bluuebunny/crossref_metadata_2025_split huggingface dataset:
Off-the-Shelf Partial HLA Matching SARS-CoV-2 Antigen Specific T Cell Therapy: A New Possibility for COVID-19 Treatment
Authors: Kim Nayoun , Lee Jong-Min , Oh Eun-Jee , Jekarl Dong Wook , Lee Dong-Gun , Im Keon-Il , Cho Seok-Goo 
Published: December 2021

BackgroundImmunological characteristics of COVID-19 show pathological hyperinflammation associated with lymphopenia and dysfunctional T cell responses. These features provide a rationale for restoring functional T cell immunity in COVID-19 patients by adoptive transfer of SARS-CoV-2 specific T cells.MethodsTo generate SARS-CoV-2 specific T cells, we isolated peripheral blood mononuclear cells from 7 COVID-19 recovered and 13 unexposed donors. Consequently, we stimulated cells with SARS-CoV-2 peptide mixtures covering spike, membrane and nucleocapsid proteins. Then, we culture expanded cells with IL-2 for 21 days. We assessed immunophenotypes, cytokine profiles, antigen specificity of the final cell products.ResultsOur results show that SARS-CoV-2 specific T cells could be expanded in both COVID-19 recovered and unexposed groups. Immunophenotypes were similar in both groups showing CD4+ T cell dominance, but CD8+ and CD3+CD56+ T cells were also present. Antigen specificity was determined by ELISPOT, intracellular cytokine assay, and cytotoxicity assays. One out of 14 individuals who were previously unexposed to SARS-CoV-2 failed to show antigen specificity. Moreover, ex-vivo expanded SARS-CoV-2 specific T cells mainly consisted of central and effector memory subsets with reduced alloreactivity against HLA-unmatched cells suggesting the possibility for the development of third-party partial HLA-matching products.DiscussionIn conclusion, our findings show that SARS-CoV-2 specific T cell can be readily expanded from both COVID-19 and unexposed individuals and can therefore be manufactured as a biopharmaceutical product to treat severe COVID-19 patients.One Sentence SummaryEx-vivo expanded SARS-CoV-2 antigen specific T cells developed as third-party partial HLA-matching products may be a promising approach for treating severe COVID-19 patients that do not respond to previous treatment options.
SARS-CoV-2-Encoded MiRNAs Inhibit Host Type I Interferon Pathway and Mediate Allelic Differential Expression of Susceptible Gene
Authors: Zhu Youwei , Zhang Zhaoyang , Song Jia , Qian Weizhou , Gu Xiangqian , Yang Chaoyong , Shen Nan , Xue Feng , Tang Yuanjia 
Published: December 2021

Infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the rapid spread of coronavirus disease 2019 (COVID-19), has generated a public health crisis worldwide. The molecular mechanisms of SARS-CoV-2 infection and virus–host interactions are still unclear. In this study, we identified four unique microRNA-like small RNAs encoded by SARS-CoV-2. SCV2-miR-ORF1ab-1-3p and SCV2-miR-ORF1ab-2-5p play an important role in evasion of type I interferon response through targeting several genes in type I interferon signaling pathway. Particularly worth mentioning is that highly expressed SCV2-miR-ORF1ab-2-5p inhibits some key genes in the host innate immune response, such as IRF7, IRF9, STAT2, OAS1, and OAS2. SCV2-miR-ORF1ab-2-5p has also been found to mediate allelic differential expression of COVID-19-susceptible gene OAS1. In conclusion, these results suggest that SARS-CoV-2 uses its miRNAs to evade the type I interferon response and links the functional viral sequence to the susceptible genetic background of the host.
Response and Duration of Serum Anti-SARS-CoV-2 Antibodies After Inactivated Vaccination Within 160 Days
Authors: Xu Qiu-Yan , Xue Jian-Hang , Xiao Yao , Jia Zhi-Juan , Wu Meng-Juan , Liu Yan-Yun , Li Wei-Li , Liang Xian-Ming , Yang Tian-Ci 
Published: December 2021

BackgroundA vaccine against coronavirus disease 2019 (COVID-19) with highly effective protection is urgently needed. The anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response and duration after vaccination are crucial predictive indicators.ObjectivesTo evaluate the response and duration for 5 subsets of anti-SARS-CoV-2 antibodies after vaccination and their predictive value for protection.MethodsWe determined the response and duration for 5 subsets of anti-SARS-CoV-2 antibodies (neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA) in 61 volunteers within 160 days after the CoronaVac vaccine. A logistic regression model was used to determine the predictors of the persistence of neutralizing antibody persistence.ResultsThe seropositivity rates of neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA were only 4.92%, 27.87%, 21.31%, 3.28% and 0.00%, respectively, at the end of the first dose (28 days). After the second dose, the seropositivity rates reached peaks of 95.08%, 100.00%, 100.00%, 59.02% and 31.15% in two weeks (42 days). Their decay was obvious and the seropositivity rate remained at 19.67%, 54.10%, 50.82%, 3.28% and 0.00% on day 160, respectively. The level of neutralizing antibody reached a peak of 149.40 (101.00–244.60) IU/mL two weeks after the second dose (42 days) and dropped to 14.23 (7.62–30.73) IU/mL at 160 days, with a half-life of 35.61(95% CI, 32.68 to 39.12) days. Younger participants (≤31 years) had 6.179 times more persistent neutralizing antibodies than older participants (&gt;31 years) (P&lt;0.05). Participants with anti-Spike IgA seropositivity had 4.314 times greater persistence of neutralizing antibodies than participants without anti-Spike IgA seroconversion (P&lt;0.05).ConclusionsAntibody response for the CoronaVac vaccine was intense and comprehensive with 95.08% neutralizing seropositivity rate, while decay was also obvious after 160 days. Therefore, booster doses should be considered in the vaccine strategies.
Inflammatory Cell Composition and Immune-Related microRNA Signature of Temporal Artery Biopsies From Patients With Giant Cell Arteritis
Authors: Bolha Luka , Hočevar Alojzija , Suljič Alen , Jurčić Vesna 
Published: December 2021

ObjectivesThe aim of this study was to quantitatively assess distinct immune cell subsets comprising inflammatory infiltrate in temporal artery biopsies (TABs) from patients with giant cell arteritis (GCA), and to link the obtained histopathological data with expression profiles of immune-related microRNAs (miRNAs).MethodsThe study included 68 formalin-fixed, paraffin-embedded TABs from treatment-naïve patients, including 30 histologically positive GCA and 16 negative GCA TABs, and 22 control non-GCA TABs. Quantitative assessment of histological parameters was performed using histopathological and immunohistochemical techniques. miRNA expression analysis was performed by quantitative real-time PCR.ResultsIntense transmural mononuclear inflammatory infiltrates in TAB-positive GCA arteries were predominantly composed of CD3+, CD4+ and CD8+ T lymphocytes, and CD68+ macrophages, accompanied by a strong nuclear overexpression of the nuclear factor of activated T cells, cytoplasmic 1 (NFATC) in the lymphocyte infiltrate fraction. Furthermore, TAB-positive GCA arteries were characterized by significant overexpression of nine pro-inflammatory miRNAs (miR-132-3p/-142-3p/-142-5p/-155-5p/-210-3p/-212-3p/-326/-342-5p/-511-5p) and a significant under-expression of six regulatory immune-related miRNAs (miR-30a-5p/-30b-5p/-30c-5p/-30d-5p/-30e-5p/-124-3p), whose expression levels significantly associated with most evaluated histopathological parameters. Notably, we revealed miR-132-3p/-142-3p/-142-5p/-155-5p/-212-3p/-511-5p as major promoters of arterial inflammation and miR-30a-5p/-30c-5p/-30d-5p as putative regulators of NFATC signaling in TAB-positive GCA arteries.ConclusionOverall, we demonstrated that an altered arterial tissue-specific pro-inflammatory miRNA signature favors enhanced T cell-driven inflammation and macrophage activity in TAB-positive GCA arteries. Moreover, dysregulation of several immune-related miRNAs seems to contribute crucially to GCA pathogenesis, through impairing their regulatory activity towards T cell-mediated immune responses driven by the calcineurin (CaN)/NFAT signaling pathway, indicating their therapeutic, diagnostic and prognostic potential.
Using Nomograms to Predict the PPCs of Patients With Diffuse Peritonitis Undergoing Emergency Gastrointestinal Surgery
Authors: Xue Qiong , Zhu Yu , Wang Ying , Yang Jian-Jun , Zhou Cheng-Mao 
Published: December 2021

Objective: To develop and validate a nomogram model for predicting postoperative pulmonary complications (PPCs) in patients with diffuse peritonitis undergoing emergency gastrointestinal surgery.Methods: We used the least absolute shrinkage and selection operator (LASSO) regression model to analyze the independent risk factors for PPCs in patients with diffuse peritonitis who underwent emergency gastrointestinal surgery. Using R, we developed and validated a nomogram model for predicting PPCs in patients with diffuse peritonitis undergoing emergency gastrointestinal surgery.Results: The LASSO regression analysis showed that AGE, American Society of Anesthesiologists physical status classification (ASA), DIAGNOSIS, platelets (on the 3rd day after surgery), cholesterol (on the 3rd day after surgery), ALBUMIN (on the first day after surgery), and preoperative ALBUMIN were independent risk factors for PPCs in patients with diffuse peritonitis undergoing emergency gastrointestinal surgery. The area under the curve (AUC) value of the nomogram model in the training group was 0.8240; its accuracy was 0.7000, and its sensitivity was 0.8658. This demonstrates that the nomogram has a high prediction value. Also in the test group, the AUC value of the model established by the variables AGE, ASA, and platelets (on the 3rd day after surgery), cholesterol (on the 3rd day after surgery), ALBUMIN (on the first day after surgery), and preoperative ALBUMIN was 0.8240; its accuracy was 0.8000; and its specificity was 0.8986. In the validation group, the same results were obtained. The results of the clinical decision curve show that the benefit rate was also high.Conclusion: Based on the risk factors AGE, ASA, DIAGNOSIS, platelets (on the 3rd day after surgery), cholesterol (on the 3rd day after surgery), ALBUMIN (on the first day after surgery), and preoperative ALBUMIN, the nomogram model established in this study for predicting PPCs in patients with diffuse peritonitis undergoing emergency gastrointestinal surgery has high accuracy and discrimination.
Effect of Temperature and Cell Viability on Uranium Biomineralization by the Uranium Mine Isolate Penicillium simplicissimum
Authors: Schaefer Sebastian , Steudtner Robin , Hübner René , Krawczyk-Bärsch Evelyn , Merroun Mohamed L. 
Published: December 2021

The remediation of heavy-metal-contaminated sites represents a serious environmental problem worldwide. Currently, cost- and time-intensive chemical treatments are usually performed. Bioremediation by heavy-metal-tolerant microorganisms is considered a more eco-friendly and comparatively cheap alternative. The fungus Penicillium simplicissimum KS1, isolated from the flooding water of a former uranium (U) mine in Germany, shows promising U bioremediation potential mainly through biomineralization. The adaption of P. simplicissimum KS1 to heavy-metal-contaminated sites is indicated by an increased U removal capacity of up to 550 mg U per g dry biomass, compared to the non-heavy-metal-exposed P. simplicissimum reference strain DSM 62867 (200 mg U per g dry biomass). In addition, the effect of temperature and cell viability of P. simplicissimum KS1 on U biomineralization was investigated. While viable cells at 30°C removed U mainly extracellularly via metabolism-dependent biomineralization, a decrease in temperature to 4°C or use of dead-autoclaved cells at 30°C revealed increased occurrence of passive biosorption and bioaccumulation, as confirmed by scanning transmission electron microscopy. The precipitated U species were assigned to uranyl phosphates with a structure similar to that of autunite, via cryo-time-resolved laser fluorescence spectroscopy. The major involvement of phosphates in U precipitation by P. simplicissimum KS1 was additionally supported by the observation of increased phosphatase activity for viable cells at 30°C. Furthermore, viable cells actively secreted small molecules, most likely phosphorylated amino acids, which interacted with U in the supernatant and were not detected in experiments with dead-autoclaved cells. Our study provides new insights into the influence of temperature and cell viability on U phosphate biomineralization by fungi, and furthermore highlight the potential use of P. simplicissimum KS1 particularly for U bioremediation purposes.Graphical Abstract
Preliminary Application of a Quantitative Collateral Assessment Method in Acute Ischemic Stroke Patients With Endovascular Treatments: A Single-Center Study
Authors: Cao Ruoyao , Qi Peng , Jiang Yun , Hu Shen , Ye Gengfan , Zhu Yaxin , Li Ling , You Zilong , Chen Juan 
Published: December 2021

Objectives: To develop an efficient and quantitative assessment of collateral circulation on time maximum intensity projection CT angiography (tMIP CTA) in patients with acute ischemic stroke (AIS).Methods: Eighty-one AIS patients who underwent one-stop CTA-CT perfusion (CTP) from February 2016 to October 2020 were retrospectively reviewed. Single-phase CTA (sCTA) and tMIP CTA were developed from CTP data. Ischemic core (IC) volume, ischemic penumbra volume, and mismatch ratio were calculated. The Tan scale was used for the qualitative evaluation of collateral based on sCTA and tMIP CTA. Quantitative collateral circulation (CCq) parameters were calculated semi-automatically with software by the ratio of the vascular volume (V) on both hemispheres, including tMIP CTA VCCq and sCTA VCCq. Spearman correlation analysis was used to analyze the correlation of collateral-related parameters with final infarct volume (FIV). ROC and multivariable regression analysis were calculated to compare the significance of the above parameters in clinical outcome evaluation. The analysis time of the observers was also compared.Results: tMIP CTA VCCq (r = 0.61, p &lt; 0.01), IC volume (r = 0.66, p &lt; 0.01), Tan score on tMIP CTA (r = 0.52, p &lt; 0.01) and mismatch ratio (r = 0.60, p &lt; 0.01) showed moderate negative correlations with FIV. tMIP CTA VCCq showed the best prognostic value for clinical outcome (AUC = 0.93, p &lt; 0.001), and was an independent predictive factor of clinical outcome (OR = 0.14, p = 0.009). There was no difference in analysis time of tMIP CTA VCCq among observers (p = 0.079).Conclusion: The quantitative evaluation of collateral circulation on tMIP CTA is associated with clinical outcomes in AIS patients with endovascular treatments.
Association Between 18-FDG Positron Emission Tomography and MRI Biomarkers of Plaque Vulnerability in Patients With Symptomatic Carotid Stenosis
Authors: Giannotti Nicola , McNulty Jonathan , Foley Shane , McCabe John , Barry Marey , Crowe Morgan , Dolan Eamon , Harbison Joseph , Horgan Gillian , Kavanagh Eoin , O'Connell Martin , Marnane Michael , Murphy Sean , Donnell Ciaran Mc , O'Donohoe Martin , Williams David , Kelly Peter J. 
Published: December 2021

Purpose: Pathologic studies suggest that unstable plaque morphology and inflammation are associated with cerebrovascular events. 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) is a validated technique for non-invasive imaging of inflammation-related plaque metabolism, and MRI can identify morphologic features of plaque instability. The aim of this study was to investigate the association of selected imaging characteristics of plaque vulnerability measured with MRI and PET in patients with symptomatic carotid stenosis.Methods: Patients from the BIOVASC study were selected based on the following inclusion criteria: (1) age ≥ 50 years; (2) recent (&lt;30 days) ischaemic stroke (modified Rankin scale ≤3) or motor/speech/vision TIA; (3) ipsilateral internal carotid artery stenosis (≥5 0% lumen-narrowing); (4) carotid PET/CTA and MRI completed. Semi-automated plaque analysis of MRI images was performed to quantify morphologic features of plaque instability. PET images were co-registered with CTA and inflammation-related metabolism expressed as maximum standardised uptake value (SUVmax).Results: Twenty-five patients met inclusion criteria (72% men, mean age 65 years). MRI-measured plaque volume was greater in men (1,708–1,286 mm3, p = 0.03), patients who qualified with stroke (1,856–1,440 mm3, p = 0.05), and non-statin users (1,325–1,797 mm3, p = 0.03). SUVmax was associated with MRI-measured plaque lipid-rich necrotic core (LRNC) in the corresponding axial slice (rs = 0.64, p &lt; 0.001) and was inversely associated with whole-plaque fibrous cap thickness (rs = −0.4, p = 0.02) and calcium volume (rs = −0.4, p = 0.03).Conclusion: This study demonstrated novel correlations of non-invasive imaging biomarkers of inflammation-related plaque metabolism with morphological MRI markers of plaque instability. If replicated, our findings may support the application of combined MRI and PET to detect vulnerable plaque in future clinical practise and randomised trials.
Heart Rate Variability and Recurrent Stroke and Myocardial Infarction in Patients With Acute Mild to Moderate Stroke
Authors: von Rennenberg Regina , Krause Thomas , Herm Juliane , Hellwig Simon , Scheitz Jan F. , Endres Matthias , Haeusler Karl Georg , Nolte Christian H. 
Published: December 2021

Objectives: In patients with acute ischemic stroke, reduced heart rate variability (HRV) may indicate poor outcome. We tested whether HRV in the acute phase of stroke is associated with higher rates of mortality, recurrent stroke, myocardial infarction (MI) or functional outcome.Materials and Methods: Patients with acute mild to moderate ischemic stroke without known atrial fibrillation were prospectively enrolled to the investigator-initiated Heart and Brain interfaces in Acute Ischemic Stroke (HEBRAS) study (NCT 02142413). HRV parameters were assessed during the in-hospital stay using a 10-min section of each patient's ECG recording at day- and nighttime, calculating time and frequency domain HRV parameters. Frequency of a combined endpoint of recurrent stroke, MI or death of any cause and the respective individual events were assessed 12 months after the index stroke. Patients' functional outcome was measured by the modified Rankin Scale (mRS) at 12 months.Results: We included 308 patients (37% female, median NIHSS = 2 on admission, median age 69 years). Complete follow-up was achieved in 286/308 (93%) patients. At 12 months, 32 (9.5%), 5 (1.7%) and 13 (3.7%) patients had suffered a recurrent stroke, MI or death, respectively. After adjustment for age, sex, stroke severity and vascular risk factors, there was no significant association between HRV and recurrent stroke, MI, death or the combined endpoint. We did not find a significant impact of HRV on a mRS ≥ 2 12 months after the index stroke.Conclusion: HRV did not predict recurrent vascular events in patients with acute mild to moderate ischemic stroke.
Interdisciplinary Surgical Treatments and Long-Term Outcomes of Lumbar Spinal Tumors With Retroperitoneal Involvements: A Retrospective Case Series Study
Authors: He Shaohui , Bi Yifeng , Ye Chen , Peng Dongyu , Xiao Jianru , Wei Haifeng 
Published: December 2021

PurposeSurgical treatments are technically challenging for lumbar spinal tumor (LST) with extensive retroperitoneal involvements. Our study aimed to report the experience and outcomes concerning interdisciplinary surgical collaborations in managing such LSTs.Patients and MethodsNine patients underwent interdisciplinary surgical treatments which were performed by specialists, namely, spinal, vascular, and urinary surgeries. Data on clinical characteristics were collected, and the Visual Analogue Scale (VAS) and the Japanese Orthopaedic Association Score (JOAS) were used in the evaluation before and after surgery. The postoperative complications and the long-term outcomes were reported as well.ResultsThe interdisciplinary work included double J catheter indwelling (n = 9), nephrostomy (n = 5), replacement of the common iliac vein (n = 2), abdominal aorta repair (n = 3), and vital vessel repair (n = 8). The early-stage complications included complaints of moderate low back pain and slight implant shift (n = 1, 11.1%) and tardive ureterodialysis (n = 1, 11.1%). The 3- and 5-year disease-free survival rates were 76.2 ± 14.8 and 50.8 ± 23.0%, respectively, during the mean follow-up of 34.6 ± 17.9 months (range, 9.5–68.7). Besides this, more blood loss was associated with recurrent and metastatic tumor status (p = 0.043) and surgery time &gt;5 h (p = 0.023). Remarkable pain relief and favorable quality of life were achieved based on the postoperative VAS (3.3 ± 0.9, p &lt; 0.001) and JOAS (16.6 ± 0.5, p &lt; 0.001).ConclusionsThe treatments of LSTs with wide-range retroperitoneal involvements require interdisciplinary surgical collaborations to lower the risks and improve the long-term outcomes. High-quality prospective cohort studies with large samples are warranted to establish general surgical protocols in managing LSTs with extensive retroperitoneal involvements.
Prognostic Role of Soluble Programmed Death Ligand 1 in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Liao Guixiang , Zhao Zhihong , Qian Yuting , Ling Xiean , Chen Shanyi , Li Xianming , Kong Feng-Ming (Spring) 
Published: December 2021

ObjectiveThe objective of this study was to explore whether soluble programmed death ligand 1 (sPD-L1) is a potential prognostic biomarker in patients with non-small cell lung cancer (NSCLC).MethodsA comprehensive search of electronic databases was carried out. Original studies with inclusion of sPD-L1, progression-free survival, and overall survival in NSCLC were eligible. The primary endpoints were overall survival and progression-free survival. Hazard ratios (HRs) and 95% confidence intervals (CIs) were applied for data analysis.ResultsEight studies involving 710 patients with NSCLC were included in the analysis. A pooled data analysis revealed that high levels of sPD-L1 were correlated with poorer overall survival (HR = 2.34; 95% CI = 1.82–3.00; P &lt; 0.001) and progression-free survival (HR = 2.35; 95% CI = 1.62–3.40, P &lt; 0.001). A subgroup analysis revealed that high levels of sPD-L1 were correlated with poor overall survival in patients treated with immunotherapy (HR = 2.40; 95% CI = 1.79–3.22; P &lt; 0.001).ConclusionThis pooled analysis of published data suggests that sPD-L1 may serve as a readily available biomarker for survival in NSCLC patients treated with ICI based treatment. Prospective studies with well-designed standard assessment methods should be conducted to validate the prognostic role of sPD-L1 in NSCLC.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021283177.