bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic and Prognostic Value of Lung Ultrasound B-Lines in Acute Heart Failure With Concomitant Pneumonia
Authors: Mazzola Matteo , Pugliese Nicola Riccardo , Zavagli Martina , De Biase Nicolò , Bandini Giulia , Barbarisi Giorgia , D'Angelo Gennaro , Sollazzo Michela , Piazzai Chiara , David Simon , Masi Stefano , Moggi-Pignone Alberto , Gargani Luna 
Published: August 2021

Purpose: To evaluate the potential confounding effect of concomitant pneumonia (PNM) on lung ultrasound (LUS) B-lines in acute heart failure (AHF).Methods: We enrolled 86 AHF patients with (31 pts, AHF/PNM) and without (55 pts, AHF) concomitant PNM. LUS B-lines were evaluated using a combined antero-lateral (AL) and posterior (POST) approach at admission (T0), after 24 h from T0 (T1), after 48 h from T0 (T2) and before discharge (T3). B-lines score was calculated at each time point on AL and POST chest, dividing the number of B-lines by the number of explorable scanning sites. The decongestion rate (DR) was calculated as the difference between the absolute B-lines number at discharge and admission, divided by the number of days of hospitalization. Patients were followed-up and hospital readmission for AHF was considered as adverse outcome.Results: At admission, AHF/PNM patients showed no difference in AL B-lines score compared with AHF patients [AHF/PNM: 2.00 (IQR: 1.44–2.94) vs. AHF: 1.65 (IQR: 0.50–2.66), p = 0.072], whereas POST B-lines score was higher [AHF/PNM: 3.76 (IQR: 2.70–4.77) vs. AHF = 2.44 (IQR: 1.20–3.60), p &lt; 0.0001]. At discharge, AL B-lines score [HR: 1.907 (1.097–3.313), p = 0.022] and not POST B-lines score was found to predict adverse events (AHF rehospitalization) after a median follow-up of 96 days (IQR: 30–265) in the overall population.Conclusions: Assessing AL B-lines alone is adequate for diagnosis, pulmonary congestion (PC) monitoring and prognostic stratification in AHF patients, despite concomitant PNM.
Association of Circulating, Inflammatory-Response Exosomal mRNAs With Acute Myocardial Infarction
Authors: He Guo-dong , Huang Yu-qing , Liu Lin , Huang Jia-yi , Lo Kenneth , Yu Yu-ling , Chen Chao-lei , Zhang Bin , Feng Ying-qing 
Published: August 2021

Background: Although many cardiovascular disease studies have focused on the microRNAs of circulating exosomes, the profile and the potential clinical diagnostic value of plasma exosomal long RNAs (exoLRs) are unknown for acute myocardial infarction (AMI).Methods: In this study, the exoLR profile of 10 AMI patients, eight stable coronary artery disease (CAD) patients, and 10 healthy individuals was assessed by RNA sequencing. Bioinformatic approaches were used to investigate the characteristics and potential clinical value of exoLRs.Results: Exosomal mRNAs comprised the majority of total exoLRs. Immune cell types analyzed by CIBERSORT showed that neutrophils and monocytes were significantly enriched in AMI patients, consistent with clinical baseline values. Biological process enrichment analysis and co-expression network analysis demonstrated neutrophil activation processes to be enriched in AMI patients. Furthermore, two exosomal mRNAs, ALPL and CXCR2, were identified as AMI biomarkers that may be useful for evaluation of the acute inflammatory response mediated by neutrophils.Conclusions: ExoLRs were assessed in AMI patients and found to be associated with the acute inflammatory response mediated by neutrophils. Exosomal mRNAs, ALPL and CXCR2, were identified as potentially useful biomarkers for the study of AMI.
Non-Canonical Effects of ACTH: Insights Into Adrenal Insufficiency
Authors: Hasenmajer Valeria , Bonaventura Ilaria , Minnetti Marianna , Sada Valentina , Sbardella Emilia , Isidori Andrea M. 
Published: August 2021

IntroductionAdrenocorticotropic hormone (ACTH) is produced from proopiomelanocortin, which is predominantly synthetized in the corticotroph and melanotroph cells of the anterior and intermediate lobes of the pituitary gland and the arcuate nucleus of the hypothalamus. Although ACTH clearly has an effect on adrenal homeostasis and maintenance of steroid hormone production, it also has extra-adrenal effects that require further elucidation.MethodsWe comprehensively reviewed English language articles, regardless of whether they reported the presence or absence of adrenal and extra-adrenal ACTH effects.ResultsIn the present review, we provide an overview on the current knowledge on adrenal and extra-adrenal effects of ACTH. In the section on adrenal ACTH effects, we focused on corticosteroid rhythmicity and effects on steroidogenesis, mineralocorticoids and adrenal growth. In the section on extra-adrenal effects, we have analyzed the effects of ACTH on the osteoarticular and reproductive systems, adipocytes, immune system, brain and skin. Finally, we focused on adrenal insufficiency.ConclusionsThe role of ACTH in maintaining the function of the hypothalamic–pituitary–adrenal axis is well known. Conversely, if we broaden our vision and analyze its role as a potential treatment strategy in other conditions, it will be evident in the literature that researchers seem to have abandoned this aspect in studies conducted several years ago. We believe it is worth re-evaluating the role of ACTH considering its noncanonical effects on the adrenal gland itself and on extra-adrenal organs and tissues; however, this would not have been possible without the recent advances in the pertinent technologies.
Identification of a Novel Glycolysis-Related LncRNA Signature for Predicting Overall Survival in Patients With Bladder Cancer
Authors: Zheng Zhenming , Lai Cong , Li Wenshuang , Zhang Caixia , Ma Kaiqun , Yao Yousheng 
Published: August 2021

BackgroundBoth lncRNAs and glycolysis are considered to be key influencing factors in the progression of bladder cancer (BCa). Studies have shown that glycolysis-related lncRNAs are an important factor affecting the overall survival and prognosis of patients with bladder cancer. In this study, a prognostic model of BCa patients was constructed based on glycolysis-related lncRNAs to provide a point of reference for clinical diagnosis and treatment decisions.MethodsThe transcriptome, clinical data, and glycolysis-related pathway gene sets of BCa patients were obtained from The Cancer Genome Atlas (TCGA) database and the Gene Set Enrichment Analysis (GSEA) official website. Next, differentially expressed glycolysis-related lncRNAs were screened out, glycolysis-related lncRNAs with prognostic significance were identified through LASSO regression analysis, and a risk scoring model was constructed through multivariate Cox regression analysis. Then, based on the median of the risk scores, all BCa patients were divided into either a high-risk or low-risk group. Kaplan-Meier (KM) survival analysis and the receiver operating characteristic (ROC) curve were used to evaluate the predictive power of the model. A nomogram prognostic model was then constructed based on clinical indicators and risk scores. A calibration chart, clinical decision curve, and ROC curve analysis were used to evaluate the predictive performance of the model, and the risk score of the prognostic model was verified using the TCGA data set. Finally, Gene Set Enrichment Analysis (GSEA) was performed on glycolysis-related lncRNAs.ResultsA total of 59 differentially expressed glycolysis-related lncRNAs were obtained from 411 bladder tumor tissues and 19 pericarcinomatous tissues, and 9 of those glycolysis-related lncRNAs (AC099850.3, AL589843.1, MAFG-DT, AC011503.2, NR2F1-AS1, AC078778.1, ZNF667-AS1, MNX1-AS1, and AC105942.1) were found to have prognostic significance. A signature was then constructed for predicting survival in BCa based on those 9 glycolysis-related lncRNAs. ROC curve analysis and a nomogram verified the accuracy of the signature.ConclusionThrough this study, a novel prognostic prediction model for BCa was established based on 9 glycolysis-related lncRNAs that could effectively distinguish high-risk and low-risk BCa patients, and also provide a new point of reference for clinicians to make individualized treatment and review plans for patients with different levels of risk.
A Novel microRNA of Japanese Flounder Regulates Antimicrobial Immunity Involving a Bacteria-Binding CSF3
Authors: Li Wenrui , Guan Xiaolu , Sun Bin , Sun Li 
Published: August 2021

MicroRNAs (miRNAs) are small non-coding RNAs that regulate diverse biological processes including immunity. In a previous high-throughput RNA sequencing study, a novel miRNA, pol-miR-novel_642, was identified from Japanese flounder (Paralichthys olivaceus), a farmed fish species with important economic value. In this study, we investigated the regulatory mechanism and the function of pol-miR-novel_642 and its target gene. We found that pol-miR-novel_642 targeted, in a sequence-specific manner, a flounder gene encoding an uncharacterized protein that is a structural homologue of murine granulocyte colony stimulating factor 3 (CSF3). The expression of pol-miR-novel_642 and its target gene (named PoCSF3-1) was regulated, in different manners, by the bacterial pathogen Edwardsiella tarda and the viral pathogen megalocytivirus. Overexpression of pol-miR-novel_642 or interference with PoCSF3-1 expression in flounder cells strongly potentiated E. tarda infection. Consistently, in vivo knockdown of PoCSF3-1 enhanced bacterial dissemination in flounder tissues but blocked viral replication, whereas in vivo overexpression of PoCSF3-1 inhibited bacterial dissemination and facilitated viral infection. Overexpression/knockdown of PoCSF3-1 and pol-miR-novel_642 also affected the activation of autophagy. Recombinant PoCSF3-1 (rPoCSF3-1) interacted with and inhibited the growth of Gram-negative bacteria in a manner relying on a PoCSF3-1-characteristic structural motif that is absent in mouse CSF3. rPoCSF3-1 also regulated the proliferation, inflammatory response, and immune defense of flounder head kidney leukocytes in a structure-dependent fashion. Together, these results reveal the function of a novel miRNA-CSF3 regulatory system of flounder, and add new insights into the role and mechanism of fish miRNA and CSF3 in antimicrobial immunity.
Different Profiles of Antibodies and Cytokines Were Found Between Severe and Moderate COVID-19 Patients
Authors: Guo Yaolin , Li Tianyi , Xia Xinyi , Su Bin , Li Hanping , Feng Yingmei , Han Jingwan , Wang Xiaolin , Jia Lei , Bao Zuoyi , Li Jingyun , Liu Yongjian , Li Lin 
Published: August 2021

ObjectivesOur objective was to determine the antibody and cytokine profiles in different COVID-19 patients.MethodsCOVID-19 patients with different clinical classifications were enrolled in this study. The level of IgG antibodies, IgA, IgM, IgE, and IgG subclasses targeting N and S proteins were tested using ELISA. Neutralizing antibody titers were determined by using a toxin neutralization assay (TNA) with live SARS-CoV-2. The concentrations of 8 cytokines, including IL-2, IL-4, IL-6, IL-10, CCL2, CXCL10, IFN-γ, and TNF-α, were measured using the Protein Sample Ella-Simple ELISA system. The differences in antibodies and cytokines between severe and moderate patients were compared by t-tests or Mann-Whitney tests.ResultsA total of 79 COVID-19 patients, including 49 moderate patients and 30 severe patients, were enrolled. Compared with those in moderate patients, neutralizing antibody and IgG-S antibody titers in severe patients were significantly higher. The concentration of IgG-N antibody was significantly higher than that of IgG-S antibody in COVID-19 patients. There was a significant difference in the distribution of IgG subclass antibodies between moderate patients and severe patients. The positive ratio of anti-S protein IgG3 is significantly more than anti-N protein IgG3, while the anti-S protein IgG4 positive rate is significantly less than the anti-N protein IgG4 positive rate. IL-2 was lower in COVID-19 patients than in healthy individuals, while IL-4, IL-6, CCL2, IFN-γ, and TNF-α were higher in COVID-19 patients than in healthy individuals. IL-6 was significantly higher in severe patients than in moderate patients. The antibody level of anti-S protein was positively correlated with the titer of neutralizing antibody, but there was no relationship between cytokines and neutralizing antibody.ConclusionsOur findings show the severe COVID-19 patients’ antibody levels were stronger than those of moderate patients, and a cytokine storm is associated with COVID-19 severity. There was a difference in immunoglobulin type between anti-S protein antibodies and anti-N protein antibodies in COVID-19 patients. And clarified the value of the profile in critical prevention.
ATENA–A Novel Rapidly Manufactured Medical Invasive Ventilator Designed as a Response to the COVID-19 Pandemic: Testing Protocol, Safety, and Performance Validation
Authors: Rebelo Tiago , Neutel Elizabete , Alves Eurico Castro , Barros Francisco , Oliveira Hélder , Machado Humberto , Mendonça Joana , Araújo João Fortuna , Luís João , Pêgo José M. , Silva José , Oliveira Manuel , Sousa Nuno , Figueiredo Paulo , Barata Pedro , Magalhães Raquel Silva , Magalhães Rui Miguel , Gomes Sara H. 
Published: August 2021

Background: The urgent need for mechanical ventilators to support respiratory insufficiency due to SARS-CoV-2 led to a worldwide effort to develop low-cost, easily assembled, and locally manufactured ventilators. The ATENA ventilator project was developed in a community-based approach targeting the development, prototyping, testing, and decentralized manufacturing of a new mechanical ventilator.Objective: This article aims to demonstrate ATENA's adequate performance and safety for clinical use.Material: ATENA is a low-cost ventilator that can be rapidly manufactured, easily assembled, and locally produced anywhere in the world. It was developed following the guidelines and requirements provided by European and International Regulatory Authorities (MHRA, ISO 86201) and National Authorities (INFARMED). The device was thoroughly tested using laboratory lung simulators and animal models.Results: The device meets all the regulatory requirements for pandemic ventilators. Additionally, the pre-clinical experiences demonstrated security and adequate ventilation and oxygenation, in vivo.Conclusion: The ATENA ventilator had a good performance in required tests in laboratory scenarios and pre-clinical studies. In a pandemic context, ATENA is perfectly suited for safely treating patients in need of mechanical ventilation.
Binding Potassium to Improve Treatment With Renin-Angiotensin-Aldosterone System Inhibitors: Results From Multiple One-Stage Pairwise and Network Meta-Analyses of Clinical Trials
Authors: Lizaraso-Soto Frank , Gutiérrez-Abejón Eduardo , Bustamante-Munguira Juan , Martín-García Débora , Chimeno María Montserrat , Nava-Rebollo Álvaro , Maurtua-Briseño-Meiggs Álvaro , Fernández-Zoppino Darío , Bustamante-Munguira Elena , de Paz Félix Jesús , Grande-Villoria Jesús , Ochoa-Sangrador Carlos , Pascual Manuel , Álvarez F. Javier , Herrera-Gómez Francisco 
Published: August 2021

This manuscript presents findings from the first dichotomous data pooling analysis on clinical trials (CT) regarding the effectiveness of binding potassium. The results emanated from pairwise and network meta-analyses aiming evaluation of response to commercial potassium-binding polymers, that is, to achieve and maintain normal serum potassium (n = 1,722), and the association between this response and an optimal dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) needing individuals affected by heart failure (HF) or resistant hypertension, who may be consuming other hyperkalemia-inducing drugs (HKID) (e.g., β-blockers, heparin, etc.), and frequently are affected by chronic kidney disease (CKD) (n = 1,044): According to the surface under the cumulative ranking area (SUCRA), sodium zirconium cyclosilicate (SZC) (SUCRA &gt;0.78), patiromer (SUCRA &gt;0.58) and sodium polystyrene sulfonate (SPS) (SUCRA &lt;0.39) were different concerning their capacity to achieve normokalemia (serum potassium level (sK+) 3.5–5.0 mEq/L) or acceptable kalemia (sK+ ≤ 5.1 mEq/L) in individuals with hyperkalemia (sK+ &gt;5.1 mEq/L), and, when normokalemia is achieved, patiromer 16.8–25.2 g/day (SUCRA = 0.94) and patiromer 8.4–16.8 g/day (SUCRA = 0.41) can allow to increase the dose of spironolactone up to 50 mg/day in subjects affected by heart failure (HF) or with resistant hypertension needing treatment with other RAASi. The potential of zirconium cyclosilicate should be explored further, as no data exists to assess properly its capacity to optimize dosing of RAASi, contrarily as it occurs with patiromer. More research is also necessary to discern between benefits of binding potassium among all type of hyperkalemic patients, for example, patients with DM who may need treatment for proteinuria, patients with early hypertension, etc.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020185614, CRD42020185558, CRD42020191430.
Development of an Early Warning Model for Predicting the Death Risk of Coronavirus Disease 2019 Based on Data Immediately Available on Admission
Authors: Wang Hai , Ai Haibo , Fu Yunong , Li Qinglin , Cui Ruixia , Ma Xiaohua , Ma Yan-fen , Wang Zi , Liu Tong , Long Yunxiang , Qu Kai , Liu Chang , Zhang Jingyao 
Published: August 2021

Introduction: COVID-19 has overloaded worldwide medical facilities, leaving some potentially high-risk patients trapped in outpatient clinics without sufficient treatment. However, there is still a lack of a simple and effective tool to identify these patients early.Methods: A retrospective cohort study was conducted to develop an early warning model for predicting the death risk of COVID-19. Seventy-five percent of the cases were used to construct the prediction model, and the remaining 25% were used to verify the prediction model based on data immediately available on admission.Results: From March 1, 2020, to April 16, 2020, a total of 4,711 COVID-19 patients were included in our study. The average age was 63.37 ± 16.70 years, of which 1,148 (24.37%) died. Finally, age, SpO2, body temperature (T), and mean arterial pressure (MAP) were selected for constructing the model by univariate analysis, multivariate analysis, and a review of the literature. We used five common methods for constructing the model and finally found that the full model had the best specificity and higher accuracy. The area under the ROC curve (AUC), specificity, sensitivity, and accuracy of full model in train cohort were, respectively, 0.798 (0.779, 0.816), 0.804, 0.656, and 0.768, and in the validation cohort were, respectively, 0.783 (0.751, 0.815), 0.800, 0.616, and 0.755. Visualization tools of the prediction model included a nomogram and an online dynamic nomogram (https://wanghai.shinyapps.io/dynnomapp/).Conclusion: We developed a prediction model that might aid in the early identification of COVID-19 patients with a high probability of mortality on admission. However, further research is required to determine whether this tool can be applied for outpatient or home-based COVID-19 patients.
Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis
Authors: Li Yin , Yang Xue , Yan Peijing , Sun Tong , Zeng Zhi , Li Sheyu 
Published: August 2021

Importance/Background: The coronavirus disease (COVID-19) pandemic is a critical public health issue. Evidence has shown that metformin favorably influences COVID-19 outcomes. This study aimed to assess the benefits and risks of metformin in COVID-19 patients.Methods: We searched the PubMed, Embase, Cochrane Library, and Chinese Biomedical Literature Database from inception to February 18, 2021. Observational studies assessing the association between metformin use and the outcomes of COVID-19 patients were included. The primary outcome was mortality, and the secondary outcomes included intubation, deterioration, and hospitalization. Random-effects weighted models were used to pool the specific effect sizes. Subgroup analyses were conducted by stratifying the meta-analysis by region, diabetic status, the adoption of multivariate model, age, risk of bias, and timing for adding metformin.Results: We identified 28 studies with 2,910,462 participants. Meta-analysis of 19 studies showed that metformin is associated with 34% lower COVID-19 mortality [odds ratio (OR), 0.66; 95% confidence interval (CI), 0.56–0.78; I2 = 67.9%] and 27% lower hospitalization rate (pooled OR, 0.73; 95% CI, 0.53–1.00; I2 = 16.8%). However, we did not identify any subgroup effects. The meta-analysis did not identify statistically significant association between metformin and intubation and deterioration of COVID-19 (OR, 0.94; 95% CI, 0.77–1.16; I2 = 0.0% for intubation and OR, 2.04; 95% CI, 0.65–6.34; I2 = 79.4% for deterioration of COVID-19), respectively.Conclusions: Metformin use among COVID-19 patients was associated with a reduced risk of mortality and hospitalization. Our findings suggest a relative benefit for metformin use in nursing home and hospitalized COVID-19 patients. However, randomized controlled trials are warranted to confirm the association between metformin use and COVID-19 outcomes.Study Registration: The study was registered on the PROSPERO on Feb 23, 2021 (CRD42021238722).
Effects of Telemedicine on Obese Patients With Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis
Authors: Saokaew Surasak , Kanchanasurakit Sukrit , Kositamongkol Chayanis , Chaiyo Kanyanat , Jirapisut Thirada , Aomsin Narakorn , Leewongsakorn Pit , Chaiyakunapruk Nathorn , Phisalprapa Pochamana 
Published: August 2021

Background: Little is known of the efficacy of telemedicine on the clinical outcomes of the high-risk group of non-alcoholic fatty liver disease (NAFLD) patients, such as those with obesity. This study aimed to determine the effects of telemedicine vs. usual care for the management of obese patients with NAFLD.Methods: Literature searches were performed from inception to 1st June 2021 in the following databases: Cochrane CENTRAL, ScienceDirect, PubMed, and Scopus. Prospective trials assessed the effects of telemedicine on obese patients with NAFLD were included. The outcomes of interest were alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride, high-density lipoprotein cholesterol levels, and body mass index, which were reported as weighted mean difference (WMD) with 95% confidence interval (CI).Results: Four studies were examined in the systematic review, one was excluded from the meta-analysis due to an inappropriate group-comparison. In all, 285 obese patients with NAFLD were included in the meta-analysis (70% of those received telemedicine intervention). The mean ages of the patients in the telemedicine and usual-care groups were 51.78 ± 5.91 and 47.30 ± 8.14 years, respectively. Telemedicine significantly decreased ALT levels compared with usual care (WMD = −18.93 U/L [95%CI: −25.97, −11.90]; I2 = 53.8%), and it significantly decreased AST levels (WMD = −10.24 U/L [95%CI: −13.43, −7.05]; I2 = 0.0%). However, telemedicine did not show significant benefits for the remaining outcomes.Conclusion: Compared with usual care, telemedicine significantly reduced the AST and ALT levels of obese patients with NAFLD. Further long-term studies with clinical endpoints are needed to determine the best characteristics of telemedicine and to confirm the benefits.Systematic Review Registration: PROSPERO [CRD42020207451].