bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the genetic association of allergic diseases with cardiovascular diseases: a bidirectional Mendelian randomization study
Authors: Wang Shilin , Liu Hao , Yang Peiwen , Wang Zhiwen , Hu Poyi , Ye Ping , Xia Jiahong , Chen Shu 
Published: June 2023

BackgroundIn observational and experimental studies, allergic diseases (AD) have been reported to be associated with some types of cardiovascular diseases (CVD), as both share common pathophysiological processes involving inflammation and metabolic disorders. However, the direction of the causal association between them remains unclear. This Mendelian randomization (MR) study aims to examine the bidirectional causality between AD and CVD.MethodsWe utilized publicly available genome-wide association study (GWAS) summary statistics data from European participants in the UK Biobank and the IEU Open GWAS database. Genetic variants associated with AD, asthma, and CVD were identified and used as instrumental variables to investigate the genetically causal association between them. MR analyses were performed using various analytical methods, including inverse variance weighted-fixed effects (IVW-FE), inverse variance weighted-multiplicative random effects (IVW-RE), MR-Egger, weighted median, weighted mode, and maximum likelihood. Sensitivity tests were conducted to assess the validity of the causality.ResultsThe MR analysis with the IVW method revealed a genetically predicted association between AD and essential hypertension [odds ratio (OR)=0.9987, 95% confidence interval (CI): 0.9976-0.9998, P=0.024], as well as between asthma and atrial fibrillation (OR=1.001, 95% CI: 1.0004-1.0017, P=6.43E-05). In the reverse MR analyses, heart failure was associated with allergic diseases (OR=0.0045, 95% CI: 1.1890E-04 - 0.1695, P=0.004), while atherosclerosis (OR=8.7371E-08, 95% CI: 1.8794E-14 - 4.0617E-01, P=0.038) and aortic aneurysm and dissection (OR=1.7367E-07, 95% CI: 3.8390E-14 – 7.8567E-01, P=0.046) might be protective factors of asthma. However, after a Bonferroni correction, only the association between asthma and atrial fibrillation remained robust.ConclusionThe MR study revealed that asthma is a predominant risk of atrial fibrillation in European individuals, consistent with most experimental and observational studies. Whether AD affects other CVD and the causality between them needs further investigation.
The roles of different forms of IL-15 in human melanoma progression
Authors: Di Matteo Sabina , Munari Enrico , Fiore Piera Filomena , Santopolo Silvia , Sampaoli Camilla , Pelosi Andrea , Chouaib Salem , Tumino Nicola , Vacca Paola , Mariotti Francesca Romana , Ebert Stefan , Machwirth Markus , Haas Dorothee , Pezzullo Marco , Pietra Gabriella , Grottoli Melania , Buart Stephanie , Mortier Erwan , Maggi Enrico , Moretta Lorenzo , Caruana Ignazio , Azzarone Bruno 
Published: June 2023

BackgroundMelanoma is a lethal skin cancer, and the risk of developing it is increased by exposure to ultraviolet (UV) radiation. The production of cytokines such as interleukin-15 (IL-15), induced by the exposure of skin cells to UV rays, could also promote melanoma development. The aim of this study is to investigate the possible role of Interleukin-15/Interleukin-15 Receptor α (IL-15/IL-15Rα) complexes in melanoma development.MethodsThe expression of IL-15/IL-15Rα complexes by melanoma cells was evaluated both ex vivo and in vitro by tissue microarray, PCR, and flow cytometry. The presence of the soluble complex (sIL-15/IL-15Rα) in the plasma of metastatic melanoma patients was detected using an ELISA assay. Subsequently, we investigated the impact of natural killer (NK) cell activation after rIL-2 starvation followed by exposure to the sIL-15/IL-15Rα complex. Finally, by analyzing public datasets, we studied the correlation between IL-15 and IL-15Rα expressions and melanoma stage, NK and T-cell markers, and overall survival (OS).ResultsAnalysis of a melanoma tissue microarray shows a significant increase in the number of IL-15+ tumor cells from the benign nevi to metastatic melanoma stages. Metastatic melanoma cell lines express a phorbol-12-myristate-13-acetate (PMA)-cleavable membrane-bound IL-15 (mbIL-15), whereas cultures from primary melanomas express a PMA-resistant isoform. Further analysis revealed that 26% of metastatic patients present with consistently high plasmatic levels of sIL-15/IL-15Rα. When the recombinant soluble human IL-15/IL-15Rα complex is added to briefly starved rIL-2-expanded NK cells, these cells exhibit strongly reduced proliferation and levels of cytotoxic activity against K-562 and NALM-18 target cells. The analysis of public gene expression datasets revealed that high IL-15 and IL-15Rα intra-tumoral production correlates with the high levels of expression of CD5+ and NKp46+ (T and NK markers) and significantly correlates with a better OS in stages II and III, but not in stage IV.ConclusionsMembrane-bound and secreted IL-15/IL-15Rα complexes are continuously present during progression in melanoma. It is notable that, although IL-15/IL-15Rα initially promoted the production of cytotoxic T and NK cells, at stage IV promotion of the development of anergic and dysfunctional cytotoxic NK cells was observed. In a subgroup of melanoma metastatic patients, the continuous secretion of high amounts of the soluble complex could represent a novel NK cell immune escape mechanism.
Case Report: Imaging immune checkpoint inhibitor-induced yin-yang effects in the brain
Authors: Bol K. F. , Peeters E. , van Herpen C. M. L. , Westdorp H. , Aarntzen E. H. J. G. 
Published: June 2023

BackgroundTreatment with immune checkpoint inhibitors (ICI) can induce durable responses in cancer patients, but it is commonly associated with serious immune-related side effects. Both effects are suggested to be mediated by CD8+ T-cell infiltration. Whole body CD8+ T-cell distribution can be visualized by PET imaging of a 89Zr-labeled anti-humanCD8a minibody, currently investigated in a phase 2b trial.Main bodyAn adult patient diagnosed with metastatic melanoma developed ICI-related hypophysitis after two courses of combined immunotherapy (ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) at 3 weeks interval). On a [89Zr]Zr-crefmirlimab berdoxam PET/CT scan, made 8 days before clinical symptoms occurred, increased CD8+ T-cell infiltration in the pituitary gland was detected. Simultaneously, tracer uptake in a cerebral metastasis was increased, indicating ICI-induced tumor infiltration by CD8+ T-cells.ConclusionsThe observations in this case report underscore the role of CD8+ T-cell in non-tumor tissues in ICI-related toxicity. In addition, it illustrates a potential role for molecular imaging by PET/CT for investigation and monitoring of ICI-induced effects.
A modified Ranson score to predict disease severity, organ failure, pancreatic necrosis, and pancreatic infection in patients with acute pancreatitis
Authors: Luo Xiuping , Wang Jie , Wu Qing , Peng Peng , Liao Guolin , Liang Chenghai , Yang Huiying , Huang Jiean , Qin Mengbin 
Published: June 2023

BackgroundAlthough there are several scoring systems currently used to predict the severity of acute pancreatitis, each of them has limitations. Determine the accuracy of a modified Ranson score in predicting disease severity and prognosis in patients with acute pancreatitis (AP).MethodsAP patients admitted or transferred to our institution were allocated to a modeling group (n = 304) or a validation group (n = 192). A modified Ranson score was determined by excluding the fluid sequestration parameter and including the modified computed tomography severity index (CTSI). The diagnostic performance of the modified Ranson score was compared with the Ranson score, modified CTSI, and bedside index of severity in acute pancreatitis (BISAP) score in predicting disease severity, organ failure, pancreatic necrosis and pancreatic infection.ResultsThe modified Ranson score had significantly better accuracy that the Ranson score in predicting all four outcome measures in the modeling group and in the validation group (all p &lt; 0.05). For the modeling group the modified Ranson score had the best accuracy for predicting disease severity and organ failure, and second-best accuracy for predicting pancreatic necrosis and pancreatic infection. For the verification group, it had the best accuracy for predicting organ failure, second-best accuracy for predicting disease severity and pancreatic necrosis, and third-best accuracy for predicting pancreatic infection.ConclusionThe modified Ranson score provided better accuracy than the Ranson score in predicting disease severity, organ failure, pancreatic necrosis and pancreatic infection. Relative to the other scoring systems, the modified Ranson system was superior in predicting organ failure.
Association between obstructive sleep apnea and resistant hypertension: systematic review and meta-analysis
Authors: Ahmed Abass Mahamoud , Nur Salman Mohamud , Xiaochen Yuan 
Published: June 2023

IntroductionObstructive sleep apnea syndrome (OSAS) is a chronic disorder characterized by recurring episode obstruction and collapse of upper airways during sleep, leading to hypoxia and sleep disruption. OSAS is commonly associated with an increased prevalence of hypertension. The underlying mechanism in OSA with hypertension is related to intermittent hypoxia. This hypoxia induces endothelial dysfunction, overactivity of sympathetic effects, oxidative stress, and systemic inflammation. Hypoxemia triggers the sympathetic process's overactivity, leading to the development of resistant hypertension in OSA. Thus, we hypothesize to evaluate the association between resistant hypertension and OSA.MethodsThe PubMed, ClinicalTrails.gov, CINAHL, Google Scholar, Cochrane Library, and Science Direct databases were searched from 2000 to January 2022 for studies demonstrating the association between resistant hypertension and OSA. The eligible articles underwent quality appraisal, meta-analysis, and heterogeneity assessment.ResultsThis study comprises seven studies, including 2,541 patients ranged from 20 to 70 years. The pooled analysis of six studies demonstrated that OSAS patients with a history of increased age, gender, obesity, and smoking status are at an increased risk for resistant hypertension (OR: 4.16 [3.07, 5.64], I2:0%) than the non-OSAS patients. Similarly, the pooled effect demonstrated that patients with OSAS were at an increased risk of resistant hypertension (OR: 3.34 [2.44, 4.58]; I2:0%) than the non-OSAS patients when all associated risk factors were adjusted using multivariate analysis.ConclusionThis study concludes that OSAS patients with or without related risk factors demonstrated increased risk for resistant hypertension.
Evaluation of Low-Cost Phage-Based Microbial Source Tracking Tools for Elucidating Human Fecal Contamination Pathways in Kolkata, India
Authors: Kapoor Renuka , Ebdon James , Wadhwa Ashutosh , Chowdhury Goutam , Wang Yuke , Raj Suraja J. , Siesel Casey , Durry Sarah E. , Mairinger Wolfgang , Mukhopadhyay Asish K. , Kanungo Suman , Dutta Shanta , Moe Christine L. 
Published: June 2023

Graphical AbstractPhages infecting Bacteroides fragilis strain GB-124 and non-source specific somatic coliphages (SOMCPH) were deployed for identification of fecal contamination pathways in Kolkata, India. Analyses of environmental samples representative of nine different exposure pathways, pooled sewage from shared community toilets and sewage from pumping stations showed the presence of both SOMCPH and GB-124 phages in all the sample types.
Epidemiology and zoonotic transmission of mcr-positive and carbapenemase-producing Enterobacterales on German turkey farms
Authors: Nordhoff Katja , Scharlach Martina , Effelsberg Natalie , Knorr Carolin , Rocker Dagmar , Claussen Katja , Egelkamp Richard , Mellmann Alexander C. , Moss Andreas , Müller Ilona , Roth Sarah Andrea , Werckenthin Christiane , Wöhlke Anne , Ehlers Joachim , Köck Robin 
Published: June 2023

IntroductionThe emergence of carbapenem-resistant bacteria causing serious infections may lead to more frequent use of previously abandoned antibiotics like colistin. However, mobile colistin resistance genes (mcr) can jeopardise its effectiveness in both human and veterinary medicine. In Germany, turkeys have been identified as the food-producing animal most likely to harbour mcr-positive colistin-resistant Enterobacterales (mcr-Col-E). Therefore, the aim of the present study was to assess the prevalence of both mcr-Col-E and carbapenemase-producing Enterobacterales (CPE) in German turkey herds and humans in contact with these herds.MethodsIn 2018 and 2019, 175 environmental (boot swabs of turkey faeces) and 46 human stool samples were analysed using a combination of enrichment-based culture, PCR, core genome multilocus sequence typing (cgMLST) and plasmid typing.Resultsmcr-Col-E were detected in 123 of the 175 turkey farms in this study (70.3%). mcr-Col-E isolates were Escherichia coli (98.4%) and Klebsiella spp. (1.6%). Herds that had been treated with colistin were more likely to harbour mcr-Col-E, with 82.2% compared to 66.2% in untreated herds (p = 0.0298). Prevalence also depended on husbandry, with 7.1% mcr-Col-E in organic farms compared to 74.5% in conventional ones (p &lt; 0.001). In addition, four of the 46 (8.7%) human participants were colonised with mcr-Col-E. mcr-Col-E isolates from stables had minimum inhibitory concentrations (MICs) from 4 to ≥ 32 mg/l, human isolates ranged from 4 to 8 mg/l. cgMLST showed no clonal transmission of isolates. For one farm, plasmid typing revealed great similarities between plasmids from an environmental and a human sample. No CPE were found in turkey herds or humans.DiscussionThese findings confirm that mcr-Col-E-prevalence is high in turkey farms, but no evidence of direct zoonotic transmission of clonal mcr-Col-E strains was found. However, the results indicate that plasmids may be transmitted between E. coli isolates from animals and humans.
Quantitative plasma profiling by 1H NMR-based metabolomics: impact of sample treatment
Authors: Madrid-Gambin Francisco , Oller Sergio , Marco Santiago , Pozo Óscar J. , Andres-Lacueva Cristina , Llorach Rafael 
Published: June 2023

Introduction: There is evidence that sample treatment of blood-based biosamples may affect integral signals in nuclear magnetic resonance-based metabolomics. The presence of macromolecules in plasma/serum samples makes investigating low-molecular-weight metabolites challenging. It is particularly relevant in the targeted approach, in which absolute concentrations of selected metabolites are often quantified based on the area of integral signals. Since there are a few treatments of plasma/serum samples for quantitative analysis without a universally accepted method, this topic remains of interest for future research.Methods: In this work, targeted metabolomic profiling of 43 metabolites was performed on pooled plasma to compare four methodologies consisting of Carr-Purcell-Meiboom-Gill (CPMG) editing, ultrafiltration, protein precipitation with methanol, and glycerophospholipid solid-phase extraction (g-SPE) for phospholipid removal; prior to NMR metabolomics analysis. The effect of the sample treatments on the metabolite concentrations was evaluated using a permutation test of multiclass and pairwise Fisher scores.Results: Results showed that methanol precipitation and ultrafiltration had a higher number of metabolites with coefficient of variation (CV) values above 20%. G-SPE and CPMG editing demonstrated better precision for most of the metabolites analyzed. However, differential quantification performance between procedures were metabolite-dependent. For example, pairwise comparisons showed that methanol precipitation and CPMG editing were suitable for quantifying citrate, while g-SPE showed better results for 2-hydroxybutyrate and tryptophan.Discussion: There are alterations in the absolute concentration of various metabolites that are dependent on the procedure. Considering these alterations is essential before proceeding with the quantification of treatment-sensitive metabolites in biological samples for improving biomarker discovery and biological interpretations. The study demonstrated that g-SPE and CPMG editing are effective methods for removing proteins and phospholipids from plasma samples for quantitative NMR analysis of metabolites. However, careful consideration should be given to the specific metabolites of interest and their susceptibility to the sample treatment procedures. These findings contribute to the development of optimized sample preparation protocols for metabolomics studies using NMR spectroscopy.
MCR-ALS-based muscle synergy extraction method combined with LSTM neural network for motion intention detection
Authors: Zhao Dazheng , Ma Yehao , Meng Jingyan , Hu Yang , Hong Mengqi , Zhang Jiaji , Zuo Guokun , Lv Xiao , Liu Yunfeng , Shi Changcheng 
Published: June 2023

IntroductionThe time-varying and individual variability of surface electromyographic signals (sEMG) can lead to poorer motor intention detection results from different subjects and longer temporal intervals between training and testing datasets. The consistency of using muscle synergy between the same tasks may be beneficial to improve the detection accuracy over long time ranges. However, the conventional muscle synergy extraction methods, such as non-negative matrix factorization (NMF) and principal component analysis (PCA) have some limitations in the field of motor intention detection, especially in the continuous estimation of upper limb joint angles.MethodsIn this study, we proposed a reliable multivariate curve-resolved-alternating least squares (MCR-ALS) muscle synergy extraction method combined with long-short term memory neural network (LSTM) to estimate continuous elbow joint motion by using the sEMG datasets from different subjects and different days. The pre-processed sEMG signals were then decomposed into muscle synergies by MCR-ALS, NMF and PCA methods, and the decomposed muscle activation matrices were used as sEMG features. The sEMG features and elbow joint angular signals were input to LSTM to establish a neural network model. Finally, the established neural network models were tested by using sEMG dataset from different subjects and different days, and the detection accuracy was measured by correlation coefficient.ResultsThe detection accuracy of elbow joint angle was more than 85% by using the proposed method. This result was significantly higher than the detection accuracies obtained by using NMF and PCA methods. The results showed that the proposed method can improve the accuracy of motor intention detection results from different subjects and different acquisition timepoints.DiscussionThis study successfully improves the robustness of sEMG signals in neural network applications using an innovative muscle synergy extraction method. It contributes to the application of human physiological signals in human-machine interaction.
Toxic encephalopathy and peripheral neuropathy of poisoning by Avermectin Pyridine: a case report and a review of the literature
Authors: Diao Jiuzhou , Zhou Qingbo 
Published: June 2023

BackgroundAvermectin Pyridaben (AVP) is an insecticide with extreme neurotoxicity in human, causing critical symptoms such as nausea, vomiting, coma and respiratory failure within a short time after oral ingestion. Neurological sequelae or even death may occur because of delayed treatment or excessive toxic dose.Case presentationWe report a 15-year-old girl who presented with coma, respiratory failure, limb weakness, ataxia symptoms after ingestion of a toxic dose of AVP. Soon after the poisoning, the patient was treated with life-saving mechanical ventilation and haemodialysis. Subsequently brain Magnetic Resonance Imaging (MRI) and nerve conduction study (NCS) and electromyography (EMG) demonstrated toxic encephalopathy and peripheral nerve injury. Over the next 2 months the patient’s limb function gradually recovered under treatment with hyperbaric oxygen, glucocorticoid pulses and neurotrophic drugs.ConclusionThis case documents a rare presentation of toxic encephalopathy complicated with peripheral neuropathy following AVP poisoning. Seven other similar cases of poisoning in terms of common symptoms and effective treatment have also been summarised for providing clinicians with experience in diagnosis and therapy.
Comparison of children with and without dyslexia using functional head impulse test and pediatric balance scale
Authors: Ölçek Gül , Çelik İlayda , Başoǧlu Yuşa , Kaymakçı Sude , Gürlek Emre 
Published: June 2023

PurposeThe aim of this study is to compare functionality of vestibulo-ocular reflex (VOR) responses to evaluate the functional properties of the vestibular system and daily balance performance in children with dyslexia and children with normal development.MethodFifteen participants diagnosed with dyslexia were included in the study group (SG), and 15 healthy participants were included in the control group (CG). All groups underwent Functional Head Impulse Test (f-HIT) and Pediatric Balance Scale (PBS). f-HIT was performed with at least 15 head impulses at 4000-5000-6000°/s2 randomly to the right and left in the plane of the horizontal semicircular canal (SCC). Statistical analysis was performed using descriptive statistics and the Mann-Whitney U test.ResultsSG percentage values were obtained lower than CG percentage values. Comparisons between the two groups showed that there was a significant difference in all parameters (4000-5000-6000°/s2 and total) in the right-side stimulation, there was significant difference for 4,000 s2 and total correct answers in the left side. In addition, although there was no significant difference between the groups in terms of the PBS score, the SG scores were lower (p = 0.062).ConclusionsAs a novel test, f-HIT, revealed the difference in functionality of vestibular performance in the dyslexia group. In the dyslexia group, f-HIT may be helpful in evaluating and monitoring the vestibular system.