bluuebunny/crossref_metadata_2025_split huggingface dataset:
Approaches to Improve the Quantitation of Oxytocin in Human Serum by Mass Spectrometry
Authors: Hering Anke , Jieu Beverly , Jones Alun , Muttenthaler Markus 
Published: June 2022

The neuropeptide oxytocin (OT) regulates several peripheral and central functions and is a molecule of interest in psychiatric diseases such as autism spectrum disorder, schizophrenia, anxiety and depression. The study of OT in human serum samples is however hampered by inconsistent sample preparation and analysis as well as low endogenous blood concentration (1–10 pM). This results in varying reports on OT’s blood levels and interpretation of OT’s role in different (patho)physiological states. Quantitative mass spectrometry (MS) is a highly promising technology to address this problem but still requires large sample volumes to achieve adequate sensitivity and reliability for the quantitation of compounds at low concentrations. We therefore systematically evaluated sample preparation methods for MS to achieve a reliable sample preparation protocol with good peptide recovery, minimal matrix effects and good overall method efficiency in line with FDA guidelines for bioanalytic method development and validation. Additionally, we investigated a strategy to improve the ionization efficiency of OT by adding charged and/or hydrophobic moieties to OT to improve the lower limit of quantitation. Optimized sample preparation in combination with OT modification with a quaternary pyridinium ion improved the sensitivity of OT by ∼40-fold on a tandem triple quadrupole mass spectrometer (API4000 QTRAP), resulting in a lower limit of quantitation of 5 pM in water (linear range 5 pM – 1 mM) and 2 nM in human serum (linear range 2 nM – 1 mM) compared to 200 pM in water and 86 nM in serum with unmodified OT. This approach and protocol provide a solid foundation towards method development for OT quantitation using MS, which should be of high value for fundamental research as well as clinical monitoring of OT upon drug treatments.
GPHB5 Is a Biomarker in Women With Metabolic Syndrome: Results From Cross-Sectional and Intervention Studies
Authors: Xiang Ting , Zhang Siliang , Li Qinge , Li Ling , Liu Hua , Chen Chen , Yang Gangyi , Yang Mengliu 
Published: June 2022

BackgroundAnimal studies have found that GPHB5 has a similar effect on system metabolism as TSH. However, the relationship between GPHB5 and metabolic diseases remains unknown. This study investigates the relationship between GPHB5 and MetS in young women.MethodsBioinformatics analysis was undertaken to explore the relationship between GPHB5 and metabolic-related genes and signaling pathways. EHC and OGTT were performed on all individuals. Lipid-infusion, physical activity, and cold-exposure tests were performed on healthy individuals. Serum GPHB5 concentrations were measured by an ELISA kit.ResultsPPI network showed that 11 genes interacted with GPHB5, in which POMC and KISS1R were involved in glucose and lipid metabolism. GO analysis showed 56 pathways for BP and 16 pathways for MF, in which OPRM1 and MCR families were related to energy metabolism. KEGG analysis found that GPHB5 is associated with lipolysis and neuroactive ligand-receptor interaction pathways. The levels of circulating GPHB5 were significantly increased, while serum adiponectin levels were lower in MetS women compared with healthy women. Obese/overweight individuals had lower adiponectin levels and higher GPHB5 levels. Circulating GPHB5 levels were positively correlated with BMI, WHR, blood pressure, FBG, 2 h-BG, HbA1c, FIns, 2h-Ins, LDL-C, FFA, HOMA-IR, and AUCg, etc. but negatively correlated with HDL-C, adiponectin, and M-values. Serum GPHB5 levels did not change significantly during the OGTT, EHC, and lipid infusion. Physical activity and cold-exposure tests did not lead to changes in GPHB5 levels. GLP-1RA treatment resulted in a significant decrease in serum GPHB5 levels.ConclusionsGPHB5 may be a biomarker for MetS.
A Novel Signature of Necroptosis-Associated Genes as a Potential Prognostic Tool for Head and Neck Squamous Cell Carcinoma
Authors: Huang Jing , Huo Hongqi , Lu Rong 
Published: June 2022

Background: Head and neck squamous cell carcinoma (HNSCC) arises from squamous cells in the oral cavity, pharynx and larynx. Although HNSCC is sensitive to radiotherapy, patient prognosis is poor. Necroptosis is a novel programmed form of necrotic cell death. The prognostic value of necroptosis-associated gene expression in HNSCC has not been explored.Material and Methods: We downloaded mRNA expression data of HNSCC patients from TCGA databases and Gene Expression Omnibus (GEO) databases, and compared gene expression between tumor tissues and adjacent normal tissues to identify differentially expressed genes (DEGs) and necroptosis-related prognostic genes. A model with necroptosis-related genes was established to predict patient prognosis via LASSO method and Kaplan-Meier analysis. GSE65858 data set (n = 270) from GEO was used to verify the model’s predictive ability. Gene set enrichment analyses, immune microenvironment analysis, principal component analysis, and anti-tumor compound IC50 prediction were also performed.Results: We identified 49 DEGs and found 10 DEGs were associated with patient survival (p &lt; 0.05). A risk model of 6-gene signature was constructed using the TCGA training data set and further validated with the GEO data set. Patients in the low-risk group survived longer than those in the high-risk group (p &lt; 0.05) in the GEO validation sets. Functional analysis showed the two patient groups were associated with distinct immunity conditions and IC50.Conclusion: We constructed a prognostic model with 6 necroptosis-associated genes for HNSCC. The model has potential usage to guide treatment because survival was different between the two groups.
Endothelin B Receptor Immunodynamics in Pulmonary Arterial Hypertension
Authors: Tabeling Christoph , González Calera Carla R. , Lienau Jasmin , Höppner Jakob , Tschernig Thomas , Kershaw Olivia , Gutbier Birgitt , Naujoks Jan , Herbert Julia , Opitz Bastian , Gruber Achim D. , Hocher Berthold , Suttorp Norbert , Heidecke Harald , Burmester Gerd-R. , Riemekasten Gabriela , Siegert Elise , Kuebler Wolfgang M. , Witzenrath Martin 
Published: June 2022

IntroductionInflammation is a major pathological feature of pulmonary arterial hypertension (PAH), particularly in the context of inflammatory conditions such as systemic sclerosis (SSc). The endothelin system and anti-endothelin A receptor (ETA) autoantibodies have been implicated in the pathogenesis of PAH, and endothelin receptor antagonists are routinely used treatments for PAH. However, immunological functions of the endothelin B receptor (ETB) remain obscure.MethodsSerum levels of anti-ETB receptor autoantibodies were quantified in healthy donors and SSc patients with or without PAH. Age-dependent effects of overexpression of prepro-endothelin-1 or ETB deficiency on pulmonary inflammation and the cardiovascular system were studied in mice. Rescued ETB-deficient mice (ETB-/-) were used to prevent congenital Hirschsprung disease. The effects of pulmonary T-helper type 2 (Th2) inflammation on PAH-associated pathologies were analyzed in ETB-/- mice. Pulmonary vascular hemodynamics were investigated in isolated perfused mouse lungs. Hearts were assessed for right ventricular hypertrophy. Pulmonary inflammation and collagen deposition were assessed via lung microscopy and bronchoalveolar lavage fluid analyses.ResultsAnti-ETB autoantibody levels were elevated in patients with PAH secondary to SSc. Both overexpression of prepro-endothelin-1 and rescued ETB deficiency led to pulmonary hypertension, pulmonary vascular hyperresponsiveness, and right ventricular hypertrophy with accompanying lymphocytic alveolitis. Marked perivascular lymphocytic infiltrates were exclusively found in ETB-/- mice. Following induction of pulmonary Th2 inflammation, PAH-associated pathologies and perivascular collagen deposition were aggravated in ETB-/- mice.ConclusionThis study provides evidence for an anti-inflammatory role of ETB. ETB seems to have protective effects on Th2-evoked pathologies of the cardiovascular system. Anti-ETB autoantibodies may modulate ETB-mediated immune homeostasis.
Screening New Blood Indicators for Non-alcoholic Fatty Liver Disease (NAFLD) Diagnosis of Chinese Based on Machine Learning
Authors: Wang Cheng , Yan Junbin , Zhang Shuo , Xie Yiwen , Nie Yunmeng , Chen Zhiyun , Xu Sumei 
Published: June 2022

BackgroundThe prevalence of NAFLD is increasing annually. The early diagnosis and control are crucial for the disease. Currently, metabolic indicators are always used clinically as an auxiliary diagnosis of NAFLD. However, the prevalence of NAFLD is not only increased in obese/metabolic-disordered populations. NAFLD patients with thin body are also increasing. Only using metabolic indicators to assist in the diagnosis of NAFLD may have some deficiencies. Continue to develop more clinical auxiliary diagnostic indicators is pressing.MethodsMachine learning methods are applied to capture risk factors for NAFLD in 365 adults from Zhejiang Province. Predictive models are constructed for NAFLD using fibrinolytic indicators and metabolic indicators as predictors respectively. Then the predictive effects are compared; ELISA kits were used to detect the blood indicators of non-NAFLD and NAFLD patients and compare the differences.ResultsThe prediction accuracy for NAFLD based on fibrinolytic indicators [Tissue Plasminogen Activator (TPA), Plasminogen Activator Inhibitor-1 (PAI-1)] is higher than that based on metabolic indicators. TPA and PAI-1 are more suitable than metabolic indicators to be selected to predict NAFLD.ConclusionsThe fibrinolytic indicators have a stronger association with NAFLD than metabolic indicators. We should attach more importance to TPA and PAI-1, in addition to TC, HDL-C, LDL-C, and ALT/AST, when conducting blood tests to assess NAFLD.
The Impact of Seropositivity on Systemic Bone Loss in Rheumatoid Arthritis—A 3-Year Interim Analysis of a Longitudinal Observational Cohort Study
Authors: Yu Shan-Fu , Chen Jia-Feng , Chen Ying-Chou , Wang Yu-Wei , Hsu Chung-Yuan , Lai Han-Ming , He Hsiao-Ru , Ko Chi-Hua , Chiu Wen-Chan , Cheng Tien-Tsai 
Published: June 2022

ObjectiveTo explore the impact of seropositivity on systemic bone loss in rheumatoid arthritis (RA).MethodsWe conducted an interim analysis of the RA registry. Patients were examined with dual-energy X-ray absorptiometry at baseline and again 3 years later. Participants were grouped into seropositive (SPRA) and seronegative (SNRA) based on the presence or absence of rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibodies (ACPA). After matching (1:2) for age and sex, SNRA and SPRA patients were divided into groups A and B. Each matched group (A or B) was further subdivided according to the number of antibodies present (0, group I; 1, group II; 2, group III). Multiple ordinary least squares regression was used with the dependent variables to develop a model to predict bone mineral density (BMD) change.ResultsA total of 477 participants who completed a 3-year observation period were included. After matching, 312 participants were enrolled (group A, 104; group B, 208). Three years later, group B had significant BMD reduction in the femoral neck (FN) (p &lt; 0.001), total hip (TH) (p = 0.001), and first through fourth lumbar vertebrae (L1–4) (p = 0.006), while group A had bone loss only at FN (p = 0.002). Groups I, II, and III included 104, 52, and 156 participants, respectively. Compared to baseline, BMD decreased significantly at FN (p = 0.002) in group I, FN (p &lt; 0.001) in group II, and FN (p &lt; 0.001), TH (p = 0.002), and L1–4 (p = 0.016) in group III. In terms of regression-adjusted percent change in BMD, more significantly negative changes were found at all measured sites in group B (p &lt; 0.001, all) and at TH and L1–4 within groups I-III (p for trend &lt; 0.001 and &lt; 0.001, respectively). Regardless of antibodies, anti-osteoporotic therapy can preserve bone density in RA patients.ConclusionAfter 3 years, SPRA patients lost more bone density than SNRA patients. More attention should be paid to SPRA patients, especially those with double-positive antibodies, including a vigorous evaluation of BMD and fracture risk. Anti-osteoporotic therapy can prevent BMD loss irrespective of autoantibodies.
Tph Cells Expanded in Primary Sjögren’s Syndrome
Authors: Chen Weiqian , Yang Fan , Lin Jin 
Published: June 2022

ObjectivesPD-1+CXCR5–CD4+T peripheral helper cells, named Tph cells, contribute to B-cell immune responses and the production of antibodies in systemic lupus erythematosus and rheumatoid arthritis. However, the role of Tph cells was unknown in the pathogenesis of primary Sjögren’s syndrome (pSS). Here, we aim to explore the contribution of Tph cells in the development of pSS.MethodsSixty patients with pSS and 61 age and sex-matched healthy individuals were recruited for this study. The frequency of Tph cells in the blood was measured by flow cytometry. The expression of inducible T-cell costimulator (ICOS), MHC-II, IL-21, CCR2, CCR5, and CCR9 was evaluated in Tph cells. The relationship between Tph cells and indicators of clinical disease was assessed. Co-expression levels of PD-1, CXCR5, CD4, CCR2, and CCR5 in the salivary gland specimens from patients with pSS and patients with dry mouth and eyes but normal pathology were also analyzed.ResultsWe demonstrated increased circulating Tph cells (7.53 ± 6.65% vs. 3.08 ± 1.31%, p &lt; 0.0001) in patients with pSS (n = 60) compared to healthy controls (n = 61). Tph cells were significantly associated with the ESSDAI disease activity scores, IgG, ESR, IL-21, anti-SSA antibody, and CD138+/CD19+ plasma cells. Furthermore, ICOS was highly expressed in Tfh and Tph cells in patients with pSS. IL-21, MHC-II, CCR2, and CCR5 expression was higher in pSS Tph cells, and CCR9 expression was lower in pSS Tph cells than in pSS Tfh cells. Moreover, Tph cells and CCR2+CD4+T and CCR5+CD4+T cells were found in the labial gland of patients with pSS.ConclusionOur data show that Tph cells were enriched in peripheral blood and labial gland of patients with pSS. Circulating Tph cells correlated with disease activity scores, suggesting a crucial role of Tph in the development of pSS.
Epidemiology and Clinical Features of Listeriosis in Gipuzkoa, Spain, 2010–2020
Authors: Vallejo Pedro , Cilla Gustavo , López-Olaizola Maddi , Vicente Diego , Marimón José María 
Published: June 2022

BackgroundListeriosis continues to be one of the most important notifiable foodborne diseases. Nonetheless, in Spain, there are few data on the molecular epidemiology of Listeria monocytogenes infections in recent years.AimTo describe clinical features and the molecular epidemiology of human listeriosis over an 11-year period (2010–2020) in Gipuzkoa, Northern Spain.MethodsA total of 111 isolates, all but one from invasive disease, were studied. Serotyping (agglutination and multiplex polymerase chain reaction [PCR]) and multilocus sequence typing were performed for all isolates. Antibiotic susceptibility was assessed by the broth microdilution method.ResultsThe average annual incidence of listeriosis in non-pregnancy-associated cases was 1.55 per 100,000 population, with a 1-month mortality rate of 22.2%. In pregnant women, the average incidence was 0.45 cases per 1,000 pregnancies. Twenty-four sequence types were identified, serotype 4b ST1 (24.3%) being the most frequent followed by 1/2b ST87 (18.9%), which caused two long outbreaks in 2013–2014. A significant association was observed between ST219 and meningitis (p &lt; 0.001). All isolates were susceptible to ampicillin as well as other antibiotics used in listeriosis treatment.ConclusionDespite current control measures, listeriosis continues to be an important cause of mortality in the elderly, preterm birth, and miscarriages in pregnant women. Improvements in the control and diagnosis of listeriosis are needed to reduce the impact of this infection on vulnerable populations.
Legume Plant Peptides as Sources of Novel Antimicrobial Molecules Against Human Pathogens
Authors: Lima Rui M. , Rathod Balaji Baburao , Tiricz Hilda , Howan Dian H. O. , Al Bouni Mohamad Anas , Jenei Sándor , Tímár Edit , Endre Gabriella , Tóth Gábor K. , Kondorosi Éva 
Published: June 2022

Antimicrobial peptides are prominent components of the plant immune system acting against a wide variety of pathogens. Legume plants from the inverted repeat lacking clade (IRLC) have evolved a unique gene family encoding nodule-specific cysteine-rich NCR peptides acting in the symbiotic cells of root nodules, where they convert their bacterial endosymbionts into non-cultivable, polyploid nitrogen-fixing cells. NCRs are usually 30–50 amino acids long peptides having a characteristic pattern of 4 or 6 cysteines and highly divergent amino acid composition. While the function of NCRs is largely unknown, antimicrobial activity has been demonstrated for a few cationic Medicago truncatula NCR peptides against bacterial and fungal pathogens. The advantages of these plant peptides are their broad antimicrobial spectrum, fast killing modes of actions, multiple bacterial targets, and low propensity to develop resistance to them and no or low cytotoxicity to human cells. In the IRLC legumes, the number of NCR genes varies from a few to several hundred and it is possible that altogether hundreds of thousands of different NCR peptides exist. Due to the need for new antimicrobial agents, we investigated the antimicrobial potential of 104 synthetic NCR peptides from M. truncatula, M. sativa, Pisum sativum, Galega orientalis and Cicer arietinum against eight human pathogens, including ESKAPE bacteria. 50 NCRs showed antimicrobial activity with differences in the antimicrobial spectrum and effectivity. The most active peptides eliminated bacteria at concentrations from 0.8 to 3.1 μM. High isoelectric point and positive net charge were important but not the only determinants of their antimicrobial activity. Testing the activity of shorter peptide derivatives against Acinetobacter baumannii and Candida albicans led to identification of regions responsible for the antimicrobial activity and provided insight into their potential modes of action. This work provides highly potent lead molecules without hemolytic activity on human blood cells for novel antimicrobial drugs to fight against pathogens.
Long Term Performance of a Bi-Directional Neural Interface for Deep Brain Stimulation and Recording
Authors: Stanslaski Scott R. , Case Michelle A. , Giftakis Jonathon E. , Raike Robert S. , Stypulkowski Paul H. 
Published: June 2022

Background: In prior reports, we described the design and initial performance of a fully implantable, bi-directional neural interface system for use in deep brain and other neurostimulation applications. Here we provide an update on the chronic, long-term neural sensing performance of the system using traditional 4-contact leads and extend those results to include directional 8-contact leads.Methods: Seven ovine subjects were implanted with deep brain stimulation (DBS) leads at different nodes within the Circuit of Papez: four with unilateral leads in the anterior nucleus of the thalamus and hippocampus; two with bilateral fornix leads, and one with bilateral hippocampal leads. The leads were connected to either an Activa PC+S® (Medtronic) or Percept PC°ledR (Medtronic) deep brain stimulation and recording device. Spontaneous local field potentials (LFPs), evoked potentials (EPs), LFP response to stimulation, and electrode impedances were monitored chronically for periods of up to five years in these subjects.Results: The morphology, amplitude, and latencies of chronic hippocampal EPs evoked by thalamic stimulation remained stable over the duration of the study. Similarly, LFPs showed consistent spectral peaks with expected variation in absolute magnitude dependent upon behavioral state and other factors, but no systematic degradation of signal quality over time. Electrode impedances remained within expected ranges with little variation following an initial stabilization period. Coupled neural activity between the two nodes within the Papez circuit could be observed in synchronized recordings up to 5 years post-implant. The magnitude of passive LFP power recorded from directional electrode segments was indicative of the contacts that produced the greatest stimulation-induced changes in LFP power within the Papez network.Conclusion: The implanted device performed as designed, providing the ability to chronically stimulate and record neural activity within this network for up to 5 years of follow-up.
The Relationship Between Vitamin D and Postoperative Atrial Fibrillation: A Prospective Cohort Study
Authors: Ohlrogge Amelie H. , Brederecke Jan , Ojeda Francisco M. , Pecha Simon , Börschel Christin S. , Conradi Lenard , Rimkus Vanessa , Blankenberg Stefan , Zeller Tanja , Schnabel Renate B. 
Published: June 2022

Background and AimsThe relationship between postoperative atrial fibrillation (POAF) and 25-hydroxyvitamin D [25(OH)D] concentration as well as vitamin D supplementation has been discussed controversially. The relation of pre-operative vitamin D status and POAF remains unclear.Methods and ResultsWe analysed the risk of POAF in a prospective, observational cohort study of n = 201 patients undergoing coronary artery bypass graft surgery (CABG) with 25(OH)D concentration. The median age was 66.6 years, 15.4% were women. The median (25th/75th percentile) vitamin D concentration at baseline was 17.7 (12.6/23.7) ng/ml. During follow-up we observed 48 cases of POAF. In age, sex, and creatinine-adjusted analyses, 25(OH)D was associated with an increased risk of POAF, though with borderline statistical significance [odds ratio (OR) 1.85, 95% confidence interval (CI) 0.87–3.92, p-value 0.107], in further risk factor-adjusted analyses the results remained stable (OR 1.99, 95% CI 0.90–4.39, p-value 0.087). The subgroup with vitamin D supplementation at baseline showed an increased risk of POAF (OR 5.03, 95% CI 1.13–22.33, p-value 0.034).ConclusionIn our contemporary mid-European cohort, higher 25(OH)D concentration did not show a benefit for POAF in CABG patients and may even be harmful, though with borderline statistical significance. Our data are in line with a recent randomised study in community-based adults and call for further research to determine both, the clinical impact of elevated 25(OH)D concentration and vitamin D supplementation as well as the possible underlying pathophysiological mechanisms.