Identification of distinct clinical phenotypes of acute respiratory distress syndrome with differential responses to treatment.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome, and the identification of homogeneous subgroups and phenotypes is the first step toward precision critical care. We aimed to explore whether ARDS phenotypes can be identified using clinical data, are reproducible and are associated with clinical outcomes and treatment response. METHODS: This study is based on a retrospective analysis of data from the telehealth intensive care unit (eICU) collaborative research database and three ARDS randomized controlled trials (RCTs) (ALVEOLI, FACTT and SAILS trials). We derived phenotypes in the eICU by cluster analysis based on clinical data and compared the clinical characteristics and outcomes of each phenotype. The reproducibility of the derived phenotypes was tested using the data from three RCTs, and treatment effects were evaluated. RESULTS: Three clinical phenotypes were identified in the training cohort of 3875 ARDS patients. Of the three phenotypes identified, phenotype I (n = 1565; 40%) was associated with fewer laboratory abnormalities, less organ dysfunction and the lowest in-hospital mortality rate (8%). Phenotype II (n = 1232; 32%) was correlated with more inflammation and shock and had a higher mortality rate (18%). Phenotype III (n = 1078; 28%) was strongly correlated with renal dysfunction and acidosis and had the highest mortality rate (22%). These results were validated using the data from the validation cohort (n = 3670) and three RCTs (n = 2289) and had reproducibility. Patients with these ARDS phenotypes had different treatment responses to randomized interventions. Specifically, in the ALVEOLI cohort, the effects of ventilation strategy (high PEEP vs low PEEP) on ventilator-free days differed by phenotype (p = 0.001); in the FACTT cohort, there was a significant interaction between phenotype and fluid-management strategy for 60-day mortality (p = 0.01). The fluid-conservative strategy was associated with improved mortality in phenotype II but had the opposite effect in phenotype III. CONCLUSION: Three clinical phenotypes of ARDS were identified and had different clinical characteristics and outcomes. The analysis shows evidence of a phenotype-specific treatment benefit in the ALVEOLI and FACTT trials. These findings may improve the identification of distinct subsets of ARDS patients for exploration in future RCTs.

A hybrid solution for extracting structured medical information from unstructured data in medical records via a double-reading/entry system.

BACKGROUND: Healthcare providers generate a huge amount of biomedical data stored in either legacy system (paper-based) format or electronic medical records (EMR) around the world, which are collectively referred to as big biomedical data (BBD). To realize the promise of BBD for clinical use and research, it is an essential step to extract key data elements from unstructured medical records into patient-centered electronic health records with computable data elements. Our objective is to introduce a novel solution, known as a double-reading/entry system (DRESS), for extracting clinical data from unstructured medical records (MR) and creating a semi-structured electronic health record database, as well as to demonstrate its reproducibility empirically. METHODS: Utilizing the modern cloud-based technologies, we have developed a comprehensive system that includes multiple subsystems, from capturing MRs in clinics, to securely transferring MRs, storing and managing cloud-based MRs, to facilitating both machine learning and manual reading, and to performing iterative quality control before committing the semi-structured data into the desired database. To evaluate the reproducibility of extracted medical data elements by DRESS, we conduct a blinded reproducibility study, with 100 MRs from patients who have undergone surgical treatment of lung cancer in China. The study uses Kappa statistic to measure concordance of discrete variables, and uses correlation coefficient to measure reproducibility of continuous variables. RESULTS: Using the DRESS, we have demonstrated the feasibility of extracting clinical data from unstructured MRs to create semi-structured and patient-centered electronic health record database. The reproducibility study with 100 patient's MRs has shown an overall high reproducibility of 98 %, and varies across six modules (pathology, Radio/chemo therapy, clinical examination, surgery information, medical image and general patient information). CONCLUSIONS: DRESS uses a double-reading, double-entry, and an independent adjudication, to manually curate structured data elements from unstructured clinical data. Further, through distributed computing strategies, DRESS protects data privacy by dividing MR data into de-identified modules. Finally, through internet-based computing cloud, DRESS enables many data specialists to work in a virtual environment to achieve the necessary scale of processing thousands MRs within days. This hybrid system represents probably a workable solution to solve the big medical data challenge.

Identification of a c-type heme oxygenase and its function during acclimation of cyanobacteria to nitrogen fluctuations.

The mechanisms of acclimating to a nitrogen-fluctuating environment are necessary for the survival of aquatic cyanobacteria in their natural habitats, but our understanding is still far from complete. Here, the synthesis of phycobiliprotein is confirmed to be much earlier than that of photosystem components during recovery from nitrogen chlorosis and an unknown protein Ssr1698 is discovered to be involved in this synthetic process. The unknown protein is further identified as a c-type heme oxygenase (cHO) in tetrapyrrole biosynthetic pathway and catalyzes the opening of heme ring to form biliverdin IXα, which is required for phycobilin production and ensuing phycobiliprotein synthesis. In addition, the cHO-dependent phycobiliprotein is found to be vital for the growth of cyanobacterial cells during chlorosis and regreening through its nitrogen-storage and light-harvesting functions, respectively. Collectively, the cHO expressed preferentially during recovery from nitrogen chlorosis is identified in photosynthetic organisms and the dual function of this enzyme-dependent phycobiliprotein is proposed to be an important mechanism for acclimation of aquatic cyanobacteria to a nitrogen-fluctuating environment.

Pathways and Kinetics for Autocatalytic Reduction of CO2 into Formic Acid with Fe under Hydrothermal Conditions.

The utilization of CO2, as a cheap and abundant carbon source to produce useful chemicals or fuels, has been regarded as one of the promising ways to reduce CO2 emissions and minimize the green-house effect. Previous studies have demonstrated that CO2 (or HCO3 -) can be efficiently reduced to formic acid with metal Fe under hydrothermal conditions without additional hydrogen and any catalyst. However, the pathways and kinetics of the autocatalytic CO2 reduction remain unknown. In the present work, the reaction kinetics were carefully investigated according to the proposed reaction pathways, and a phenomenological kinetic model was developed for the first time. The results showed that the hydrothermal conversion of HCO3 - into formic acid with Fe can be expressed as the first-order reaction, and the activation energy of HCO3 - is 28 kJ/mol under hydrothermal conditions.

Degradation of PVC waste into a flexible polymer by chemical modification using DINP moieties.

In consideration of the toxicity and high migration capacity of plasticizers, the possibility to obtain flexible PVC via chemical modification of PVC was investigated for feedstock recycling. In this work, some Cl atoms of PVC were substituted with fragments of the common plasticizer DINP (diisononyl phthalate) in the presence of K2CO3 (potassium carbonate) or DIEA (N,N-diisopropylethylamine), and the simultaneous elimination of PVC was suppressed. 1H NMR (1H nuclear magnetic resonance spectroscopy) and 1H-1H COSY (1H-1H correlation spectroscopy) were used to evaluate the substitution while a novel method of calculating the substitution and elimination ratios was developed using a combination of 1H NMR and elemental analysis. A maximum substitution rate of 35.7% was achieved using thiophenol as a nucleophile in the presence of DIEA, while the corresponding elimination of HCl was just 4.4%. In addition, the thermal stability of the modified PVCs was very close to that of pure PVC, which suggested that the main characteristics of PVC were preserved. Moreover, the T g values of all the modified PVCs were less than that of PVC, which means it is feasible to improve the plasticity of PVC via substituting some Cl on PVC with DINP moieties. Therefore, an alternative approach for feedstock recycling of PVC by chemical modification was developed in this work.

Controlling the selectivity to chemicals from catalytic depolymerization of kraft lignin with in-situ H2.

Catalytic depolymerization of kraft lignin was successfully carried out in isopropanol/water mixture system over Rh/La2O3/CeO2-ZrO2 catalyst at 373 °C for 2 h with Fe as reductant. The selectivity of in-situ H2 was increasing from 67 wt% to 98 wt% by changing the proportion of isopropanol and water with metal Fe. A one-to-one correspondence was established between liquid products distribution and H2. It was an efficient method for predicting the composition of the liquid oil by H2 selectivity detection or converting kraft lignin to desirable liquid products optionally, which administered to reduce the dependence on the specific catalysts. Other temperatures and catalysts were a viable option for the relationship.