The Epidemiology of Circulating Respiratory Pathogens during the COVID-19 Pandemic.

Objective To survey the epidemiology of respiratory pathogens during the coronavirus disease 2019 (COVID-19) pandemic using multiplex polymerase chain reaction (PCR). Methods Specimens were assayed using multiplex nested PCR. Materials Specimens were obtained from outpatients who presented with symptoms of upper respiratory tract infection and asymptomatic outpatients who had contact with patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at Tohoku Medical and Pharmaceutical University Hospital in Sendai, Japan, from November 1, 2020, to May 31, 2023. The analysis included multiple specimens collected from the same patients at different time-points. Data were collected from the electronic records after testing. Results This study included 8,335 patients (4,311 men) with a median age of 59 years old, and 11,741 total specimens were collected. At least 1 positive SARS-CoV-2 result was obtained for 1,710 (14.6%) specimens. Furthermore, 15 pathogens were identified in the positive specimens, and rhinovirus/enterovirus was detected more frequently than other viruses. We identified a larger number of SARS-CoV-2-positive specimens in patients ≥10 years old. In contrast, in patients 0-9 years old, we identified a larger number of specimens positive for rhinovirus/enterovirus than for other viruses. Conclusion In this study, we examined the epidemiology of circulating respiratory pathogens during the COVID-19 pandemic era.

Long-Term Efficacy of Immune Checkpoint Inhibitor for Squamous Cell Carcinoma Lesion Transformed From EGFR-Mutated Adenocarcinoma After Osimertinib Treatment: A Case Report.

Histologic transformation is one of the mechanisms of resistance to EGFR tyrosine kinase inhibitor in patients with NSCLC with EGFR mutation. The transformation from adenocarcinoma to squamous cell carcinoma (SCC) has been recently recognized as a mechanism of resistance to osimertinib. The prognosis after transformation to SCC is considered to be poor, and the therapeutic strategy for these patients is unclear. Herein, we report a case of long-term response to pembrolizumab monotherapy for an SCC-transformed lesion in a patient with EGFR-mutated adenocarcinoma after osimertinib treatment. A 68-year-old man underwent right upper lobectomy and was diagnosed with lung adenocarcinoma, pathologic stage IIA, with EGFR L858R. Five years after the surgery, he was diagnosed with recurrence and administered osimertinib. Ten months after, biopsy for an enlarged subpleural lesion revealed SCC with EGFR L858R, leading to a diagnosis of histologic transformation. Notably, the programmed death-ligand 1 expression level of the transformed lesion was higher than that of the adenocarcinoma (90% versus <1%). The size of the SCC lesion had reduced with pembrolizumab monotherapy, and the reduction was maintained for over 47 months since transformation. Nevertheless, the original adenocarcinoma lesion progressed after pembrolizumab therapy and was controlled by other cytotoxic drugs and readministration of osimertinib. Immune checkpoint inhibitor therapy is generally ineffective against EGFR-mutated adenocarcinoma. Nevertheless, it may be promising for achieving a good prognosis when EGFR-mutated adenocarcinoma transforms to SCC after developing EGFR tyrosine kinase inhibitor resistance-particularly if the transformed lesion has high programmed death-ligand 1 expression.

PD-L1-negative Non-small-cell Lung Cancer Treated with Nivolumab Plus Ipilimumab during Maintenance Hemodialysis Results in Rapid Initial Progression Followed by a Long-lasting Response.

Nivolumab plus ipilimumab is one of the first-line treatments for advanced non-small-cell lung cancer (NSCLC), but the safety and efficacy in patients on hemodialysis (HD) is unclear. We herein report a patient with NSCLC on HD in whom nivolumab and ipilimumab were initiated. We observed general deterioration and enlarged lesions, followed by a long-term response. The patient developed secondary hypoadrenocorticism, an immune-related adverse event that was easily controlled. Nivolumab plus ipilimumab can be used safely for patients with NSCLC on HD. Long-term effectiveness can be observed after initial progression, so we should carefully assess the response.

Broadband Tip-Enhanced Nonlinear Optical Response in a Plasmonic Nanocavity.

We report a significantly broad nonlinear optical response enhanced in a tip-substrate plasmonic nanocavity. Focusing on the near-field second harmonics of the wavelength-tunable femtosecond laser, we demonstrate that the tip-enhancement of nonlinear optical effects efficiently works over the broad wavelength range through the visible to infrared region. We also found that this broadband nonlinear optical property is directly affected not only by the nanometer-scale sharpness of the tip apexes but also by the micrometer-scale surface geometry of the tip shafts. While spatially nonlocal plasmonic modes excited throughout the micrometer-scale tip shafts enhance near-to-mid-infrared incoming light, the radiation of visible-to-near-infrared second harmonics is boosted by localized plasmons at the nanogap. These two plasmonic modes simultaneously affect the excitation and emission processes, realizing the strong and broad enhancement of second harmonic generation. Our results provide a new basis for the physical understanding and fine manipulation of nonlinear optical phenomena enhanced in plasmonic nanocavities.

Use of a multiplex polymerase chain reaction assay for the early detection of an outbreak of human parainfluenza virus type 3 infection in a nursery school during the COVID-19 pandemic.

Introduction: Although outbreaks of parainfluenza virus type 3 (PIV-3) have been reported in children, to our knowledge none have been reported in a nursery school. As the symptoms of PIV-3 infection are similar to those of COVID-19 infection, accurate diagnosis of PIV-3 and other respiratory viruses is important during the COVID-19 pandemic. Aims: We experienced an outbreak of upper respiratory symptoms at a nursery school in Miyagi Prefecture, Japan, from 29/5/2021 to 13/6/2021 and aimed to determine the causative organism(s). Methods: A multiplex polymerase chain reaction (PCR) assay which enabled rapid detection of a variety of causative microorganisms of respiratory tract infections was used to analyse 13 nasopharyngeal swabs collected during the outbreak. Infection Prevention and control measures were implemented to prevent further spread of infection. Results: All 13 samples were positive for PIV-3 infection. 2 of the 13 samples were also positive for rhinovirus/enterovirus and 1 sample was also positive rhinovirus/enterovirus and coronavirus NL 63. No samples were positive for SARS-CoV-2. Discussion: Children in school settings are especially vulnerable to respiratory viral infections, including COVID-19. Children under two years are unable to wear masks reliably, and the COVID-19 vaccine was approved only for older children. Multiplex PCR assays can be used for the rapid diagnosis of respiratory infections. Conclusion: We identified an outbreak of PIV-3 in a nursery school during the COVID-19 pandemic. The investigation of the outbreak highlighted that it was important not to overlook other respiratory infections including PIV-3 during the COVID-19 pandemic. The multiplex PCR assay provided rapid and accurate diagnosis of the causative organisms in the outbreak and helped to direct appropriate interventions to control the outbreak.

A Prehospital Triage System to Detect Traumatic Intracranial Hemorrhage Using Machine Learning Algorithms.

Importance: An adequate system for triaging patients with head trauma in prehospital settings and choosing optimal medical institutions is essential for improving the prognosis of these patients. To our knowledge, there has been no established way to stratify these patients based on their head trauma severity that can be used by ambulance crews at an injury site. Objectives: To develop a prehospital triage system to stratify patients with head trauma according to trauma severity by using several machine learning techniques and to evaluate the predictive accuracy of these techniques. Design, Setting, and Participants: This single-center retrospective cohort study was conducted by reviewing the electronic medical records of consecutive patients who were transported to Tokyo Medical and Dental University Hospital in Japan from April 1, 2018, to March 31, 2021. Patients younger than 16 years with cardiopulmonary arrest on arrival or with a significant amount of missing data were excluded. Main Outcomes and Measures: Machine learning-based prediction models to detect the presence of traumatic intracranial hemorrhage were constructed. The predictive accuracy of the models was evaluated with the area under the receiver operating curve (ROC-AUC), area under the precision recall curve (PR-AUC), sensitivity, specificity, and other representative statistics. Results: A total of 2123 patients (1527 male patients [71.9%]; mean [SD] age, 57.6 [19.8] years) with head trauma were enrolled in this study. Traumatic intracranial hemorrhage was detected in 258 patients (12.2%). Among several machine learning algorithms, extreme gradient boosting (XGBoost) achieved the mean (SD) highest ROC-AUC (0.78 [0.02]) and PR-AUC (0.46 [0.01]) in cross-validation studies. In the testing set, the ROC-AUC was 0.80, the sensitivity was 74.0% (95% CI, 59.7%-85.4%), and the specificity was 74.9% (95% CI, 70.2%-79.3%). The prediction model using the National Institute for Health and Care Excellence (NICE) guidelines, which was calculated after consultation with physicians, had a sensitivity of 72.0% (95% CI, 57.5%-83.8%) and a specificity of 73.3% (95% CI, 68.7%-77.7%). The McNemar test revealed no statistically significant differences between the XGBoost algorithm and the NICE guidelines for sensitivity or specificity (P = .80 and P = .55, respectively). Conclusions and Relevance: In this cohort study, the prediction model achieved a comparatively accurate performance in detecting traumatic intracranial hemorrhage using only the simple pretransportation information from the patient. Further validation with a prospective multicenter data set is needed.

Vertically Oriented Metallic Heterodimer Array Semiembedded in Flat Conductive Carbon Film for Electrochemical Application.

General synthesis of a highly oriented metallic heterodimer array based on a selective electrodeposition technique onto a metal nanoparticle-embedded carbon film is proposed, which enables the preparation of heterodimers with a wide variety of metal combinations. This method requires no surfactant, capping agent, organic solvent, or heat treatment. As a representative metal combination, a nickel (Ni)/palladium (Pd) heterodimer array was prepared by selective electrodeposition of Ni nanoparticles (Ni NPs) on top of partially exposed Pd NPs embedded in carbon film electrodes fabricated by a cosputtering technique. Such a selective electrodeposition becomes possible by utilizing the difference in electrodeposition overpotentials between carbon and Pd NP surfaces. X-ray photoelectron spectroscopy revealed a charge transfer from Ni NPs to Pd NPs, implying that the catalytic and optical properties can be expected to be controllable. The formed heterodimer array structure was mechanically stable against ultrasonication in ethanol for over 1 h because most parts of the Pd NPs were tightly embedded in the carbon film. After conversion from Ni to nickel hydroxide (Ni(OH)2), the electrode showed high electrocatalytic activity toward glucose oxidation, with a higher turnover rate and lower overpotential compared to Ni(OH)2 electrodeposited on pure carbon film electrodes.

Drug-Tea Polyphenol Interaction (III) Incompatibility between Aripiprazole Oral Solution and Green Tea.

The details of incompatibility between aripiprazole (ARIP) oral solution and green tea were examined. When the ARIP oral solution was mixed with a commercial PET bottled green tea beverage, the residual rate of ARIP in the mixed solution decreased to 15.7-17.6%. Mixing with ARIP reduced the content of gallate-type green tea polyphenols (GTPs) in the mixed solution but not the content of non-gallate-type GTPs. Furthermore, using pH 3.0 lactic acid buffer, 2.23 mM ARIP solution and 2.23 mM GTP solution were prepared, and the same volumes of ARIP solution and GTP solution were mixed. When the gallate-type GTP solution was mixed, the residual rate of ARIP in the mixed solution decreased. On the other hand, when the non-gallate-type GTP solution was mixed, the residual rate of ARIP in the mixed solution did not decrease. From the above results, it was found that the main reason for the incompatibility between ARIP oral solution and green tea was the formation of an insoluble substance composed of ARIP and gallate-type GTPs in green tea. Furthermore, experimental results using the continuous variation method revealed that ARIP and (-)-epigallocatechin gallate, which is the most representative gallate-type GTP, interact at a molar ratio of 3 : 2.

Hybrid Carbon Film Electrodes for Electroanalysis.

Carbon materials have been widely used for electrochemical analysis and include carbon nanotubes, graphene, and boron-doped diamond electrodes in addition to conventional carbon electrodes, such as those made of glassy carbon and graphite. Of the carbon-based electrodes, carbon film has advantages because it can be fabricated reproducibly and micro- or nanofabricated into electrodes with a wide range of shapes and sizes. Here, we report two categories of hybrid-type carbon film electrodes for mainly electroanalytical applications. The first category consists of carbon films doped or surface terminated with other atoms such as nitrogen, oxygen and fluorine, which can control surface hydrophilicity and lipophilicity or electrocatalytic performance, and are used to detect various electroactive biochemicals. The second category comprises metal nanoparticles embedded in carbon film electrodes fabricated by co-sputtering, which exhibits high electrocatalytic activity for environmental and biological samples including toxic heavy metal ions and clinical sugar markers, which are difficult to detect at pure carbon-based electrodes.

Electrochemical Analysis of Coffee Extractions at Different Roasting Levels Using a Carbon Nanotube Electrode.

This study reports on the electrochemical analysis of coffee extractions at different roasting levels by using a carbon nanotube (CNT) electrode. The roasting levels, ranging from 1 (low) to 6 (high), were determined according to the roasting time after fixing the roasting temperature. Level 1 roasting resulted in light roasted beans and level 6 in dark roasted ones. Based on the roasting level, the concentration of chlorogenic acids, including 3-caffeoylquinic (3CQ), 4-caffeoylquinic (4CQ), and 5-caffeoylquinic (5CQ) acid, can be determined. Cyclic voltammetry (CV) experiments revealed that the reduction current at +0.27 V was proportional to the concentration of chlorogenic acids. High-performance liquid chromatography (HPLC) revealed an inverse correlation between the roasting level and chlorogenic acid amount. The total amounts of chlorogenic acids in coffee extractions determined by HPLC were in agreement with those obtained by CV using the CNT electrode at roasting levels 1 - 5. At level 6, the amount of chlorogenic acids determined by the current peak was larger than that detected by HPLC. As a result, the chlorogenic acid amount was overestimated in the CV experiment at +0.27 V, indicating that electrochemically active materials were generated at level 6. The CV profile showed that the reduction peak at +0.10 V increased with an increase in roasting level. Thus, the peak intensity at +0.10 V can be used to evaluate the roasting level even if the concentration or dilution conditions are provided.

Supporting effects of a N-doped carbon film electrode on an electrodeposited Ni@Ni(OH)2 core-shell nanocatalyst in accelerating electrocatalytic oxidation of oligosaccharides.

The supporting effect of a N-doped carbon film induced superior crystallinity in electrodeposited Ni@Ni(OH)2 core-shell nanoparticles. This improvement resulted in a much higher regeneration rate of catalytic sites (NiOOH), leading to higher oxidation currents of sugars. Also, the overpotential of the maltopentaose (G5) oxidation reaction decreased significantly, probably due to the effect of the electrostatic interaction between NPs and G5.

Electrochemical Detection of Curcumin in Food with a Carbon Nanotube-Carboxymethylcellulose Electrode.

Herein, an electrochemical method is presented for the detection of curcumin in food using a carbon nanotube (CNT)-carboxymethylcellulose (CMC) electrode. The CNT-CMC electrode exhibited ideal characteristics for curcumin detection, namely, a high response current and adequate peak separation toward curcumin oxidation. Cyclic voltammetry revealed two oxidation peaks. In the first scan, only the irreversible peak (Peak I) was observed at a higher potential. In the second scan, the reversible redox peak pairs (Peaks II and II') appeared at lower potentials, and the potential of Peak I was decreased. Peak I corresponded to oxidation of the hydroxyl groups of the benzene ring to the catechol group via a phenoxy radical, while Peaks II and II' indicated the redox loop system of the generated catechol group. The current at Peak II was used to quantify the concentration of curcumin in the linear range of 1 - 48 µM and detection limit of 0.084 µM. The concentrations of curcumin determined by the CNT-CMC electrode in real food samples were consistent with those determined by high-performance liquid chromatography.

Decoupling from a Thermal Bath via Molecular Polariton Formation.

The coupling between an electronic system and an environmental bath plays a decisive role in the excited state dynamics of artificial/natural molecular condensed phases. Although it is generally difficult to control the coupling between the system and the thermal bath in condensed matter, a strong light-matter coupling can control system-bath coupling properties using the polaron decoupling effect, in which a coherent interaction between excitons and photons reduces the reorganization energy. Here we demonstrate that this polaron decoupling strongly reduces the fluctuations in electronic energy in tetraphenyldibenzoperiflanthene thin films embedded in an optical microcavity. Using two-dimensional electronic spectroscopy, the frequency-fluctuation correlation function of the lower polariton state was revealed, showing that the dynamic inhomogeneity due to bath coupling inside the microcavity almost vanishes completely. This was attributed to a significant delocalization of the lower polariton state over 105 molecules in the cavity, reducing the effective coupling strength of the bath modes.

Singlet fission of amorphous rubrene modulated by polariton formation.

The excited-state dynamics of molecular aggregates are governed by their potential energy landscape that can hardly be controlled artificially. However, it is possible to alter the excited state dynamics by a strong coupling between light and molecules (polariton formation) because it can decouple the electronic and vibrational degrees of freedom. Here, we demonstrate this polaron decoupling effect on the photochemical dynamics in singlet fission (SF) of amorphous rubrene thin films embedded in optical microcavities. The vibronic feature of polariton states in this system is characterized through the analysis of steady state absorption spectra by using the Holstein-Tavis-Cummings model. On the basis of this analysis, we show with time-resolved spectroscopy that the SF rate following a resonant excitation of the lowest energy polariton state is indeed modulated when the cavity photon energy is changed. A numerical simulation by using Fermi's golden rule formula with the vibronic polariton feature successfully accounts for the observed modulation of the SF rate, indicating that the polaron decoupling plays a decisive role in the nonadiabatic dynamics.

Electrochemical determination with a long-length carbon nanotube electrode of quercetin glucosides in onion, apple peel, and tartary buckwheat.

Since the intake of quercetin glucosides has healthy benefits, the analysis of quercetin glucosides in food is useful. The electrochemical determination of individual quercetin glucosides (quercetin-3-glucoside (Q3G), quercetin-4'-glucoside (Q4'G), and quercetin-3,4'-diglucoside (Q34'G)) in food is carried out. For the detection of quercetin glucosides, a long-length carbon nanotube electrode offers attractive properties such as well-defined current peaks, high sensitivity, and high reproducibility. Cyclic voltammetry (CV) demonstrates distinct and specific peak currents: the oxidation peaks at +0.37, +0.45, and +0.78 V are assigned to the catechol group in the B-ring of Q3G, the 3-hydroxy group in the C-ring of Q4'G, and the resorcinol group in the A-ring of both Q4'G and Q34'G, respectively. Currents, which are determined by CV, of individual quercetin glucosides at the peak potential are proportional to the concentrations of onion, apple peel, and tartary buckwheat, which show good agreement with those obtained by high-performance liquid chromatography.

Effects of synbiotics containing Bifidobacterium animalis subsp. lactis GCL2505 and inulin on intestinal bifidobacteria: A randomized, placebo-controlled, crossover study.

A number of studies have shown the bifidogenic effects of either probiotic bifidobacteria or inulin, and this bifidogenic shift in the composition of the colonic microbiota is likely the basis for their positive impact on human health. This study aimed to evaluate the effects of synbiotics containing the probiotic bacterium Bifidobacterium animalis subsp. lactis (B. lactis) GCL2505 and inulin on the levels of intestinal bifidobacteria compared with B. lactis GCL2505 alone. A randomized, double-blind, placebo-controlled, crossover trial was carried out involving 60 healthy subjects with a tendency for constipation using fermented milk containing B. lactis GCL2505 and inulin (synbiotic), only B. lactis GCL2505 (probiotic), and placebo. Fecal samples were collected at the end of each 2-week intervention period, and the bifidobacterial count was analyzed by quantitative real-time PCR. The numbers of total bifidobacteria and B. lactis in feces were significantly increased during the probiotic and synbiotic intake periods compared with the placebo intake period. Furthermore, the numbers of total bifidobacteria and endogenous bifidobacteria were significantly higher in the synbiotic intake period compared with the probiotic intake period, while there was no difference in the number of B. lactis. These results suggested that the synbiotics containing B. lactis GCL2505 and inulin had a greater effect on the number of bifidobacteria than a drink containing probiotics alone and could be useful for the improvement of the intestinal environment.

Polyphenol Analysis in Black Tea with a Carbon Nanotube Electrode.

An electrochemical analysis of polyphenols (theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin-3'-gallate (TF2B), theaflavin-3,3'-digallate (TF3), and epigallocatechingallate (EGCG)) in a black tea infusion is demonstrated. The characterization of each polyphenol in a solution containing only a single type of polyphenol for a redox reaction at the CNT electrode with cyclic voltammetry (CV) was conducted. The oxidation peak at around +0.30 V for TF1 is assigned to catechol group in a benzotropolone ring. The oxidation peak at around +0.35 V for TF2A, TF2B, and TF3 is assigned to both of the catechol groups in the benzotropolone ring and the pyrogallol group in the gallate ring. The oxidation peak at around +0.35 V for EGCG is assigned to a pyrogallol group in the gallate ring. Current changes of those individual polyphenols at the peak potential are proportional to their concentrations (linear range 0.28 - 94 µM; detection limit 0.11 µM). The CV curve for real black tea, which is mainly composed of a mixture of the mentioned five compounds, is produced by the sum of those. The current change of the mixture solution of polyphenols is also proportional to the mass concentration of the total polyphenols and the sensitivity defined as the slope of current vs. concentration plot is independent of the ratio of the individual polyphenols. This indicates that the peak current at around +0.35 V can quantify the total amount of polyphenols in a black tea. Additionally, the shape of the CV curve can roughly estimate the ratio of [catechins]/[theaflavins]. The values for real samples determined from CVs show good agreement with that obtained by high-performance liquid chromatography.

Separationless and Adsorptionless Quantification of Individual Catechins in Green Tea with a Carbon Nanotube-Carboxymethylcellulose Electrode.

We demonstrate the electrochemical quantification of individual catechins (epicatechin, EC; epigallocatechin, EGC; epicatechingallate, ECG; and epigallocatechingallate, EGCG) in a green tea infusion without a separation process nor any adsorption complication. In the detection of catechins, long-length carbon nanotube (CNT)-carboxymethylcellulose (CMC) thin-film electrodes have attractive properties, such as well-defined current peaks, high reproducibility from sample to sample, high repeatability, and low background current. Cyclic voltammograms (CVs) for real green tea, which is mainly composed of a mixture of the four catechins, are produced by the sum of those catechins. A set of three specific peaks in the CVs of the real green tea samples, as catechin-mixture solutions, was used for quantification of the individual catechins. The CVs of the real samples are similar to the CVs of intentionally prepared mixture solutions with the catechin-component ratios determined by high-performance liquid chromatography (HPLC). The values for the real samples determined from the CVs show good agreement with those obtained by HPLC. The novelty of the work is the demonstration of the usefulness of the CNT-CMC electrode and the separationless quantification of individual catechins in green tea for the first time.

Conformational Planarization versus Singlet Fission: Distinct Excited-State Dynamics of Cyclooctatetraene-Fused Acene Dimers.

A set of flapping acene dimers fused with an 8π cyclooctatetraene (COT) ring showed distinct excited-state dynamics in solution. While the anthracene dimer showed a fast V-shaped-to-planar conformational change within 10 ps in the lowest excited singlet state, reminding us of extended Baird aromaticity, the tetracene dimer and the pentacene dimer underwent intramolecular singlet fission (SF) in different manners: A fast and reversible SF with a characteristic delayed fluorescence (FL), and a fast and quantitative SF, respectively. Conformational flexibility of the fused COT linkage plays an important role in these ultrafast dynamics, demonstrating the utility of the flapping molecular series as a versatile platform for designing photofunctional systems.