Soft phenotyping for sepsis via EHR time-aware soft clustering.

OBJECTIVE: Sepsis is one of the most serious hospital conditions associated with high mortality. Sepsis is the result of a dysregulated immune response to infection that can lead to multiple organ dysfunction and death. Due to the wide variability in the causes of sepsis, clinical presentation, and the recovery trajectories, identifying sepsis sub-phenotypes is crucial to advance our understanding of sepsis characterization, to choose targeted treatments and optimal timing of interventions, and to improve prognostication. Prior studies have described different sub-phenotypes of sepsis using organ-specific characteristics. These studies applied clustering algorithms to electronic health records (EHRs) to identify disease sub-phenotypes. However, prior approaches did not capture temporal information and made uncertain assumptions about the relationships among the sub-phenotypes for clustering procedures. METHODS: We developed a time-aware soft clustering algorithm guided by clinical variables to identify sepsis sub-phenotypes using data available in the EHR. RESULTS: We identified six novel sepsis hybrid sub-phenotypes and evaluated them for medical plausibility. In addition, we built an early-warning sepsis prediction model using logistic regression. CONCLUSION: Our results suggest that these novel sepsis hybrid sub-phenotypes are promising to provide more accurate information on sepsis-related organ dysfunction and sepsis recovery trajectories which can be important to inform management decisions and sepsis prognosis.

Expression of Shh, Gli1, and Cyr61 in Gastric Cancer Predicts Overall Survival of Patients: A Retrospective Study.

OBJECTIVE: This study aimed to evaluate the expression levels of Shh, Gli1, and Cyr61 proteins in gastric cancer tissues and analyze the relationship between these three proteins and the clinicopathological factors and prognosis of patients. METHODS: This was a retrospective study. Four hundred gastric cancer tissue specimens from patients who underwent radical gastrectomy in Zhangye People's Hospital affiliated to Hexi University between February 2013 and February 2021 underwent immunohistochemical analysis. RESULTS: The positive expression rates of Shh, Gli1, and Cyr61 in gastric cancer tissues were 55.5%, 56.5%, and 64.5%, respectively. The expressions of Shh, Gli1, and Cyr61 in gastric cancer tissues were significantly correlated with tumor size, depth of invasion, and degree of differentiation (P < .05). The expression of Shh protein was positively correlated with the expression of Gli1 protein (P < .01), and the expression of Gli1 protein was positively correlated with the expression of Cyr61 protein (P < .01). Univariate and multivariate analyses showed that the expression of Shh, Gli1, and Cyr61 could predict the prognosis of patients (P < .05). Receiver operating characteristic curve analysis combined with TNM staging could better predict the three-year overall survival of patients (P < .05). CONCLUSION: Shh, Gli1, and Cyr61 proteins are significantly expressed in gastric cancer tissues and are risk factors for the prognosis of patients with gastric cancer.

Determining the Covertness of COVID-19 - Wuhan, China, 2020.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has been going on for over a year and has reemerged in several regions. Therefore, understanding the covertness of COVID-19 is critical to more precisely estimating the pandemic size, especially the population of hidden carriers (those with very mild or no symptoms). METHODS: A stochastic dynamic model was proposed to capture the transmission mechanism of COVID-19 and to depict the covertness of COVID-19. The proposed model captured unique features of COVID-19, changes in the diagnosis criteria, and escalating containment measures. RESULTS: The model estimated that, for the epidemic in Wuhan, 79.8% (76.7%-82.7%) of the spread was caused by hidden carriers. The overall lab-confirmation rate in Wuhan up until March 8, 2020 was 0.17 (0.15-0.19). The diagnostic rate among patients with significant symptoms went up to 0.82 on March 8, 2020 from 0.43 on January 1, 2020 with escalating containment measures and nationwide medical supports. The probability of resurgence could be as high as 0.72 if containment measures were lifted after zero new reported (lab-confirmed or clinically confirmed) cases in a consecutive period of 14 days. This probability went down to 0.18 and 0.01 for measures lifted after 30 and 60 days, respectively. DISCUSSION: Consistent with the cases detected in Wuhan in mid-May, 2020, this study suggests that much of the COVID-19 pandemic is underreported and highly covert, which suggests that strict measures must be enforced continuously to contain the spread of the pandemic.

Ultra-low-power four-wave mixing wavelength conversion in high-Q chalcogenide microring resonators.

A compact Ge11.5As24Se64.5 chalcogenide microring resonator is fabricated with an intrinsic quality factor of 3.0×105 in the telecom band. By taking advantage of the strong nonlinearity and cavity enhancement, highly efficient wavelength conversion via four-wave mixing is demonstrated using a microring resonator. Conversion efficiency of -33.7dB is obtained by using an ultra-low pump power of 63.8 µW. This work shows that Ge11.5As24Se64.5 chalcogenide microring devices are promising for quantum photonics.

Transmission Dynamics, Heterogeneity and Controllability of SARS-CoV-2: A Rural-Urban Comparison.

Few studies have examined the transmission dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in rural areas and clarified rural-urban differences. Moreover, the effectiveness of non-pharmaceutical interventions (NPIs) relative to vaccination in rural areas is uncertain. We addressed this knowledge gap through using an improved statistical stochastic method based on the Galton-Watson branching process, considering both symptomatic and asymptomatic cases. Data included 1136 SARS-2-CoV infections of the rural outbreak in Hebei, China, and 135 infections of the urban outbreak in Tianjin, China. We reconstructed SARS-CoV-2 transmission chains and analyzed the effectiveness of vaccination and NPIs by simulation studies. The transmission of SARS-CoV-2 showed strong heterogeneity in urban and rural areas, with the dispersion parameters k = 0.14 and 0.35, respectively (k < 1 indicating strong heterogeneity). Although age group and contact-type distributions significantly differed between urban and rural areas, the average reproductive number (R) and k did not. Further, simulation results based on pre-control parameters (R = 0.81, k = 0.27) showed that in the vaccination scenario (80% efficacy and 55% coverage), the cumulative secondary infections will be reduced by more than half; however, NPIs are more effective than vaccinating 65% of the population. These findings could inform government policies regarding vaccination and NPIs in rural and urban areas.

In-situ monitoring of the electrochemical behavior of cellular structured biomedical Ti-6Al-4V alloy fabricated by electron beam melting in simulated physiological fluid.

Ti-6Al-4V alloys with cellular structure fabricated by additive manufacturing are currently of significant interest because their modulus is comparable to bone and the cellular structure allows the cells to penetrate and exchange nutrients, promoting osseointegration. We describe here a unique simulation device that replaces the traditional steady electrochemistry approach, enabling in-situ study of variation of ion concentration and surface potential with pore depth for cellular structured Ti-6Al-4V alloys fabricated by electron beam melting (EBM) in phosphate buffered saline (PBS). This approach addresses the scientific gap on the electrochemical behavior of cellular structured titanium alloys. The study indicated that concentration of H+ and Cl- increased with the increase of pore depth, while the surface potential decreased. The exposed surface of inner cellular structure was not corroded but passivated after immersing in PBS at 37 °C for 14 days, which was independent of pore depth. Furthermore, X-ray photoelectron spectroscopy (XPS) and Mott-Schottky (M-S) studies suggested that a thinner passive film containing a greater donor density was formed on the surface of cellular structured Ti-6Al-4V alloy at the deepest pore depth. This is attributed to insufficient oxygen supply and Cl-adsorption on the surface inside the pores. STATEMENT OF SIGNIFICANCE: Porous titanium alloys are promising implants in biomedical applications. However, it is a challenge to accurately characterize the corrosion behavior of porous titanium alloys with complex pore structure using traditional electrochemical methods. In this study, we have adopted a special device to simulate the environment within the pore structure. The variation in ion concentration and surface potential of Ti-6Al-4V fabricated by EBM with pore depth was in-situ monitored. After immersing in PBS for 14 days, Ti-6Al-4V exhibited good corrosion properties and the samples with less than 60 mm pore depth were not corroded but passivated. Also, we analyzed the difference in corrosion property at different pore depth. This type of in-situ corrosion performance monitoring in EBM-produced Ti-6Al-4V has not been previously studied.

[Secondary Organic Aerosol Mass Yield and Characteristics from 4-ethylguaiacol Aqueous·OH Oxidation: Effects of Initial Concentration].

Aqueous-phase chemical processing, as an essential formation pathway of secondary organic aerosol (SOA), has attracted widespread attention from within atmospheric chemistry fields. Due to the complicated reaction nature, reaction mechanisms, and product characteristics of aqueous-phase chemical processing, its contribution to the SOA budget is still not fully understood. In this work, we investigate how the initial concentration (0.03-3 mmol·L-1) of 4-ethylguaiacol affects SOA formation of aqueous·OH photochemical oxidation. We use soot-particle aerosol mass spectrometry (SP-AMS) to monitor SOA mass yield and oxidation character, and gas chromatography-mass spectrometry (GC-MS) and ion chromatography (IC) to measure products and organic acids. Additionally, we use ultraviolet visible spectroscopy (UV-vis) and high-performance liquid spectrometry (HPLS) to track the formation of light-absorbing products such as humic-like substances (HULIS). Our research indicated that the range of the O/C ratio of EG-aqSOA measured by the SP-AMS exhibited increasing trends with increased reaction time 0.42-0.61 (0.03 mmol·L-1), 0.49-0.84 (0.3 mmol·L-1), and 0.49-0.63 (3 mmol·L-1). Dimers (C16H18 O2+, m/z 302) via SP-AMS were obviously higher under a higher initial concentration, thereby demonstrating that the oligomerization reaction proceeded more easily. The absorption at 250 nm recorded by UV-vis was distinctly enhanced, which might be attributed to new light-absorbing products with absorbance at 250 nm. Furthermore, the HULIS concentration increased with reaction time, in accordance with enhancement of absorbance in the 300-400 nm region, thus suggesting that aqueous-phase processing formed brown carbon. Small organic acids, including formic acid, malic acid, and oxalic acid, were detected by IC in all reaction solutions, with the highest concentration being for formic acid. GC/MS detected ketone, an OH monomer, and dimers in the aqSOA, which further indicates that functionalization and oligomerization took place.

Novel Wavelength-Specific Blue Light-Emitting Headlamp for 5-Aminolevulinic Acid Fluorescence-Guided Resection of Glioblastoma.

OBJECTIVE: Extent of resection of glioblastoma is an important predictor for overall survival, and 5-aminolevulinic acid fluorescence-guided surgery can improve outcomes. However, the technique requires the installation of a blue light module on operative microscopes and may be cost prohibitive. A novel and economical blue light-emitting headlamp was designed, and its clinical utility was explored. METHODS: A remote-controlled dual light emitting diode headlamp system was constructed with 1 diode emitting white light and the other blue. Spectrographic analysis of the blue light emitted from a commercial operative microscope and the headlamp was performed. A comparative evaluation of the 2 illumination systems was conducted for 3 patients who underwent craniotomy for glioblastoma resection. Histologic examination of the fluorescing tissue detected by the headlamp was performed, and the extent of resection was assessed by postoperative day 1 magnetic resonance imaging. RESULTS: Spectrography of blue light emitted from the headlamp system was wavelength specific with a single emission peak at 416 nm and a linewidth of 35 nm. In contrast, blue light from the microscope (peak: 426 nm) had a wider linewidth of 54 nm and was not wavelength specific with additional infrared radiation detected. Gross or near-total resection of contrast-enhancing glioblastoma was performed for all 3 patients. Intraoperatively, comparable tumor fluorescence was observed under microscope and headlamp blue light illumination. Histologic examination of tissue fluorescing under headlamp blue light confirmed the presence of glioblastoma. CONCLUSIONS: This novel proof-of-concept blue light-emitting headlamp device may offer an opportunity for institutions with limited resources to implement 5-aminolevulinic acid fluorescence-guided glioblastoma resections.

[Secondary Organic Aerosols from Aqueous Reaction of Aerosol Water].

Liquid water (cloud/fog droplets and aerosols) is ubiquitous in the atmosphere and can provide an important reaction media for aqueous-phase chemical reactions. Gaseous precursors (mainly VOCs) or their gas-phase initial or first-generation oxidation products (including intermediate-volatility and semi-volatile organic compounds; I/SVOCs) can undergo chemical reactions in the atmospheric condensed phase (aqueous phase) to form low-volatility, highly oxidized organic matter[e.g., some key tracer species such as organosulfates (OSs) and organonitrogens (ONs)]. These products largely remain in the particle phase upon water evaporation and are referred to as aqueous secondary organic aerosols (aqSOAs). aqSOAs have been emerging as a research hot topic in atmospheric chemistry, as they can contribute significantly to OAs and thus have important impacts on the environment, climate, and human health. Despite considerable progress, so far, aqSOAs remain poorly understood owing to their complex formation mechanisms. In this review, we focus mainly on the relevant research results on the SOAs formed in aerosol water-aqueous aerosol SOAs (aaSOAs)-including gas-phase precursors, formation mechanisms, laboratory simulations, and field observations, as well as SOA yield and contribution to OAs. Meanwhile, we propose future directions regarding studies of sources and formation mechanisms of aaSOAs, including identification of unknown aaSOA precursors and tracer products, photosensitizer-triggered radical chemistry, formation pathways of OS and ON compounds, field observations and model simulations of aaSOAs.

High-bit rate ultra-compact light routing with mode-selective on-chip nanoantennas.

Optical nanoantennas provide a promising pathway toward advanced manipulation of light waves, such as directional scattering, polarization conversion, and fluorescence enhancement. Although these functionalities were mainly studied for nanoantennas in free space or on homogeneous substrates, their integration with optical waveguides offers an important "wired" connection to other functional optical components. Taking advantage of the nanoantenna's versatility and unrivaled compactness, their imprinting onto optical waveguides would enable a marked enhancement of design freedom and integration density for optical on-chip devices. Several examples of this concept have been demonstrated recently. However, the important question of whether nanoantennas can fulfill functionalities for high-bit rate signal transmission without degradation, which is the core purpose of many integrated optical applications, has not yet been experimentally investigated. We introduce and investigate directional, polarization-selective, and mode-selective on-chip nanoantennas integrated with a silicon rib waveguide. We demonstrate that these nanoantennas can separate optical signals with different polarizations by coupling the different polarizations of light vertically to different waveguide modes propagating into opposite directions. As the central result of this work, we show the suitability of this concept for the control of optical signals with ASK (amplitude-shift keying) NRZ (nonreturn to zero) modulation [10 Gigabit/s (Gb/s)] without significant bit error rate impairments. Our results demonstrate that waveguide-integrated nanoantennas have the potential to be used as ultra-compact polarization-demultiplexing on-chip devices for high-bit rate telecommunication applications.

CMOS compatible fabrication of micro, nano convex silicon lens arrays by conformal chemical vapor deposition.

We present a novel CMOS-compatible fabrication technique for convex micro-nano lens arrays (MNLAs) with high packing density on the wafer scale. By means of conformal chemical vapor deposition (CVD) of hydrogenated amorphous silicon (a-Si:H) following patterning of silicon pillars via electron beam lithography (EBL) and plasma etching, large areas of a close packed silicon lens array with the diameter from a few micrometers down to a few hundred nanometers was fabricated. The resulting structure shows excellent surface roughness and high uniformity. The optical focusing properties of the lenses at infrared wavelengths were verified by experimental measurements and numerical simulation. This approach provides a feasible solution for fabricating silicon MNLAs compatible for next generation large scale, miniaturized optical imaging detectors and related optical devices.

[Pollution Characteristics and Light Extinction Contribution of Water-soluble Ions of PM2.5 in Hangzhou].

The pollution characteristics and light extinction contribution of water-soluble ions of PM2.5 in Hangzhou were investigated by sampling and laboratory analysis of aerosol samplers in 2013. The water-soluble ions were dominant in PM2.5 and the total mass concentration was 37.5 µg·m-3, accounting for 44.4% of the PM2.5 mass concentration. Water-soluble ions were mainly composed of secondary ions(SO42-,NO3- and NH4+), which accounted for 83.4% of total ions. The highest mass concentrations of PM2.5 and major ions were observed in winter and the lowest in summer. The proportions of water-soluble ions in PM2.5 in summer and autumn were obviously higher than those in winter and spring and proportions of secondary ions in water-soluble ions were very close in each season. The contribution was the greatest to PM2.5 from secondary ions generation caused by fuel combustion and automobile exhaust. The annual average values of SOR and NOR were 0.27 and 0.15 respectively, the conversion rate of SO2 in atmosphere was greater than that of NOx. There was obvious positive correlation between SOR or NOR and humidity which indicated the important contribution of heterogeneous oxidation process to the generation of SO42- and NO3-. The annual average of[NO3-]/[SO42-] was 0.63, and the aerosol pollution was primarily affected by emissions from coal burning. In haze days, with the increase of haze pollution level, the mass concentrations of PM2.5, water-soluble ions, secondary ions as well as SOR and NOR all increased gradually, and the stable weather condition in haze days could efficiently promote the accumulation and secondary conversion of pollutants. There were obvious positive correlations between mass concentrations of PM2.5 and SNA and the atmospheric light extinction coefficient. The IMPROVE formula which was used to calculate the light extinction coefficients of different chemical components could efficiently indicate the tendency of aerosol scattering. The extinction contribution of SNA could reach 60.8%. The extinction coefficient of SNA was the highest in winter and lowest in summer, and its value and contribution proportion both increased gradually as the haze pollution level rose.

[Pollution Characteristics and Source Identification of PAHs in Atmospheric PM2.5 in Changzhou City].

A total of 55 ambient fine particle (PM2.5) samples were collected in Changzhou City from January to August 2016. The concentrations of 17 PM2.5-bound PAHs in the samples were analyzed by GC-MS. Results showed that seasonal average mass concentrations of PAHs in winter, spring, and summer were 140.24, 41.42, and 2.96 ng·m-3, respectively, which indicating that the pollution of PAHs in winter appeared more serious than in the other two seasons, and 4-6-ring high molecular weight PAHs were predominant in all three seasons. The average daily level of BaP was 3.64 ng·m-3 and the days it exceeded the permitted standard accounted for 41% of total days. PAH concentration had significant negative correlations with temperature (correlation coefficient: -0.643) and visibility (correlation coefficient: -0.466), whereas it had good positive correlations with atmospheric pressure (correlation coefficient: 0.544) and poor correlations with wind speed and relative humidity. PAH concentrations were higher at nighttime than at daytime, because of the influences of temperature difference, atmospheric stratification, as well as pollution sources. The results from the air backward trajectory model indicated that PM2.5-bound PAHs in Changzhou were mainly affected by local emission sources and short-distance transportation, whereas the contribution of long-distance transmission was small (only 11%). Based on analysis of characteristic ratios, PAHs were mainly sourced from coal burning, vehicle emissions, and biomass burning. An incremental lifetime cancer risk (ILCR) model was used to evaluate the health impact of PAHs via breathing exposure pathways. Results revealed that the ILCR of adults was higher than that of children. The ILCRs of the group for winter and spring were slightly higher than the risk threshold, but a difference was not obvious for summer.

[Pollution Characteristics of Aerosol Number Concentration in Winter and Spring in a Northern Suburb of Nanjing].

Using APS-3321, the atmospheric aerosol number concentrations (0.5-20 µm) were continuously monitored to analyze the characteristics of winter and spring pollution in 2014 in a northern suburb of Nanjing. The average number concentrations were (364.8±297.8) cm-3 and (79.6±62.4) cm-3 in winter and spring, respectively; fine particles (0.5-1.0 µm) accounted for 87.8% and 86.6% of the total, respectively. There were significant variations in number concentration at different periods. The diurnal variations in number concentrations were evident with high concentrations at night and low concentrations during the day. The early peaks were at 07:00 and 09:00, and number concentrations began to increase rapidly starting at 17:00 and 18:00 in winter and spring, respectively. The distribution of the number concentrations was unimodal, with peak sizes between 0.583 and 0.626 µm in winter and less than 0.542 µm in spring. With the increase in relative humidity, aerosol number concentrations increased gradually; at the same time, the peak size moved to a larger diameter which reflected the influence of hygroscopic growth of aerosols. During the total observation period, it reached 83.3% of the proportion of hazy days. The number concentration of particles less than 2.0 µm increased significantly with the increase in the haze pollution level, which was more obvious in winter. In spring, the proportion of fine particles increased with the increase in the haze level but in winter, it decreased during hazy days due to a significant increase in particle size caused by aging. The analysis of the typical pollution process in January indicated that there was a strong correlation between the source of air mass and the surface wind direction. Pollutants transmitted from the northern Jiangsu Province and the accumulation of pollutants due to slow winds were important causations of the pollution process.

Temporal variation in the response of tumors to hyperoxia with breathing carbogen and oxygen.

The effect of hyperoxygenation with carbogen (95% O2 + 5% CO2) and 100% oxygen inhalation on partial pressure of oxygen (pO2) of radiation-induced fibrosarcoma (RIF-1) tumor was investigated. RIF-1 tumors were innoculated in C3H mice, and aggregates of oximetry probe, lithium phthalocyanine (LiPc), was implanted in each tumor. A baseline tumor pO2 was measured by electron paramagnetic resonance (EPR) oximetry for 20 minutes in anesthetized mice breathing 30% O2 and then the gas was switched to carbogen or 100 % oxygen for 60 minutes. These experiments were repeated for 10 days. RIF-1 tumors were hypoxic with a baseline tissue pO2 of 6.2-8.3 mmHg in mice breathing 30% O2. Carbogen and 100% oxygen significantly increased tumor pO2 on days 1 to 5, with a maximal increase at approximately 32-45 minutes on each day. However, the extent of increase in pO2 from the baseline declined significantly on day 5 and day 10. The results provide quantitative information on the effect of hyperoxic gas inhalation on tumor pO2 over the course of 10 days. EPR oximetry can be effectively used to repeatedly monitor tumor pO2 and test hyperoxic methods for potential clinical applications.

Two-Dimensional Infrared Study of Vibrational Coupling between Azide and Nitrile Reporters in a RNA Nucleoside.

The vibrations in the azide, N3, asymmetric stretching region and nitrile, CN, symmetric stretching region of 2'-azido-5-cyano-2'-deoxyuridine (N3CNdU) are examined by two-dimensional infrared (2D IR) spectroscopy. At earlier waiting times, the 2D IR spectrum shows the presence of both vibrational transitions along the diagonal and off-diagonal cross peaks indicating vibrational coupling. The coupling strength is determined from the off-diagonal anharmonicity to be 66 cm(-1) for the intramolecular distance of ∼7.9 Å, based on a structural map generated for this model system. In addition, the frequency-frequency correlation decay is detected, monitoring the solvent dynamics around each individual probe position. Overall, these vibrational reporters can be utilized in tandem to simultaneously track global structural information and fast structural fluctuations.

Experimental demonstration of linearly polarized 2-10 µm supercontinuum generation in a chalcogenide rib waveguide.

This Letter reports the production of a supercontinuum extending from ≈2 µm to >10 µm generated using a chalcogenide buried rib waveguide pumped with 330 femtosecond pulses at 4.184 µm. This is, to the best of our knowledge, the broadest mid-infrared supercontinuum generated in any planar waveguide platform. Because the waveguide is birefringent, quasi-single-mode, and uses an optimized dispersion design, the supercontinuum is linearly polarized with an extinction ratio >100. Dual beam spectrophotometry is performed easily using this source.