bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severe SARS-CoV-2 infection is defined by a shift in the serum lipidome resulting in dysregulation of eicosanoid lipid immune mediators
Authors: Schwarz Benjamin , Sharma Lokesh , Roberts Lydia , Peng Xiaohua , Bermejo Santos , Leighton Ian , Casanovas-Massana Arnau , Farhadian Shelli , Ko Albert , Team Yale IMPACT , Cruz Charles Dela , Bosio Catharine 
Published: July 2020

Abstract
The COVID-19 pandemic has affected more than 10 million people worldwide with mortality exceeding3 half a million patients. Risk factors associated with severe disease and mortality include advanced age,4 hypertension, diabetes, and obesity.1 Clear mechanistic understanding of how these comorbidities5 converge to enable severe infection is lacking. Notably each of these risk factors pathologically disrupts6 the lipidome and this disruption may be a unifying feature of severe COVID-19.1-7 Here we provide the first in depth interrogation of lipidomic changes, including structural-lipids as well as the eicosanoids and docosanoids lipid mediators (LMs), that mark COVID-19 disease severity. Our data reveal that progression from moderate to severe disease is marked by a loss of specific immune regulatory LMs and increased pro-inflammatory species. Given the important immune regulatory role of LMs, these data provide mechanistic insight into the immune balance in COVID-19 and potential targets for therapy with currently approved pharmaceuticals.8
Hydrocortisone vs Tocilizumab Effects on Cytokine Storm in Critically Ill Patients with COVID-19.
Authors: Vargas Maria , Buonanno Pasquale , Iacovazzo Carmine , Spigna Gaetano Di , Spalletti Daniela , Savoia Marcella , Postiglione Loredana , Servillo Giuseppe 
Published: July 2020

Abstract
Introduction: Patients with severe pneumonia due COVID-19 are reported to have substantially lower lymphocyte counts and higher plasma concentrations of a number of inflammatory cytokines. In the late stages of COVID-19, cytokine storms are the mainly cause of disease progression and death. We performed a prospective observational study to evaluate the impact of tocilizumab and hydrocortisone on cytokine storm in critically ill patients with COVID-19.Methods: We included all adult patients with laboratory-confirmed COVID-19 infection and severe respiratory failure admitted to our ICU from March 10 to April 30. As therapeutic options, patients received tocilizumab od hydrocortisone. The primary end point was the evaluation of cytokine storm in terms of variation of the IL-6 and IL-6R, sgp130 and TNF-α concentrations during time to different treatment.Results: Eight patients received tocilizumab while 15 patients received hydrocortisone. IL-6 levels were lower in the hydrocortisone group with statistical significance was found at the days 2, 3, 8 and 9. The levels of IL-6R were lower during the days in the hydrocortisone group with statistical significance at days 1, 2, 3, 4, 5, 6, 8 and 10. Hydrocortisone group had higher levels of TNF-α at days 2, 3 and 4. The levels of sgo130 between tocilizumab and hydrocortisone groups were not statistically different during the days.Conclusions: In critically ill patients with severe COVID-19, the use of hydrocortisone allowed a better control of the cytokine storms, was further associated to less days of curarization, pronation and length of stay in ICU, and speed up the time to get negative RT-PCR swab.
Early Critical Care Transthoracic Echocardiography Improves The Mortality Of Patients Undergoing Mechanical Ventilation: Observational Data From Two Large Databases
Authors: Yu Xueshu , Pan Xiaojun , Zhang Xianwei , Chen Zhiqiang , Pan Hao , Jiang Hao , Chen Wenjing , Pan Lingling , Fang Zhendong , Shu Jie , Hu Yufeng , Ye Yincai , Pan Jingye 
Published: July 2020

Abstract
Background: Critical care transthoracic echocardiography (TTE) can quickly and accurately assess haemodynamic changes in ICU patients. However, it is not clear whether transthoracic echocardiography improves the prognosis of mechanically ventilated patients. In this study, we hypothesized that early critical care transthoracic echocardiography independently contributes to improvements in mortality in mechanically ventilated patients in the ICU.Methods: This was a retrospective study based on the Medical Information Mart for Intensive Care III (MIMIC-III) database and the eICU Collaborative Research Database (eICU-CRD). Patients undergoing mechanical ventilation for more than 48 hours were selected. The exposure of interest was early TTE. The primary outcome was in-hospital mortality. We used propensity score matching to analyse the association between early TTE and in-hospital mortality and sensitivity analysis, including the inverse probability weighting model and covariate balancing propensity score model, to ensure the robustness of our findings.Results: A total of 8862 patients undergoing mechanical ventilation were enrolled. The adjusted OR showed a favourable effect between the early TTE group and in-hospital mortality [MIMIC: OR 0.77, 95% CI (0.63–0.94), (P=0.01); eICU-CRD: OR 0.78, 95% CI (0.68–0.89), (P<0.01) ]. Furthermore, TTE was also associated with 30-day mortality in the MIMIC database [OR 0.74, 95% CI (0.6-0.92), P=0.01].Conclusions: Early application of critical care transthoracic echocardiography during mechanical ventilation is beneficial for improving in-hospital mortality. Further investigation with prospectively collected data is required to validate this relationship.
Application of Nitrogen Shock Fracturing Technology on Coalbed Methane Well
Authors: Tian Qingling , Hao Chunsheng , Li Junjun , Wang Wei 
Published: July 2020

Abstract
Water sensitivity exists in reservoir during traditional hydraulic fracturing. Nitrogen shock fracturing was put forward to solve these problems. By suddenly pushing high-energied nitrogen into perforated casing ,This technology clears the near-wellbore way gas out. A set of down-hole tool string, together with the fracturing ground units and nitrogen shock fracturing project, form a nitrogen shock fracturing system. The on-site researches show that this kind of system can do the nitrogen shock fracturing as designed. It actually makes the gas production better. In the future researches, we are committed to improve this technology to suit for more geological condition .
Overcoming challenges in teaching calculus remotely during COVID-19 pandemic
Authors: Ng David C. , Mahmoud Seedahmed S. , Hald Eric S. , Fang Qiang 
Published: July 2020

Abstract
Purpose:This tutorial provides two specific examples to demonstrate how we tackled challenges in teaching Calculus remotely to first year undergraduate biomedical engineering students of XYZ University during a pandemic.Methods: Lessons and education materials were delivered remotely using XYZ University’s version of open-source Moodle learning management system and Tencent’s WeChat social media platform. We implemented transformative learning theory and active learning principles in our initiatives.Results: Students motivation and engagement improved through appropriate challenges and application of timely real-life examples in Calculus based-on positive feedback received anonymously from students via end-of-course surveys.Conclusion: Remote learning is an evolving paradigm which challenges instructors to use novel and creative ways to engage with students.
Differential Expression of Immune-Regulatory Protein C5AR1, NLRP3 and CLEC4A on Peripheral Blood Mononuclear Cells in Early-Stage Non-Small Cell Lung Cancer Patients
Authors: Sathitruangsak Chirawadee , Khunsri Siriporn , Pornpatrananrak Nopporn , Aporntewan Chatchawit , Chantranuwat Poonchavist , Sriuranp Virote , Mutirangura Apiwat , Vinayanuwattikun Chanida 
Published: July 2020

Abstract
Background: Previous studies from our group reported paracrine signal-induced peripheral mononuclear cell (PBMC) gene upregulation in various cancer types through epigenetic regulation. We speculated protein expression on circulating T- lymphocytes which might represent T-lymphocyte trafficking before infiltrating into tumor microenvironment. The possibility to use protein expression on circulating T-lymphocytes as a biomarker to discriminate early stage lung cancer has been explored.Methods: PBMC gene expression was explored, using 4 independent gene expression microarray datasets (GSE12771, GSE13255, GSE20189 and GSE3934). We selected 3 candidate proteins, C5AR1, NLRP3 and CLEC4A, based on their significant protein expression in tumor-infiltrating lymphocytes but not in normal lymphoid tissue. A validation study using automated flow cytometry was conducted in 121 participants including 44 treatment-naïve early stage non-small cell lung cancer patients (NSCLC), 19 non-malignant pulmonary diseases and 62 healthy individuals. Results: The ratio of C5AR1, NLRP3 and CLEC4A specific antibody staining to CD3 positive was significantly higher in early stage NSCLC compared to healthy control. Median ratio of C5AR1, NLRP3 and CLEC4A expression in early stage NSCLC were 0.65 [range 0.27-0.96; 95% CI: 0.55-0.70], 0.83 [range 0.27-0.99; 95% CI: 0.73-0.86] and 0.75 [range 0.21-0.98; 95% CI: 0.65-0.81], respectively. While, median ratio of C5AR1, NLRP3 and CLEC4A expression in healthy control were 0.21 [range 0.05-0.81; 95% CI: 0.23-0.42, p-value <0.001], 0.32 [range 0.04-0.94; 95% CI: 0.28-0.46, p-value <0.001] and 0.22 [range 0.04-0.97; 95% CI: 0.27-0.48, p-value < 0.001], respectively. This led to 87.5-100% sensitivity, 50.9-64.7% specificity and 71.4-75% accuracy. However, those PBMC protein expressions could not discriminate early stage NSCLC from malignant-mimic inflammation and infection.Conclusions: Our proof-of-principle findings strengthen the hypothesis that malignancies generate distinctive protein expression fingerprints on circulating T-lymphocytes. Trial registration: This trial was registered with clinicaltrials.in.th, Number TCTR20190508003.
Identification of crucial genes in metastatic osteosarcoma and prognostic biomarker in osteosarcoma patients
Authors: Wang Weihao , Liu Zhaoyong , Lu Weiqing , Guo Huancheng , Zhou Chunbin , Lin Youbin , Wang Hu 
Published: July 2020

Abstract
Background Osteosarcoma is still a challenging cancer that poses a huge threat to human health worldwide, especially in young people. The aim of this study was to identify prognostic genes associated with neoplasm metastasis in osteosarcoma, and construct a prognostic nomogram to help the orthopedist to assess prognosis of osteosarcoma patients.Methods Gene expression and clinical information were extracted from the TARGET database. Differentially expressed genes (DEGs) associated with osteosarcoma metastasis were identified and subjected to GO functional and KEGG pathway enrichment analyses. Survival and Cox analyses were used to identify prognostic genes.Results First, 214 DEGs were identified as crucial genes associated with osteosarcoma metastasis. Then functional enrichment analyses showed that DEGs were enriched in cell-cell signaling, inflammatory response, and immune response. Survival and Cox analyses identified five prognostic genes (MUC17, MYC, TAC4, HERC5, OR8G5) that were related to the prognosis of patients. This five-genes signature has a great diagnostic value for prognosis because it was not affected by age at diagnosis, gender, metastasis or relapse.Conclusions The present study identifies five target genes related to the metastasis of osteosarcoma. This five-genes signature can be used to predict the prognosis of osteosarcoma patients and may become new potential therapeutic targets for the treatment of osteosarcoma.
Genetic Diversity of Landraces and Improved Varieties of Rice (Oryza sativa L.) in Taiwan
Authors: Hour Ai-ling , Hsieh Wei-hsun , Chang Su-huang , Wu Yong-pei , Chin Han-shiuan , Lin Yann-rong 
Published: July 2020

Abstract
Background: Rice, the most important crop in Asia, has been cultivated in Taiwan for more than 5,000 years. The landraces preserved by indigenous peoples and brought by immigrants from China hundreds of years ago exhibit large variation in morphology, implying that they comprise rich genetic resources. Breeding goals according to the preferences of farmers, consumers and government policies also alter gene pools and genetic diversity of improved varieties. To unveil how genetic diversity is affected by natural, farmers’, and breeders’ selections is crucial for germplasm conservation and crop improvement.Results: A diversity panel of 148 rice accessions, including 47 cultivars and 59 landraces from Taiwan and 42 accessions from other countries, were genotyped by using 75 molecular markers that revealed an average of 12.7 alleles per locus with mean polymorphism information content of 0.72. These accessions could be grouped into five subpopulations corresponding to wild rice, japonica landraces, indica landraces, indica cultivars and japonica cultivars. The genetic diversity within subpopulations was: wild rices > landraces > cultivars; and indica rice > japonica rice. Despite having less variation among cultivars, japonica landraces had greater genetic variation than indica landraces because the majority of Taiwanese japonica landraces preserved by indigenous peoples were classified as tropical japonica. Two major clusters of indica landraces were formed by phylogenetic analysis, in accordance with immigration from two origins. Genetic erosion had occurred in later japonica varieties due to a narrow selection of germplasm being incorporated into breeding programs for premium grain quality. Genetic differentiation between early and late cultivars was significant in japonica (FST = 0.3751) but not in indica (FST = 0.0045), indicating effects of different breeding goals on modern germplasm. Indigenous landraces with unique intermediate and admixed genetic backgrounds were untapped, representing valuable resources for rice breeding.Conclusions: The genetic diversity of improved rice varieties has been substantially shaped by breeding goals, leading to differentiation between indica and japonica cultivars. Taiwanese landraces with different origins possess various and unique genetic backgrounds. Taiwanese rice germplasm provides diverse genetic variation for association mapping to unveil useful genes and is a precious genetic reservoir for rice improvement.
Progressive worsening of the respiratory and gut microbiome in children during the first two months of COVID-19
Authors: Xu Rong , Liu Pengcheng , Zhang Tao , Wu Qunfu , Zeng Mei , Ma Yingying , Jin Xia , Xu Jin , Zhang Zhigang , Zhang Chiyu 
Published: July 2020

Abstract
Background

Children are less susceptible to COVID-19 and manifests lower morbidity and mortality after infection, for which a multitude of mechanisms may be proposed. Whether the normal development of gut-airway microbiome is affected by COVID-19 has not been evaluated.
Results

We demonstrate that COVID-19 alters the respiratory and gut microbiome of children. Alteration of the microbiome was divergent between the respiratory tract and gut, albeit the dysbiosis was dominated by genus Pseudomonas and sustained for up to 25–58 days in different individuals. The respiratory microbiome distortion persisted in 7/8 children for at least 19–24 days after discharge from the hospital. The gut microbiota showed early dysbiosis towards later restoration in some children, but not others.
Conclusions

Disturbed development of both gut and respiratory microbiomes, and prolonged respiratory dysbiosis in children imply possible long-term complications after clinical recovery from COVID-19, such as predisposition to an increased health risk in the post-COVID-19 era.
Association Effects Of Comorbid Versus Uncomorbid Diabetes And Blood Glucose Concentrations On Short-term Outcomes In Patients With Critical Illness: A Real-World Study Based On Propensity Score Analyses
Authors: Lin Shan , Ge Shanhui , He Wanmei , Zeng Mian 
Published: July 2020

Abstract
Background: The effects of combined diabetes and glycemic control strategies on the short-term prognosis in patients with a critical illness are currently ambiguous. The objectives of our study were to determine whether comorbid diabetes affects short-term prognosis and the optimal range of glycemic control in critically ill patients.Methods: We performed this study with the critical care database. The primary outcomes were 28-day mortality in critically ill patients with comorbid diabetes and the optimal range of glycemic control. Association of comorbid diabetes with 28-day mortality was assessed by multivariable Cox regression model with inverse probability weighting. Smooth curves were applied to fit the association for glucose and 28-day mortality.Results: Of the 33,680 patients enrolled in the study, 8,701 (25.83%) had diabetic comorbidity. Cox model with inverse probability weighting showed that the 28-day mortality rate was reduced by 29% (HR=0.71, 95% CI 0.67-0.76) in the group with diabetes in comparison to the group without diabetes. The E value of 2.17 indicated robustness to unmeasured confounders. The effect of the association between comorbid diabetes and 28-day mortality was generally in line for all subgroup variables, significant interactions were observed for glucose on first day, admission type, and use of insulin or not (Interaction P <0.05). A V-shaped relationship was observed between glucose concentrations and 28-day mortality in patients without diabetes, with the lowest 28-day mortality corresponding to the glucose level was 101.75 mg/dl (95% CI 94.64-105.80 mg/dl); whereas in patients with comorbid diabetes, the effect of glucose concentration on 28-day mortality was structurally softer than in those with uncomorbid diabetes. Lastly, of all patients, hyperglycemia had the greatest deleterious effect on patients admitted to CSRU.Conclusions: Our study further confirmed the protective effect of comorbid diabetes on the short-term prognosis of critically ill patients, resulting in an approximately 29% reduction in 28-day mortality. Besides, we also demonstrated the personalized glycemic control strategy for critically ill patients. Lastly, clinicians should be aware of the occurrence and the prompt management of hyperglycemia in critically ill patients admitted to the CSRU.
Noninvasive Ventilatory Support As First-Line Treatment For COVID-19 Critically Ill Patients With Acute Hypoxemic Respiratory Failure
Authors: Menga Luca Salvatore , Cese Luca Delle , Bongiovanni Filippo , Lombardi Gianmarco , Luciani Filippo , Cicetti Marta , Timpano Jacopo , Ferrante Maria Cristina , Cesarano Melania , Tanzarella Eloisa S. , Cutuli Salvatore Lucio , Pintaudi Gabriele , Pascale Gennaro De , Dell'Anna Antonio Maria , Bello Giuseppe , Maggiore Salvatore M. , Maviglia Riccardo , Grieco Domenico Luca , Antonelli Massimo 
Published: July 2020

Abstract
Background: Although widely applied, noninvasive ventilatory support (NIVS) efficacy in COVID-19 disease is unknown. Early identification of treatment failure is warranted to avoid delays in endotracheal intubation and protective ventilation. We conducted a study to determine the rate of and factors associated to NIVS failure in critically ill patients with COVID-19 disease, and to compare NIVS failure rate in COVID-19 patients to that of a matched cohort with hypoxemic respiratory failure of other origins. Methods: All consecutive patients receiving first-line treatment NIVS for hypoxemic respiratory failure due to COVID-19 in the ICU of a University Hospital in Italy up to April 20th, 2020, were studied: laboratory data were collected on arrival, 28-day outcome was recorded. After one-to-one propensity score matching based on simplified acute physiology (SAPS) II score, age, PaO2/FiO2 and PaCO2 at arrival, NIVS failure rate in COVID-19 patients was compared to a previously published cohort who received NIVS during hypoxemic respiratory failure from other causes. Results: Eighty-five patients received first-line treatment with NIVS, mainly with helmet noninvasive ventilation and high-flow nasal cannula. Fifty-two patients (61%) needed endotracheal intubation. Independent predictors of NIVS failure were SAPSII score (adjusted hazard ratio 1.039 [1.018-1.061], <0.001), and serum lactate de-hydrogenase at enrolment (adjusted hazard ratio: 1.002 [1.000-1.004], p=0.013): 88% of patients with SAPSII≥33 and serum lactate de-hydrogenase≥405 Units/Liter needed endotracheal intubation vs. 32% of patients with SAPS<33 and lactate de-hydrogenase<405 Units/Liter. In the propensity-matched cohorts (108 patients), COVID-19 patients showed higher risk of NIVS failure than other causes of hypoxemic respiratory failure (59% vs. 35%, p=0.02), with an adjusted hazard ratio of 2 (CI95% [1.1-3.6], p=0.01). Conclusions: COVID-19 patients receiving first-line NIVS are burdened by high risk of needing endotracheal intubation: this appears greater than that of patients affected by hypoxemic respiratory failure of other origins. In order to not delay endotracheal intubation, if logistically sustainable, NIVS use in the intensive care unit should be avoided in severe patients (SAPSII score≥33) with serum lactate de-hydrogenase≥405 Units/Liter.
Individualized Flow-Controlled Ventilation Compared To Best Clinical Practice Pressure-Controlled Ventilation: A Prospective Randomized Porcine Study.
Authors: Spraider Patrick , Martini Judith , Abram Julia , Putzer Gabriel , Glodny Bernhard , Hell Tobias , Barnes Tom , Enk Dietmar 
Published: July 2020

Abstract
Background: Flow-controlled ventilation is a novel ventilation method which allows to individualize ventilation according to dynamic lung mechanic limits based on direct tracheal pressure measurement at a stable constant gas flow during inspiration and expiration. The aim of this porcine study was to compare individualized flow-controlled ventilation (FCV) and current guideline-conform pressure-controlled ventilation (PCV) in long-term ventilation.Methods: Anesthetized pigs were ventilated with either FCV or PCV over a period of ten hours with a fixed FiO2 of 0.3. FCV settings were individualized by compliance-guided positive end-expiratory pressure (PEEP) and peak pressure (Ppeak) titration. Flow was adjusted to maintain normocapnia and the inspiration to expiration ratio (I:E ratio) was set at 1:1. PCV was performed with a PEEP of 5 cm H2O and Ppeak was set to achieve a tidal volume (VT) of 7 ml/kg. The respiratory rate was adjusted to maintain normocapnia and the I:E ratio was set at 1:1.5. Repeated measurements during observation period were assessed by linear mixed-effects model.Results: In FCV (n=6) respiratory minute volume was significantly reduced (6.0 vs 12.7, MD -6.8 (-8.2 to -5.4) l/min; p<0.001) as compared to PCV (n=6). Oxygenation was improved in the FCV group (paO2 119.8 vs 96.6, MD 23.2 (9.0 to 37.5) torr; 15.97 vs 12.87, MD 3.10 (1.19 to 5.00) kPa; p=0.010) and CO2 removal was more efficient (paCO2 40.1 vs 44.9, MD -4.7 (-7.4 to -2.0) torr; 5.35 vs 5.98, MD -0.63 (-0.99 to -0.27) kPa; p=0.006). Ppeak and driving pressure were comparable in both groups, whereas PEEP was significantly lower in FCV (p=0.002). Computed tomography revealed a significant reduction in non-aerated lung tissue in individualized FCV (p=0.026) and no significant difference in overdistended lung tissue, although a significantly higher VT was applied (8.2 vs 7.6, MD 0.7 (0.2 to 1.2) ml/kg; p=0.025).Conclusion: Our long-term ventilation study demonstrates the applicability of a compliance-guided individualization of FCV settings, which resulted in significantly improved gas exchange and lung tissue aeration without signs of overinflation as compared to best clinical practice PCV.