A Challenge for Emphysema Quantification Using a Deep Learning Algorithm With Low-dose Chest Computed Tomography.

PURPOSE: We aimed to identify clinically relevant deep learning algorithms for emphysema quantification using low-dose chest computed tomography (LDCT) through an invitation-based competition. MATERIALS AND METHODS: The Korean Society of Imaging Informatics in Medicine (KSIIM) organized a challenge for emphysema quantification between November 24, 2020 and January 26, 2021. Seven invited research teams participated in this challenge. In total, 558 pairs of computed tomography (CT) scans (468 pairs for the training set, and 90 pairs for the test set) from 9 hospitals were collected retrospectively or prospectively. CT acquisition followed the hospitals' protocols to reflect the real-world clinical setting. Using the training set, each team developed an algorithm that generated converted LDCT by changing the pixel values of LDCT to simulate those of standard-dose CT (SDCT). The agreement between SDCT and LDCT was evaluated using the intraclass correlation coefficient (ICC; 2-way random effects, absolute agreement, and single rater) for the percentage of low-attenuated area below -950 HU (LAA-950 HU), κ value for emphysema categorization (LAA-950 HU, <5%, 5% to 10%, and ≥10%) and cosine similarity of LAA-950 HU. RESULTS: The mean LAA-950 HU of the test set was 14.2%±10.5% for SDCT, 25.4%±10.2% for unconverted LDCT, and 12.9%±10.4%, 11.7%±10.8%, and 12.4%±10.5% for converted LDCT (top 3 teams). The agreement between the SDCT and converted LDCT of the first-place team was 0.94 (95% confidence interval: 0.90, 0.97) for ICC, 0.71 (95% confidence interval: 0.58, 0.84) for categorical agreement, and 0.97 (interquartile range: 0.94 to 0.99) for cosine similarity. CONCLUSIONS: Emphysema quantification with LDCT was feasible through deep learning-based CT conversion strategies.

Nanoparticle delivery of recombinant IL-2 (BALLkine-2) achieves durable tumor control with less systemic adverse effects in cancer immunotherapy.

Recent strategies in cancer immunotherapy based on interleukin-2 (IL-2) are generally focused on reducing regulatory T cell (Treg) development by modifying IL-2 receptor alpha (IL-2Rα) domain. However, the clinical utility of high-dose IL-2 treatment is mainly limited by severe systemic toxicity. We find that peritumorally injectable 'BALLkine-2', recombinant human IL-2 (rIL-2) loaded porous nanoparticle, dramatically reduces systemic side effects of rIL-2 by minimizing systemic IL-2 exposure. Notably, in cynomolgus monkeys, subcutaneous (SC)-injection of BALLkine-2 not only dramatically reduces systemic circulation of rIL-2 in the blood, but also increases half-life of IL-2 compared to IV- or SC-injection of free rIL-2. Peritumorally-injected BALLkine-2 enhances intratumoral lymphocyte infiltration without inducing Treg development and more effectively synergizes with PD-1 blockade than high-dose rIL-2 administration in B16F10 melanoma model. BALLkine-2 could be a highly potent therapeutic option due to higher anti-tumor efficacy with lower and fewer doses and reduced systemic toxicity compared to systemic rIL-2.

Neutrophil to Lymphocyte Ratio in Maternal Blood: A Clue to Suspect Amnionitis.

There is no information about whether maternal neutrophil to lymphocyte ratios (NLRs) progressively increase with respect to the progression of acute histologic chorioamnionitis (acute-HCA) and increased maternal NLR is a risk factor for amnionitis, known as advanced acute-HCA, in pregnant women at risk for spontaneous preterm birth (PTB). The objective of the current study is to examine this issue. The study population included 132 singleton PTB (<34 weeks) due to either preterm labor or preterm-PROM with both placental pathology and maternal CBC results within 48 h before delivery. We examined maternal NLRs according to the progression of acute-HCA in extra-placental membranes (EPM) (i.e., group-0, inflammation-free EPM; group-1, inflammation restricted to decidua; group-2, inflammation restricted to the membranous trophoblast of chorion and the decidua; group-3, inflammation in the connective tissue of chorion but not amnion; group-4, amnionitis). Maternal NLRs significantly and progressively increased with the progression of acute-HCA (Spearman's rank correlation test, γ = 0.363, p = 0.000019). Moreover, the increased maternal NLR (≥7.75) (Odds-ratio 5.56, 95% confidence-interval 1.26-24.62, p < 0.05) was a significant independent risk factor for amnionitis even after the correction for potential confounders. In conclusion, maternal NLRs significantly and progressively increased according to the progression of acute-HCA and the increased maternal NLR (≥7.75) was an independent risk factor for amnionitis in spontaneous PTB. The evaluation of the performance of NLR should clearly require a prospective description of this parameter in a cohort of patients with either threatened PTL or preterm-PROM.

Surface Activity-Tuned Metal Oxide Chemiresistor: Toward Direct and Quantitative Halitosis Diagnosis.

Continuous monitoring of hydrogen sulfide (H2S) in human breath for early stage diagnosis of halitosis is of great significance for prevention of dental diseases. However, fabrication of a highly selective and sensitive H2S gas sensor material still remains a challenge, and direct analysis of real breath samples has not been properly attempted, to the best of our knowledge. To address the issue, herein, we introduce facile cofunctionalization of WO3 nanofibers with alkaline metal (Na) and noble metal (Pt) catalysts via the simple addition of sodium chloride (NaCl) and Pt nanoparticles (NPs), followed by electrospinning process. The Na-doping and Pt NPs decoration in WO3 grains induces the partial evolution of the Na2W4O13 phase, causing the buildup of Pt/Na2W4O13/WO3 multi-interface heterojunctions that selectively interacts with sulfur-containing species. As a result, we achieved the highest-ranked sensing performances, that is, response (Rair/Rgas) = 780 @ 1 ppm and selectivity (RH2S/REtOH) = 277 against 1 ppm ethanol, among the chemiresistor-based H2S sensors, owing to the synergistic chemical and electronic sensitization effects of the Pt NP/Na compound cocatalysts. The as-prepared sensing layer was proven to be practically effective for direct, and quantitative halitosis analysis based on the correlation (accuracy = 86.3%) between the H2S concentration measured using the direct breath signals obtained by our test device (80 cases) and gas chromatography. This study offers possibilities for direct, highly reliable and rapid detection of H2S in real human breath without the need of any collection or filtering equipment.

Growth and NO2-Sensing Properties of Biaxial p-SnO/n-ZnO Heterostructured Nanowires.

Biaxial p-SnO/n-ZnO heterostructured nanowires (average length of 10 µm) were grown onto a glass substrate by thermal evaporation in vacuum. These nanowires had spherical ball tips, and the size of the SnO part increased gradually from the top to the bottom of the nanowire, but the corresponding size of ZnO varied slightly. The Sn-Zn alloy formed in the tips resulted in determined as the catalyst of the growth of the ZnO nanowires. The growth process of the p-SnO/n-ZnO biaxial nanowires is discussed based on vapor-liquid-solid (VLS) based on the subsequent growth process: the VLS catalytic growth of the ZnO nanowire and subsequent epitaxial SnO growth on the sidewall of the pregrown ZnO nanowire. An epitaxial relationship, (001)SnO//(110)ZnO and [110]SnO//[002]ZnO, was observed in the biaxial p-SnO/n-ZnO heterostructured nanowires. The gas-sensing properties of the as-synthesized p-SnO/n-ZnO nanowires were investigated. The results show that the device exhibit a good performance to the ppb-level NO2 at room temperature (25 °C) without light illumination. The detection limit of the p-SnO/n-ZnO sensor to NO2 is 50 ppb. Moreover, the NO2-sensing properties of the p-SnO/n-ZnO device were investigated under various relative humidity. Finally, the NO2-sensing mechanism of the p-SnO/n-ZnO nanowires was proposed and discussed.

Hypoglycemic effect of whole grain diet in C57BL/KsJ-db/db mice by activating PI3K/Akt and AMPK pathways.

Type II diabetes mellitus (T2DM), characterized by abnormal blood glucose level, is a metabolic disease caused by pancreatic ß-cell dysfunction and insulin resistance. Previous studies have reported that whole grain intake alleviated various metabolic syndromes. Here, the hypoglycemic effect of whole grain diet (WGD) on type II diabetes was investigated in C57BL/KsJ-db/db mice. WGD improved the regulation of fasting and postprandial blood glucose levels and reduced weight gain and lipid accumulation. On the molecular level, WGD up-regulated the glucose transporter type 4 and stimulated the insulin receptor substrate 1/phosphoinositide 3-kinase ((PI3K)/Akt) pathway. WGD stimulated the AMP-activated protein kinase (AMPK)/p38/Acetyl-CoA carboxylate pathway related to lipid metabolism and glucose uptake, and down-regulated the pro-inflammatory cytokines, C-reactive protein, interleukin (IL)-6, IL-1ß, and tumor necrosis factor-alpha. Taken together, whole grains can be employed as functional food ingredients to alleviate T2DM by enhancing the PI3K/Akt and AMPK pathways.

Stretchable Supercapacitors Based on Carbon Nanotubes-Deposited Rubber Polymer Nanofibers Electrodes with High Tolerance against Strain.

We report a new fabrication method for a fully stretchable supercapacitor based on single wall carbon nanotube (SWCNT)-coated electrospun rubber nanofibers as stretchable supercapacitor electrodes. The deposition conditions of SWCNT on hydrophobic rubber nanofibers are experimentally optimized to induce a uniform coating of SWCNT. For surfactant-assisted coating of SWCNT, both water contact angle and sheet resistance were lower compared to the cases with other surface treatment methods, indicating a more effective coating approach. The excellent electromechanical properties of this electrode under stretching conditions are demonstrated by the measurement of Young's modulus and normalized sheet resistance. The superb tolerance of the electrode with respect to stretching is the result of (i) high aspect ratios of both nanofiber templates and the SWCNT conductors, (ii) the highly elastic nature of rubbery nanofibers, and (iii) the strong adherence of SWCNT-coated nanofibers on the elastic ecoflex substrate. Electrochemical and electromechanical measurements on stretchable supercapacitor devices reveal that the volumetric capacitance (15.2 F cm-3 at 0.021 A cm-3) of the unstretched state is maintained for strains of up to 40%. At this level of strain, the capacitance after 1,000 charge/discharge cycles was not significantly reduced. The high stability of our stretchable device suggests potential future applications in various types of wearable energy storage devices.

Enhanced Moisture-Reactive Hydrophilic-PTFE-Based Flexible Humidity Sensor for Real-Time Monitoring.

Flexible sensors connected to cell phones are a promising technology that can aid in continuously monitoring signals in our daily lives, such as an individual's health status and information from buildings, farms, and industry. Among such signals, real-time humidity monitoring is crucial to a comfortable life, as human bodies, plants, and industrial environments require appropriate humidity to be maintained. We propose a hydrophilic polytetrafluoroethylene (H-PTFE)-based flexible humidity sensor integrated with readout circuitry, wireless communication, and a mobile battery. To enhance its sensitivity, linearity, and reliability, treatment with sodium hydroxide implements additional hydroxyl (OH) groups, which further enhance the sensitivity, create a strong linearity with respect to variations in relative humidity, and produce a relatively free hysteresis. Furthermore, to create robust mechanical stability, cyclic upward bending was performed for up to 3000 cycles. The overall electrical and mechanical results demonstrate that the flexible real-time H-PTFE humidity sensor system is suitable for applications such as wearable smart devices.

Evaluation of a Behavioral Intervention With Multiple Components Among Low-Income and Uninsured Adults With Obesity and Diabetes.

PURPOSE: To examine the effects of a community-based behavioral intervention with multiple components on health outcomes among low-income and uninsured adults who were obese and had diabetes and treated in a "real-world" setting. DESIGN: A longitudinal design with a retrospective comparison group was used to examine the ability of a health promotion program to improve body mass index (BMI) and hemoglobin A1c (HbA1c) among 87 treatment group and 62 comparison group participants. SETTING: Urban/metropolitan city in the United States. INTERVENTION: A community-based behavioral intervention with 3 components including health-coach visits, registered dietitian visits, and exercise consultations delivered over 12 months. MEASURES: Biometric measurements were collected at baseline, 3, 6, 9, 12, and 18 months, whereas self-reported measurements were collected at baseline, 6 months, and 12 months. ANALYSIS: Linear mixed models with participant-level random intercepts were fitted for BMI and HbA1c. RESULTS: The treatment group demonstrated reductions in BMI (percentage change = -2.1%, P < .001) and HbA1c (-0.6%, P < .001) as well as improvement in diabetes knowledge (+5.4%, P = .025), whereas the comparison group did not show any improvements in biometric measures. Dietitian visits were the most effective treatment component to reduce HbA1c (coefficient = -0.08, P = .025). CONCLUSION: Multiple component behavioral intervention in community settings, particularly when delivered by registered dietitians, shows promise to combat the dual epidemic of obesity and diabetes among low-income and uninsured patients.

Label-Free and Recalibrated Multilayer MoS2 Biosensor for Point-of-Care Diagnostics.

Molybdenum disulfide (MoS2) field-effect transistor (FET)-based biosensors have attracted significant attention as promising candidates for highly sensitive, label-free biomolecule detection devices. In this paper, toward practical applications of biosensors, we demonstrate reliable and quantitative detection of a prostate cancer biomarker using the MoS2 FET biosensor in a nonaqueous environment by reducing nonspecific molecular binding events and realizing uniform chemisorption of anti-PSA onto the MoS2 surface. A systematic and statistical study on the capability of the proposed device is presented, and the biological binding events are directly confirmed and characterized through intensive structural and electrical analysis. Our proposed biosensor can reliably detect various PSA concentrations with a limit of 100 fg/mL. Moreover, rigorous theoretical simulations provide a comprehensive understanding of the operating mechanism of the MoS2 FET biosensors, and further suggests the enhancement of the sensitivity through engineering device design parameters.

Broadband pH-Sensing Organic Transistors with Polymeric Sensing Layers Featuring Liquid Crystal Microdomains Encapsulated by Di-Block Copolymer Chains.

We report broadband pH-sensing organic field-effect transistors (OFETs) with the polymer-dispersed liquid crystal (PDLC) sensing layers. The PDLC layers are prepared by spin-coating using ethanol solutions containing 4-cyano-4'-pentyl-biphenyl (5CB) and a diblock copolymer (PAA-b-PCBOA) that consists of LC-philic block [poly(4-cyano-biphenyl-4-oxyundecyl acrylate) (PCBOA)] and acrylic acid block [poly(acrylic acid) (PAA)]. The spin-coated sensing layers feature of 5CB microdomains (<5 µm) encapsulated by the PAA-b-PCBOA polymer chains. The resulting LC-integrated-OFETs (PDLC-i-OFETs) can detect precisely and reproducibly a wide range of pH with only small amounts (10-40 µL) of analyte solutions in both static and dynamic perfusion modes. The positive drain current change is measured for acidic solutions (pH < 7), whereas basic solutions (pH > 7) result in the negative change of drain current. The drain current trend in the present PDLC-i-OFET devices is explained by the shrinking-expanding mechanism of the PAA chains in the diblock copolymer layers.

Mixed Electronic and Ionic Conductor-Coated Cathode Material for High-Voltage Lithium Ion Battery.

A lithium ionic conductor, Li1.3Al0.3Ti1.7(PO4)3 (LATP), is introduced as a coating material on the surface of Mg-doped LiCoO2 to improve electrochemical performances for high-voltage (4.5 V) lithium ion batteries. Structure, morphology, elemental distribution, and electrical properties of the materials are thoroughly characterized by SEM, TEM, EELS, EDS, and C-AFM. The coating layer is electrically conductive with the aid of Mg ions which are used as a dopant for the active materials; therefore, this mixed electronic ionic conductor strongly enhances the electrochemical performances of initial capacity, cycling property, and rate capability. The LATP coating layer also demonstrates very promising applicability for 4.4 V prismatic full cells with graphite anode, which correspond to the 4.5 V half-cells with lithium anode. The 2900 mA h full cells show 85% of capacity retention after 500 cycles and more than 60% after 700 cycles.

Pattern difference of dissociated hand muscle atrophy in amyotrophic lateral sclerosis and variants.

INTRODUCTION: Split hand is considered to be a specific feature of amyotrophic lateral sclerosis (ALS). METHODS: We evaluated the pattern difference of intrinsic hand muscles of upper limb-onset ALS (UL-ALS), upper limb-onset progressive muscular atrophy (UL-PMA), brachial amyotrophic diplegia (BAD), and Hirayama disease (HD) by measuring objective electrophysiological markers. RESULTS: The abductor digiti minimi (ADM)/abductor pollicis brevis (APB) compound muscle action potential (CMAP) amplitude ratio was significantly higher in UL-ALS than other variants, but a considerable proportion of UL-ALS cases had an amplitude ratio in the range of other variants. Absent APB CMAP and abnormally high ADM/APB CMAP amplitude ratio (≥4) occurred only with UL-ALS. Conversely, an absent ADM CMAP was identified only in UL-PMA and BAD. CONCLUSIONS: The absolute ADM/APB CMAP amplitude ratio was not specific for ALS; however, several findings from simple electrophysiological measurements may help predict prognosis in patients with motor neuron diseases and may be early diagnostic markers for ALS.

Two-dimensional layered MoS2 biosensors enable highly sensitive detection of biomolecules.

We present a MoS2 biosensor to electrically detect prostate specific antigen (PSA) in a highly sensitive and label-free manner. Unlike previous MoS2-FET-based biosensors, the device configuration of our biosensors does not require a dielectric layer such as HfO2 due to the hydrophobicity of MoS2. Such an oxide-free operation improves sensitivity and simplifies sensor design. For a quantitative and selective detection of PSA antigen, anti-PSA antibody was immobilized on the sensor surface. Then, introduction of PSA antigen, into the anti-PSA immobilized sensor surface resulted in a lable-free immunoassary format. Measured off-state current of the device showed a significant decrease as the applied PSA concentration was increased. The minimum detectable concentration of PSA is 1 pg/mL, which is several orders of magnitude below the clinical cut-off level of ~4 ng/mL. In addition, we also provide a systematic theoretical analysis of the sensor platform - including the charge state of protein at the specific pH level, and self-consistent channel transport. Taken together, the experimental demonstration and the theoretical framework provide a comprehensive description of the performance potential of dielectric-free MoS2-based biosensor technology.

Folate ligand anchored liquid crystal microdroplets emulsion for in vitro detection of KB cancer cells.

A KB cancer cell-selective, liquid crystal microdroplets emulsion is prepared using folic acid-conjugated block copolymers (PS-b-PAA-FA) and sodium dodecyl sulfate (SDS) as a mediator to induce configurational transitions in 4-cyano-4'-pentylbiphenyl (5CB) liquid crystal microdroplets emulsion. The prepared liquid crystal microdroplets emulsion has shown a configurational transition from radial to bipolar on interacting with KB cancer cells, but no transition from radial to bipolar configuration is observed when liquid crystal microdroplets emulsion was allowed to interact with other normal cells such as fibroblast and osteoblast. The KB cancer cell selectivity of liquid crystal microdroplets emulsion has been considered due to the presence of KB cancer cell folate receptor-specific ligand (FA) at the surface of liquid crystal microdroplets, which allowed liquid crystal microdroplets to interact specifically with KB cancer cells. The ligand-receptor interactions have been considered responsible for triggering the configurational transitions from radial to bipolar in liquid crystal microdroplets emulsion. Thus, folate ligand anchored liquid crystal microdroplets emulsion has shown a potential to be used for in vitro detection of KB cancer cells in the early stage of tumor development.

Transmission electron microscopy study of 3.2 YSZ single crystals manufactured by the skull melting method.

Transmission electron microscopy (TEM) analyses were performed to examine the spontaneously ordered structure in single crystals of 3.2 mole% of Y2O3 added ZrO2 (3.2 YSZ) manufactured by the Skull melting method. The selected area electron diffraction patterns showed several super-structure reflections with symmetrical intensity at (100), (010), and (110) positions, indicating that Y0.5Zr0.5O(2-x) with L1(0)-like cation-ordered structure was formed in 3.2 YSZ. High-resolution TEM has been used to reveal the presence of the partially ordered structure, which was characterized by a doublet periodicity in the contrast of the {100} lattice planes.

Effects of temperature, target/substrate distance, and background pressure on growth of ZnO nanorods by pulsed laser deposition.

The growth of ZnO nanorods on the c-plane of Al2O3 substrates by PLD was been investigated by controlling processing conditions such as growth temperature, distance between target and substrate, and background oxygen pressure. ZnO nanorods were observed from the growth temperature of 600 degrees C for the oxygen pressure of 30 mTorr and the target/substrate distance of 70 mm. The diameters of the ZnO nanorods at the temperature of 700 degrees C and the oxygen pressure of 30 mTorr were approximately 200, 70, and 40 nm for the distance of 45, 70, and 100 mm, respectively. ZnO films without nanorods were observed at the distance of 70 mm and the temperature of 700 degrees C when the oxygen pressure decreased to 1 mTorr. The kinetic energy of the ablated particles by the laser decreases during collisions with background oxygen molecules, resulting in conditions that favor the growth of ZnO nanorods.

A centrifugally actuated point-of-care testing system for the surface acoustic wave immunosensing of cardiac troponin I.

A fully automated point-of-care testing (POCT) system with a surface acoustic wave (SAW) immunosensor was developed for rapid and sensitive detection of cardiac troponin I (cTnI) in body fluid (plasma and whole blood). The assay, based on gold nanoparticle sandwich immunoassay and subsequent gold staining, was performed on the SAW immunosensor packaged inside a disposable microfluidic cartridge. The entire fluidic process, including plasma separation, reagent transport, metering, and mixing, was carried out by controlling the centrifugal force acting on the rotating cartridge and laser-irradiated ferrowax microvalves. On investigation of sensor response to various cTnI concentrations, the system exhibited a high performance with a detection limit of 6.7 pg mL(-1), and the coefficient of variation was less than 10% over the entire test range (10 pg mL(-1) to 25 ng mL(-1)). On comparing this POCT system with a clinically utilized system in a physical laboratory (Centaur® XP; Siemens), a correlation coefficient of 0.998 was found, validating the diagnostic capability of the SAW immunosensor.

Low temperature growth and optical properties of ZnO nanowires using an aqueous solution method.

ZnO nanowires were grown on indium tin oxide (ITO) coated glass substrates at a low temperature of 90 degrees C using an aqueous solution method. The ZnO seeds were coated on the ITO thin films by using a spin coater. ZnO nanowires were formed in an aqueous solution containing zinc nitrate hexahydrate (Zn(NO3)2 x 6H2O) and hexamethylenetetramine (C6H12N4). The pH value and concentration of the solution play an important role in the growth and morphologies of ZnO nanowires. The size of ZnO naonowires increased as the concentration of the solution increased. It was formed with a top surface of hexagonal and tapered shape at low and high pH values respectively. Additionally, the single crystalline structure and optical property of the ZnO nanowires were investigated using high-resolution transmission electron microscopy and photoluminescence spectroscopy.

Sensitive and simultaneous detection of cardiac markers in human serum using surface acoustic wave immunosensor.

We present a rapid and sensitive surface acoustic wave (SAW) immunosensor that utilizes gold staining as a signal enhancement method. A sandwich immunoassay was performed on sensing area of the SAW sensor, which could specifically capture and detect cardiac markers (cardiac troponin I (cTnI), creatine kinase (CK)-MB, and myoglobin). The analytes in human serum were captured on gold nanoparticles (AuNPs) that were conjugated in advance with detection antibodies. Introduction of these complexes to the capture antibody-immobilized sensor surface resulted in a classic AuNP-based sandwich immunoassay format that has been used for signal amplification. In order to achieve further signal enhancement, a gold staining method was performed, which demonstrated that it is possible to obtain gold staining-mediated signal augmentation on a mass-sensitive device. The sensor response due to gold staining varied as a function of cardiac marker concentration. We also investigated effects of increasing operating frequency on sensor responses. Results showed that detection limit of the SAW sensor could be further improved by increasing the operating frequency.