bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissecting Tumor Antigens and Immune Subtypes of Glioma to Develop mRNA Vaccine
Authors: Zhong Hua , Liu Shuai , Cao Fang , Zhao Yi , Zhou Jianguo , Tang Feng , Peng Zhaohua , Li Yangsheng , Xu Shen , Wang Chunlin , Yang Guohua , Li Zhi-Qiang 
Published: September 2021

BackgroundNowadays, researchers are leveraging the mRNA-based vaccine technology used to develop personalized immunotherapy for cancer. However, its application against glioma is still in its infancy. In this study, the applicable candidates were excavated for mRNA vaccine treatment in the perspective of immune regulation, and suitable glioma recipients with corresponding immune subtypes were further investigated.MethodsThe RNA-seq data and clinical information of 702 and 325 patients were recruited from TCGA and CGGA, separately. The genetic alteration profile was visualized and compared by cBioPortal. Then, we explored prognostic outcomes and immune correlations of the selected antigens to validate their clinical relevance. The prognostic index was measured via GEPIA2, and infiltration of antigen-presenting cells (APCs) was calculated and visualized by TIMER. Based on immune-related gene expression, immune subtypes of glioma were identified using consensus clustering analysis. Moreover, the immune landscape was visualized by graph learning-based dimensionality reduction analysis.ResultsFour glioma antigens, namely ANXA5, FKBP10, MSN, and PYGL, associated with superior prognoses and infiltration of APCs were selected. Three immune subtypes IS1–IS3 were identified, which fundamentally differed in molecular, cellular, and clinical signatures. Patients in subtypes IS2 and IS3 carried immunologically cold phenotypes, whereas those in IS1 carried immunologically hot phenotype. Particularly, patients in subtypes IS3 and IS2 demonstrated better outcomes than that in IS1. Expression profiles of immune checkpoints and immunogenic cell death (ICD) modulators showed a difference among IS1–IS3 tumors. Ultimately, the immune landscape of glioma elucidated considerable heterogeneity not only between individual patients but also within the same immune subtype.ConclusionsANXA5, FKBP10, MSN, and PYGL are identified as potential antigens for anti-glioma mRNA vaccine production, specifically for patients in immune subtypes 2 and 3. In summary, this study may shed new light on the promising approaches of immunotherapy, such as devising mRNA vaccination tailored to applicable glioma recipients.
Circulating Placental Vesicles Carry HLA-DR in Pre-Eclampsia: A New Potential Marker of the Syndrome
Authors: Tersigni Chiara , Lucchetti Donatella , Franco Rita , Colella Filomena , Neri Caterina , Crispino Laura , Sgambato Alessandro , Lanzone Antonio , Scambia Giovanni , Vatish Manu , Di Simone Nicoletta 
Published: September 2021

BackgroundPre-eclampsia (PE) is a common disorder of pregnancy that usually presents with hypertension and proteinuria. The clinical presentation arises from soluble factors released into the maternal circulation from the placenta owing to the stress of syncytiotrophoblast, consequence of defective placentation occurring in the first half of pregnancy. Reduced tolerance of the semiallogeneic fetus by the maternal immune system has been proposed as first trigger leading to poor placentation. We previously observed aberrant expression of human leukocyte antigen (HLA)-DR molecules in the syncytiotrophoblast of a subset of women with PE. Aim of this study was to investigate abnormal expression of circulating HLA-DR in syncytiotrophoblast-derived extracellular vesicles (STBEVs) in women with PE compared to normal pregnant women.Methodsperipheral venous blood was collected from 22 women with PE and 22 normal pregnant women. Circulating STBEVs were collected by ultra-centrifugation (120000 g) and analyzed for the expression of HLA-DR and placental alkaline phosphatase (PLAP), a specific marker of the placenta, by Western blot analysis and flow cytometry.Resultscirculating STBEVs positive for HLA-DR were observed in 64% of PE women while no HLA-DR positivity was detected in any of the controls (P&lt;0.01).ConclusionsAberrant expression of HLA-DR in circulating STBEVs is specifically associated to PE. Further studies are required: a) to define the role of aberrant placental expression of HLA-DR molecules in the pathogenesis of PE; b) evaluate a possible application of detecting circulating HLA-DR positive STBEVs in the diagnosis and prediction of PE in the first and second trimester of pregnancy.
The Potential Roles of Mucosa-Associated Invariant T Cells in the Pathogenesis of Gut Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation
Authors: Gao Meng-Ge , Hong Yan , Zhao Xiang-Yu , Pan Xin-An , Sun Yu-Qian , Kong Jun , Wang Zhi-Dong , Wang Feng-Rong , Wang Jing-Zhi , Yan Chen-Hua , Wang Yu , Huang Xiao-Jun , Zhao Xiao-Su 
Published: September 2021

Gut acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with high mortality. Mucosa-associated invariant T (MAIT) cells are a group of innate-like T cells enriched in the intestine that can be activated by riboflavin metabolites from various microorganisms. However, little is known about the function or mechanism of action of MAIT cells in the occurrence of gut aGVHD in humans. In our study, multiparameter flow cytometry (FCM) was used to evaluate the number of MAIT cells and functional cytokines. 16S V34 region amplicon sequencing analysis was used to analyze the intestinal flora of transplant patients. In vitro stimulation and coculture assays were used to study the activation and function of MAIT cells. The number and distribution of MAIT cells in intestinal tissues were analyzed by immunofluorescence technology. Our study showed that the number and frequency of MAIT cells in infused grafts in gut aGVHD patients were lower than those in no-gut aGVHD patients. Recipients with a high number of MAITs in infused grafts had a higher abundance of intestinal flora in the early posttransplantation period (+14 days). At the onset of gut aGVHD, the number of MAIT cells decreased in peripheral blood, and the activation marker CD69, chemokine receptors CXCR3 and CXCR4, and transcription factors Rorγt and T-bet tended to increase. Furthermore, when gut aGVHD occurred, the proportion of MAIT17 was higher than that of MAIT1. The abundance of intestinal flora with non-riboflavin metabolic pathways tended to increase in gut aGVHD patients. MAIT cells secreted more granzyme B, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ under the interleukin (IL)-12/IL-18 stimulation [non-T-cell receptor (TCR) signal] and secreted most of the IL-17 under the cluster of differentiation (CD)3/CD28 stimulation (TCR signal). MAIT cells inhibited the proliferation of CD4+ T cells in vitro. In conclusion, the lower number of MAIT cells in infused grafts was related to the higher incidence of gut aGVHD, and the number of MAIT cells in grafts may affect the composition of the intestinal flora of recipients early after transplantation. The flora of the riboflavin metabolism pathway activated MAIT cells and promoted the expression of intestinal protective factors to affect the occurrence of gut aGVHD in humans.
Non-Coding RNAs in Human Breast Milk: A Systematic Review
Authors: Tingö Lina , Ahlberg Emelie , Johansson Lovisa , Pedersen Sindre Andre , Chawla Konika , Sætrom Pål , Cione Erika , Simpson Melanie Rae 
Published: September 2021

Breast milk is the primary source of nutrition and hydration for the newborn infant but also plays an important role in the child’s first immune defense. Additionally, several breast milk factors have been implicated in immune-related health outcomes later in life, including immunoglobulins, cytokines, chemokines, growth factors and, more recently, non-coding RNA (ncRNA) species. In this systematic review, we provide a comprehensive summary of the current literature on endogenous ncRNAs found in human breast milk. Thirty (30) relevant studies were identified and, whilst the majority studies focused on microRNAs (miRNAs), there is evidence that breast milk contains high quantities of RNA which also include long-coding RNAs, circular RNAs, as well as other short RNAs and fragmented tRNA and rRNAs. Among studies investigating miRNAs, miR-148a-3p, miR-30a/d-5p, miR-22-3p, miR-146b-5p, miR-200a/c-3p, and the 5p end of the let-7 miRNAs were commonly reported among the top 10 miRNAs in the cell, lipid, and skim milk fractions of breast milk. Methodological difference and small sample sizes limit the possibility of conclusively identifying which maternal and infant characteristics affect the miRNA profile. The highly expressed miRNAs were generally reported to be similar across lactational stage, milk fraction, maternal and infant characteristics, or infant growth and health. All the same, individual studies identify potential differences in miRNA expression levels which should be confirmed by future studies. Stability, uptake, and physiological functions of miRNAs were also considered in several studies. Breast milk miRNAs are relatively resistant to a range of harsh conditions and uptake experiments suggest that extracellular vesicles containing miRNAs and circular RNAs can be taken up by intestinal epithelial cells. Although the evidence regarding the functional effect of breast milk miRNAs is limited, the predicted functions range from metabolic and biosynthetic processes to signaling pathways, cellular adhesion, communication, growth, and differentiation. Finally, this systematic review highlights some of the methodological challenges and knowledge gaps which can help direct future research in this field. In particular, it is important to further investigate the bioavailability of miRNAs in different milk fractions, and to characterize other ncRNAs which are largely unstudied.Systematic Review RegistrationPROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=138989, identifier CRD42020138989.
Chronic Diseases as a Predictor for Severity and Mortality of COVID-19: A Systematic Review With Cumulative Meta-Analysis
Authors: Geng JinSong , Yu XiaoLan , Bao HaiNi , Feng Zhe , Yuan XiaoYu , Zhang JiaYing , Chen XiaoWei , Chen YaLan , Li ChengLong , Yu Hao 
Published: September 2021

Introduction: Given the ongoing coronavirus disease 2019 (COVID-19) pandemic and the consequent global healthcare crisis, there is an urgent need to better understand risk factors for symptom deterioration and mortality among patients with COVID-19. This systematic review aimed to meet the need by determining the predictive value of chronic diseases for COVID-19 severity and mortality.Methods: We searched PubMed, Embase, Web of Science, and Cumulative Index to Nursing and Allied Health Complete to identify studies published between December 1, 2019, and December 31, 2020. Two hundred and seventeen observational studies from 26 countries involving 624,986 patients were included. We assessed the risk of bias of the included studies and performed a cumulative meta-analysis.Results: We found that among COVID-19 patients, hypertension was a very common condition and was associated with higher severity, intensive care unit (ICU) admission, acute respiratory distress syndrome, and mortality. Chronic obstructive pulmonary disease was the strongest predictor for COVID-19 severity, admission to ICU, and mortality, while asthma was associated with a reduced risk of COVID-19 mortality. Patients with obesity were at a higher risk of experiencing severe symptoms of COVID-19 rather than mortality. Patients with cerebrovascular disease, chronic liver disease, chronic renal disease, or cancer were more likely to become severe COVID-19 cases and had a greater probability of mortality.Conclusions: COVID-19 patients with chronic diseases were more likely to experience severe symptoms and ICU admission and faced a higher risk of mortality. Aggressive strategies to combat the COVID-19 pandemic should target patients with chronic diseases as a priority.
The Effect of Oxycodone on Post-operative Pain and Inflammatory Cytokine Release in Elderly Patients Undergoing Laparoscopic Gastrectomy
Authors: Lao Wei-long , Song Qi-liang , Jiang Zong-ming , Chen Wen-di , Zheng Xian-he , Chen Zhong-hua 
Published: September 2021

Background: To evaluate the effect of oxycodone on post-operative pain and inflammation in elderly patients undergoing laparoscopic gastrectomy.Methods: Sixty patients who were of both sexes, American Society of Anesthesiologists Physical Status (ASA-PS) Class I or II, over 65 years of age and undergoing an elective laparoscopic radical gastrectomy were randomly divided into two groups: an oxycodone group (Group O) including 20 males and 10 females and a sufentanil group (Group S) including 21 males and 9 females. The post-operative analgesia regimen was as follows: 40 mg of parecoxib sodium and 0.1 mg/kg of oxycodone was intravenously injected into Group O before the abdomen closure, while 40 mg of parecoxib sodium and 0.1 μg/kg of sufentanil was injected intravenously into Group S. Both groups were infiltrated with 20 ml of 1% ropivacaine at the end of the operation. The level of serum IL-6 and IL-10 were assayed immediately at the following timepoints: at the conclusion of surgery (T1), 1 h (T2), 6 h (T3), and 24 h (T4) after the completion of the surgery. The numerical rating scale (NRS), the Ramsay sedation score, analgesic-related adverse events, post-operative pulmonary inflammation events and the post-operative stay were recorded.Results: Compared with Group S, the serum IL-6 concentrations of Group O decreased at T3 and T4, while the serum IL-10 concentrations increased (P &lt; 0.05). In Group O, the serum IL-6 concentrations at T3 and T4 were lower than those at T1 (P &lt; 0.05). The incidence of post-operative nausea and vomiting (PONV) and pulmonary inflammation in Group O was lower than that in Group S (P &lt; 0.05). At each time point, the NRS of visceral pain in Group O was lower than that in Group S. At 6 and 24 h after extubation, the NRS of incision pain in Group O was lower than that in Group S (P &lt; 0.05).Conclusion: Oxycodone can regulate the level of inflammatory cytokines and reduce post-operative inflammatory response.
Follow-Ups on Persistent Symptoms and Pulmonary Function Among Post-Acute COVID-19 Patients: A Systematic Review and Meta-Analysis
Authors: Long Qiuyue , Li Jiwei , Hu Xiaoyi , Bai Yangyuyan , Zheng Yali , Gao Zhancheng 
Published: September 2021

Objective:As the number of recovering COVID-19 patients increases worldwide, the persistence of symptoms and signs through the post-acute phase indicates an urgent need for prolonged follow-up care. To explore existing data about post-acute COVID-19 syndrome, this meta-analysis assesses the prevalence of persistent manifestations in multiple systems and abnormalities in lung function, as well as their related risks in patients with various severities.Methods:Articles about discharged COVID-19 patients (published from January 1, 2020 to February 23, 2021) were obtained by searching four databases. Cohort studies with follow-up periods &gt;1 month post-discharge or &gt;2 months post-admission were included.Results:A total of 4,478 COVID-19 patients from 16 cohort studies were included in this meta-analysis. Fatigue or weakness (47%) were the most prevalent physical effects of post-acute COVID-19 syndrome, while psychosocial (28%) symptoms were the most common manifestations among several systems. Abnormalities in lung function of recovering patients, i.e., DLCO &lt;80% (47%, 95% CI: 32–61%) persisted for long periods. Severe patients were more likely to present joint pain (OR 1.84, 95% CI: 1.11–3.04) and decreased lung functions compared with non-severe patients, with pooled ORs for abnormal TLC, FEV1, FVC, and DLCO of 3.05 (95% CI: 1.88–4.96), 2.72 (95% CI: 1.31–5.63), 2.52 (95% CI: 1.28–4.98), and 1.82 (95% CI: 1.32–2.50), respectively.Conclusions:Our research indicates that patients recovering from COVID-19 manifest long-term, multi-system symptoms, and the adverse effects on psychosocial health and lung functions were the most extensive and persistent. These findings together may facilitate much needed in-depth study of clinical treatments for long-term, post-acute phase symptoms that affect a great number of recovering COVID-19 patients.
Plasma Macrophage Migration Inhibitory Factor Predicts Graft Function Following Kidney Transplantation: A Prospective Cohort Study
Authors: Ye Yongrong , Han Fei , Ma Maolin , Sun Qipeng , Huang Zhengyu , Zheng Haofeng , Yang Zhe , Luo Zihuan , Liao Tao , Li Heng , Hong Liangqing , Na Ning , Sun Qiquan 
Published: September 2021

Background:Delayed graft function (DGF) is a common complication after kidney transplantation (KT) with a poor clinical outcome. There are no accurate biomarkers for the early prediction of DGF. Macrophage migration inhibitory factor (MIF) release during surgery plays a key role in protecting the kidney, and may be a potential biomarker for predicting post-transplant renal allograft recovery.Methods:Recipients who underwent KT between July 2020 and December 2020 were enrolled in the study. Plasma MIF levels were tested in recipients at different time points, and the correlation between plasma MIF and DGF in recipients was evaluated. This study was registered in the Chinese Clinical Trial Registry (ChiCTR2000035596).Results:Intraoperative MIF levels were different between immediate, slowed, and delayed graft function groups (7.26 vs. 6.49 and 5.59,P&lt; 0.001). Plasma MIF was an independent protective factor of DGF (odds ratio = 0.447, 95% confidence interval [CI] 0.264–0.754,P= 0.003). Combining plasma MIF level and donor terminal serum creatinine provided the best predictive power for DGF (0.872; 95%CI 0.795–0.949). Furthermore, plasma MIF was significantly associated with allograft function at 1-month post-transplant (R2= 0.42,P&lt; 0.001).Conclusion:Intraoperative MIF, as an independent protective factor for DGF, has excellent diagnostic performance for predicting DGF and is worthy of further exploration.
Pilates Reducing Falls Risk Factors in Healthy Older Adults: A Systematic Review and Meta-Analysis
Authors: da Silva Larissa Donatoni , Shiel Agnes , McIntosh Caroline 
Published: September 2021

Background: The main theme of this systematic review and meta-analysis is to synthesize the evidence of randomized controlled trial of evidence of Pilates intervention, in comparison to control groups and other forms of exercise, for falls prevention in healthy older adults.Methods: The following electronic databases were searched up to October 2020; EMBASE, Scopus, Google Scholar, MEDLINE (Ovid), Science Direct, Cochrane, and CINAHL. The recommendations of the Preferred Reporting Items of Systematic Reviews and Meta-Analyses were followed. A PICOS approach was adopted as a framework to formulate the research question and set the inclusion and exclusion criteria. Participants were healthy older adults, defined as older adults who have maintained functional ability, including participants of both genders, those with a falls history, non-fallers, and individuals who were considered to be sedentary or active. Randomized controlled trials studies, written in the English language, from the decade, were included if they focused on specific outcome measures to decrease falls risk; functional mobility, mobility, fear of falling, gait, and postural stability. The PEDro scale was used to assess risk of bias.Results: There were included 12 studies. In total, 702 healthy older adults' participants were included. Pilates showed an effect in mediolateral directions in comparison to control groups (MD = −1.77, 95% CI, −2.84 to −0.70, p = 0.001, heterogeneity: I2 = 3%), mobility (MD = 9.23, 95% CI, 5.74 to 12.73, p &lt; 0.00001, heterogeneity: I2 = 75%) and fear of falling (MD = −8.61, 95% CI, −10.16 to −7.07, p &lt; 0.00001, heterogeneity: I2 = 88%). In relation to other exercises group, Pilates showed positive effects in functional mobility (MD = −1.21, 95% CI, −2.30 to −0.11, p = 0.03, heterogeneity: I2 = 80%), mobility (MD = 3.25, 95% CI, 1.46 to 5.04, p &lt; 0.0004, heterogeneity: I2 = 0%). No evidence of an improvement was found between the groups for dynamic gait index (MD = 2.26, 95% CI, −0.05 to 4.56, p = 0.06, heterogeneity: I2 = 86%), anteroposterior directions of balance (MD = −1.58, 95% CI, −3.74 to −0.59, p = 0.15, heterogeneity: I2 = 51%) and functional mobility when compared to control groups (no exercise) (MD = −1.24, 95% CI, −2.48 to −0.00, p = 0.05, heterogeneity: I2 = 87%).Discussion: Pilates may be effective in decreasing the risk of falls in older adults. Pilates intervention was found to improve functional mobility, mobility, gait, fear of falling and postural stability and therefore there is some evidence to suggest that Pilates reduces certain risk factors for falls in healthy older adults. However, there is an absence of high-quality evidence in regards to the impact of Pilates on reducing falls and further robust RCTs are needed.Systematic Review Registration: [PROSPERO], identifier [CRD42021206134].
ROCK1 Mediates Retinal Glial Cell Migration Promoted by Acrolein
Authors: Fukutsu Kanae , Murata Miyuki , Kikuchi Kasumi , Yoshida Shiho , Noda Kousuke , Ishida Susumu 
Published: September 2021

Objective: Acrolein is a highly reactive aldehyde that covalently binds to cellular macromolecules and subsequently modulates cellular function. Our previous study demonstrated that acrolein induces glial cell migration, a pathological hallmark of diabetic retinopathy; however, the detailed cellular mechanism remains unclear. The purpose of this study was to investigate the role of acrolein in retinal glial cell migration by focusing on rho-associated coiled-coil-containing protein kinases (ROCKs).Methods: Immunofluorescence staining for ROCK isoforms was performed using sections of fibrovascular tissue obtained from the eyes of patients with proliferative diabetic retinopathy (PDR). Rat retinal Müller glial cell line, TR-MUL5, was stimulated with acrolein and the levels of ROCK1 were evaluated using real-time PCR and western blotting. Phosphorylation of the myosin-binding subunit of myosin light chain phosphatase [myosin phosphatase target subunit 1, (MYPT1)] and myosin light chain 2 (MLC2) was assessed. The cell migration rate of TR-MUL5 cells exposed to acrolein and/or ripasudil, a non-selective ROCK inhibitor, was measured using the Oris cell migration assay.Results: ROCK isoforms, ROCK1 and ROCK2, were positively stained in the cytosol of glial cells in fibrovascular tissues. In TR-MUL5 cells, the mRNA expression level of Rock1, but not Rock2, was increased following acrolein stimulation. In line with the PCR data, western blotting showed increase in ROCK1 and cleaved ROCK1 protein in TR-MUL5 cells stimulated with acrolein. N-acetylcysteine (NAC) suppressed acrolein-associated Rock1 upregulation in TR-MUL5 cells. Acrolein augmented the phosphorylation of MYPT1 and MLC2 and increased the cell migration rate of TR-MUL5 cells, both of which were abrogated by ripasudil.Conclusions: Our study demonstrated that ROCK1 mediates the migration of retinal glial cells promoted by the unsaturated aldehyde acrolein.