bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelets-related signature based diagnostic model in rheumatoid arthritis using WGCNA and machine learning
Authors: Liu Yuchen , Jiang Haixu , Kang Tianlun , Shi Xiaojun , Liu Xiaoping , Li Chen , Hou Xiujuan , Li Meiling 
Published: June 2023

Background and aimRheumatoid arthritis (RA) is an autoinflammatory disease that may lead to severe disability. The diagnosis of RA is limited due to the need for biomarkers with both reliability and efficiency. Platelets are deeply involved in the pathogenesis of RA. Our study aims to identify the underlying mechanism and screening for related biomarkers.MethodsWe obtained two microarray datasets (GSE93272 and GSE17755) from the GEO database. We performed Weighted correlation network analysis (WGCNA) to analyze the expression modules in differentially expressed genes identified from GSE93272. We used KEGG, GO and GSEA enrichment analysis to elucidate the platelets-relating signatures (PRS). We then used the LASSO algorithm to develop a diagnostic model. We then used GSE17755 as a validation cohort to assess the diagnostic performance by operating Receiver Operating Curve (ROC).ResultsThe application of WGCNA resulted in the identification of 11 distinct co-expression modules. Notably, Module 2 exhibited a prominent association with platelets among the differentially expressed genes (DEGs) analyzed. Furthermore, a predictive model consisting of six genes (MAPK3, ACTB, ACTG1, VAV2, PTPN6, and ACTN1) was constructed using LASSO coefficients. The resultant PRS model demonstrated excellent diagnostic accuracy in both cohorts, as evidenced by area under the curve (AUC) values of 0.801 and 0.979.ConclusionWe elucidated the PRSs occurred in the pathogenesis of RA and developed a diagnostic model with excellent diagnostic potential.
Renal injury, biomarkers, and myositis, an understudied aspect of disease: prospective study in the MyoCite cohort
Authors: Conticini Edoardo , Naveen R. , Sen Parikshit , Singh Mantabya , Rathore Upendra , Anuja Anamika Kumari , Rai Mohit Kumar , Yadav Brijesh , Prasad Narayan , Agarwal Vikas , Gupta Latika 
Published: June 2023

IntroductionThe mechanisms leading to chronic kidney disease (CKD) in patients with idiopathic inflammatory myopathies (IIMs) are poorly understood. We assessed the prevalence of subclinical renal injury in patients with IIMs, through elevation in biomarker levels of tubular injury and fibrosis (NGAL, KIM1, Activin A, CD163, and Cys-c), and assessed differences between subtypes of IIMs, and the effect of disease activity and duration.Materials and methodsClinical data, core set measures, sera and urine were prospectively collected from all patients enrolled in the MyoCite cohort from 2017 to 2021. Twenty healthy subjects (HC) and 16 patients with acute kidney injury (AKI) were included as controls. Baseline and follow up data for IIMs were included. Enzyme-linked immunosorbent assay (ELISA) was used to measure urine NGAL (Human Lipocalin-2/NGAL Duoset ELISA, Cat no: DY1757), KIM1 (Human TIM-1/KIM 1/HAVCR Duoset ELISA, Cat.no: DY1750B), Activin A (Human Activin A Duoset ELISA, Cat no: DY338), CD163 (Human CD163 Duoset ELISA,Cat no: DY1607-05), and Cys-c (Human Cystatin C Duoset ELISA, Cat. no.: DY1196) levels, while eGFR (unit mL/min/1.73 m2) was calculated by the Cockcroft-Gault formula and CKD-EPI formula.ResultsAnalysis of 201 visits of 110 adult patients with IIMs indicated higher normalized biomarker levels compared to HCs, and comparable to patients with AKI, with the exception of NGAL, which was higher in the AKI group. Notably 72 (49%) patients with IIMs had eGFR&lt;90; the levels of the 5 biomarkers were comparable between active and inactive IIMs, and different subtypes of IIMs. Similarly, a poor correlation between urine biomarker levels and core set measures of activity and damage was found. Changes in biomarker levels on follow-up did not correlate with eGFR changes.DiscussionThis exploratory analysis of urinary biomarkers identified low eGFR and elevated biomarkers of CKD in nearly half of the patients with IIMs, comparable to patients with AKI and higher than HCs, indicative of potential renal damage in IIMs that may have a lead to complications in other systems.
Association between the mental domain of the comprehensive geriatric assessment and prolonged length of stay in hospitalized older adults with mild to moderate frailty
Authors: Yu Yung-Chen , Su Chien-Chou , Yang Deng-Chi 
Published: June 2023

IntroductionPrevious researches have shown the risk factors of prolonged length of stay (PLOS) in hospitalized older adults, but it is unclear what are the risk factors of PLOS in hospitalized older adults with mild to moderate frailty.ObjectiveTo identify the risk factors of PLOS in hospitalized older adults with mild to moderate frailty.MethodsWe recruited adults aged ≥65 years old with mild to moderate frailty admitted to a tertiary medical center in the southern Taiwan from June 2018 to September 2018. Each individual underwent a structural questionnaire interview within 72 h after admission and 72 h after discharge. The data were collected face-to-face, including demographic characteristics, comorbidities, length of stay (LOS), and multiple domains of the comprehensive geriatric assessment. The main outcome was PLOS.ResultsIndividuals who had two or more drugs, were female, did not have cognitive impairment and had a Geriatric Depression Scale score ≥ 1 had a higher risk of PLOS (probability = 0.81), and these individuals accounted for 29% of the overall study population. Among male individuals younger than 87 years old, those with cognitive impairment had a higher risk of PLOS (probability = 0.76), and among male individuals without cognitive impairment, living alone was associated with a higher risk of PLOS (probability = 0.88).ConclusionEarly detection and management of mood and cognition in older adults, together with comprehensive discharge planning and transition care, may be an important part of reducing LOS in hospitalized older adults with mild to moderate frailty.
Association of amino acids and parameters of bone metabolism with endothelial dysfunction and vasculopathic changes in limited systemic sclerosis
Authors: Jud Philipp , Meinitzer Andreas , Strohmaier Heimo , Arefnia Behrouz , Wimmer Gernot , Obermayer-Pietsch Barbara , Foris Vasile , Kovacs Gabor , Odler Balazs , Moazedi-Fürst Florentine , Brodmann Marianne , Hafner Franz 
Published: June 2023

ObjectivesPathways contributing to endothelial dysfunction in patients with limited cutaneous systemic sclerosis (lcSSc) are largely unknown. The aim of this study was to investigate potential associations of amino acids and parameters of bone metabolism with endothelial dysfunction and vasculopathy-related changes in patients with lcSSc and early-stage vasculopathy.MethodsAmino acids, calciotropic parameters, including 25-hydroxyvitamin D and parathyroid hormone (PTH), and bone turnover parameters, including osteocalcin and N-terminal peptide of procollagen-3 (P3NP), were measured in 38 lcSSc patients and 38 controls. Endothelial dysfunction was assessed by biochemical parameters, pulse-wave analysis, flow-mediated and nitroglycerine-mediated dilation. Additionally, vasculopathy-related and SSc-specific clinical changes including capillaroscopic, skin, renal, pulmonary, gastrointestinal and periodontal parameters were recorded.ResultsNo significant differences in amino acids, calciotropic and bone turnover parameters were observed between lcSSc patients and controls. In patients with lcSSc, several significant correlations were found between selected amino acids, parameters of endothelial dysfunction, vasculopathy-related and SSc-specific clinical changes (all with p &lt; 0.05). In addition, significant correlations were observed between PTH and 25-hydroxyvitamin D with homoarginine, and between osteocalcin, PTH and P3NP with modified Rodnan skin score and selected periodontal parameters (all with p &lt; 0.05). Vitamin D deficiency defined as 25-hydroxyvitamin D &lt; 20 ng/ml was associated with the presence of puffy finger (p = 0.046) and early pattern (p = 0.040).ConclusionSelected amino acids may affect endothelial function and may be associated to vasculopathy-related and clinical changes in lcSSc patients, while the association with parameters of bone metabolism seems to be minor.
Evaluation of Leptospira interrogans knockdown mutants for LipL32, LipL41, LipL21, and OmpL1 proteins
Authors: Fernandes Luis G. V. , Teixeira Aline F. , Nascimento Ana L. T. O. 
Published: June 2023

IntroductionLeptospirosis is a worldwide zoonosis caused by pathogenic and virulent species of the genus Leptospira, whose pathophysiology and virulence factors remain widely unexplored. Recently, the application of CRISPR interference (CRISPRi) has allowed the specific and rapid gene silencing of major leptospiral proteins, favoring the elucidation of their role in bacterial basic biology, host-pathogen interaction and virulence. Episomally expressed dead Cas9 from the Streptococcus pyogenes CRISPR/Cas system (dCas9) and single-guide RNA recognize and block transcription of the target gene by base pairing, dictated by the sequence contained in the 5′ 20-nt sequence of the sgRNA.MethodsIn this work, we tailored plasmids for silencing the major proteins of L. interrogans serovar Copenhageni strain Fiocruz L1-130, namely LipL32, LipL41, LipL21 and OmpL1. Double- and triple-gene silencing by in tandem sgRNA cassettes were also achieved, despite plasmid instability.ResultsOmpL1 silencing resulted in a lethal phenotype, in both L. interrogans and saprophyte L. biflexa, suggesting its essential role in leptospiral biology. Mutants were confirmed and evaluated regarding interaction with host molecules, including extracellular matrix (ECM) and plasma components, and despite the dominant abundance of the studied proteins in the leptospiral membrane, protein silencing mostly resulted in unaltered interactions, either because they intrinsically display low affinity to the molecules assayed or by a compensation mechanism, where other proteins could be upregulated to fill the niche left by protein silencing, a feature previously described for the LipL32 mutant. Evaluation of the mutants in the hamster model confirms the augmented virulence of the LipL32 mutant, as hinted previously. The essential role of LipL21 in acute disease was demonstrated, since the LipL21 knockdown mutants were avirulent in the animal model, and even though mutants could still colonize the kidneys, they were found in markedly lower numbers in the animals' liver. Taking advantage of higher bacterial burden in LipL32 mutant-infected organs, protein silencing was demonstrated in vivo directly in leptospires present in organ homogenates.DiscussionCRISPRi is now a well-established, attractive genetic tool that can be applied for exploring leptospiral virulence factors, leading to the rational for designing more effective subunit or even chimeric recombinant vaccines.
Pharmacological effects and mechanisms of YiYiFuZi powder in chronic heart disease revealed by metabolomics and network pharmacology
Authors: Wang Yuming , Li Xue , Qi Min , Li Xiaokai , Zhang Fangfang , Wang Yuyu , Wu Junke , Shu Lexin , Fan Simiao , Li Yunfei , Li Yubo 
Published: June 2023

Introduction: YiYiFuZi powder (YYFZ) is a classical formula in Chinese medicine, which is commonly used clinically for the treatment of Chronic Heart Disease (CHD), but it’s pharmacological effects and mechanism of action are currently unclear.Methods: An adriamycin-induced CHD model rat was established to evaluate the pharmacological effects of YYFZ on CHD by the results of inflammatory factor level, histopathology and echocardiography. Metabolomic studies were performed on rat plasma using UPLC-Q-TOF/MS to screen biomarkers and enrich metabolic pathways; network pharmacology analysis was also performed to obtain the potential targets and pathways of YYFZ for the treatment of CHD.Results: The results showed that YYFZ significantly reduced the levels of TNF-α and BNP in the serum of rats, alleviated the disorder of cardiomyocyte arrangement and inflammatory cell infiltration, and improved the cardiac function of rats with CHD. The metabolomic analysis identified a total of 19 metabolites, related to amino acid metabolism, fatty acid metabolism, and other metabolic pathways. Network pharmacology showed that YYFZ acts through PI3K/Akt signaling pathway, MAPK signaling pathway and Ras signaling pathway.Discussion: YYFZ treatment of CHD modulates blood metabolic pattern and several protein phosphorylation cascades but importance specific changes for therapeutic effect require further studies.
Case report: Hypnic headache responds to agomelatine–a potential prophylactic treatment option
Authors: Xu Sui-yi , Li Ling , Sun Wen-xiu , Shen Jia-yu , Li Chang-xin 
Published: June 2023

IntroductionHypnic headache (HH) is a rare primary headache that is characterized by strict sleep-related attacks. However, the pathophysiology of HH remains unclear. The nocturnal nature of this activity suggests a hypothalamic involvement. The pathogenesis of HH may involve the brain structure that regulates circadian rhythms and is related to an imbalance between hormones, such as melatonin and serotonin. Currently, evidence-based medicine for HH pharmacotherapy is lacking. Acute and prophylactic treatment of HH is based on only a few case reports. Here, we report a case study in which agomelatine showed desirable responsiveness for the prophylactic treatment of HH for the first time.Case descriptionWe present the case of a 58-year-old woman with a 3-year history of nocturnal left temporal pain that awakened her during the wee hours. Brain magnetic resonance imaging did not reveal any midline structural abnormalities associated with circadian rhythms. Polysomnography revealed headache-related awakening at approximately 5:40 am, after the last rapid eye movement phase. No sleep apnea-hypopnea events were observed, without oxygen saturation or blood pressure abnormalities. The patient was prescribed agomelatine 25 mg at bedtime as a prophylactic treatment. In the following month, the frequency and severity of the headaches decreased by 80%. After 3 months, the patient’s headache completely resolved, and the medication was discontinued.ConclusionHH only occurs during sleep in the real world, leading to substantial sleep disturbances in older populations. Headache center neurologists need to focus on the prophylactic treatment of patients before bedtime to avoid nocturnal awakening. Agomelatine is a potential prophylactic treatment option for patients with HH.
Overt speech decoding from cortical activity: a comparison of different linear methods
Authors: Le Godais Gaël , Roussel Philémon , Bocquelet Florent , Aubert Marc , Kahane Philippe , Chabardès Stéphan , Yvert Blaise 
Published: June 2023

IntroductionSpeech BCIs aim at reconstructing speech in real time from ongoing cortical activity. Ideal BCIs would need to reconstruct speech audio signal frame by frame on a millisecond-timescale. Such approaches require fast computation. In this respect, linear decoder are good candidates and have been widely used in motor BCIs. Yet, they have been very seldomly studied for speech reconstruction, and never for reconstruction of articulatory movements from intracranial activity. Here, we compared vanilla linear regression, ridge-regularized linear regressions, and partial least squares regressions for offline decoding of overt speech from cortical activity.MethodsTwo decoding paradigms were investigated: (1) direct decoding of acoustic vocoder features of speech, and (2) indirect decoding of vocoder features through an intermediate articulatory representation chained with a real-time-compatible DNN-based articulatory-to-acoustic synthesizer. Participant's articulatory trajectories were estimated from an electromagnetic-articulography dataset using dynamic time warping. The accuracy of the decoders was evaluated by computing correlations between original and reconstructed features.ResultsWe found that similar performance was achieved by all linear methods well above chance levels, albeit without reaching intelligibility. Direct and indirect methods achieved comparable performance, with an advantage for direct decoding.DiscussionFuture work will address the development of an improved neural speech decoder compatible with fast frame-by-frame speech reconstruction from ongoing activity at a millisecond timescale.
Vitamin D intake and determinants of vitamin D status during pregnancy in The Norwegian Mother, Father and Child Cohort Study
Authors: Amberntsson Anna , Bärebring Linnea , Winkvist Anna , Lissner Lauren , Meltzer Helle Margrete , Brantsæter Anne Lise , Papadopoulou Eleni , Augustin Hanna 
Published: June 2023

BackgroundNorwegian data on vitamin D status among pregnant women indicate a moderate to high prevalence of insufficient vitamin D status (25-hydroxyvitamin D (25OHD) concentrations ≤50  nmol/L). There is a lack of population-based research on vitamin D intake and determinants of 25OHD in pregnant women from northern latitudes. The aims of this study were (1) to evaluate total vitamin D intake from both diet and supplements, (2) to investigate determinants of vitamin D status, and (3) to investigate the predicted response in vitamin D status by total vitamin D intake, in pregnant Norwegian women.MethodsIn total, 2,960 pregnant women from The Norwegian Environmental Biobank, a sub-study within The Norwegian Mother, Father and Child Cohort Study (MoBa), were included. Total vitamin D intake was estimated from a food frequency questionnaire in gestational week 22. Concentrations of plasma 25OHD was analyzed by automated chemiluminescent microparticle immunoassay method in gestational week 18. Candidate determinant variables of 25OHD were chosen using stepwise backward selection and investigated using multivariable linear regression. Predicted 25OHD by total vitamin D intake, overall and stratified by season and pre-pregnancy BMI, was explored using restricted cubic splines in an adjusted linear regression.ResultsOverall, about 61% of the women had a total vitamin D intake below the recommended intake. The main contributors to total vitamin D intake were vitamin D supplements, fish, and fortified margarine. Higher 25OHD concentrations were associated with (in descending order of the beta estimates) summer season, use of solarium, higher vitamin D intake from supplements, origin from high income country, lower pre-pregnancy BMI, higher age, higher vitamin D intake from foods, no smoking during pregnancy, higher education and energy intake. During October–May, a vitamin D intake according to the recommended intake was predicted to reach sufficient 25OHD concentrations &gt;50  nmoL/L.ConclusionThe findings from this study highlight the importance of the vitamin D intake, as one of few modifiable determinants, to reach sufficient 25OHD concentrations during months when dermal synthesis of vitamin D is absent.
Essential nutrients and cerebral small vessel diseases: a two-sample Mendelian randomization study
Authors: Li Jiayi , Xia Kailin , Wang Zhengrui , Liu Yanru , Tong Yicheng , Wang Yuwei , Zhou Yumou , Zhang Linjing , Tang Lu , Fan Dongsheng , Yang Qiong 
Published: June 2023

BackgroundPrevious studies have suggested a potential association between nutrients and cerebral small vessel disease (CSVD), but this association has not been fully addressed.ObjectWe intended to clarify the causal associations between four categories of essential nutrients (amino acids, polyunsaturated fatty acids, minerals and vitamins) and two acute manifestations of CSVD (intracerebral hemorrhage and small vessel stroke) using two-sample Mendelian randomization (MR) analysis.MethodWe obtained European-based large-scale genome-wide association studies (GWASs) related to CSVD (6,255 cases and 233,058 controls) and nutrient concentrations. Causality evaluation mainly included the results of the inverse variance-weighted (IVW) method. The simple median method, the weighted median method and the MR–Egger method were adopted for sensitivity analyses.ResultsFor ICH or SVS, increased levels of phenylalanine (OR = 1.188, p &lt; 0.001) and dihomo-gamma-linolenic acid (DGLA) (OR = 1.153, p = 0.001) showed risk effects, while docosapentaenoic acid (DPA) (OR = 0.501, p &lt; 0.001), zinc (OR = 0.919, p &lt; 0.001), and arachidonic acid (OR = 0.966, p = 0.007) showed protective effects. For lobar hemorrhage or SVS, AA (OR = 0.978, p &lt; 0.001), zinc (OR = 0.918, p &lt; 0.001), and retinol (OR = 0.753, p &lt; 0.001) showed risk effects; DPA (OR = 0.682, p = 0.022), gamma-linolenic acid (OR = 0.120, p = 0.033) and 25(OH)D (OR = 0.874, p = 0.040) showed protective effects. For nonlobar hemorrhage or SVS, DGLA (OR = 1.088, p &lt; 0.001) and phenylalanine (OR = 1.175, p = 0.001) showed risk effects.ConclusionOur study analyzed the effect of nutrients on CSVD risk from a genetic perspective, with implications for CSVD prevention through nutrient supplementation.
Adherence to Mediterranean diet and its association with multiple colonic polyps of unknown origin: a case-control study
Authors: Bujanda-Miguel Gabriela , Martínez-Roca Alejandro , García-Heredia Anabel , Guill-Berbegal David , Roche Enrique , Jover Rodrigo 
Published: June 2023

IntroductionMultiple colonic polyps do not have a genetic origin in most patients, and the cause of this phenotype remains elusive. Environmental factors, such as diet, could be related to this phenotype. Our aim was to investigate the relationship between the adherence to Mediterranean diet and multiple colonic polyps of unknown origin.MethodsA case-control pilot study was carried out with a sample of 38 individuals, including 23 cases with more than 10 adenomatous or serrated polyps from the national multicenter project EPIPOLIP and 15 healthy controls with normal colonoscopy. A validated Spanish version of the MEDAS questionnaire was administered to cases and controls.ResultsAdherence to Mediterranean diet was higher in controls than in patients with multiple colonic polyps (MEDAS score: 8.6 ± 1.4 vs. 7.0 ± 1.6; p = 0.01). Optimal overall adherence to the Mediterranean diet pattern was significantly higher among the controls than among cases (MEDAS score &gt;9: 46% vs. 13%; OR 0.17; 95% CI 0.03–0.83). Non-optimal adherence to the Mediterranean diet acts as a risk factor for developing colorectal cancer derived from colorectal polyps.ConclusionOur results suggest that environmental factors play a role in the pathogenesis of this phenotype.
Effect of fermentation using different lactic acid bacteria strains on the nutrient components and mineral bioavailability of soybean yogurt alternative
Authors: Gan Jing , Kong Xiao , Wang Kuaitian , Chen Yuhang , Du Mengdi , Xu Bo , Xu Jingru , Wang Zhenhua , Cheng Yongqiang , Yu Tianying 
Published: June 2023

IntroductionAnalysis of the composition of yogurt alternatives (YAs) during fermentation provides critical information for evaluating its quality and nutritional attributes.MethodWe investigated the effects of homotypic (HO) and heterotypic (HE) lactic acid bacteria on the nutritional and mineral bioavailabilities of soybean YA (SYA) during fermentation.ResultThe acidic amino acid (Glu, Asp) and organic acid contents in HO-fermented YA were increased from 2.93, 1.71, and 7.43 mg/100 g to 3.23, 1.82, and 73.47 mg/100 g, respectively. Moreover, both HO and HE lactic acid bacteria fermentation enhanced mineral absorptivity. They altered the molecular speciation of minerals from a large molecular type (2,866 Da) to a small molecular type (1,500 Da), which was manifested in a time-dependent manner. Furthermore, YA substantially increased the bone mass in a zebrafish osteoporosis model, further highlighting the potential of lactic acid bacterial fermentation for mineral bioavailability.DiscussionThis study provides a foundation for understanding the effects of fermentation conditions on the composition and bioavailability of minerals in YA and can assist in its production.