This study evaluated the effect of hyperbilirubinemia on the accuracy of continuous non-invasive hemoglobin (SpHb) measurements in liver transplantation recipients. Overall, 1465 SpHb and laboratory ...hemoglobin (Hb) measurement pairs (n = 296 patients) were analyzed. Patients were grouped into normal (< 1.2 mg/dL), mild-to-moderate (1.2-3.0 mg/dL), and severe (> 3.0 mg/dL) hyperbilirubinemia groups based on the preoperative serum total bilirubin levels. Bland-Altman analysis showed a bias of 0.20 (95% limit of agreement, LoA: - 2.59 to 3.00) g/dL, 0.98 (95% LoA: - 1.38 to 3.35) g/dL, and 1.23 (95% LoA: - 1.16 to 3.63) g/dL for the normal, mild-to-moderate, and severe groups, respectively. The four-quadrant plot showed reliable trending ability in all groups (concordance rate > 92%). The rates of possible missed transfusion (SpHb > 7.0 g/dL for Hb < 7.0 g/dL) were higher in the hyperbilirubinemia groups (2%, 7%, and 12% for the normal, mild-to-moderate, and severe group, respectively. all P < 0.001). The possible over-transfusion rate was less than 1% in all groups. In conclusion, the use of SpHb in liver transplantation recipients with preoperative hyperbilirubinemia requires caution due to the positive bias and high risk of missed transfusion. However, the reliable trending ability indicated its potential use in clinical settings.
We aimed to investigate the optimal surgical timing in patients with preoperative coronavirus disease 2019 (COVID-19) infection to minimize postoperative morbidity and mortality during the COVID-19 ...vaccination era.
The Korean nationwide data on patients who underwent standard surgery under general anesthesia in 2021 were analyzed. Patients were categorized based on the time from COVID-19 diagnosis to surgery: 0-4, 5-8, > 8 weeks, and those without preoperative COVID-19 infection. Multivariable logistic regression analysis, considering preoperative COVID-19 vaccination status (fully vaccinated vs. unvaccinated or partially vaccinated), was performed to associate the preoperative COVID-19 infection timing with 30- and 90-day postoperative mortality and 30-day respiratory complications.
Among the 750,175 included patients, 28.2% were preoperatively fully vaccinated. Compared with patients without prior COVID-19 infection, those who had surgery 0-4 weeks (adjusted odds ratio OR: 4.28, 95% CI 1.81, 10.13, P = 0.001) and 5-8 weeks (adjusted OR: 3.38, 95% CI 1.54, 7.44, P = 0.002) after COVID-19 infection had a significantly increased risk of 30-day mortality. Preoperative full vaccination was significantly associated with a decrease in 90-day mortality (adjusted OR: 0.93, 95% CI 0.89, 0.98, P = 0.007) and 30-day respiratory complications (adjusted OR: 0.85, 95% CI 0.82, 0.87, P < 0.001), but not with 30-day mortality (P = 0.916).
COVID-19 infection eight weeks preoperatively was associated with an increased 30-day postoperative mortality. Preoperative full vaccination was not associated with 30-day mortality but was related to lower risk of 90-day mortality and 30-day respiratory complications.
P-type silicon nanowires (SiNWs) have attracted significant attention for their potential in miniaturizing sensing devices, attributed to the observed giant piezoresistive (PZR) effects. However, the ...application of these advantageous PZR properties of SiNWs to microelectromechanical systems (MEMS) has been hindered by unclear noise levels and complicated fabrication methods. Additionally, several previous reports of anomalous PZR effects, such as doping-type inversion in hydrogen fluoride (HF)-treated p-type SiNWs, have introduced further complexities. Consequently, addressing these unclear challenges is necessary to effectively utilize the PZR effects of SiNWs for MEMS sensing applications. In this paper, the primary causes of uncertain noises and resistance levels in HF-treated p-SiNWs and their dependence on surface effects were analyzed to optimize NW parameters. SiNWs were fabricated using a suitable MEMS fabrication method, and their noises with PZR effects were measured and compared. The results indicated that SiNWs with abnormal PZR characteristics were worse in signal-to-noise ratio (SNR) than those with bulk PZR properties attributed to the significant noise increments from the depletion effects. Based on the NW experiment and additional mechanical analyses, suitable SiNW conditions for MEMS sensing unit were optimized and selected. A miniaturized 3-axis accelerometer utilizing the optimized SiNW was developed and tested. The experimental results showed that the developed accelerometer successfully reduced the total area of the sensor structure by 35.4% when compared to commercial capacitive accelerometers while maintaining competitive performance. This result was achieved without relying on the giant or anomalous PZR effects.
Air flow measurements provide significant information required for understanding the characteristics of insect movement. This study proposes a four-channel low-noise readout integrated circuit (IC) ...in order to measure air flow (air velocity), which can be beneficial to insect biomimetic robot systems that have been studied recently. Instrumentation amplifiers (IAs) with low-noise characteristics in readout ICs are essential because the air flow of an insect’s movement, which is electrically converted using a microelectromechanical systems (MEMS) sensor, generally produces a small signal. The fundamental architecture employed in the readout IC is a three op amp IA, and it accomplishes low-noise characteristics by chopping. Moreover, the readout IC has a four-channel input structure and implements an automatic offset calibration loop (AOCL) for input offset correction. The AOCL based on the binary search logic adjusts the output offset by controlling the input voltage bias generated by the R-2R digital-to-analog converter (DAC). The electrically converted air flow signal is amplified using a three op amp IA, which is passed through a low-pass filter (LPF) for ripple rejection that is generated by chopping, and converted to a digital code by a 12-bit successive approximation register (SAR) analog-to-digital converter (ADC). Furthermore, the readout IC contains a low-dropout (LDO) regulator that enables the supply voltage to drive digital circuits, and a serial peripheral interface (SPI) for digital communication. The readout IC is designed with a 0.18 μm CMOS process and the current consumption is 1.886 mA at 3.3 V supply voltage. The IC has an active area of 6.78 mm2 and input-referred noise (IRN) characteristics of 95.4 nV/√Hz at 1 Hz.
Cryptococcus neoformans is the leading cause of death by fungal meningoencephalitis; however, treatment options remain limited. Here we report the construction of 264 signature-tagged gene-deletion ...strains for 129 putative kinases, and examine their phenotypic traits under 30 distinct in vitro growth conditions and in two different hosts (insect larvae and mice). Clustering analysis of in vitro phenotypic traits indicates that several of these kinases have roles in known signalling pathways, and identifies hitherto uncharacterized signalling cascades. Virulence assays in the insect and mouse models provide evidence of pathogenicity-related roles for 63 kinases involved in the following biological categories: growth and cell cycle, nutrient metabolism, stress response and adaptation, cell signalling, cell polarity and morphology, vacuole trafficking, transfer RNA (tRNA) modification and other functions. Our study provides insights into the pathobiological signalling circuitry of C. neoformans and identifies potential anticryptococcal or antifungal drug targets.
Optimizing endotracheal tube (ETT) shape is important for successful videolaryngoscope-aided intubation. This prospective randomized controlled study aimed to compare the tube-handling time between a ...C-curved and hockey stick-shaped stylet in infants and neonates using the C-MAC® videolaryngoscope Miller blade.
A total of 110 infants (age < 1 year) were randomly assigned to either the hockey stick-curved stylet group (group H, n = 53) or the C-curved stylet group (group C, n = 57). The primary outcome was tube handling time after glottis visualization and the secondary outcomes were the total intubation time, incidence of successful intubation, initial tube tip location at the laryngeal inlet, and numerical rating scale for ease of intubation.
Tube insertion time and total intubation duration (both in seconds) were significantly shorter in group C than in group H (13.3 ± 8.9 vs. 25.1 ± 27.0, P = 0.002; 19.9 ± 9.4 vs. 32.8 ± 27.1, P = 0.001, respectively). Group C displayed a higher rate of intubation success within 30 s than group H (87.7% vs. 69.8%, P = 0.029). The initial tube tip was located at the center in 34 children in group C (59.6%) and 12 children in group H (26.1%, P < 0.001). Laryngoscope operators rated intubation as easier when provided with a C-curved stylet.
In neonates and infants, modification of the ETT shape into a C-curve may reduce tube handling time compared to the conventional hockey stick-shaped tube during intubation using a C-MAC® video laryngoscope Miller blade.
Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits ...opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which metal chelation modulates morphogenetic circuitry and echinocandin resistance, and illuminate a novel facet to metal homeostasis at the host-pathogen interface, with broad therapeutic potential.
Dynamic adhesion and detachment of subcellular regions occur during cell migration, thus a technique allowing precise control of subcellular detachment of cells will be useful for cell migration ...study. Previous methods for cell detachment were developed either for harvesting cells or cell sheets attached on surfaces with low resolution patterning capability, or for detaching subcellular regions located on predefined electrodes. In this paper, a method that allows in situ subcellular detachment of cells with ≈1.5 µm critical feature size while observing cells under a fluorescence microscope is introduced using a cell‐friendly photoresist and spatially modulated light. Using this method, a single cell, regions in cell sheets, and a single focal adhesion complex within a cell are successfully detached. Furthermore, different subcellular regions of migrating cells are detached and changes in cell polarity and migration direction are quantitatively analyzed. This method will be useful for many applications in cell detachment, in particular when subcellular resolution is required.
A method that allows in situ high‐resolution subcellular region detachment is developed. Using this method, a single cell, cells in cell sheets, and a single focal adhesion complex within a cell are successfully detached. In addition, different subcellular regions of migrating cells are detached and influences of subcellular detachment in cell polarity and migration are quantitatively analyzed.
Silicon nanowires (SiNWs) have received attention in recent years due to their anomalous piezoresistive (PZR) effects. Although the PZR effects of SiNWs have been extensively researched, they are ...still not fully understood. Herein, we develop a new model of the PZR effects of SiNWs to characterize the PZR effects. First, the resistance of SiNW is modeled based on the surface charge density. The characteristics of SiNW, such as surface charge and effective conducting area, can be estimated by using this resistance model. Then, PZR effects are modeled based on stress concentration and piezopinch effects. Stress concentration as a function of the physical geometry of SiNWs can amplify PZR effects by an order of magnitude. The piezopinch effects can also result in increased PZR effects that are at least two times greater than that of bulk silicon. Experimental results show that the proposed model can predict the PZR effects of SiNWs accurately.
Cryptococcus neoformans is an opportunistic human pathogenic fungus that causes meningoencephalitis. Due to the increasing global risk of cryptococcosis and the emergence of drug-resistant strains, ...the development of predictive genetics platforms for the rapid identification of novel genes governing pathogenicity and drug resistance of C. neoformans is imperative. The analysis of functional genomics data and genome-scale mutant libraries may facilitate the genetic dissection of such complex phenotypes but with limited efficiency. Here, we present a genome-scale co-functional network for C. neoformans, CryptoNet, which covers ~81% of the coding genome and provides an efficient intermediary between functional genomics data and reverse-genetics resources for the genetic dissection of C. neoformans phenotypes. CryptoNet is the first genome-scale co-functional network for any fungal pathogen. CryptoNet effectively identified novel genes for pathogenicity and drug resistance using guilt-by-association and context-associated hub algorithms. CryptoNet is also the first genome-scale co-functional network for fungi in the basidiomycota phylum, as Saccharomyces cerevisiae belongs to the ascomycota phylum. CryptoNet may therefore provide insights into pathway evolution between two distinct phyla of the fungal kingdom. The CryptoNet web server (www.inetbio.org/cryptonet) is a public resource that provides an interactive environment of network-assisted predictive genetics for C. neoformans.
PDF
