Neural Architecture Search Survey: A Computer Vision Perspective.

In recent years, deep learning (DL) has been widely studied using various methods across the globe, especially with respect to training methods and network structures, proving highly effective in a wide range of tasks and applications, including image, speech, and text recognition. One important aspect of this advancement is involved in the effort of designing and upgrading neural architectures, which has been consistently attempted thus far. However, designing such architectures requires the combined knowledge and know-how of experts from each relevant discipline and a series of trial-and-error steps. In this light, automated neural architecture search (NAS) methods are increasingly at the center of attention; this paper aimed at summarizing the basic concepts of NAS while providing an overview of recent studies on the applications of NAS. It is worth noting that most previous survey studies on NAS have been focused on perspectives of hardware or search strategies. To the best knowledge of the present authors, this study is the first to look at NAS from a computer vision perspective. In the present study, computer vision areas were categorized by task, and recent trends found in each study on NAS were analyzed in detail.

Clinical impact of pneumothorax in patients with Pneumocystis jirovecii pneumonia and respiratory failure in an HIV-negative cohort.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) with acute respiratory failure can result in development of pneumothorax during treatment. This study aimed to identify the incidence and related factors of pneumothorax in patients with PCP and acute respiratory failure and to analyze their prognosis. METHODS: We retrospectively reviewed the occurrence of pneumothorax, including clinical characteristics and results of other examinations, in 119 non-human immunodeficiency virus patients with PCP and respiratory failure requiring mechanical ventilator treatment in a medical intensive care unit (ICU) at a tertiary-care center between July 2016 and April 2019. RESULTS: During follow up duration, twenty-two patients (18.5%) developed pneumothorax during ventilator treatment, with 45 (37.8%) eventually requiring a tracheostomy due to weaning failure. Cytomegalovirus co-infection (odds ratio 13.9; p = 0.013) was related with occurrence of pneumothorax in multivariate analysis. And development of pneumothorax was not associated with need for tracheostomy and mortality. Furthermore, analysis of survivor after 28 days in ICU, patients without pneumothorax were significantly more successful in weaning from mechanical ventilator than the patients with pneumothorax (44% vs. 13.3%, p = 0.037). PCP patients without pneumothorax showed successful home discharges compared to those who without pneumothorax (p = 0.010). CONCLUSIONS: The development of pneumothorax increased in PCP patient with cytomegalovirus co-infection, pneumothorax might have difficulty in and prolonged weaning from mechanical ventilators, which clinicians should be aware of when planning treatment for such patients.

Decreased annual risk of tuberculosis infection in South Korean healthcare workers using interferon-gamma release assay between 1986 and 2005.

BACKGROUND: Tuberculosis (TB) has been a major public health problem in South Korea. Although TB notification rate in Korea is gradually decreasing, still highest among the member countries of the Organization for Economic Cooperation and Development. To effectively control TB, understanding the TB epidemiology such as prevalence of latent tuberculosis infection (LTBI) and annual risk of TB infection (ARI) are important. This study aimed to identify the prevalence of LTBI and ARI among South Korean health care workers (HCWs) based on their interferon-gamma release assays (IGRA). METHODS: This was single center, cross-sectional retrospective study in a tertiary hospital in South Korea. We performed IGRA in HCWs between May 2017 and March 2018. We estimated ARI based on IGRA results. Logistic regression model was used to identify factors affecting IGRA positivity. RESULTS: A total of 3233 HCWs were analyzed. Median age of participants was 38.0 and female was predominant (72.6%). Overall positive rate of IGRA was 24.1% and IGRA positive rates age-group wise were 6.6%, 14.4%, 34.3%, and around 50% in the age groups 20s, 30s, 40s, and 50s and 60s, respectively. The ARIs was 0.26-1.35% between 1986 and 2005; rate of TB infection has gradually decreased in the last two decades. Multivariable analysis indicated that older age, healed TB lesion in x-ray, and male gender were risk factors for IGRA positivity, whereas working in high-risk TB departments was not. CONCLUSIONS: Results showed that ARI in South Korean HCWs gradually decreased over two decades, although LTBI remained prevalent. Our results suggest that the LTBI test result of HCWs might be greatly affected by age, rather than occupational exposure, in intermediate TB burden countries. Thus, careful interpretation considering the age structure is required.

Erythropoietin-Producing Hepatoma Receptor Tyrosine Kinase A2 Modulation Associates with Protective Effect of Prone Position in Ventilator-induced Lung Injury.

The erythropoietin-producing hepatoma (Eph) receptor tyrosine kinase A2 (EphA2) and its ligand, ephrinA1, play a pivotal role in inflammation and tissue injury by modulating the epithelial and endothelial barrier integrity. Therefore, EphA2 receptor may be a potential therapeutic target for modulating ventilator-induced lung injury (VILI). To support this hypothesis, here, we analyzed EphA2/ephrinA1 signaling in the process of VILI and determined the role of EphA2/ephrinA1 signaling in the protective mechanism of prone positioning in a VILI model. Wild-type mice were ventilated with high (24 ml/kg; positive end-expiratory pressure, 0 cm; 5 h) tidal volume in a supine or prone position. Anti-EphA2 receptor antibody or IgG was administered to the supine position group. Injury was assessed by analyzing the BAL fluid, lung injury scoring, and transmission electron microscopy. Lung lysates were evaluated using cytokine/chemokine ELISA and Western blotting of EphA2, ephrinA1, PI3Kγ, Akt, NF-κB, and P70S6 kinase. EphA2/ephrinA1 expression was higher in the supine high tidal volume group than in the control group, but it did not increase upon prone positioning or anti-EphA2 receptor antibody treatment. EphA2 antagonism reduced the extent of VILI and downregulated the expression of PI3Kγ, Akt, NF-κB, and P70S6 kinase. These findings demonstrate that EphA2/ephrinA1 signaling is involved in the molecular mechanism of VILI and that modulation of EphA2/ehprinA1 signaling by prone position or EphA2 antagonism may be associated with the lung-protective effect. Our data provide evidence for EphA2/ehprinA1 as a promising therapeutic target for modulating VILI.

TGF-ß1 T869C polymorphism may affect susceptibility to idiopathic pulmonary fibrosis and disease severity.

BACKGROUND: Transforming growth factor-ß1 (TGF-ß1) is a key cytokine that plays a critical role in idiopathic pulmonary fibrosis (IPF). The genotypes of T869C polymorphism may be associated with the susceptibility to fibrotic lung disease. METHODS: We investigated a single-nucleotide polymorphism at exon 1 nucleotide position 29 (T â†’ C) of the TGF-ß1 gene. Eighty-five healthy controls and 85 subjects with surgically confirmed IPF were investigated using polymerase chain reaction and restriction enzyme fragment length polymorphism techniques. RESULTS: The IPF patients consisted of 55 men and 30 women. The mean age was 61 ± 8 years. Fifty-one (60 %) of the 85 IPF patients were smokers and 34 were nonsmokers. The distribution of genotypes between IPF patients and controls was significantly different (IPF: TT 43.5 % and TC or CC 56.5 %; controls: TT 27.1 % and TC or CC 72.9 %, p = 0.037). TT genotype was significantly associated with decreased PaO2 and increased D(A-a)O2 upon initial diagnosis (p = 0.006 and 0.009, respectively). There was a positive association between TT genotype and IPF development (odds ratio [OR] = 2.1, 95 % confidence interval [CI] = 1.1-4.0, p = 0.028). CONCLUSIONS: This study suggests that the TGF-ß1 gene T869C polymorphism may affect susceptibility to IPF in Koreans. Larger studies are required to confirm the genetic association of TGF-ß1 gene polymorphism and IPF.

Risk factors for occurrence and 30-day mortality for carbapenem-resistant Acinetobacter baumannii bacteremia in an intensive care unit.

To assess the risk factors for carbapenem-resistant Acinetobacter baumannii (CRAB) bacteremia and for 30-day mortality in patients with CRAB bacteremia in the intensive care unit (ICU), we conducted a retrospective study in the ICU at Severance Hospital in Korea from January 2008 to December 2009. Patients who acquired CRAB bacteremia in the ICU were enrolled as the case group and patients whose specimens of blood culture, sputum/endotracheal aspirate and urine revealed no AB were enrolled as controls. The case group comprised 106 patients and 205 patients were included as controls. Risk factors independently associated with CRAB bacteremia included prior chemotherapy or radiotherapy treatment (Odds ratio [OR], 3.6; P = 0.003), recent central venous catheter insertion (OR, 5.7; P < 0.001) or abdominal drainage insertion (OR, 21.9; P = 0.004), the number of antibiotics treated with (OR, 1.3; P = 0.016), and respiratory failure in the ICU (OR, 2.5; P = 0.035). The 30-day mortality was 79.8%. Renal failure during ICU stay was independently associated with 30-day mortality (OR, 3.7; P = 0.047). It is important to minimize invasive procedures, and to restrict excessive use of antibiotics, especially in immunocompromised patients, in order to prevent the development of CRAB bacteremia. Greater concern for CRAB bacteremia patients is needed when renal failure develops during ICU stay.

Necrotizing Soft-Tissue Infections: A Retrospective Review of Predictive Factors for Limb Loss.

Background: Emergent diagnosis and treatment are important for the survival of patients with necrotizing soft-tissue infections (NSTIs). Death is the most catastrophic outcome, but limb loss is also one of the most important complications that can have a significant impact on the rest of the patient's life. The purpose of this study was to identify predictive factors for limb loss caused by NSTIs. Methods: The data of patients at our center who were diagnosed with NSTIs from May 2003 to January 2019 were analyzed retrospectively. The inclusion criteria were patients with a definite diagnosis of NSTI involving the upper or lower limb. A total of 49 patient records were analyzed in terms of demography, laboratory data, microbiological causes, treatment, and final outcome. Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) scores at initial admission were also collected as laboratory data. Final outcomes were classified into survival with limb salvage and survival with limb loss. Results: The limb loss rate was 20.4% (10/49) in our study. On comparison between the limb salvage group and the limb loss group, independent risk factors of limb loss were as follows: presence of hypotension at admission (odds ratio [OR], 8.2; 95% confidence interval [CI], 1.7-38.3; p = 0.008); LRINEC score ≥ 9 (OR, 5.8; 95% CI, 1.3-25.6; p = 0.012), and glucose level > 300 mg/dL (OR, 4.5; 95% CI, 0.9-21.9; p = 0.041). Various microbiological organisms were isolated; the most prevalent specimen was streptococci (32.6%), followed by staphylococci (26.5%). Poor outcomes including limb loss and mortality had no correlation with microbiological organisms. Conclusions: For patients with NSTIs, the presence of hypotension at admission, a high glucose level (> 300 mg/dL), and a high LRINEC score (> 9) were independent risk factors for limb loss.

Healthcare-associated pneumonia among hospitalized patients in a Korean tertiary hospital.

BACKGROUND: Healthcare-associated pneumonia (HCAP) has more similarities to nosocomial pneumonia than to community-acquired pneumonia (CAP). However, there have only been a few epidemiological studies of HCAP in South Korea. We aimed to determine the differences between HCAP and CAP in terms of clinical features, pathogens, and outcomes, and to clarify approaches for initial antibiotic management. METHODS: We conducted a retrospective, observational study of 527 patients with HCAP or CAP who were hospitalized at Severance Hospital in South Korea between January and December 2008. RESULTS: Of these patients, 231 (43.8%) had HCAP, and 296 (56.2%) had CAP. Potentially drug-resistant (PDR) bacteria were more frequently isolated in HCAP than CAP (12.6% vs. 4.7%; P = 0.001), especially in the low-risk group of the PSI classes (41.2% vs. 13.9%; P = 0.027). In-hospital mortality was higher for HCAP than CAP patients (28.1% vs. 10.8%, P < 0.001), especially in the low-risk group of PSI classes (16.4% vs. 3.1%; P = 0.001). Moreover, tube feeding and prior hospitalization with antibiotic treatment within 90 days of pneumonia onset were significant risk factors for PDR pathogens, with odds ratios of 14.94 (95% CI 4.62-48.31; P < 0.001) and 2.68 (95% CI 1.32-5.46; P = 0.007), respectively. CONCLUSIONS: For HCAP patients with different backgrounds, various pathogens and antibiotic resistance of should be considered, and careful selection of patients requiring broad-spectrum antibiotics is important when physicians start initial antibiotic treatments.

Delta neutrophil index as an early marker of disease severity in critically ill patients with sepsis.

BACKGROUND: The immature granulocyte count has been reported to be a marker of infection and sepsis. The difference in leukocyte subfractions (delta neutrophil index, DNI) in ADVIA 2120 reflects the fraction of circulating immature granulocytes in the blood. This study evaluated the clinical utility of DNI as a severity and prediction marker in critically ill patients with sepsis. METHODS: One hundred and three patients admitted to the medical intensive care unit with sepsis were studied. DNI (the difference in leukocyte subfractions identified by myeloperoxidase and nuclear lobularity channels) was determined using a specific blood cell analyzer. RESULTS: Forty four patients (42.7%) were diagnosed with severe sepsis/septic shock. Overt disseminated intravascular coagulation (DIC) occurred in 40 (38.8%). DNI was significantly higher in patients with severe sepsis/septic shock and overt DIC than in patients without (p < 0.05). DNI correlated with DIC score (r = 0.54, p < 0.001). We observed a monotonic increase in the proportion of overt DIC and severe sepsis/septic shock associated with increasing quartiles of DNI (p < 0.001). A DNI value > 6.5% was a better indicator of severe sepsis/septic shock than C-reactive protein, lactate, white blood cell count, and absolute neutrophil count (sensitivity, 81.3%; specificity, 91.0%; positive predictive value, 88.6%; and negative predictive value, 84.7%). In 36 (82%) of the 44 patients with severe sepsis/septic shock, DNI values were already elevated up to 12 hours before the onset of organ/circulatory failure. CONCLUSIONS: DNI may be used as a marker of disease severity in critically ill patients with sepsis. High levels of DNI may help to identify patients with an impending risk of developing severe sepsis/septic shock.

Morphological and Chemical Evaluations of Leaf Surface on Particulate Matter2.5 (PM2.5) Removal in a Botanical Plant-Based Biofilter System.

Particulate matter has been increasing worldwide causing air pollution and serious health hazards. Owing to increased time spent indoors and lifestyle changes, assessing indoor air quality has become crucial. This study investigated the effect of watering and drought and illumination conditions (constant light, light/dark cycle, and constant dark) on particulate matter2.5 (PM2.5) removal and surface characterization of leaf in a botanical plant-based biofilter system. Using Ardisia japonica and Hedera helix as experimental plants in the plant-based biofilter system, PM2.5, volatile organic carbon, and CO2, as the evaluators of indoor air quality, were estimated using a sensor. Morphological and chemical changes of the leaf surface (i.e., roughness and wax) associated with PM2.5 removal were characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, and atomic force microscopy. The highest PM2.5 removal efficiency, stomata closure, high leaf roughness, and wax layer were observed under drought with constant light condition. Consequently, PM2.5 removal was attributed to the combined effect of leaf roughness and wax by adsorption rather than stomatal uptake. These results suggest that operating conditions of indoor plant-based biofilter system such as watering (or drought) and illumination may be applied as a potential strategy for enhancing PM2.5 removal.

Network-assisted protein identification and data interpretation in shotgun proteomics.

Protein assembly and biological interpretation of the assembled protein lists are critical steps in shotgun proteomics data analysis. Although most biological functions arise from interactions among proteins, current protein assembly pipelines treat proteins as independent entities. Usually, only individual proteins with strong experimental evidence, that is, confident proteins, are reported, whereas many possible proteins of biological interest are eliminated. We have developed a clique-enrichment approach (CEA) to rescue eliminated proteins by incorporating the relationship among proteins as embedded in a protein interaction network. In several data sets tested, CEA increased protein identification by 8-23% with an estimated accuracy of 85%. Rescued proteins were supported by existing literature or transcriptome profiling studies at similar levels as confident proteins and at a significantly higher level than abandoned ones. Applying CEA on a breast cancer data set, rescued proteins coded by well-known breast cancer genes. In addition, CEA generated a network view of the proteins and helped show the modular organization of proteins that may underpin the molecular mechanisms of the disease.

Risk factors for multi-drug resistant Acinetobacter baumannii bacteremia in patients with colonization in the intensive care unit.

BACKGROUND: Epidemic outbreaks of multi-drug resistant (MDR) Acinetobacter baumannii (AB) in intensive care units (ICUs) are increasing. The incidence of MDR AB bacteremia, which develops as a result of colonization, is increasing through widespread dissemination of the pathogen, and further colonization. We sought to determine risk factors for MDR AB bacteremia in patients colonized with MDR AB in the ICU. METHODS: We conducted a retrospective, observational study of 200 patients colonized with MDR AB in the ICU at Severance Hospital, South Korea during the outbreak period between January 2008 and December 2009. RESULTS: Of the 200 patients colonized with MDR AB, 108 developed MDR AB bacteremia, and 92 did not. APACHE II scores were higher in bacteremic than non-bacteremic patients at the time of ICU admission and colonization (24.0 vs. 21.6; P = 0.035, 22.9 vs. 16.8; P < 0.001, respectively). There was no difference between the two groups in the duration of time from ICU admission to colonization (7.1 vs. 7.2 days; P = 0.923), but the duration of time at risk was shorter in bacteremic patients (12.1 vs. 6.0 days; P = 0.016). A recent invasive procedure was a significant risk factor for development of bacteremia (odds ratio = 3.85; 95% CI 1.45-10.24; P = 0.007). Multivariate analysis indicated infection and respiratory failure at the time of ICU admission, maintenance of mechanical ventilation, maintenance of endotracheal tube instead of switching to a tracheostomy, recent central venous catheter insertion, bacteremia caused by other microorganism after colonization by MDR AB, and prior antimicrobial therapy, were significant risk factors for MDR AB bacteremia. CONCLUSIONS: Patients in the ICU, colonized with MDR AB, should be considered for minimizing invasive procedures and early removal of the invasive devices to prevent development of MDR AB bacteremia.

Triethoxysilane-derived SiOx-assisted structural reinforcement of Si/carbon nanotube composite for lithium-ion battery.

Herein, triethoxysilane-derived SiOx is used as a robust adhesive anchor to bind Si nanoparticles (NPs) and carbon nanotubes (CNTs) to prepare a structurally reinforced Si/CNT microsphere composite. The chemical reaction between the silanol groups of triethoxysilane with the hydroxyl groups on the Si surface and acid-treated CNTs induce strong chemical bonds between the Si NPs and CNTs and among neighboring CNTs, facilitating electron-conduction pathways and structural integrity of the composite, even under severe stress/strain. Thus, the structurally reinforced Si/CNT/SiOx microsphere composite exhibits superior cyclability: ∼88% of its initial capacity of 1112 mA h g-1 is retained after 100 cycles at 0.5 A g-1. Moreover, the Si/CNT/SiOx composite exhibits a negligible change in electrode thickness after 100 cycles. The stable electrochemical behavior and negligible change in the electrode thickness are attributed to the maintenance of the electron-conduction pathways and structural integrity of the Si/CNT/SiOx composite, enabled by the binding of neighboring CNTs with the SiOx anchor.

From pull-down data to protein interaction networks and complexes with biological relevance.

MOTIVATION: Recent improvements in high-throughput Mass Spectrometry (MS) technology have expedited genome-wide discovery of protein-protein interactions by providing a capability of detecting protein complexes in a physiological setting. Computational inference of protein interaction networks and protein complexes from MS data are challenging. Advances are required in developing robust and seamlessly integrated procedures for assessment of protein-protein interaction affinities, mathematical representation of protein interaction networks, discovery of protein complexes and evaluation of their biological relevance. RESULTS: A multi-step but easy-to-follow framework for identifying protein complexes from MS pull-down data is introduced. It assesses interaction affinity between two proteins based on similarity of their co-purification patterns derived from MS data. It constructs a protein interaction network by adopting a knowledge-guided threshold selection method. Based on the network, it identifies protein complexes and infers their core components using a graph-theoretical approach. It deploys a statistical evaluation procedure to assess biological relevance of each found complex. On Saccharomyces cerevisiae pull-down data, the framework outperformed other more complicated schemes by at least 10% in F(1)-measure and identified 610 protein complexes with high-functional homogeneity based on the enrichment in Gene Ontology (GO) annotation. Manual examination of the complexes brought forward the hypotheses on cause of false identifications. Namely, co-purification of different protein complexes as mediated by a common non-protein molecule, such as DNA, might be a source of false positives. Protein identification bias in pull-down technology, such as the hydrophilic bias could result in false negatives.

Performance of the tuberculin skin test and interferon-gamma release assay for detection of tuberculosis infection in immunocompromised patients in a BCG-vaccinated population.

BACKGROUND: Interferon-gamma release assay (IGRA) may improve diagnostic accuracy for latent tuberculosis infection (LTBI). This study compared the performance of the tuberculin skin test (TST) with that of IGRA for the diagnosis of LTBI in immunocompromised patients in an intermediate TB burden country where BCG vaccination is mandatory. METHODS: We conducted a retrospective observational study of patients given the TST and an IGRA, the QuantiFERON-TB Gold In-Tube (QFT-IT), at Severance Hospital, a tertiary hospital in South Korea, from December 2006 to May 2009. RESULTS: Of 211 patients who underwent TST and QFT-IT testing, 117 (55%) were classified as immunocompromised. Significantly fewer immunocompromised than immunocompetent patients had positive TST results (10.3% vs. 27.7%, p 0.001), whereas the percentage of positive QFT-IT results was comparable for both groups (21.4% vs. 25.5%). However, indeterminate QFT-IT results were more frequent in immunocompromised than immunocompetent patients (21.4% vs. 9.6%, p 0.021). Agreement between the TST and QFT-IT was fair for the immunocompromised group (kappa = 0.38), but moderate agreement was observed for the immunocompetent group (kappa = 0.57). Indeterminate QFT-IT results were associated with anaemia, lymphocytopenia, hypoproteinemia, and hypoalbuminemia. CONCLUSION: In immunocompromised patients, the QFT-IT may be more sensitive than the TST for detection of LTBI, but it resulted in a considerable proportion of indeterminate results. Therefore, both tests may maximise the efficacy of screening for LTBI in immunocompromised patients.

Magnéli Phase Titanium Oxide as a Novel Anode Material for Potassium-Ion Batteries.

Recently, K-ion batteries (KIBs) have attracted attention for potential applications in next-generation energy storage devices principally on the account of their abundancy and lower cost. Herein, for the first time, we report an anatase TiO2-derived Magnéli phase Ti6O11 as a novel anode material for KIBs. We incorporate pristine carbon nanotube (CNT) on the TiO2 host materials due to the low electronic conductivity of the host materials. TiO2 transformed to Magnéli phase Ti6O11 after the first insertion/deinsertion of K ions. From the second cycle, Magnéli phase Ti6O11/CNT composite showed reversible charge/discharge profiles with ∼150 mA h g-1 at 0.05 A g-1. Ex situ X-ray diffraction and transmission electron microscopy analyses revealed that the charge storage process of Magnéli phase Ti6O11 proceeded via the conversion reaction during potassium ion insertion/deinsertion. The Magnéli phase Ti6O11/CNT composite electrode showed long-term cycling life over 500 cycles at 200 mA g-1, exhibiting a capacity retention of 76% and a high Coulombic efficiency of 99.9%. These salient results presented here provide a novel understanding of the K-ion storage mechanisms in the extensively investigated oxide-based material for Li-ion batteries and Na-ion batteries, shedding light on the development of promising electrode materials for next-generation batteries.

A multi-level cache model for run-time optimization of remote visualization.

Remote visualization is an enabling technology aiming to resolve the barrier of physical distance. While many researchers have developed innovative algorithms for remote visualization, previous work has focused little on systematically investigating optimal configurations of remote visualization architectures. In this paper, we study caching and prefetching, an important aspect of such architecture design, in order to optimize the fetch time in a remote visualization system. Unlike a processor cache or web cache, caching for remote visualization is unique and complex. Through actual experimentation and numerical simulation, we have discovered ways to systematically evaluate and search for optimal configurations of remote visualization caches under various scenarios, such as different network speeds, sizes of data for user requests, prefetch schemes, cache depletion schemes, etc. We have also designed a practical infrastructure software to adaptively optimize the caching architecture of general remote visualization systems, when a different application is started or the network condition varies. The lower bound of achievable latency discovered with our approach can aid the design of remote visualization algorithms and the selection of suitable network layouts for a remote visualization system.

Value of Serum Cystatin C Measurement in the Diagnosis of Sepsis-Induced Kidney Injury and Prediction of Renal Function Recovery.

PURPOSE: Acute kidney injury (AKI) is common in critically ill patients. Serum cystatin C has emerged as a reliable marker of AKI. We sought to assess the value of serum cystatin C for early detection and prediction of renal function recovery in patients with sepsis. MATERIALS AND METHODS: Sepsis patients (113 AKI patients and 49 non-AKI patients) admitted to the intensive care unit (ICU) were included. Serum creatinine and cystatin C levels and glomerular filtration rate were measured on days 0, 1, 3, and 7. RESULTS: Serum cystatin C levels were significantly higher in AKI patients than in non-AKI patients at all time points. Multivariate analysis showed that only serum cystatin C levels on day 0 were associated with AKI development [odds ratio (OR)=19.30; 95% confidence interval (CI)= 2.58-144.50, p<0.001]. Linear mixed model analysis showed significant variation in cystatin C levels between the recovery and non-recovery groups over time (p=0.001). High levels of serum cystatin C at day 0 (OR=1.64; 95% CI=1.00-2.68, p=0.048) were associated with recovery of AKI. CONCLUSION: Serum cystatin C level was found to be associated with the development and worsening of AKI in ICU patients with sepsis.

In silico discovery of enzyme-substrate specificity-determining residue clusters.

The binding between an enzyme and its substrate is highly specific, despite the fact that many different enzymes show significant sequence and structure similarity. There must be, then, substrate specificity-determining residues that enable different enzymes to recognize their unique substrates. We reason that a coordinated, not independent, action of both conserved and non-conserved residues determine enzymatic activity and specificity. Here, we present a surface patch ranking (SPR) method for in silico discovery of substrate specificity-determining residue clusters by exploring both sequence conservation and correlated mutations. As case studies we apply SPR to several highly homologous enzymatic protein pairs, such as guanylyl versus adenylyl cyclases, lactate versus malate dehydrogenases, and trypsin versus chymotrypsin. Without using experimental data, we predict several single and multi-residue clusters that are consistent with previous mutagenesis experimental results. Most single-residue clusters are directly involved in enzyme-substrate interactions, whereas multi-residue clusters are vital for domain-domain and regulator-enzyme interactions, indicating their complementary role in specificity determination. These results demonstrate that SPR may help the selection of target residues for mutagenesis experiments and, thus, focus rational drug design, protein engineering, and functional annotation to the relevant regions of a protein.

An evolution-based analysis scheme to identify CO2/O2 specificity-determining factors for ribulose 1,5-bisphosphate carboxylase/oxygenase.

Ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCo) catalyzes a rate-limiting step in photosynthetic carbon assimilation (reacting with CO2) and its competitive photo-respiratory carbon oxidation (reacting with O2). RuBisCo enzyme with an enhanced CO2/O2 specificity would boost the ability to make great progress in agricultural production and environmental management. RuBisCos in marine non-green algae, resulting from an earlier endo-symbiotic event, diverge greatly from those in green plants and cyanobacteria and, further, have the highest CO2/O2 specificity whereas RuBisCos in cyanobacteria have the lowest. We assumed that there exist different levels of CO2/O2 specificity-determining factors, corresponding to different evolutionary events and specificity levels. Based on this assumption, we devised a scheme to identify these substrate-determining factors. From this analysis, we are able to discover different categories of the CO2/O2 specificity-determining factors that show which residue substitutions account for (relatively) small specificity changes, as happened in green plants, or a tremendous enhancement, as observed in marine non-green algae. Therefore, the analysis can improve our understanding of molecular mechanisms in the substrate specificity development and prioritize candidate specificity-determining surface residues for site-directed mutagenesis.