Nanoarchitectonics of highly dispersed polythiophene on paper for accurate quantitative detection of metal ions.

π-Conjugated polymers such as polythiophene provide intramolecular wire effects upon analyte capture, which contribute to sensitive detection in chemical sensing. However, inherent aggregation-induced quenching causes difficulty in fluorescent chemical sensing in the solid state. Herein, we propose a solid-state fluorescent chemosensor array device made of a paper substrate (PCSAD) for the qualitative and quantitative detection of metal ions. A polythiophene derivative modified by dipicolylamine moieties (1poly), which shows optical changes upon the addition of target metal ions (i.e., Cu2+, Cd2+, Ni2+, Co2+, Pb2+, Zn2+, and Hg2+), was highly dispersed on the paper substrate using office apparatus. In this regard, morphological observation of the PCSAD after printing of 1poly suggested the contribution of the fiber structures of the paper substrate to the homogeneous dispersion of 1poly ink to suppress aggregation-induced quenching. The optical changes in the PCSAD upon the addition of metal ions was rapidly recorded using a smartphone, which was further applied to imaging analysis and pattern recognition techniques for high-throughput sensing. Indeed, the printed PCSAD embedded with 1poly achieved the accurate detection of metal ions at ppm levels contained in river water. The limit of detection of the PCSAD-based sensing system using a smartphone (48 ppb for Cu2+ ions) is comparable to that of a solution-based sensing system using a stationary spectrophotometer (16 ppb for Cu2+ ions). Therefore, the methodology based on a combination of a paper-based sensor array and a π-conjugated polymer will be a promising approach for solid-state fluorescent chemosensors.

Association of coexistence of frailty and depressive symptoms with mortality in community-dwelling older adults: Kashiwa Cohort Study.

OBJECTIVES: This study aimed to determine the longitudinal associations of the coexistence of frailty and depressive symptoms with mortality among older adults. METHODS: The study participants were community-dwelling older adults aged ≥65 years who participated in the baseline survey of the Kashiwa Cohort Study in Japan in 2012. We used Fried's frailty phenotype criteria to classify participants as non-frail (score = 0), pre-frail (1 or 2), or frail (≥3). Depressive symptoms were assessed using the GDS-15 (≥6 points). Cox proportional hazards models were used to evaluate the association of co-occurring frailty and depressive symptoms with all-cause mortality, after adjusting for sociodemographic and clinical characteristics. RESULTS: The study included 1920 participants, including 810 non-frail, 921 pre-frail, and 189 frail older adults, of which 9.0 %, 15.7 %, and 36.0 %, respectively, had depressive symptoms. Ninety-one (4.7 %) participants died during the average follow-up period of 4.8 years. Compared with non-frail participants without depressive symptoms, frail participants had greater adjusted hazard ratios for mortality: 2.47 (95 % CI, 1.16 to 5.25) for frail participants without depressive symptoms and 4.34 (95 % CI, 1.95 to 9.65) for frail participants with depressive symptoms. However, no statistically significant associations were observed in non-frail or pre-frail participants irrespective of depressive symptoms. CONCLUSION: Frail older adults with depressive symptoms have a substantially greater risk of mortality. Screening for depressive symptoms and frailty in older adults should be incorporated into health checkups and clinical practice to identify high-risk populations.

An organic transistor for detecting the oxidation of an organic sulfur compound at a solid-liquid interface and its chemical sensing applications.

The development of chemical sensors has advanced due to an increase in demand; however, the potential of chemical sensors as devices to monitor organic reactions has not been revealed yet. Thus, we aim to propose a chemical sensor platform for facile monitoring of chemical reactions, especially at a solid-liquid interface. In this study, an extended-gate-type organic field-effect transistor (OFET) has been employed as a platform to detect chemical reactions at an interface between the extended-gate electrode and an aqueous solution. The OFET device functionalized with 4,4'-thiobisbenzenthiol has shown time- and concentration-dependent shifts in transistor characteristics upon adding H2O2. In a selectivity test using seven oxidant agents, the transistor responses depended on the oxidation of the organic sulfur compound (i.e., 4,4'-thiobisbenzenthiol) stemming from the ability of the oxidant agents. Therefore, the observed changes in the transistor characteristics have suggested the generation of sulfur-oxidized products at the interface. In this regard, the observed responses were caused by disulfide formation accompanied by changes in the charges under neutral pH conditions. Meanwhile, weak transistor responses derived from the generation of oxygen adducts have also been observed, which were caused by changes in the dipole moments. Indeed, the yields of the oxygen adducts have been revealed by X-ray photoelectron spectroscopy. The monitoring of gradual changes originating from the decrease in the disulfide formation and the increase in the oxygen adducts implied a novel aspect of the OFET device as a platform to simultaneously detect reversible and irreversible reactions at interfaces without using large-sized analytical instruments. Sulfur oxidation by H2O2 on the OFET device has been further applied to the indirect monitoring of an enzymatic reaction in solution. The OFET-based chemical sensor has shown continuous changes with an increase in a substance (i.e., lactate) in the presence of an enzyme (i.e., lactate oxidase), which indicates that the OFET response depends on the H2O2 generated through the enzymatic reaction in the solution. In this study, we have clarified the versatility of organic devices as platforms to monitor different chemical reactions using a single detection method.

An Autopsy Case of Post-COVID-19 Interstitial Lung Disease with Acute Exacerbation.

The prognosis of patients with post-coronavirus disease 2019 (COVID-19) interstitial lung disease remains unclear. We herein report an autopsy case in which serial progression after the onset of post-COVID-19 interstitial lung disease resulted in an acute exacerbation, leading to a fatal outcome. Autopsy findings included hyaline membrane formation/interstitial inflammatory cell infiltration, suggestive of acute lesions, and severe regional fibrosis, indicating a preexisting chronic condition. In the present case, we histopathologically confirmed the acute exacerbation of post-COVID-19 interstitial lung disease.

Leaf-Inspired Host-Guest Complexation-Dictating Supramolecular Gas Sensors.

We report unique conductive leaf-inspired (in particular, stomata-inspired) supramolecular gas sensors in which acetylated cyclodextrin derivatives rule the electric output. The gas sensors consist of polymers bearing acetylated cyclodextrin, adamantane, and carbon black. Host-guest complexes between acetylated cyclodextrin and adamantane corresponding to the closed stomata realize a flexible polymeric matrix. Effective recombination of the cross-links contributes to the robustness. As gas sensors, the supramolecular materials detect ammonia as well as various other gases at 1 ppm in 10 min. The free acetylated cyclodextrin corresponding to open stomata recognized the guest gases to alter the electric resistivity. Interestingly, the conductive device failed to detect ammonia gases at all without acetylated cyclodextrin. The molecular recognition was studied by molecular dynamics simulations. The gas molecules existed stably in the cavity of free acetylated cyclodextrin. These findings show the potential for developing wearable gas sensors.

Spontaneous preparation of a fluorescent ratiometric chemosensor for metal ions using off-the-shelf materials.

A self-assembled chemosensor prepared using off-the-shelf materials has shown various fluorescence responses including ratiometric and simple ON-OFF switching profiles by adding different toxic metal ions. The unique fingerprint-like responses have been applied to pattern recognition of metal ions in river water for environmental analysis.

Zn(II)-Dipicolylamine-Attached Amphiphilic Polythiophene for Quantitative Pattern Recognition of Oxyanions in Mixtures.

Herein, we propose a novel amphiphilic polythiophene-based chemosensor functionalized with a Zn(II)-dipicolylamine side chain (1poly ⋅ Zn) for the pattern recognition of oxyanions. Optical changes in amphiphilic 1poly ⋅ Zn can be induced by the formation of a random coil from a backbone-planarized structure upon the addition of target oxyanions, which results in blueshifts in the UV-vis absorption spectra and turn-on-type fluorescence responses. Dynamic behavior in a polythiophene wire and/or among wires could be a driving force for obtaining visible color changes, while the molecular wire effect is dominant in obtaining fluorescence sensor responses. Notably, the magnitude of optical changes in 1poly ⋅ Zn has depended on differences in properties of oxyanions, such as their binding affinity, hydrophilicity, and molecular geometry. Thus, various colorimetric and fluorescence response patterns of 1poly ⋅ Zn to oxyanions were obtained, albeit using a single chemosensor. A constructed information-rich dataset was applied to pattern recognition for the simultaneous group categorization of phosphate and carboxylate groups and the prediction of similar structural oxyanions at a different order of concentrations in their mixture solutions.

Evaluating the one-time chair stand test for predicting the coronavirus disease severity in patients during hospital admission: a cohort study in Japan.

BACKGROUND: This study aimed to understand whether the one-time chair stand test (CS-1) is useful for predicting the severity of coronavirus disease (COVID-19) in 101 patients admitted to the hospital with acute respiratory failure. METHODS: This single-centered, prospective observational cohort study enrolled 101 critically ill adult patients hospitalized with COVID-19 who underwent the CS-1 as a dynamic evaluation tool in clinical practice between late April 2020 and October 2021. Data on demographic characteristics, symptoms, laboratory values, computed tomography findings, and clinical course after admission were collected. Furthermore, the data was compared, and the association between the intubation and non-intubation groups was determined. We also calculated the cutoff point, area under the curve (AUC), and 95% confidence interval (CI) of the change in oxygen saturation (ΔSpO2) during the CS-1. RESULTS: Thirty-three out of 101 patients (33%) were intubated during hospitalization. There was no significant difference in the resting SpO2 (93.3% versus 95.2%, P = 0.22), but there was a significant difference in ΔSpO2 during the CS-1 between the intubation and non-intubation groups (10.8% versus 5.5%, P < 0.01). In addition, there was a significant correlation between hospitalization and ΔSpO2 during the CS-1 (ρ = 0.60, P < 0.01). The generated cutoff point was calculated as 9.5% (AUC = 0.94, 95% CI = 0.88-1.00). CONCLUSION: For COVID-19 patients with acute respiratory failure, the CS-1 performed on admission was useful for predicting the severity of COVID-19. Furthermore, the CS-1 can be utilized as a remote and simple evaluation parameter. Thus, it could have potential clinical applications in the future.

Printed colorimetric chemosensor array on a 96-microwell paper substrate for metal ions in river water.

Here, we propose a printed 96-well microtiter paper-based chemosensor array device (PCSAD) to simultaneously detect metal ions for river water assessment. Colorimetric chemosensors for metal ions have been designed based on molecular self-assembly using off-the-shelf catechol dyes and a phenylboronic acid (PBA) derivative. The colorimetric self-assembled chemosensors consisting of catechol dyes and a PBA derivative on a 96-well microtiter paper substrate demonstrated various color changes according to the disassembly of the ensembles by the addition of nine types of metal ions. An in-house-made algorithm was used to automate imaging analysis and extract color intensities at seven types of color channels from a captured digital image, allowing for rapid data processing. The obtained information-rich inset data showed fingerprint-like colorimetric responses and was applied to the qualitative and quantitative pattern recognition of metal ions using chemometric techniques. The feasibility of the 96-well microtiter PCSAD for environmental assessment has been revealed by the demonstration of a spike-and-recovery test against metal ions in a river water sample.

Non-enzymatic detection of glucose levels in human blood plasma by a graphene oxide-modified organic transistor sensor.

We herein report an organic transistor functionalized with a phenylboronic acid derivative and graphene oxide for the quantification of plasma glucose levels, which has been achieved by the minimization of interferent effects derived from physical protein adsorption on the detection electrode.

An organic transistor for the selective detection of tropane alkaloids utilizing a molecularly imprinted polymer.

This study proposes a chemical sensing approach for the selective detection of tropane alkaloid drugs based on an extended-gate-type organic field-effect transistor (OFET) functionalized with a molecularly imprinted polymer (MIP). From the viewpoint of pharmaceutical chemistry, the development of versatile chemical sensors to determine the enantiomeric purity of over-the-counter (OTC) tropane drugs is important because of their side effects and different pharmacological activities depending on their chirality. To this end, we newly designed an OFET sensor with an MIP (MIP-OFET) as the recognition element for tropane drugs based on a high complementarity among a template (i.e., (S)-hyoscyamine) and functional monomers such as N-isopropylacrylamide and 2,2-dimethyl-4-pentenoic acid. Indeed, the MIP optimized by density functional theory (DFT) has succeeded in the sensitive and selective detection of (S)-hyoscyamine (as low as 1 µM) by the combination of the OFET with highly selective recognition sites in the MIP. The MIP-OFET was further applied to determine the enantiomeric excess (ee) of commercially available (S)-hyoscyamine, and the linearity changes in the threshold voltages of the OFET corresponded to the % ee values of (S)-hyoscyamine. Overall, the validation with tropane alkaloids revealed the potential of the MIP combined with OFET as a chemical sensor chip for OTC drugs in real-world scenarios.

Factors influencing use of conventional and traditional Korean medicine-based health services: a nationwide cross-sectional study.

BACKGROUND: In Korea, conventional medicine (CM) and traditional Korean medicine (KM) are run as a dual healthcare system; however, the backgrounds and characteristics of the users of both medical services have not yet been compared. This study aimed to identify the differences in factors determining the use of CM and KM health services. METHODS: A secondary data analysis of a nationwide cross-sectional survey was conducted in this study. The Survey on the Experience with Healthcare Services 2017 asked participants about their most recent outpatient visit to a health service. Initially, a descriptive analysis was performed on respondents who visited the CM or KM health service in the last 12 months. Then, logistic regression analysis using Andersen's behavioral model was performed, to identify the factors affecting health service selection, by classifying demographic variables into predisposing, enabling, and need factors. Respondents who replied they did not frequently use CM/KM and those with missing data were excluded. RESULTS: Of the total 11,098 respondents, 7,116 (64.1%) reported to have used CM/KM: 2,034 (18.3%), 4,475 (40.3%), and 607 (5.5%) for hospital CM, clinic CM, and KM, respectively. In logistic regression analysis, of the 2,723 (24.5%) respondents analyzed, 822 (7.4%) went to a hospital, 1,689 (15.2%) to a clinic, and 212 (1.9%) opted for KM service. Respondents with a higher number of chronic diseases were less likely to use KM (one disease, odds ratio: 0.52, 95% confidence interval: 0.36-0.76; two diseases: 0.51, 0.31-0.85; three to five diseases: 0.26, 0.10-0.69). Respondents with a high income were likely to go to the hospital (4Q vs. 1Q: 1.92, 1.35-2.72) and less likely to go to the clinic (4Q vs. 1Q: 0.49, 0.35-0.68). CONCLUSIONS: Significant differences were observed on the enabling factor (income) for CM and need factors (number of chronic diseases) for KM. Our analysis suggests that through the healthcare policy, we should consider stratifying user backgrounds and needs for each medical service.

Printed 384-Well Microtiter Plate on Paper for Fluorescent Chemosensor Arrays in Food Analysis.

We propose a printed 384-well microtiter paper-based fluorescent chemosensor array device (384-well microtiter PCAD) to simultaneously categorize and discriminate saccharides and sulfur-containing amino acids for food analysis. The 384-well microtiter PCAD requiring 1 µL/4 mm2 of each well can allow high-throughput sensing. The device embedded with self-assembled fluorescence chemosensors displayed a fingerprint-like response pattern for targets, the image of which was rapidly captured by a portable digital camera. Indeed, the paper-based chemosensor array system combined with imaging analysis and pattern recognition techniques not only successfully categorized saccharides and sulfur-containing amino acids but also classified mono- and disaccharide groups. Furthermore, the quantitative detectability of the printed device was revealed by a spike and recovery test for fructose and glutathione in a diluted freshly made tomato juice. We believe that the 384-well microtiter PCAD using the imaging analysis system will be a powerful sensor for multi-analytes at several categorized groups in real samples.

Freshness monitoring of raw fish by detecting biogenic amines using a gold nanoparticle-based colorimetric sensor array.

We herein report the quantitative detection of biogenic amines using a gold nanoparticle-based colorimetric chemosensor array for food analysis. The gold nanoparticles are functionalized with carboxylate derivatives, which capture target amines through hydrogen bonds and electrostatic interactions. The simultaneous discrimination of 10 amine derivatives was achieved by a linear discriminant analysis with a 100% correct classification based on the multi-colorimetric response pattern of structural differences. Furthermore, a real sample analysis for raw fish (i.e., tuna) demonstrated highly accurate determination of histamine concentrations by a support vector machine, the result of which was matched with high-performance liquid chromatography. Most importantly, the chemosensor array succeeded in detecting the time-dependent concentration change of histamine in the raw fish, meaning that the decomposition of the fish could be monitored by the colorimetric changes. Hence, the proposed chemosensor array combined with pattern recognition techniques can be a user-friendly analytical method for food freshness monitoring.

A microfluidic organic transistor for reversible and real-time monitoring of H2O2 at ppb/ppt levels in ultrapure water.

A microfluidic organic transistor functionalized with phenylboronic acid firstly succeeded in reversible and real-time monitoring of H2O2 at ppb/ppt levels in ultrapure water, which would be used not only as portable chemical sensors but also as monitoring tools to clarify unknown reaction mechanisms of phenylboronic acid with H2O2.

Oxytocin detection at ppt level in human saliva by an extended-gate-type organic field-effect transistor.

Herein, we report an extended-gate-type organic field-effect transistor (OFET) sensor for oxytocin. The fabricated OFET-based immunosensor has successfully detected oxytocin at a ppt level in human saliva with high recovery rates (96-102%). We believe our sensor would pave the way for the realization of portable sensors for healthcare monitoring.

Multi-Oxyanion Detection by an Organic Field-Effect Transistor with Pattern Recognition Techniques and Its Application to Quantitative Phosphate Sensing in Human Blood Serum.

We herein report an organic field-effect transistor (OFET) based chemical sensor for multi-oxyanion detection with pattern recognition techniques. The oxyanions ubiquitously play versatile roles in biological systems, and accessing the chemical information they provide would potentially facilitate fundamental research in diagnosis and pharmacology. In this regard, phosphates in human blood serum would be a promising indicator for early case detection of significant diseases. Thus, the development of an easy-to-use chemical sensor for qualitative and quantitative detection of oxyanions is required in real-world scenarios. To this end, an extended-gate-type OFET has been functionalized with a metal complex consisting of 2,2'-dipicolylamine and a copper(II) ion (CuII-dpa), allowing a compact chemical sensor for oxyanion detection. The OFET combined with a uniform CuII-dpa-based self-assembled monolayer (SAM) on the extended-gate gold electrode shows a cross-reactive response, which suggests a discriminatory power for pattern recognition. Indeed, the qualitative detection of 13 oxyanions (i.e., hydrogen monophosphate, pyrophosphate, adenosine monophosphate, adenosine diphosphate, adenosine triphosphate, terephthalate, phthalate, isophthalate, malonate, oxalate, lactate, benzoate, and acetate) has been demonstrated by only using a single OFET-based sensor with linear discriminant analysis, which has shown 100% correct classification. The OFET has been further applied to the quantification of hydrogen monophosphate in human blood serum using a support vector machine (SVM). The multiple predictions of hydrogen monophosphate at 49 and 89 µM have been successfully realized with low errors, which indicates that the OFET-based sensor with pattern recognition techniques would be a practical sensing platform for medical assays. We believe that a combination of the OFET functionalized with the SAM-based recognition scaffold and powerful pattern recognition methods can achieve multi-analyte detection from just a single sensor.