immune cells and Parkinson’s Disease through the MR method, which could provide a new direction for the mechanistic research and clinical treatment of PD.
The ratio of the maximum density values: a new method for predicting hemorrhagic transformation in acute ischemic stroke patients undergoing mechanical thrombectomy
Authors: Qiao Xiaohong , Zheng Fuhao , Wei Manman , Zhao Zhenming 
Published: March 2024

BackgroundIt is challenging yet critical to differentiate between hemorrhagic transformation (HT) and contrast extravasation on non-contrast-enhanced computed tomography (NCCT) scans following mechanical thrombectomy (MT) in patients with acute ischemic stroke. We propose a new method called the ratio of maximum density values (RMDV) to minimize the confusion of contrast extravasation and to evaluate the diagnostic significance of RMDV in predicting HT on immediate post-interventional NCCT scans.MethodsWe conducted a retrospective analysis of the prospective patients’ database who received MT for acute ischemic stroke caused by occlusion of the intracranial large artery and showed postinterventional cerebral hyperdensities (PCHDs) on NCCT scans immediately after MT. Based on the subsequent NCCT scans, we divided patients with PCHDs into the HT and the non-HT groups. The clinical characters and radiological details were collected and compared to the two groups. We assessed the ability of RMDV &gt;1 to predict HT by analyzing the receiver operating characteristic curve.ResultsOne hundred and three patients showed PCHDs; 58 (56.31%) were classified as HT, while 45 (43.69%) were classified as non-HT. The only notable distinction between the two groups was the proportion of RMDV &gt;1 in the HT group. The correlation between HT and RMDV &gt;1 with an area under the curve of 0.826 (95% confidence interval, 0.739 to 0.894). The sensitivity, specificity, positive, and negative predictive values of RMDV &gt;1 on NCCT for predicting HT were 89.66, 75.56, 82.54, and 85.00%, respectively.ConclusionThe utilization of RMDV &gt;1 on immediate NCCT scans after MT can predict early HT with good sensitivity and specificity.
Early cortico-muscular coherence and cortical network changes in Parkinson’s patients treated with MRgFUS
Authors: Visani Elisa , Panzica Ferruccio , Franceschetti Silvana , Golfrè Andreasi Nico , Cilia Roberto , Rinaldo Sara , Rossi Sebastiano Davide , Lanteri Paola , Eleopra Roberto 
Published: March 2024

IntroductionTo investigate cortical network changes using Magnetoencephalography (MEG) signals in Parkinson’s disease (PD) patients undergoing Magnetic Resonance-guided Focused Ultrasound (MRgFUS) thalamotomy.MethodsWe evaluated the MEG signals in 16 PD patients with drug-refractory tremor before and after 12-month from MRgFUS unilateral lesion of the ventralis intermediate nucleus (Vim) of the thalamus contralateral to the most affected body side. We recorded patients 24 h before (T0) and 24 h after MRgFUS (T1). We analyzed signal epochs recorded at rest and during the isometric extension of the hand contralateral to thalamotomy. We evaluated cortico-muscular coherence (CMC), the out-strength index from non-primary motor areas to the pre-central area and connectivity indexes, using generalized partial directed coherence. Statistical analysis was performed using RMANOVA and post hoct-tests.ResultsMost changes found at T1 compared to T0 occurred in the beta band and included: (1) a re-adjustment of CMC distribution; (2) a reduced out-strength from non-primary motor areas toward the precentral area; (3) strongly reduced clustering coefficient values. These differences mainly occurred during motor activation and with few statistically significant changes at rest. Correlation analysis showed significant relationships between changes of out-strength and clustering coefficient in non-primary motor areas and the changes in clinical scores.DiscussionOne day after MRgFUS thalamotomy, PD patients showed a topographically reordered CMC and decreased cortico-cortical flow, together with a reduced local connection between different nodes. These findings suggest that the reordered cortico-muscular and cortical-networks in the beta band may represent an early physiological readjustment related to MRgFUS Vim lesion.
Explainable artificial intelligence (xAI) in neuromarketing/consumer neuroscience: an fMRI study on brand perception
Authors: Marques dos Santos José Paulo , Marques dos Santos José Diogo 
Published: March 2024

IntroductionThe research in consumer neuroscience has identified computational methods, particularly artificial intelligence (AI) and machine learning, as a significant frontier for advancement. Previously, we utilized functional magnetic resonance imaging (fMRI) and artificial neural networks (ANNs) to model brain processes related to brand preferences in a paradigm exempted from motor actions. In the current study, we revisit this data, introducing recent advancements in explainable artificial intelligence (xAI) to gain insights into this domain. By integrating fMRI data analysis, machine learning, and xAI, our study aims to search for functional brain networks that support brand perception and, ultimately, search for brain networks that disentangle between preferred and indifferent brands, focusing on the early processing stages.MethodsWe applied independent component analysis (ICA) to overcome the expected fMRI data’s high dimensionality, which raises hurdles in AI applications. We extracted pertinent features from the returned ICs. An ANN is then trained on this data, followed by pruning and retraining processes. We then apply explanation techniques, based on path-weights and Shapley values, to make the network more transparent, explainable, and interpretable, and to obtain insights into the underlying brain processes.ResultsThe fully connected ANN model obtained an accuracy of 54.6%, which dropped to 50.4% after pruning. However, the retraining process allowed it to surpass the fully connected network, achieving an accuracy of 55.9%. The path-weights and Shapley-based analysis concludes that, regarding brand perception, the expected initial participation of the primary visual system is followed. Other brain areas participate in early processing and discriminate between preferred and indifferent brands, such as the cuneal and the lateral occipital cortices.DiscussionThe most important finding is that a split between processing brands|preferred from brands|indifferent may occur during early processing stages, still in the visual system. However, we found no evidence of a “decision pipeline” that would yield if a brand is preferred or indifferent. The results suggest the existence of a “tagging”-like process in parallel flows in the extrastriate. Network training dynamics aggregate specific processes within the hidden nodes by analyzing the model’s hidden layer. This yielded that some nodes contribute to both global brand appraisal and specific brand category classification, shedding light on the neural substrates of decision-making in response to brand stimuli.
Comparative development of the serotonin- and FMRFamide-immunoreactive components of the nervous system in two distantly related ribbon worm species (Nemertea, Spiralia)
Authors: von Döhren Jörn 
Published: March 2024

IntroductionNeurodevelopment in larval stages of non-model organisms, with a focus on the serotonin- and FMRFamide-immunoreactive components, has been in the focus of research in the recent past. However, some taxonomic groups remain understudied. Nemertea (ribbon worms) represent such an understudied clade with only few reports on nervous system development mostly from phylogenetically or developmentally derived species. It would be insightful to explore neurodevelopment in additional species to be able to document the diversity and deduce common patterns to trace the evolution of nervous system development.MethodsFluorescent immunohistochemical labeling with polyclonal primary antibodies against serotonin and FMRF-amide and a monoclonal antibody against synapsin performed on series of fixed larval stages of two nemertean species Cephalothrix rufifrons (Archinemertea, Palaeonemertea) and Emplectonema gracile (Monostilifera, Hoplonemertea) were analyzed with confocal laser scanning microscopy.ResultsThis contribution gives detailed accounts on the development of the serotonin- and FMRFamide-immunoreactive subsets of the nervous system in two nemertean species from the first appearance of the respective signals. Additionally, data on synapsin-like immunoreactivity illustrates the general structure of neuropil components. Events common to both investigated species are the appearance of serotonin-like immunoreactive signals before the appearance of FMRF-like immunoreactive signals and the strict progression of the development of the lateral nerve cords from the anteriorly located, ring-shaped brain toward the posterior pole of the larva. Notable differences are (1) the proboscis nervous system that is developing much earlier in investigated larval stages of E. gracile and (2) distinct early, but apparently transient, serotonergic neurons on the frontal and caudal pole of the larva in E. gracile that seem to be absent in C. rufifrons.DiscussionAccording to the results from this investigation and in line with previously published accounts on nervous system development, the hypothetical last common ancestor of Nemertea had a ring-shaped brain arranged around the proboscis opening, from which a pair of ventro-lateral nerve cords develops in anterior to posterior progression. Early frontal and caudal serotonergic neurons that later degenerate or cease to express serotonin are an ancestral character of Nemertea that they share with several other spiralian clades.
The correlation between fruit intake and all-cause mortality in hypertensive patients: a 10-year follow-up study
Authors: Sun Chuang , Li Jie , Zhao Zeyuan , Ren Shupeng , Guan Yue , Zhang Miaoan , Li Tianfeng , Tan Linglin , Yao Qiying , Chen Liang 
Published: March 2024

ObjectiveExtensive research has consistently shown the beneficial impact of fruit consumption on overall health. While some studies have proposed a potential association between fruit consumption and hypertension management, the influence of fruit consumption on mortality rates among hypertensive individuals remains uncertain. Consequently, aim of this study is to evaluate whether fruit consumption is associated with all-cause mortality among hypertensive patients.MethodsData were obtained from the National Health and Nutrition Examination Survey (NHANES), conducted between 2003 and 2006. Ten-year follow-up data from the National Death Index (NDI) were used to assess all-cause mortality. Cox proportional hazard model was utilized to explore the impact of fruit intake on all-cause mortality among hypertensive individuals.ResultsThe study included a cohort of 2,480 patients diagnosed with hypertension, and during the follow-up period, a total of 658 deaths from various causes were recorded. The COX regression analysis demonstrated that hypertensive patients who consumed apples three to six times per week exhibited a significantly reduced risk of all-cause mortality (HR = 0.60, 95%CI: 0.45–0.78, p &lt; 0.001) in comparison to those who consumed apples less than once per month. Likewise, consuming bananas three to six times per week also led to a comparable outcome (HR = 0.76, 95%CI: 0.59–0.97, p = 0.027). Moreover, Combined consumption of bananas and apples three to six times per week exhibited a noteworthy decrease in all-cause mortality (HR = 0.57, 95%CI: 0.39–0.84, p = 0.005) when compared to individuals who consumed these fruits less frequently. Conversely, no significant association was found between the consumption of other fruits, including pears, pineapples, and grapes, and all-cause mortality.ConclusionThe study discovered that moderate consumption of apples and bananas was associated with a reduced risk of all-cause mortality in patients with hypertension.