bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL4I1 in M2-like macrophage promotes glioma progression and is a promising target for immunotherapy
Authors: Ye Feng , Wang Lichong , Li Yuanyou , Dong Chengyuan , Zhou Liangxue , Xu Jianguo 
Published: January 2024

BackgroundGlioma is the prevailing malignant intracranial tumor, characterized by an abundance of macrophages. Specifically, the infiltrating macrophages often display the M2 subtype and are known as tumor-associated macrophages (TAMs). They have a critical role in promoting the oncogenic properties of tumor cells. Interleukin-4-induced-1 (IL4I1) functions as an L-phenylalanine oxidase, playing a key part in regulating immune responses and the progression of various tumors. However, there is limited understanding of the IL4I1-mediated cross-talk function between TAMs and glioma cell in the glioma microenvironment.MethodsTCGA, GTEx, and HPA databases were applied to assess the IL4I1 expression, clinical characteristics, and prognostic value of pan-cancer. The link between IL4I1 levels and the prognosis, methylation, and immune checkpoints (ICs) in gliomas were explored through Kaplan–Meier curve, Cox regression, and Spearman correlation analyses. The IL4I1 levels and their distribution were investigated by single-cell analysis and the TIMER 2 database. Additionally, validation of IL4I1 expression was performed by WB, RT-qPCR, IHC, and IF. Co-culture models between glioma cells and M2-like macrophages were used to explore the IL4I1-mediated effects on tumor growth, invasion, and migration of glioma cells. Moreover, the function of IL4I1 on macrophage polarization was evaluated by ELISA, RT-qPCR, WB, and siRNA transfection.ResultsBoth transcriptome and protein levels of IL4I1 were increased obviously in various tumor types, and correlated with a dismal prognosis. Specifically, IL4I1 was implicated in aggressive progression and a dismal prognosis for patients with glioma. A negative association was noticed between the glioma grade and DNA promoter methylation of IL4I1. Enrichment analyses in glioma patients suggested that IL4I1 was linked to cytokine and immune responses, and was positively correlated with ICs. Single-cell analysis, molecular experiments, and in vitro assays showed that IL4I1 was significantly expressed in TAMs. Importantly, co-culture models proved that IL4I1 significantly promoted the invasion and migration of glioma cells, and induced the polarization of M2-like macrophages.ConclusionIL4I1 could be a promising immunotherapy target for selective modulation of TAMs and stands as a novel macrophage-related prognostic biomarker in glioma.
Visceral adipose tissue and osteoarthritis, a two-sample Mendelian randomized study
Authors: Zhang Yinzhen , Wang Yanpeng , Xu Ji , Wang Zhengyan , Zhao Wenhai , Zhao Changwei 
Published: January 2024

BackgroundThe relationship between visceral adipose tissue and osteoarthritis is not clear. The purpose of our study was to explore the relationship between visceral adipose tissue and osteoarthritis.MethodsWe used a two-sample Mendelian randomization method to select single-nucleotide polymorphisms (SNPs) significantly associated with visceral adipose tissue as instrumental variables to explore the relationship between visceral adipose tissue and all osteoarthritis, hand osteoarthritis, hip osteoarthritis, knee osteoarthritis, and spine osteoarthritis. The reliability of the results was tested using sensitivity analysis.ResultsOur findings indicated that visceral adipose tissue was associated with all osteoarthritis, hip osteoarthritis, knee osteoarthritis, and spine osteoarthritis (all osteoarthritis: OR = 1.399, 95% CI: 1.335–1.467, p = 7.95e-44; hip osteoarthritis: OR = 1.399, 95% CI: 1.284–1.524, p = 1.41e-14; knee osteoarthritis: OR = 1.794, 95% CI: 1.662–1.937, p = 1.33e-50; and spine osteoarthritis: OR = 1.445, 95% CI: 1.314–1.589, p = 2.89e-14). Sensitivity analysis demonstrated the reliability of these results.ConclusionOur study suggests that genetically predicted visceral adipose tissue is associated with osteoarthritis. Reducing the accumulation of visceral adipose tissue could potentially have an impact on the incidence of osteoarthritis.
Strengthening the genomic surveillance of Francisella tularensis by using culture-free whole-genome sequencing from biological samples
Authors: Isidro Joana , Escudero Raquel , Luque-Larena Juan José , Pinto Miguel , Borges Vítor , González-Martín-Niño Rosa , Duarte Sílvia , Vieira Luís , Mougeot François , Vidal Dolors , Herrera-Rodríguez Daniel , Rodríguez-Pastor Ruth , Herrero-Cófreces Silvia , Jubete-Tazo Fernando , Gomes João Paulo , Lopes de Carvalho Isabel 
Published: January 2024

IntroductionFrancisella tularensis is a highly infectious bacterium that causes the zoonotic disease tularemia. The development of genotyping methods, especially those based on whole-genome sequencing (WGS), has recently increased the knowledge on the epidemiology of this disease. However, due to the difficulties associated with the growth and isolation of this fastidious pathogen in culture, the availability of strains and subsequently WGS data is still limited.MethodsTo surpass these constraints, we aimed to implement a culture-free approach to capture and sequence F. tularensis genomes directly from complex samples. Biological samples obtained from 50 common voles and 13 Iberian hares collected in Spain were confirmed as positive for F. tularensis subsp. holarctica and subjected to a WGS target capture and enrichment protocol, using RNA oligonucleotide baits designed to cover F. tularensis genomic diversity.ResultsWe obtained full genome sequences of F. tularensis from 13 animals (20.6%), two of which had mixed infections with distinct genotypes, and achieved a higher success rate when compared with culture-dependent WGS (only successful for two animals). The new genomes belonged to different clades commonly identified in Europe (B.49, B.51 and B.262) and subclades. Despite being phylogenetically closely related to other genomes from Spain, the detected clusters were often found in other countries. A comprehensive phylogenetic analysis, integrating 599 F. tularensis subsp. holarctica genomes, showed that most (sub)clades are found in both humans and animals and that closely related strains are found in different, and often geographically distant, countries.DiscussionOverall, we show that the implemented culture-free WGS methodology yields timely, complete and high-quality genomic data of F. tularensis, being a highly valuable approach to promote and potentiate the genomic surveillance of F. tularensis and ultimately increase the knowledge on the genomics, ecology and epidemiology of this highly infectious pathogen.
A multiplex real-time fluorescence-based quantitative PCR assay for calf diarrhea viruses
Authors: Meng Wenxin , Chen Zihan , Jiang Qifeng , Chen Jinping , Guo Xiaoying , Ma Zihang , Jia Kun , Li Shoujun 
Published: January 2024

IntroductionCalf diarrhea is a significant condition that has a strong effect on the cattle industry, resulting in huge economic losses annually. Bovine torovirus (BToV), bovine enterovirus (BEV), bovine norovirus (BNoV), bovine coronavirus (BCoV), bovine rotavirus (BRV), and bovine viral diarrhea virus (BVDV) are key pathogens that have been implicated in calf diarrhea. Among these viruses, there remains limited research on BToV, BEV, and BNoV, with no available vaccines or drugs for their prevention and control. Although commercial vaccines exist for BCoV, BRV, and BVDV, the prevalence of these diseases remains high.MethodsTo address this issue, we developed a multiplex real-time fluorescence quantitative PCR method for detecting BToV, BEV, BNoV, BCoV, BRV, and BVDV. This method can be used to effectively monitor the prevalence of these six viruses and serve as a reference for future prevention and control strategies. In this study, we specifically designed primers and probes for the BNoV Rdrp, BEV 5′UTR, BToV M, BCoV N, BRV NSP5, and BVDV 5′UTR genes.ResultsThis method was determined to be efficient, stable, and sensitive. The lowest detectable levels of plasmids for BNoV, BEV, BToV, BRV, BCoV, and BVDV were 1.91 copies/μL, 96.0 copies/μL, 12.8 copies/μL, 16.4 copies/μL, 18.2 copies/μL, and 65.3 copies/μL, respectively. Moreover, the coefficients of variation for all six detection methods were &lt; 3%; they also exhibited a strong linear relationship (R2 ≥ 0.98), and an amplification efficiency of 90%−110%. A total of 295 fecal and anal swabs were collected from calves with diarrhea in Guangdong, China. The positive rates for BToV, BEV, BNoV, BCoV, BR, and BVDV were determined to be 0.34% (1/295), 6.10% (18/295), 0.68% (2/295), 1.36% (4/295), 10.85% (32/295), and 2.03% (6/295), respectively. Notably, BEV and BRV exhibited the highest prevalence.DiscussionAdditionally, this study identified the occurrence of BToV and BNoV in Guangdong for the first time. In summary, this study successfully established an effective method for detecting several important bovine viruses; ultimately, this holds strong implications for the future development of the cattle industry.
Evaluation of the antibacterial effect of Epigallocatechin gallate on the major pathogens of canine periodontal disease and therapeutic effects on periodontal disease mice
Authors: Song Peijia , Hao Yibing , Lin Degui , Jin Yipeng , Lin Jiahao 
Published: January 2024

BackgroundPeriodontal disease (PD) is a prevalent oral affliction in canines, with limited therapeutic options available. The potential transmission of oral bacteria from canines to humans through inter-species contact poses a risk of zoonotic infection. Epigallocatechin gallate (EGCG), the principal catechin in green tea polyphenols, exhibits antibacterial properties effective against human PD. Given the clinical parallels between canine and human PD, this study explores the feasibility of employing EGCG as a therapeutic agent for canine PD.Methods and resultsInitially, a survey and statistical analysis of bacterial infection data related to canine PD in China were conducted. Subsequently, the primary pathogenic bacteria of canine PD were isolated and cultivated, and the in vitro antibacterial efficacy of EGCG was assessed. Furthermore, verify the therapeutic effect of EGCG on a mouse PD model in vivo. The high-throughput 16S rRNA gene sequencing identified Porphyromonas, Fusobacterium, Treponema, Moraxella, and Capnocytophaga as the genera that distinguishing PD from healthy canines’ gingival crevicular fluid (GCF) samples in China. The anaerobic culture and drug susceptibility testing isolated a total of 92 clinical strains, representing 22 species, from 72 canine GCF samples, including Porphyromonas gulae, Prevotella intermedia, Porphyromonas macacae, etc. The minimum inhibitory concentration (MIC) ranging of EGCG was from 0.019 to 1.25 mg/mL. Following a 7 days oral mucosal administration of medium-dose EGCG (0.625 mg/mL), the abundance of periodontal microorganisms in PD mice significantly decreased. This intervention ameliorated alveolar bone loss, reducing the average cementoenamel junction to the alveolar bone crest (CEJ-ABC) distance from 0.306 mm ± 0.050 mm to 0.161 mm ± 0.026 mm. Additionally, EGCG (0.3125 mg/mL) markedly down-regulated the expression of inflammatory factor IL-6 in the serum of PD mice.ConclusionOur research demonstrates the significant antibacterial effects of EGCG against the prevalent bacterium P. gulae in canine PD. Moreover, EGCG exhibits anti-inflammatory properties and proves effective in addressing bone loss in a PD mouse model. These findings collectively suggest the therapeutic potential of EGCG in the treatment of canine PD. The outcomes of this study contribute valuable data, laying the foundation for further exploration and screening of alternative antibiotic drugs to advance the management of canine PD.
Network analysis of multimorbidity and health outcomes among persons with spinal cord injury in Canada
Authors: Fallah Nader , Hong Heather A. , Wang Di , Humphreys Suzanne , Parsons Jessica , Walden Kristen , Street John , Charest-Morin Raphaele , Cheng Christiana L. , Cheung Candice J. , Noonan Vanessa K. 
Published: January 2024

IntroductionMultimorbidity, defined as the coexistence of two or more health conditions, is common in persons with spinal cord injury (SCI). Network analysis is a powerful tool to visualize and examine the relationship within complex systems. We utilized network analysis to explore the relationship between 30 secondary health conditions (SHCs) and health outcomes in persons with traumatic (TSCI) and non-traumatic SCI (NTSCI). The study objectives were to (1) apply network models to the 2011–2012 Canadian SCI Community Survey dataset to identify key variables linking the SHCs measured by the Multimorbidity Index-30 (MMI-30) to healthcare utilization (HCU), health status, and quality of life (QoL), (2) create a short form of the MMI-30 based on network analysis, and (3) compare the network-derived MMI to the MMI-30 in persons with TSCI and NTSCI.MethodsThree network models (Gaussian Graphical, Ising, and Mixed Graphical) were created and analyzed using standard network measures (e.g., network centrality). Data analyzed included demographic and injury variables (e.g., age, sex, region of residence, date, injury severity), multimorbidity (using MMI-30), HCU (using the 7-item HCU questionnaire and classified as “felt needed care was not received” [HCU-FNCNR]), health status (using the 12-item Short Form survey [SF-12] Physical and Mental Component Summary [PCS-12 and MCS-12] score), and QoL (using the 11-item Life Satisfaction questionnaire [LiSAT-11] first question and a single item QoL measure).ResultsNetwork analysis of 1,549 participants (TSCI: 1137 and NTSCI: 412) revealed strong connections between the independent nodes (30 SHCs) and the dependent nodes (HCU-FNCNR, PCS-12, MCS-12, LiSAT-11, and the QoL score). Additionally, network models identified that cancer, deep vein thrombosis/pulmonary embolism, diabetes, high blood pressure, and liver disease were isolated. Logistic regression analysis indicated the network-derived MMI-25 correlated with all health outcome measures (p &lt;0.001) and was comparable to the MMI-30.DiscussionThe network-derived MMI-25 was comparable to the MMI-30 and was associated with inadequate HCU, lower health status, and poor QoL. The MMI-25 shows promise as a follow-up screening tool to identify persons living with SCI at risk of having poor health outcomes.
The usefulness of global longitudinal peak strain and left atrial volume index in predicting atrial fibrillation in patients with ischemic stroke
Authors: Park Soo-Hyun , Kim Yerim , Lee Minwoo , Lee Sang-Hwa , Bae Jong Seok , Lee Ju-Hun , Kim Tae Jung , Ko Sang-Bae , Jeong Sang-Wuk , Kim Dong-Eog , Ryu Wi-Sun 
Published: January 2024

IntroductionDetection of atrial fibrillation (AF) is crucial for preventing recurrence in patients with ischemic stroke. We aimed to examine whether the left atrial volume index (LAVI) and global longitudinal peak strain (GLPS) are associated with AF in patients with ischemic stroke.MethodsWe prospectively analyzed 678 consecutive patients with ischemic stroke. LAVI and GLPS were assessed using three-dimensional transthoracic echocardiography with speckle-tracking imaging. Multiple logistic regression was used to evaluate the association of AF with LAVI and GLPS. To evaluate the predictive value of LAVI and GLPS for the presence of AF, we used optimism-corrected c-statistics calculated by 100 bootstrap repetitions and the net reclassification improvement (NRI).ResultsThe mean patient age was 68 ± 13 years (men, 60%). Patients with AF (18%) were a higher LAVI (41.7 ml/m2 vs. 74.9 ml/m2, P &lt; 0.001) and a higher GLPS than those without AF (−14.0 vs. −17.3, P &lt; 0.001). Among the 89 patients classified with embolic stroke of unknown source, the probable cardioembolic group had higher GLPS (n= 17, −14.6 vs. −18.6, respectively; P= 0.014) than the other groups (n= 72). Adding GLPS to age, hypertension, and the LAVI significantly improved the NRI, with an overall NRI improvement of 6.1% (P= 0.03).DiscussionThe LAVI andGLPS with speckle-tracking imaging echocardiography may help identify patients with AF.
A deep learning wearable-based solution for continuous at-home monitoring of upper limb goal-directed movements
Authors: Nunes Adonay S. , Yildiz Potter İlkay , Mishra Ram Kinker , Bonato Paolo , Vaziri Ashkan 
Published: January 2024

IntroductionMonitoring upper limb function is crucial for tracking progress, assessing treatment effectiveness, and identifying potential problems or complications. Hand goal-directed movements (GDMs) are a crucial aspect of daily life, reflecting planned motor commands with hand trajectories towards specific target locations. Previous studies have shown that GDM tasks can detect early changes in upper limb function in neurodegenerative diseases and can be used to track disease progression over time.MethodsIn this study, we used accelerometer data from stroke survivor participants and controls doing activities of daily living to develop an automated deep learning approach to detect GDMs. The model performance for detecting GDM or non-GDM from windowed data achieved an AUC of 0.9, accuracy 0.83, sensitivity 0.81, specificity 0.84 and F1 0.82.ResultsWe further validated the utility of detecting GDM by extracting features from GDM periods and using these features to classify whether the measurements are collected from a stroke survivor or a control participant, and to predict the Fugl-Meyer assessment score from stroke survivors.DiscussionThis study presents a promising and reliable tool for monitoring upper limb function in a real-world setting, and assessing biomarkers related to upper limb health in neurological, neuromuscular and muscles disorders.
Electromyography varies by stage in inclusion body myositis
Authors: Mano Tomoo , Iguchi Naohiko , Eura Nobuyuki , Iwasa Naoki , Yamada Nanami , Horikawa Hirosei , Sugie Kazuma 
Published: January 2024

IntroductionInclusion body myositis (IBM) is a chronic inflammatory muscle disease that is characterized by mixed myogenic and neurogenic electromyography (EMG) findings. We investigated the association between EMG findings and the IBM stage.MethodsWe included consecutive patients diagnosed with IBM based on muscle biopsy and had needle EMG performed within 1 month of biopsy. Motor unit potential waveform (MUP) in EMG and pathological findings were compared between patients in early and late phases.ResultsIn total, 30 patients with biopsy-confirmed IBM and 254 muscles were included. The rate of abnormal discharge did not differ according to disease stage. There was a difference in the frequency of occurrence between myogenic suggestive MUP and neurogenic of biceps and flexor digitorum profundus in the late phase. Abnormal MUP was observed even in muscles without muscle weakness, and myogenic changes were predominant in biceps and gastrocnemius with muscle weakness. The biopsy findings on the contralateral side of the muscle where electromyography was performed revealed a tendency for muscles that exhibited myogenic origin to have more inflammatory cells and RV; however, the difference was not significant.ConclusionThe target muscles for EMG must be selected considering the disease stage as well. In the early stages of IBM, EMG results should be interpreted cautiously, as neurogenic suggestive pattern of MUP might also be exhibited. Contralateral electromyography findings may be helpful in selecting muscles for muscle biopsies, such as biceps and quadriceps.
Is catheter ablation associated with preservation of cognitive function? An analysis from the SAGE-AF observational cohort study
Authors: Srichawla Bahadar S. , Hamel Alexander P. , Cook Philip , Aleyadeh Rozaleen , Lessard Darleen , Otabil Edith M. , Mehawej Jordy , Saczynski Jane S. , McManus David D. , Moonis Majaz 
Published: January 2024

ObjectivesTo examine the associations between catheter ablation treatment (CA) vs. medical management and cognitive impairment among older adults with atrial fibrillation (AF).MethodsAmbulatory patients who had AF, were ≥65-years-old, and were eligible to receive oral anticoagulation could be enrolled into the SAGE (Systematic Assessment of Geriatric Elements)-AF study from internal medicine and cardiology clinics in Massachusetts and Georgia between 2016 and 2018. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) tool at baseline, 1-, and 2 years. Cognitive impairment was defined as a MoCA score ≤ 23. Multivariate-adjusted logistic regression of longitudinal repeated measures was used to examine associations between treatment with CA vs. medical management and cognitive impairment.Results887 participants were included in this analysis. On average, participants were 75.2 ± 6.7 years old, 48.6% women, and 87.4% white non-Hispanic. 193 (21.8%) participants received a CA before enrollment. Participants who had previously undergone CA were significantly less likely to be cognitively impaired during the 2-year study period (aOR 0.70, 95% CI 0.50–0.97) than those medically managed (i.e., rate and/or rhythm control), even after adjusting with propensity score for CA. At the 2-year follow-up a significantly greater number of individuals in the non-CA group were cognitively impaired (MoCA ≤ 23) compared to the CA-group (311 [44.8%] vs. 58 [30.1%], p = 0.0002).ConclusionIn this 2-year longitudinal prospective cohort study participants who underwent CA for AF before enrollment were less likely to have cognitive impairment than those who had not undergone CA.
Nomogram to predict 6-month mortality in acute ischemic stroke patients treated with endovascular treatment
Authors: Wen Rui , Wang Miaoran , Bian Wei , Zhu Haoyue , Xiao Ying , He Qian , Wang Yu , Liu Xiaoqing , Shi Yangdi , Hong Zhe , Xu Bing 
Published: January 2024

BackgroundAcute Ischemic Stroke (AIS) presents significant challenges in evaluating the effectiveness of Endovascular Treatment (EVT). This study develops a novel prognostic model to predict 6-month mortality post-EVT, aiding in identifying patients likely to benefit less from this intervention, thus enhancing therapeutic decision-making.MethodsWe employed a cohort of AIS patients from Shenyang First People’s Hospital, serving as the Validation set, to develop our model. LASSO regression was used for feature selection, followed by logistic regression to create a prognostic nomogram for predicting 6-month mortality post-EVT. The model’s performance was validated using a dataset from PLA Northern Theater Command General Hospital, assessing discriminative ability (C-index), calibration (calibration plot), and clinical utility (decision curve analysis). Statistical significance was set at p &lt; 0.05.ResultsThe development cohort consisted of 219 patients. Six key predictors of 6-month mortality were identified: “Lack of Exercise” (OR, 4.792; 95% CI, 1.731–13.269), “Initial TICI Score 1” (OR, 1.334; 95% CI, 0.628–2.836), “MRS Score 5” (OR, 1.688; 95% CI, 0.754–3.78), “Neutrophil Percentage” (OR, 1.08; 95% CI, 1.042–1.121), “Onset Blood Sugar” (OR, 1.119; 95% CI, 1.007–1.245), and “Onset NIHSS Score” (OR, 1.074; 95% CI, 1.029–1.121). The nomogram demonstrated a high predictive capability with a C-index of 0.872 (95% CI, 0.830–0.911) in the development set and 0.830 (95% CI, 0.726–0.920) in the validation set.ConclusionOur nomogram, incorporating factors such as Lack of Exercise, Initial TICI Score 1, MRS Score 5, Neutrophil Percentage, Onset Blood Sugar, and Onset NIHSS Score, provides a valuable tool for predicting 6-month mortality in AIS patients post-EVT. It offers potential to refine early clinical decision-making and optimize patient outcomes, reflecting a shift toward more individualized patient care.