bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reperfusion Strategy of ST-Elevation Myocardial Infarction: A Meta-Analysis of Primary Percutaneous Coronary Intervention and Pharmaco-Invasive Therapy
Authors: Li Kaiyin , Zhang Bin , Zheng Bo , Zhang Yan , Huo Yong 
Published: March 2022

BackgroundPharmaco-invasive therapy (PIT), combining thrombolysis and percutaneous coronary intervention, was a potential complement for primary percutaneous coronary intervention (pPCI), while bleeding risk was still a concern.ObjectivesThis study aims to compare the efficacy and safety outcomes of PIT and pPCI.MethodsA systematic search for randomized controlled trials (RCTs) and observational studies were conducted on Pubmed, Embase, Cochrane library, and Scopus. RCTs and observational studies were all collected and respectively analyzed, and combined pooled analysis was also presented. The primary efficacy outcome was short-term all-cause mortality within 30 days, including in-hospital period. The primary safety outcome was 30-day trial-defined major bleeding events.ResultsA total of 26,597 patients from 5 RCTs and 12 observational studies were included. There was no significant difference in short-term mortality [RCTs: risk ratio (RR): 1.14, 95% CI: 0.67–1.93, I2 = 0%, p = 0.64; combined results: odds ratio (OR): 1.09, 95% CI: 0.93–1.29, I2 = 0%, p = 0.30] and 30-day major bleeding events (RCTs: RR: 0.44, 95% CI: 0.07–2.93, I2 = 0%, p = 0.39; combined results: OR: 1.01, 95% CI: 0.53–1.92, I2 = 0%, p = 0.98). However, pPCI reduced risk of in-hospital major bleeding events, stroke and intracranial bleeding, but increased risk of in-hospital heart failure and 30-day heart failure in combined analysis of RCTs and observational studies, despite no significant difference in analysis of RCTs.ConclusionPharmaco-invasive therapy could be an important complement for pPCI in real-world clinical practice under specific conditions, but studies aiming at optimizing thrombolysis and its combination of mandatory coronary angiography are also warranted.
Analysis of the Dose-Response Effects of Physical Activity on Cardiocerebrovascular and All-Cause Mortality in Hypertension
Authors: Xu Jun-Peng , Zeng Rui-Xiang , Lu Hai-Ning , Zhang Yu-Zhuo , Mai Xiao-Yi , Mao Shuai , Zhang Min-Zhou 
Published: March 2022

BackgroundLeisure-time moderate-to-vigorous physical activity (MV-PA) has been consistently regarded as a protective factor to prevent and treat hypertension. However, the effect of different levels of MV-PA against cardiocerebrovascular and all-cause mortality in hypertension is still unclear. The aim of this study was to explore the dose relationships of MV-PA on these adverse outcomes in hypertension.MethodsIn the National Health and Nutritional Examination Survey (NHANES) from 1999 to 2006, participants with hypertension were enrolled and classified into inactive (0 MET-h/week), low-active (0 &lt; to &lt; 7.5 MET-h/week), and high-active (≥ 7.5 MET-h/week) groups. A multivariate Cox regression analysis was conducted with a hazard ratio (HR) and corresponding 95% confidence interval (CI). To further explore the association between different levels of MV-PA and adverse outcomes, Kaplan-Meier survival curves, subgroup analysis, and restricted cubic spline curves were performed.ResultsDuring a median 10.93-year follow-up, 1,510 and 347 patients had died from any causes and cardiocerebrovascular, respectively. The high-active group had the highest event-free survivals of all outcomes compared with low-active and inactive groups. A multivariate Cox regression analysis demonstrated that the high-active and low-active groups were associated with reduced risks of all-cause [HR: 0.70, 95% CI: 0.60–0.82; 0.76 (0.68–0.86), respectively] and cardiocerebrovascular mortality [0.56 (0.41–0.77); 0.63 (0.50–0.81), respectively] compared with the inactive group. Subgroup analysis and restricted cubic spline curves showed that MV-PA surpassing 15 MET-h/week could decrease the risks of cardiovascular and all-cause mortality with inverse relationships, which was not the case for cerebrovascular mortality, indicating a U-shaped association.ConclusionOur study suggests that highly active MV-PA of 7.5 to &lt; 15 MET-h/week was associated with the lowest risks of cardiocerebrovascular and all-cause mortality in hypertension.
Vesiculation of Rhyolitic Melts Under Oscillatory Pressure
Authors: Seropian Gilles , Kennedy Ben M. , Kendrick Jackie E. , Lavallée Yan , Nichols Alexander R. L. , von Aulock Felix W. , Dingwell Donald B. , Hess Kai-Uwe , Lamur Anthony , Schauroth Jenny , Vasseur Jérémie , Wadsworth Fabian B. 
Published: March 2022

Magma ascending in the Earth’s crust can undergo oscillations in pressure, from ultra-low frequency changes associated with tectonics, to relatively higher frequency oscillations associated with seismicity. Seismic waves travelling through shallow magma bodies can lead to a range of unrest phenomena and potentially trigger volcanic eruptions. The mechanisms by which pressure oscillations can induce unrest or eruption remain debated. Here, we experimentally impose pressure oscillations on magma and study how they affect vesiculation processes. We use cylindrical samples (4.00 mm long, 4.85 mm diameter) of hydrous rhyolitic obsidian (0.11 ± 0.01 wt% H2O) placed in alumina (AL23) crucibles and vary pressure by the uniaxial loading of an alumina plunger in a thermo-mechanical analyzer. We monitor vesiculation at temperatures of 950–990°C and confining pressure of 177 kPa. We perform two types of experiment: 1) “static” experiments (at constant pressure) and 2) “oscillating” experiments in which we impose sinusoidal pressure oscillations of up to 71 kPa upon the static pressure (i.e., between 106 and 250 kPa). In both cases, we dilatometrically observe sample expansion driven by vesiculation. Post-experimental bubble textures reveal that bubbles formed preferentially at the sample margins. For the oscillating experiments, the sample expansion rate is lower than in the static experiments, and there are fewer vesicles at the sample margins. We examine the constituent processes of bubble formation (nucleation, growth, coalescence) and gas loss (diffusion, permeable flow) occurring during static experiments and with the added element of pressure oscillations. The most likely mechanism responsible for reduced sample expansion is that pressure oscillations drive the sample in and out of water saturation conditions and thus reduce the fraction of residence time over which bubble nucleation and/or growth are driven. Future work will be needed to confirm this hypothesis. These results are relevant to the study of earthquake-volcano interactions, where a magma body that sits close to volatile saturation is subject to pressure fluctuations.
Androgen Excess Induced Mitochondrial Abnormality in Ovarian Granulosa Cells in a Rat Model of Polycystic Ovary Syndrome
Authors: Song Linyi , Yu Jin , Zhang Danying , Li Xi , Chen Lu , Cai Zailong , Yu Chaoqin 
Published: March 2022

BackgroundAndrogen excess could profoundly lead to follicular dysplasia or atresia, and finally result in polycystic ovary syndrome (PCOS); however, the exact mechanism remains to be fully elucidated.MethodsPCOS model rats were induced by dehydroepiandrosterone, and their fertility was assessed. The ovarian granulosa cells (GCs) from matured follicles of PCOS model rats were collected and identified by immunofluorescence. The mitochondrial ultrastructure was observed by transmission electron microscope and the mitochondrial function was determined by detecting the adenosine triphosphate (ATP) content and mtDNA copy number. Besides, the expressions of respiratory chain complexes and ATP synthases in relation to mitochondrial function were analyzed.ResultsThe PCOS model rats were successfully induced, and their reproductive outcomes were obviously adverse. The GCs layer of the ovarian was apparently cut down and the mitochondrial ultrastructure of ovarian GCs was distinctly destroyed. The ATP content and mtDNA copy number of ovarian GCs in PCOS model rats were greatly reduced, and the expressions of NDUFB8 and ATP5j were significantly down-regulated without obvious deletion of mtDNA 4834-bp.ConclusionsAndrogen excess could damage mitochondrial ultrastructure and function of GCs in rat ovary by down-regulating expression of NDUFB8 and ATP5j in PCOS.
Low Maternal Serum 25‐Hydroxyvitamin D Concentration Is Associated With Postpartum Hemorrhage: A Retrospective Observational Study
Authors: Li Wei-Jiun , Chen Kuo-Hu , Huang Lee-Wen , Tsai Yieh-Loong , Seow Kok-Min 
Published: March 2022

ObjectiveThe primary aim of this study is to investigate the relationship between vitamin D serum level and the incidence of postpartum hemorrhage (PPH). The secondary objective is to determine the relative risk of low vitamin D associated with PPH.MethodsThis was a retrospective observational study. A total of 600 women who had delivered their babies in a single tertiary teaching hospital were enrolled. Serum blood test for 25(OH)D was performed at 35 + 0 to 36 + 6 weeks of pregnancy to measure vitamin D. A 25(OH)D level &lt; 20 ng/mL was defined as vitamin D deficient, and a level 21–29 ng/mL as insufficient.ResultsVitamin D levels were deficient in 145 (24.1%) and insufficient in 254 (42.3%) of the women tested. Women with deficient and insufficient vitamin D levels were significantly younger than those with sufficient vitamin D levels (p &lt; 0.001). The overall rates of PPH in the deficient and insufficient groups were 6.9% (10/145) and 6.7% (17/254), respectively, and were significantly higher than the rate of the normal vitamin D group (1.5%, p = 0.009). Women with sufficient vitamin D levels had significantly higher hemoglobin levels than those with low vitamin D levels. Higher vitamin D levels were associated with a significantly low risk of PPH (AOR: 0.93, CI: 0.89–0.98, p = 0.006).ConclusionOur results suggest that a low vitamin D level is a risk factor for PPH. Low vitamin D also related to high risk of low hemoglobin before delivery. Thus, antepartum care should include vitamin D supplements for all women if possible.
Advancing Microbial Electrolysis Technology via Impedance Spectroscopy and Multi-Variate Analysis
Authors: Timmerman Lucas R. , Raghavan Sankar , Borole Abhijeet P. 
Published: March 2022

In this study, EIS data collected from three electrode half-cell configurations was used to qualitatively identify and quantitatively determine the responses of ohmic, kinetic, and mass transfer impedances to buffer concentration, flow rate, and applied potential in an MEC consisting of a bioanode and an abiotic nickel-mesh cathode separated by a microporous membrane. EIS measurements were collected during startup and growth (including an abiotic run) at closed circuit and open circuit conditions to accurately match portions of the EIS spectra with the corresponding physical processes and to quantify kinetic changes as the biofilm matured. Once the MEC reached a target current density of 10 A/m2, a multifactorial experimental design formulated as a Taguchi array was executed to assess the impact of flow rate, buffer concentration, and applied voltage on EIS and performance response variables. Multivariate analysis was conducted to ascertain the relative importance of the independent variables and identify any correlations between process conditions and system response. The liquid flow through the anode was found to be strongly correlated with the impedance parameters and the MEC performance, while applied voltage influenced them to a lesser degree. The results are important from an industrial application perspective and provide insights into parameters important for process optimization.
Autophagy and Exosome Coordinately Enhance Macrophage M1 Polarization and Recruitment in Influenza A Virus Infection
Authors: Xia Chengjie , Xu Weiming , Ai Xin , Zhu Yingqi , Geng Ping , Niu Yijun , Zhu Haiyan , Zhou Wei , Huang Hai , Shi Xunlong 
Published: March 2022

BackgroundInfluenza A virus infection results in viral pneumonia, which is often accompanied by the infiltration and recruitment of macrophages, overactivation of inflammatory responses, and obvious cell autophagy and exosome production. However, little is known about the roles of autophagy and exosome production in these inflammatory responses.MethodsIn this study, multiple methods, such as flow cytometry, real-time quantitative reverse transcription-polymerase chain reaction, immune–fluorescence technology, and western blot, were applied to explore the possible effects of autophagy and exosome production by H1N1-infected host cells.ResultsIt was observed that a high number of polarized macrophages (CD11b+/F4/80+/CD86+) were recruited to the lung tissues of infected mice, which could be mimicked by tracking the movement of macrophages to H1N1-infected cells in vitro (transwell assays). Furthermore, there was some coordinated upregulation of M1 polarization signs (iNOS/Arg-1 bias) as well as autophagy (LC3) and exosome (CD63) biomarkers in the infected macrophages and epithelial cells. Moreover, exosomes extracted from the supernatant of virus-infected cells were shown to promote the recruitment and polarization of more peritoneal macrophages than the normal group. The fluorescence colocalization of LC3-CD63 and the inhibition of autophagy and exosome signaling pathway further revealed that H1N1 infection seemed to sequentially activate the M1 polarization and recruitment of macrophages via autophagy–exosome dependent pathway.ConclusionAutophagy and exosome production coordinately enhance the M1 polarization and recruitment of macrophages in influenza virus infection, which also provides potential therapeutic targets.
Effect of Infant RSV Infection on Memory T Cell Responses at Age 2-3 Years
Authors: Chirkova Tatiana , Rosas-Salazar Christian , Gebretsadik Tebeb , Jadhao Samadhan J. , Chappell James D. , Peebles R. Stokes , Dupont William D. , Newcomb Dawn C. , Berdnikovs Sergejs , Gergen Peter J. , Hartert Tina V. , Anderson Larry J. 
Published: March 2022

BackgroundIt is unknown whether RSV infection in infancy alters subsequent RSV immune responses.MethodsIn a nested cohort of healthy, term children, peripheral blood mononuclear cells (PBMCs) were collected at ages 2-3 years to examine RSV memory T cell responses among children previously RSV infected during infancy (first year of life) compared to those RSV-uninfected during infancy. The presence vs. absence of infant RSV infection was determined through a combination of RSV molecular and serologic testing. Memory responses were measured in RSV stimulated PBMCs.ResultsCompared to children not infected with RSV during the first year of life, children infected with RSV during infancy had lower memory T cell responses at ages 2-3 years to in vitro stimulation with RSV for most tested type-1 and type-17 markers for a number of memory T cell subsets.ConclusionsRSV infection in infancy has long-term effects on memory T cell responses. This is the first study to show the potential for RSV infection in infancy to have long-term effects on the immune memory irrespective of the severity of the infection. Our results suggest a possible mechanism through which infant RSV infection may result in greater risk of subsequent childhood respiratory viral morbidity, findings also relevant to vaccine development.
Comprehensive Analysis of HHLA2 as a Prognostic Biomarker and Its Association With Immune Infiltrates in Hepatocellular Carcinoma
Authors: Ding Lin , Yu Qian , Yang Shuo , Yang Wen-Jing , Liu Te , Xian Jing-Rong , Tian Tong-Tong , Li Tong , Chen Wei , Wang Bei-Li , Pan Bai-Shen , Zhou Jian , Fan Jia , Yang Xin-Rong , Guo Wei 
Published: March 2022

BackgroundInhibitory immune checkpoint proteins promote tumor immune escape and are associated with inferior patient outcome. However, the biological functions and regulatory roles of one of its members, HHLA2, in the tumor immune microenvironment have not been explored.MethodsRandomForest analyses (371 cases), qRT-PCR (15 cases), and immunohistochemical staining (189 cases) were used to validate the prognostic value of HHLA2 in hepatocellular carcinoma (HCC) patients. Bioinformatic analyses were further performed to explore the biological functions and potential signaling pathways affected by HHLA2. Moreover, ESTIMATE, single sample gene set enrichment analysis, CIBERSORT, TIMER, and other deconvolution methods were used to analyze the composition and infiltration level of immune cells. Multiplex immunofluorescence assays were employed to validate the fractions of suppressive immune cells, and HHLA2-related molecular alterations were investigated. Finally, the clinical response to chemotherapy and immune checkpoint blockade was predicted by TIDE, Submap, and several other in silico analyses.ResultsRandomForest analysis revealed that HHLA2 was the most important inhibitory immune checkpoint associated with HCC patient prognosis (relative importance = 1). Our HCC cohorts further revealed that high HHLA2 expression was an independent prognostic biomarker of shorter overall survival (P&lt;0.01) and time to recurrence (P&lt;0.001) for HCC patients. Bioinformatics experiments revealed that HHLA2 may accelerate the cell cycle of cancer cells. Additionally, we found that high expression of HHLA2 was associated with immune infiltrates, including some immunosuppressive cells, cytokines, chemokines, and corresponding receptors, resulting in an immunosuppressive environment. Notably, HHLA2 expression was positively correlated with the infiltration of exhausted CD8+ T cells, which was validated by immunofluorescence. Genomic alteration analyses revealed that promoter hypermethylation of HHLA2 may be associated with its low expression. More importantly, patients with high HHLA2 expression may be more sensitive to chemotherapy and have better responses to immunotherapy.ConclusionsHigh expression of HHLA2 is an independent prognostic biomarker for HCC patients. It can activate the cell cycle and foster an immunosuppressive tumor microenvironment by enriching exhausted CD8+ T cells. Promoter hypermethylation might lead to low expression of HHLA2 in HCC. Thus, targeting HHLA2 may be a practical therapeutic strategy for HCC patients in the future.
Adenosinergic Pathway and Linked Suppression: Two Critical Suppressive Mechanisms of Human Donor Antigen Specific Regulatory T Cell Lines Expanded Post Transplant
Authors: Tripathi Sudipta , Martin-Moreno Paloma L. , Kavalam George , Schreiber Brittany L. , Waaga-Gasser Ana Maria , Chandraker Anil 
Published: March 2022

Regulatory T cells are an important component of an immune response shaping the overall behavior to potential antigens including alloantigens. Multiple mechanisms have been shown to contribute towards developing and sustaining a immunological regulatory response. One of the described contact dependent suppressive mechanisms regulatory cells have been shown to utilize is through the production of adenosine from extracellular ATP mediated by CD39 and CD73. In this study we demonstrate that the adenosinergic pathway plays a major role in the suppressive/regulatory effects antigen specific regulatory T cell enriched lines (ASTRLs) that have been of expanded ex vivo from stable kidney transplant patients. We have previously shown that these ASTRL cells are capable of suppressing alloimmune responses in vitro and significantly prolonging allograft survival in an animal model of kidney transplantation. For this study nineteen ASTRLs were expanded from 17 kidney transplant patients by repeated stimulation of recipient peripheral blood mononuclear cells with donor specific HLA-DR peptides. All 19 ASTRLs showed upregulation of numerous markers associated with regulatory cells and were able to inhibit donor antigen specific T cell proliferation in a dose dependent fashion. ASTRLs suppressed indirect and direct alloimmune responses compatible with our previous animal study findings. Upregulation of both CD39 and CD73 was observed post expansion and ASTRLs demonstrated extracellular hydrolysis of ATP, indicating functionality of the upregulated proteins. We also showed that inhibition of the adenosinergic pathway using inhibitors of CD39 resulted in abrogation of suppression and increased antigen specific T cell proliferation. This demonstrates that the main mechanism of action of the suppressive activity donor peptide driven ASTRLs generated from kidney transplant patients is the adenosinergic pathway. Furthermore this suggests the possibility that combining infusion of Tregs with other treatments, such as adenosine receptor agonists or increasing CD39 expression in the grafts may further enhance a regulatory response to the allograft and possibly achieve transplantation tolerance.
Identification of the Predictive Models for the Treatment Response of Refractory/Relapsed B-Cell ALL Patients Receiving CAR-T Therapy
Authors: Gu Jingxian , Liu Sining , Cui Wei , Dai Haiping , Cui Qingya , Yin Jia , Li Zheng , Kang Liqing , Qiu Huiying , Han Yue , Miao Miao , Chen Suning , Xue Shengli , Wang Ying , Jin Zhengming , Zhu Xiaming , Yu Lei , Wu Depei , Tang Xiaowen 
Published: March 2022

Background/AimsChimeric antigen receptor (CAR) T cells for refractory or relapsed (r/r) B-cell acute lymphoblastic leukemia (ALL) patients have shown promising clinical effectiveness. However, the factors impacting the clinical response of CAR-T therapy have not been fully elucidated. We here aimed to identify the independent factors of CAR-T treatment response and construct the models for predicting the complete remission (CR) and minimal residual disease (MRD)-negative CR in r/r B-ALL patients after CAR-T cell infusion.MethodsUnivariate and multivariate logistic regression analyses were conducted to identify the independent factors of CR and MRD-negative CR. The predictive models for the probability of remission were constructed based on the identified independent factors. Discrimination and calibration of the established models were assessed by receiver operating characteristic (ROC) curves and calibration plots, respectively. The predictive models were further integrated and validated in the internal series. Moreover, the prognostic value of the integration risk model was also confirmed.ResultsThe predictive model for CR was formulated by the number of white blood cells (WBC), central neural system (CNS) leukemia, TP53 mutation, bone marrow blasts, and CAR-T cell generation while the model for MRD-negative CR was formulated by disease status, bone marrow blasts, and infusion strategy. The ROC curves and calibration plots of the two models displayed great discrimination and calibration ability. Patients and infusions were divided into different risk groups according to the integration model. High-risk groups showed significant lower CR and MRD-negative CR rates in both the training and validation sets (p &lt; 0.01). Furthermore, low-risk patients exhibited improved overall survival (OS) (log-rank p &lt; 0.01), higher 6-month event-free survival (EFS) rate (p &lt; 0.01), and lower relapse rate after the allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T cell infusion (p = 0.06).ConclusionsWe have established predictive models for treatment response estimation of CAR-T therapy. Our models also provided new clinical insights for the accurate diagnosis and targeted treatment of r/r B-ALL.