bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Plasma Neurofilament Light Chain With Glycaemic Control and Insulin Resistance in Middle-Aged Adults
Authors: Thota Rohith N. , Chatterjee Pratishtha , Pedrini Steve , Hone Eugene , Ferguson Jessica J. A. , Garg Manohar L. , Martins Ralph N. 
Published: June 2022

AimsThis study aimed to determine the association of plasma neurofilament light (NfL), a marker of neurodegeneration, with diabetes status and glycaemic parameters in people with normal glycaemia (NG), pre-diabetes (PD) and type 2 diabetes (T2D).MethodsClinical and descriptive data for the diagnostic groups, NG (n=30), PD (n=48) and T2D (n=29), aged between 40 and 75 years were included in this cross-sectional analysis. Plasma NfL levels were analyzed using the ultra-sensitive single-molecule array (Simoa) platform.ResultsA positive correlation was evident between plasma NfL and fasting glucose (r = 0.2824; p = 0.0032). Plasma NfL levels were not correlated with fasting insulin and insulin resistance. Plasma Nfl levels were significantly different across the diabetes groups (T2D &gt;PD &gt;NG, p=0.0046). Post-hoc analysis indicated significantly higher plasma NfL levels in the T2D [12.4 (5.21) pg/mL] group than in the PD [10.2 (4.13) pg/mL] and NG [8.37 (5.65) pg/mL] groups. The relationship between diabetes status and NfL remained significant after adjusting for age, sex, BMI, HOMA-IR and physical activity (adjusted r2 = 0.271, p = 0.035).ConclusionsThese results show biomarker evidence of neurodegeneration in adults at risk or with T2D. Larger sample size and longitudinal analysis are required to better understand the application of NfL in people with risk and overt T2D.
Living in Temporary Ponds Loading Giant Genomes: The Neotropical Annual Killifish Genus Austrolebias as New Outstanding Evolutionary Model
Authors: García Graciela , Gutiérrez Verónica , Ríos Néstor 
Published: June 2022

The term Annual killifish describes a short-lived and amazing group of vertebrates inhabiting temporary ponds exposed to an extremely variable environment during its short lifespan in South America and Africa, leading to the death of the entire adult population during the dry season. Austrolebias is a specious genus of the family Rivulidae, with ∼58 currently recognized species, extensively distributed in the temperate Neotropical region. Herein, we reviewed different aspects of the evolutionary biology with emphasis on the genome dynamic linked to the burst speciation process in this genus. Austrolebias constitutes an excellent model to study the genomic evolutionary processes underlying speciation events, since all the species of this genus analyzed so far share an unusually large genome size, with an average DNA content of 5.95 ± 0.45 picograms per diploid cell (mean C-value of about 2.98 pg). The drastic nuclear DNA–increasing would be associated with a considerable proportion of transposable elements (TEs) found in the Austrolebias genomes. The genomic proportion of the moderately repetitive DNA in the A. charrua genome represents approximately twice (45%) the amount of the repetitive components of the highly related sympatric and syntopic rivulinae taxon Cynopoecilus melanotaenia (25%), as well as from other rivulids and actinopterygian fish. These events could explain the great genome instability, the high genetic diversity, chromosome variability, as well as the morphological diversity in species of Austrolebias. Thus, species of this genus represent new model systems linking different evolutionary processes: drastic genome increase, massive TEs genomic representation, high chromosome instability, occurrence of natural hybridization between sister species, and burst speciation events.
Autoimmune Cytopenias in Common Variable Immunodeficiency Are a Diagnostic and Therapeutic Conundrum: An Update
Authors: Chawla Sanchi , Barman Prabal , Tyagi Rahul , Jindal Ankur Kumar , Sharma Saniya , Rawat Amit , Singh Surjit 
Published: June 2022

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency (PID). CVID is a heterogenous condition and clinical manifestations may vary from increased susceptibility to infections to autoimmune manifestations, granulomatous disease, polyclonal lymphoproliferation, and increased risk of malignancy. Autoimmune manifestations may, at times, be the first and only clinical presentation of CVID, resulting in diagnostic dilemma for the treating physician.Autoimmune cytopenias (autoimmune haemolytic anaemia and/or thrombocytopenia) are the most common autoimmune complications seen in patients with CVID. Laboratory investigations such as antinuclear antibodies, direct Coomb’s test and anti-platelet antibodies may not be useful in patients with CVID because of lack of specific antibody response. Moreover, presence of autoimmune cytopenias may pose a significant therapeutic challenge as use of immunosuppressive agents can be contentious in these circumstances. It has been suggested that serum immunoglobulins must be checked in all patients presenting with autoimmune cytopenia such as immune thrombocytopenia or autoimmune haemolytic anaemia.It has been observed that patients with CVID and autoimmune cytopenias have a different clinical and immunological profile as compared to patients with CVID who do not have an autoimmune footprint. Monogenic defects have been identified in 10-50% of all patients with CVID depending upon the population studied. Monogenic defects are more likely to be identified in patients with CVID with autoimmune complications. Common genetic defects that may lead to CVID with an autoimmune phenotype include nuclear factor kappa B subunit 1 (NF-kB1), Lipopolysaccharide (LPS)-responsive beige-like anchor protein (LRBA), cytotoxic T lymphocyte antigen 4 (CTLA4), Phosphoinositide 3-kinase (PI3K), inducible T-cell costimulatory (ICOS), IKAROS and interferon regulatory factor-2 binding protein 2 (IRF2BP2).In this review, we update on recent advances in pathophysiology and management of CVID with autoimmune cytopenias.
Identification of Key Genes as Early Warning Signals of Acute Myocardial Infarction Based on Weighted Gene Correlation Network Analysis and Dynamic Network Biomarker Algorithm
Authors: Song Chenxi , Qiao Zheng , Chen Luonan , Ge Jing , Zhang Rui , Yuan Sheng , Bian Xiaohui , Wang Chunyue , Liu Qianqian , Jia Lei , Fu Rui , Dou Kefei 
Published: June 2022

PurposeThe specific mechanisms and biomarkersunderlying the progression of stable coronary artery disease (CAD) to acute myocardial infarction (AMI) remain unclear. The current study aims to explore novel gene biomarkers associated with CAD progression by analyzing the transcriptomic sequencing data of peripheral blood monocytes in different stages of CAD.Material and MethodsA total of 24 age- and sex- matched patients at different CAD stages who received coronary angiography were enrolled, which included 8 patients with normal coronary angiography, 8 patients with angiographic intermediate lesion, and 8 patients with AMI. The RNA from peripheral blood monocytes was extracted and transcriptome sequenced to analyze the gene expression and the differentially expressed genes (DEG). A Gene Oncology (GO) enrichment analysis was performed to analyze the biological function of genes. Weighted gene correlation network analysis (WGCNA) was performed to classify genes into several gene modules with similar expression profiles, and correlation analysis was carried out to explore the association of each gene module with a clinical trait. The dynamic network biomarker (DNB) algorithm was used to calculate the key genes that promote disease progression. Finally, the overlapping genes between different analytic methods were explored.ResultsWGCNA analysis identified a total of nine gene modules, of which two modules have the highest positive association with CAD stages. GO enrichment analysis indicated that the biological function of genes in these two gene modules was closely related to inflammatory response, which included T-cell activation, cell response to inflammatory stimuli, lymphocyte activation, cytokine production, and the apoptotic signaling pathway. DNB analysis identified a total of 103 genes that may play key roles in the progression of atherosclerosis plaque. The overlapping genes between DEG/WGCAN and DNB analysis identified the following 13 genes that may play key roles in the progression of atherosclerosis disease: SGPP2, DAZAP2, INSIG1, CD82, OLR1, ARL6IP1, LIMS1, CCL5, CDK7, HBP1, PLAU, SELENOS, and DNAJB6.ConclusionsThe current study identified a total of 13 genes that may play key roles in the progression of atherosclerotic plaque and provides new insights for early warning biomarkers and underlying mechanisms underlying the progression of CAD.
Neutrophil Infiltration Characterized by Upregulation of S100A8, S100A9, S100A12 and CXCR2 Is Associated With the Co-Occurrence of Crohn’s Disease and Peripheral Artery Disease
Authors: Yao Ziping , Zhang Bihui , Niu Guochen , Yan Ziguang , Tong Xiaoqiang , Zou Yinghua , Li Yuan , Yang Min 
Published: June 2022

BackgroundCrohn’s disease (CD) and peripheral arterial disease (PAD) are closely related. The pathophysiological mechanisms underlying the coexistence of CD and PAD are unknown. The aim of this study was to investigate the key molecules and pathways mediating the co-occurrence of CD and PAD through quantitative bioinformatic analysis of a public RNA sequencing database.MethodsDatasets of CD (GSE111889) and PAD (GSE120642) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using the ‘edgeR’ and ‘limma’ packages of R. Gene Ontology and Kyoto Encyclopedia analyses of common DEGs were performed to explore the functions of DEGs. Protein–protein interaction (PPI) networks were established by the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized by Cytoscape. Hub genes were selected using the plugin cytoHubba. Hub gene validation was performed in GSE95095 for CD and GSE134431 for PAD. Receiver operating characteristic curves were used to evaluate the predictive values of the hub genes. Gene set enrichment analysis and immune infiltration of the hub genes were performed.ResultsA total of 54 common DEGs (2 downregulated and 52 upregulated) were identified. Pathways of neutrophil chemotaxis, neutrophil migration and cytokine and cytokine receptors were enriched in CD and PAD. S100A8, S100A9, S100A12 and CXCR2 were identified as hub genes after validation, with all area under the curve &gt; 0.7 for both CD and PAD. Neutrophil infiltration was associated with upregulation of the hub genes. Pathways of immune processes, including neutrophil activation, neutrophil chemotaxis, neutrophil migration were significantly correlated with high expression of S100A8, S100A9, S100A12 and CXCR2 in both CD and PAD.ConclusionsThis bioinformatic study elucidates S100A8, S100A9, S100A12 and CXCR2 as hub genes for the co-occurrence of Crohn’s disease and peripheral artery disease. Inflammation and immune regulation modulated by neutrophil infiltration play a central role in the development of CD and PAD and may be potential targets for diagnosis and treatment.
Characteristics and Prognosis of Antibody Non-responders With Coronavirus Disease 2019
Authors: Ding Junyu , Liu Changxin , Wang Zhao , Guo Hua , Zhang Kan , Ma Lin , Wang Bo , Zhao Huijun , Song Manya , Guan Xizhou 
Published: June 2022

BackgroundCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been spreading globally. Information regarding the characteristics and prognosis of antibody non-responders to COVID-19 is limited.MethodsIn this retrospective, single-center study, we included all patients with confirmed COVID-19 using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) admitted to the Fire God Mountain hospital from February 3, 2020, to April 14, 2020. A total of 1,921 patients were divided into the antibody-negative (n = 94) and antibody-positive (n = 1,827) groups, and 1:1 propensity score matching was used to match the two groups.ResultsIn the antibody-negative group, 40 patients (42.6%) were men, and 49 (52.1%) were older than 65 years. Cough was the most common symptom in the antibody negative group. White blood cell counts, neutrophils, C-reactive protein, procalcitonin, interleukin-6, lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme, urea nitrogen, and creatinine were significantly higher in the antibody-negative patients than in the antibody-positive group (P &lt; 0.005). The number of days of nucleic acid-negative conversion in the antibody-negative group was shorter than that in the antibody-positive group (P &lt; 0.001). The hospitalization time of the antibody-negative patients was shorter than that of the antibody-positive patients (P &lt; 0.001).ConclusionSome COVID-19 patients without specific antibodies had mild symptoms; however, the inflammatory reaction caused by innate clinical immunity was more intense than those associated with antibodies. Non-specific immune responses played an essential role in virus clearance. There was no direct correlation between excessive inflammatory response and adverse outcomes in patients. The risk of reinfection and vaccination strategies for antibody-negative patients need to be further explored.
SARS-CoV-2 in Kidney Transplant Patients: A Real-Life Experience
Authors: Pinchera Biagio , Spirito Lorenzo , Ferreri Lucia , Rocca Roberto La , Celentano Giuseppe , Buonomo Antonio Riccardo , Foggia Maria , Scotto Riccardo , Federico Stefano , Gentile Ivan , Carrano Rosa ,   “Federico II” COVID-19 Team
Published: June 2022

BackgroundThe COVID-19 pandemic has significantly impacted the management of solid organ transplant recipients and on clinical evolution in post-transplantation. Little is known on the impact of SARS-CoV-2 infection in these patients. The severity and lethality of this disease in solid organ transplant patients are higher thanin the general population. This study aims to describe clinical characteristics of SARS-CoV-2 infection in solid organ transplant recipients followed in our center.MethodsIn this observational study, we enrolled all kidney transplant recipientsattending the A.O.U. Federico II of Naples from March 2020 to January 2021. For each patient we evaluated the epidemiological and clinical characteristics as well as outcome.ResultsWe enrolled 369 kidney transplant patients (229, male, 62%). Of these, 51 (13.8%) acquired SARS-CoV-2 infection and 29 showed symptomatic disease. Of the 51 patients with the infection, 48 (94.11%) had at least one comorbidity and such comorbidities did not constitute a risk factor for a more severe disease. Hospitalization was necessary for 7 (13.7%) patients. Of these, 2 required low-flow oxygen supplementation, 3 non-invasive/high flow ventilation and 2 invasive ventilation. Finally, 2 patients died.ConclusionsOur study shows a lower mortality and hospitalization rate compared to figures available in the literature (4% vs. 13–30% and 14% vs. 32–100%, respectively). Furthermore, the comorbidities examined (hypertension, dyslipidemia, and diabetes) did not constitute a risk factor for a more severe disease condition in this patient category. Further studies with larger sample size are necessary to confirm these data.
Risk Factors for the Onset of Frozen Shoulder in Middle-Aged and Elderly Subjects Within 1 Year of Discharge From a Hospitalization That Involved Intravenous Infusion: A Prospective Cohort Study
Authors: Cao Wenping , Chen Jiangnan , Pu Jianfeng , Fan Yunwu , Cao Ye 
Published: June 2022

AimTo investigate the incidence of frozen shoulder and risk factors for the onset of frozen shoulder in middle-aged and elderly subjects within 1 year of discharge from a hospitalization that involved intravenous infusion in Zhangjiagang Second People's Hospital.MethodsA total of 1,900 subjects who were discharged from a hospitalization that involved intravenous infusion in the hospital between May 2020 and September 2020 met the inclusion criteria for this study: 950 subjects had a mean daily duration of intravenous infusion ≤ 2 h (low exposure) and 950 subjects had a mean daily duration of intravenous infusion ≥3 h (high exposure). Subjects were followed up by telephone at 6 months ± 1 week and 12 months ± 1 week after discharge the incidence of frozen shoulder.ResultsThe cumulative incidence rate of frozen shoulder within 1 year of discharge was 5.2%. Multivariate logistic regression analysis revealed the risk of frozen shoulder was higher in subjects with a mean daily duration of intravenous infusion ≥3 h compared to ≤ 2 h (OR = 3.082, 95% CI 1.919–4.949, P &lt; 0.001); subjects hospitalized for 11–30 days had a higher risk of frozen shoulder compared to those hospitalized for 10 days or less (OR = 6.836, 95%CI 4.363–10.709, P &lt; 0.001); subjects who were overweight/ obese (BMI ≥ 25 kg/m2) had a higher risk of frozen shoulder compared to those of normal weight (BMI 18.5–24.9 kg/m2) (OR = 2.166, 95%CI 1.376–3.410, P = 0.001); subjects in the 56–70-year-old age group had a higher risk of developing frozen shoulder compared to those in the 40–55-year-old age group (OR = 1.977, 95%CI 1.154–3.387, P = 0.013); diabetes increased the risk of frozen shoulder (OR = 3.009, 95%CI 1.826–4.959, P &lt; 0.001). The 71–85 years old age group and hypertension were statistically significant in univariate analysis but not in multivariate analysis (P &gt; 0.05).ConclusionCompared with middle-aged and elderly in the general population, middle-aged and elderly subjects who received intravenous infusion during a hospitalization had a higher cumulative incidence rate of frozen shoulder within 1 year after discharge. Independent risk factors for the onset of frozen shoulder included mean daily duration of intravenous infusion ≥3 h, length of hospital stay 11–30 days, BMI ≥ 25 kg/m2, age 56–70 years, and diabetes.
Identifying Distinct Risk Thresholds of Glycated Hemoglobin and Systolic Blood Pressure for Rapid Albuminuria Progression in Type 2 Diabetes From NHANES (1999–2018)
Authors: Xu Jiahui , Xue Yan , Chen Qingguang , Han Xu , Cai Mengjie , Tian Jing , Jin Shenyi , Lu Hao 
Published: June 2022

BackgroundIt is widely recognized that glycated hemoglobin (HbA1c) and systolic blood pressure (SBP) are two key risk factors for albuminuria and renal function impairment in patients with type 2 diabetes mellitus (T2DM). Our study aimed to identify the specific numerical relationship of albumin/creatinine ratio (ACR) with HbA1c and SBP among a large population of adults with T2DM.MethodA total of 8,626 patients with T2DM were included in the data analysis from the National Health and Nutrition Examination Surveys (NHANES) (1999-2018). The multiple linear regressions were used to examine the associations of ACR with HbA1c and SBP. Generalized additive models with smooth functions were performed to identify the non-linear relations between variables and interactions were also tested.ResultsSignificantly threshold effects were observed between ACR and HbA1c or SBP after multivariable adjustment, with the risk threshold values HbA1c = 6.4% and SBP = 127 mmHg, respectively. Once above thresholds were exceeded, the lnACR increased dramatically with higher levels of HbA1c (β = 0.23, 95 CI%:0.14, 0.32, P &lt; 0.001) and SBP (β = 0.03, 95 CI%:0.03, 0.04, P &lt; 0.001). Subgroup analysis showed high protein diet was related to higher ACR. In addition, a higher risk of ACR progression was observed in central obesity participants with HbA1C ≥ 6.4% or hyperuricemia participants with SBP ≥ 127 mmHg among patients withT2DM.ConclusionWe identified thresholds of HbA1c and SBP to stratify patients with T2DM through rapid albuminuria progression. These might provide a clinical reference value for preventing and controlling diabetes kidney disease.
Presenting Patterns of Genetically Determined Developmental Encephalopathies With Epilepsy and Movement Disorders: A Single Tertiary Center Retrospective Cohort Study
Authors: Mastrangelo Mario , Galosi Serena , Cesario Serena , Renzi Alessia , Campea Lucilla , Leuzzi Vincenzo 
Published: June 2022

BackgroundThis paper aimed to evaluate the frequency of observation of genetically determined developmental encephalopathies with epilepsy and movement disorders in a specialistic center, the distribution of etiologies and presenting clinical hallmarks, and the mean times for the achievement of molecular genetic diagnosis.Patients and MethodsRetrospective data about clinical phenotypes, etiology, and diagnostic pathways were collected in all the genetically confirmed patients with developmental encephalopathies with epilepsy and movement disorders referred to our institution between 2010 and 2020. The cohort was divided into two groups according to the predominant movement disorder type: 1) Group A: patients with hyperkinetic movement disorders; 2) Group B: patients with hypokinetic movement disorders. Both groups were analyzed in terms of developmental, epileptic, and movement disorder phenotypes.ResultsThe cohort included 69 patients (Group A = 53; Group B = 16). The etiological spectrum was heterogeneous with a predominance of Rett and Angelman syndrome in Group A and neurodegenerative disorders in Group B. A moderate/severe intellectual disability was assessed in 58/69 patients (mean age at the first signs of developmental impairment = 1,87 ± 1,72 years). Group A included patients with an earlier onset of epileptic seizures (2,63 ± 3,15 vs. 4,45 ± 5,55 years of group B) and a predominant generalized motor semiology of seizures at the onset. Focal seizures were the main initial epileptic manifestations in Group B. Seizures were noticed earlier than movement disorders in Group A while the opposite occurred in Group B. A higher increase in molecular genetic diagnosis was obtained in the last five years. Mean diagnostic delay was longer in Group B than in Group A (12,26 ± 13,32 vs. 5.66 ± 6.41 years). Chorea as an initial movement disorder was associated with a significantly longer diagnostic delay and a higher age at etiological diagnosis.ConclusionsThis study suggested: (a) a higher frequency of genetic defects involving neurotransmission, neuronal excitability, or neural development in patients with hyperkinetic movement disorders; (b) a higher frequency of neurodegenerative courses and a longer diagnostic delay in patients with hypokinetic movement disorders.