bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors Influencing the Utilization of Diabetes Complication Tests Under the COVID-19 Pandemic: Machine Learning Approach
Authors: Byeon Haewon 
Published: June 2022

ObjectiveThere are still not enough studies on the prediction of non-utilization of a complication test or a glycated hemoglobin test for preventing diabetes complications by using large-scale community-based big data. This study identified the ratio of not taking a diabetes complication test (fundus examination and microprotein urination test) among adult diabetic patients over 19 years using a national survey conducted in South Korea and developed a model for predicting the probability of not taking a diabetes complication test based on it.MethodsThis study analyzed 25,811 subjects who responded that they had been diagnosed with diabetes by a doctor in the 2020 Community Health Survey. Outcome variables were defined as the utilization of the microprotein urination test and the fundus examination during the past year. This study developed a model for predicting the utilization of a diabetes complication test using logistic regression analysis and nomogram to understand the relationship of predictive factors on the utilization of a diabetes complication test.ResultsThe results of this study confirmed that age, education level, the recognition of own blood glucose level, current diabetes treatment, diabetes management education, not conducting the glycated hemoglobin test in the past year, smoking, single-person household, subjectively good health, and living in the rural area were independently related to the non-utilization of diabetes complication test after the COVID-19 pandemic.ConclusionAdditional longitudinal studies are required to confirm the causality of the non-utilization of diabetes complication screening tests.
An Immune-Related Long Noncoding RNA Pair as a New Biomarker to Predict the Prognosis of Patients in Breast Cancer
Authors: Jiang Hanwen , Sun Jingxian , Liu Fucong , Wu Xincai , Wen Zhaohui 
Published: June 2022

Background: Immune-related long non-coding RNAs (irlncRNAs) might remodel the tumor immune microenvironment by changing the inherent properties of tumor cells and the expression of immune genes, which have been used to predict the efficacy of immunotherapy and the prognosis of various tumors. However, the value of irlncRNAs in breast cancer (BRCA) remains unclear.Materials and Methods: Initially, transcriptome data and immune-related gene sets were downloaded from The Cancer Genome Atlas (TCGA) database. The irlncRNAs were extracted from the Immunology Database and Analysis Portal (ImmPort) database. Differently expressed irlncRNAs (DEirlncRNAs) were further identified by utilizing the limma R package. Then, univariate and multivariate Cox regression analyses were conducted to select the DEirlncRNAs associated with the prognosis of BRCA patients. In addition, the univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were performed to determine the DEirlncRNA pairs with the independent prediction capability of prognosis in BRCA patients. Finally, the chosen DEirlncRNA pair would be evaluated in terms of survival time, clinicopathological characteristics, tumor-infiltrating immune cells, immune checkpoints (ICs), signaling pathways, and potential small-molecule drugs.Results: A total of 21 DEirlncRNA pairs were extracted, and among them, lncRNA MIR4435-2HG and lncRNA U62317.1 were chosen to establish a risk signature that served as an independent prognostic biomarker in BRCA patients. Patients in the high-risk group had a worse prognosis than those in the low-risk group, and they also had an abundance of infiltration of CD4+ T and CD8+ T cells to enhance the immune response to tumor cells. Furthermore, the risk signature showed a strong correlation with ICs, signaling pathways, and potential small-molecule drugs.Conclusion: Our research revealed that the risk signature independent of specific DEirlncRNA pair expression was closely associated with the prognosis and tumor immune microenvironment in BRCA patients and had the potential to function as an independent prognostic biomarker and a predictor of immunotherapy for BRCA patients, which would provide new insights for BRCA accurate treatment.
The Immunological Effect of Oxygen Carriers on Normothermic Ex Vivo Liver Perfusion
Authors: Jennings Heather , Carlson Kristin N. , Little Chris , Verhagen Joshua C. , Nagendran Jeevan , Liu Yongjun , Verhoven Bret , Zeng Weifeng , McMorrow Stacey , Chlebeck Peter , Al-Adra David P. 
Published: June 2022

IntroductionNormothermic ex vivo liver perfusion (NEVLP) is an organ preservation method that allows liver graft functional assessment prior to transplantation. One key component of normothermic perfusion solution is an oxygen carrier to provide oxygen to the liver to sustain metabolic activities. Oxygen carriers such as red blood cells (RBCs) or hemoglobin-based oxygen carriers have an unknown effect on the liver-resident immune cells during NEVLP. In this study, we assessed the effects of different oxygen carriers on the phenotype and function of liver-resident immune cells.MethodsAdult Lewis rat livers underwent NEVLP using three different oxygen carriers: human packed RBCs (pRBCs), rat pRBCs, or Oxyglobin (a synthetic hemoglobin-based oxygen carrier). Hourly perfusate samples were collected for downstream analysis, and livers were digested to isolate immune cells. The concentration of common cytokines was measured in the perfusate, and the immune cells underwent phenotypic characterization with flow cytometry and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The stimulatory function of the liver-resident immune cells was assessed using mixed lymphocyte reactions.ResultsThere were no differences in liver function, liver damage, or histology between the three oxygen carriers. qRT-PCR revealed that the gene expression of nuclear factor κ light chain enhancer of activated B cells (NF-kB), Interleukin (IL-1β), C-C motif chemokine ligand 2 (CCL2), C-C motif chemokine ligand 7 (CCL7), and CD14 was significantly upregulated in the human pRBC group compared with that in the naive, whereas the rat pRBC and Oxyglobin groups were not different from that of naive. Flow cytometry demonstrated that the cell surface expression of the immune co-stimulatory protein, CD86, was significantly higher on liver-resident macrophages and plasmacytoid dendritic cells perfused with human pRBC compared to Oxyglobin. Mixed lymphocyte reactions revealed increased allogeneic T-cell proliferation in the human and rat pRBC groups compared to that in the Oxyglobin group.ConclusionsLiver-resident immune cells are important mediators of rejection after transplantation. In this study, we show that the oxygen carrier used in NEVLP solutions can affect the phenotype of these liver-resident immune cells. The synthetic hemoglobin-based oxygen carrier, Oxyglobin, showed the least amount of liver-resident immune cell activation and the least amount of allogeneic proliferation when compared to human or rat pRBCs. To mitigate liver-resident immune cell activation during NEVLP (and subsequent transplantation), Oxyglobin may be an optimal oxygen carrier.
Identification of CFHR4 as a Potential Prognosis Biomarker Associated With lmmune Infiltrates in Hepatocellular Carcinoma
Authors: Yu Hongjun , Wang Chaoqun , Ke Shanjia , Bai Miaoyu , Xu Yanan , Lu Shounan , Feng Zhigang , Qian Baolin , Xu Yue , Zhou Menghua , Li Zihao , Yin Bing , Li Xinglong , Hua Yongliang , Zhou Yongzhi , Pan Shangha , Fu Yao , Ma Yong 
Published: June 2022

BackgroundComplement factor H-related 4 (CFHR4) is a protein-coding gene that plays an essential role in multiple diseases. However, the prognostic value of CFHR4 in hepatocellular carcinoma (HCC) is unknown.MethodsUsing multiple databases, we investigated CFHR4 expression levels in HCC and multiple cancers. The relationship between CFHR4 expression levels and clinicopathological variables was further analyzed. Various potential biological functions and regulatory pathways of CFHR4 in HCC were identified by performing a Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA). Single-sample gene set enrichment analysis (ssGSEA) was performed to confirm the correlation between CFHR4 expression and immune cell infiltration. The correlations between CFHR4 expression levels in HCC and N6-methyladenosine (m6A) modifications and the competing endogenous RNA (ceRNA) regulatory networks were confirmed in TCGA cohort.ResultsCFHR4 expression levels were significantly decreased in HCC tissues. Low CFHR4 expression in HCC tissues was significantly correlated with the patients’ sex, race, age, TNM stage, pathological stage, tumor status, residual tumor, histologic grade and alpha fetal protein (AFP) level. GO and KEGG analyses revealed that differentially expressed genes related to CFHR4 may be involved in the synaptic membrane, transmembrane transporter complex, gated channel activity, chemical carcinogenesis, retinol metabolism, calcium signaling pathway, PPAR signaling pathway, insulin and gastric acid secretion. GSEA revealed that the FCGR-activated reaction, PLK1 pathway, ATR pathway, MCM pathway, cascade reactions of PI3K and FGFR1, reactant-mediated MAPK activation and FOXM1 pathway were significantly enriched in HCC with low CFHR4 expression. Moreover, CFHR4 expression was inversely correlated the levels of infiltrating Th2 cells, NK CD56bright cells and Tfh cells. In contrast, we observed positive correlations with the levels of infiltrating DCs, neutrophils, Th17 cells and mast cells. CFHR4 expression showed a strong correlation with various immunomarker groups in HCC. In addition, high CFHR4 expression significantly prolonged the overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI). We observed a substantial correlation between the expression of CFHR4 and multiple N6-methyladenosine genes in HCC and constructed potential CFHR4-related ceRNA regulatory networks.ConclusionsCFHR4 might be a potential therapeutic target for improving the HCC prognosis and is closely related to immune cell infiltration.
Antibodies to Citrullinated Protein Antigens, Rheumatoid Factor Isotypes and the Shared Epitope and the Near-Term Development of Clinically-Apparent Rheumatoid Arthritis
Authors: Bergstedt Dylan T. , Tarter Wyatt J. , Peterson Ryan A. , Feser Marie L. , Parish Mark C. , Striebich Christopher C. , Demoruelle M. Kristen , Moss LauraKay , Bemis Elizabeth A. , Norris Jill M. , Holers V. Michael , Edison Jess D. , Thiele Geoffrey M. , Mikuls Ted R. , Deane Kevin D. 
Published: June 2022

Background/PurposeIn rheumatoid arthritis (RA) autoantibodies including antibodies to citrullinated protein antigens (ACPA) and rheumatoid factor (RF) can be predictive of incident clinical RA. However, there is limited understanding of how antibody changes over time impact prediction of the likelihood and timing of future clinical RA.Materials and MethodsWe evaluated relationships between ACPA, the shared epitope (SE), RF isotypes and incident RA in a prospective cohort of 90 ACPA(+) individuals without baseline arthritis identified through health-fair testing (i.e. Healthfair). We also evaluated ACPA and RF isotypes and time-to-diagnosis of RA in a retrospective cohort of 215 individuals with RA from the Department of Defense Serum Repository (DoDSR).ResultsTwenty-six of 90 (29%) of ACPA(+) Healthfair participants developed incident RA. Baseline or incident dual RF-IgA and RF-IgM positivity was associated with increased risk for incident RA (HR 3.09; 95% CI 1.15 to 8.29) although RFs were negative in ~50% of individuals with incident RA. SE was associated with increased risk of RA (HR 2.87, 95% CI 1.22-6.76). In the DoDSR cohort, triple positivity for ACPA, RF-IgA and RF-IgM was present a median of 1-2 years prior to RA diagnosis, with some sex-specific differences.ConclusionThese findings can be used to counsel individuals at-risk for future RA and to design clinical trials for RA prevention. The findings also suggest that RF could be a surrogate outcome as a success of an immunologic intervention in RA prevention. Additional studies are needed to understand the biologic of different patterns of autoantibody elevations in RA evolution.
Long Term Time-Lapse Imaging of Geographic Atrophy: A Pilot Study
Authors: Paques Michel , Norberg Nathaniel , Chaumette Céline , Sennlaub Florian , Rossi Ethan , Borella Ysé , Grieve Kate 
Published: June 2022

Geographic atrophy (GA), the late stage of age-related macular degeneration, is a major cause of visual disability whose pathophysiology remains largely unknown. Modern fundus imaging and histology revealed the complexity of the cellular changes that accompanies atrophy. Documenting the activity of the disease in the margins of atrophy, where the transition from health to disease occurs, would contribute to a better understanding of the progression of GA. Time-lapse imaging facilitates the identification of structural continuities in changing environments. In this retrospective pilot study, we documented the long-term changes in atrophy margins by time-lapse imaging of infrared scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) images in 6 cases of GA covering a mean period of 32.8 months (range, 18–72). The mean interval between imaging sessions was 2.4 months (range, 1.4–3.8). By viewing time-lapse sequences we observed extensive changes in the pattern of marginal hyperreflective spots, which associated fragmentation, increase and/or disappearance. Over the entire span of the follow-up, the most striking changes were those affecting hyperreflective spots closest to margins of atrophy, on the non-atrophic side of the retina; a continuum between the successive positions of some of the hyperreflective spots was detected, both by SLO and OCT. This continuum in their successive positions resulted in a subjective impression of a centrifugal motion of hyperreflective spots ahead of atrophy progression. Such mobilization of hyperreflective spots was detected up to several hundred microns away from atrophic borders. Such process is likely to reflect the inflammatory and degenerative process underlying GA progression and hence deserves further investigations. These results highlight the interest of multimodal time-lapse imaging to document cell-scale dynamics during progression of GA.Clinical Trial Registrationclinicaltrials.gov, identifier: NCT04128150 and NCT04129021.
Enlarged Perivascular Spaces in the Basal Ganglia Independently Related to Gait Disturbances in Older People With Cerebral Small Vessel Diseases
Authors: Yang Shuna , Li Xuanting , Hu Wenli , Qin Wei , Yang Lei 
Published: June 2022

Background and ObjectiveGait disturbances are common in older people and are associated with adverse consequences, e.g., falls and institutionalization. Enlarged perivascular spaces in the basal ganglia (BG-EPVS) are considered an magnetic resonance imaging (MRI) marker of cerebral small vessel diseases (CSVD). However, the consequences of BG-EPVS are largely unknown. Previous studies showed that other CSVD markers were related to gait disturbances. However, the relation between BG-EPVS and gait performance is unclear. Therefore, we aimed to explore the relation between BG-EPVS and gait performance in elderly individuals.MethodsWe recruited older people with CSVD in the Neurology Department of our hospital from December 1, 2020 to October 31, 2021. Participants with BG-EPVS &gt; 20 on the unilateral side of the basal ganglia slice containing the maximum number were classified into the BG-EPVS group (n = 78), and the rest were classified into the control group (n = 164). Quantitative gait parameters and gait variability were provided by the Intelligent Device for Energy Expenditure and Activity (IDEEA; MiniSun, United States) gait analysis system. Semiquantitative gait assessment was measured with the Tinetti test. Point-biserial correlation and multivariate linear regression analysis were performed to investigate the association between BG-EPVS and gait performance.ResultsThe BG-EPVS group had a slower gait speed and cadence, shorter stride length, longer stance phase percentage, smaller pre-swing angle and footfall, and lower Tinetti gait test and balance test scores compared with those in the control group (P &lt; 0.05). There were no statistical differences in stride length variability and stride time variability between the two groups (P &gt; 0.05). A correlation analysis showed that BG-EPVS were negatively related to gait speed, cadence, stride length, pre-swing angle, and footfall (γrange = −0.497 to −0.237, P &lt; 0.001) and positively related to stance phase percentage (γ = 0.269, P &lt; 0.001). BG-EPVS was negatively related to the score of the Tinetti gait test (γ = −0.449, P &lt; 0.001) and the balance test (γ = −0.489, P &lt; 0.001). The multiple linear regression analysis indicated that BG-EPVS was an independent risk factor for gait disturbances and poor balance after adjusting for confounders, including other CSVD markers.ConclusionLarge numbers of BG-EPVS were independently related to gait disturbances in older people with CSVD. This finding provides information about the consequences of BG-EPVS and risk factors for gait disturbances.
Contributing Factors and Induced Outcomes of Psychological Stress Response in Stroke Survivors: A Systematic Review
Authors: Zhang Song , Yuan Yuan , Zhuang Wenwen , Xiong Tianqing , Xu Yijun , Zhang Jingwen , Tao Chunhua , Liang Jingyan , Wang Yingge 
Published: June 2022

BackgroundRemarkable evidence indicates that psychological stress is significantly associated with stroke. However, a uniform recommendation to identify and alleviate poststroke psychological stress responses and improve postmorbid outcomes is not currently available. Thus, this systematic review aimed to summarize the types of poststroke psychological stress, measurement tools, contributing factors, and outcomes.MethodsThis systematic review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A literature search was conducted in PubMed, Web of Science, Embase, CNKI, WanFangData, and CQVIP from database inception to November 2021. Cross-sectional and longitudinal studies were included in this research. Quality assessment was performed based on the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.ResultsEighteen quantitative, peer-reviewed studies were included for analysis. Selected articles mainly investigated perceived stress and posttraumatic stress disorder after stroke. We classified the contributing factors into four categories: sociodemographic factors, clinical disease factors, psychological factors, and behavioral and lifestyle factors. The postmorbid outcomes were divided into three categories: clinical disease outcomes, psychological outcomes, and behavioral and quality of life outcomes.ConclusionsCompared to common patients, stroke survivors with the following characteristics suffered an increased psychological stress response: younger age, the presence of caregivers, depression, unsuitable coping strategies, etc. Meanwhile, lower quality of life, worse drug compliance, worse functional independence, and more severe mental disorders were significantly associated with increased psychological stress symptoms. Further studies are required to provide more trustworthy and meaningful references for mitigating the damage caused by psychological stress after stroke.
Neurological Involvement in COVID-19 Among Non-Hospitalized Adolescents and Young Adults
Authors: Havdal Lise Beier , Berven Lise Lund , Selvakumar Joel , Stiansen-Sonerud Tonje , Leegaard Truls Michael , Tjade Trygve , Zetterberg Henrik , Blennow Kaj , Wyller Vegard Bruun Bratholm 
Published: June 2022

IntroductionCoronavirus disease 2019 (COVID-19) is prevalent among young people, and neurological involvement has been reported. We investigated neurological symptoms, cognitive test results, and biomarkers of brain injury, as well as associations between these variables in non-hospitalized adolescents and young adults with COVID-19.MethodsThis study reports baseline findings from an ongoing observational cohort study of COVID-19 cases and non-COVID controls aged 12–25 years (Clinical Trials ID: NCT04686734). Symptoms were charted using a standardized questionnaire. Cognitive performance was evaluated by applying tests of working memory, verbal learning, delayed recall, and recognition. The brain injury biomarkers, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp), were assayed in serum samples using ultrasensitive immunoassays.ResultsA total of 405 COVID-19 cases and 111 non-COVID cases were prospectively included. Serum Nfl and GFAp concentrations were significantly elevated in COVID-19 cases as compared with non-COVID controls (p = 0.050 and p = 0.014, respectively). The COVID-19 cases reported more fatigue (p &lt; 0.001) and post-exertional malaise (PEM) (p = 0.001) compared to non-COVID-19 controls. Cognitive test performance and clinical neurological examination did not differ across the two groups. Within the COVID-19 group, there were no associations between symptoms, cognitive test results, and NfL or GFAp levels. However, fatigue and PEM were strongly associated with older age and female sex.ConclusionsNon-hospitalized adolescents and young adults with COVID-19 reported more fatigue and PEM and had slightly elevated levels of brain injury markers, but showed normal cognitive performance. No associations were found between symptoms, brain injury markers, and cognitive test results, but fatigue and PEM were strongly related to female sex and older age.