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A multiple quantum barrier (MQB) avalanche photodiode (APD) structure based on GaN/AlxGa $_{1{-}x}\text{N}$ material system has been proposed in this paper which is capable of detecting infrared (IR) signal up to $6.0~\mu \text{m}$ wavelength. A self-consistent quantum drift-diffusion (SCQDD) model developed by the authors, has been used to determine the current-voltage characteristics under dark and illuminated conditions, spectral response, excess noise properties, signal-to-noise ratio, time and frequency responses. Results show that the proposed MQB APD attains peak responsivity of 60 AW $^{-1}$ at $3.0\, \mu \text{m}$ wavelength. Incorporation of a dedicated thin $n$ -type GaN layer for avalanche multiplication in between the $p^{+}$ -GaN contact layer and MQB constant-field drift-layer ensures significantly low noise equivalent power under normal operating conditions at room temperature (300 K). Optical pulse response of the device reveals that special restriction over the charge multiplication able to supress the minor peaks of the current response and consequently significantly narrow pulse response can be achieved. Narrow pulse response leads to broad bandwidth of 274.5 GHz, which is significantly broader than the existing IR photo-detectors.

Abstract Background The factors that predict the clinical response to ramucirumab plus docetaxel (RD) after first‐line chemoimmunotherapy are unresolved. We explored whether the therapeutic efficacy of prior chemoimmunotherapy could predict the outcome of RD as sequential therapy in patients with advanced non‐small cell lung cancer (NSCLC). Methods Our study comprised 288 patients with advanced NSCLC who received RD as the second‐line treatment after first‐line chemoimmunotherapy at 62 Japanese institutions. Chemoimmunotherapy consisted of a platinum‐based regimen and immune checkpoint inhibitors (ICIs). The association between several variables and the therapeutic outcome of RD was determined via logistic regression analysis. Results Of the 288 patients, 225 (78.1%) received maintenance therapy and 108 (37.5%) received both ICI treatment for >180 days and maintenance therapy. All of 108 patients having ICIs for >180 days received maintenance therapy. Univariate analysis identified performance status, histology (adenocarcinoma), maintenance therapy, and ICI treatment >180 days as significant predictors of better progression‐free survival (PFS) and overall survival (OS) after RD administration. Multivariate analysis confirmed that these factors independently predicted favorable PFS and OS. The therapeutic response and PD‐L1 expression were not closely associated with outcome after RD treatment. In particular, maintenance therapy >4 cycles was more predictive of the better prognosis for RD treatment. Conclusion Extended ICI treatment after chemoimmunotherapy and maintenance therapy enhanced the efficacy of second‐line RD treatment in patients with advanced NSCLC.

In our pursuit of high-power terahertz (THz) wave generation, we propose innovative edge-terminated single-drift region (SDR) multi-quantum well (MQW) impact avalanche transit time (IMPATT) structures based on the AlxGa1−xN/GaN/AlxGa1−xN material system, with a fixed aluminum mole fraction of x = 0.3. Two distinct MQW diode configurations, namely p+-n junction-based and Schottky barrier diode structures, were investigated for their THz potential. To enhance reverse breakdown characteristics, we propose employing mesa etching and nitrogen ion implantation for edge termination, mitigating issues related to premature and soft breakdown. The THz performance is comprehensively evaluated through steady-state and high-frequency characterizations using a self-consistent quantum drift-diffusion (SCQDD) model. Our proposed Al0.3Ga0.7N/GaN/Al0.3Ga0.7N MQW diodes, as well as GaN-based single-drift region (SDR) and 3C-SiC/Si/3C-SiC MQW-based double-drift region (DDR) IMPATT diodes, are simulated. The Schottky barrier in the proposed diodes significantly reduces device series resistance, enhancing peak continuous wave power output to approximately 300 mW and DC to THz conversion efficiency to nearly 13% at 1.0 THz. Noise performance analysis reveals that MQW structures within the avalanche zone mitigate noise and improve overall performance. Benchmarking against state-of-the-art THz sources establishes the superiority of our proposed THz sources, highlighting their potential for advancing THz technology and its applications.

Abstract Aims For long‐term management of diabetes, patients with type 2 diabetes mellitus require a high level of treatment adherence, which is associated with treatment satisfaction and their quality of life (QOL). To achieve it, patient education about diabetes self‐management is essential. We routinely conduct a 7 day inpatient diabetes education program and administer the diabetes treatment‐related (DTR)‐QOL questionnaire to all participants, both before admission and at discharge. Here, we investigated whether our program improves QOL and post‐discharge glycemic control. Materials and Methods This retrospective study utilized data from patients with type 2 diabetes mellitus who participated in our program between July 2017 and March 2020 and who had been treated in our outpatient department for more than 1 year. We evaluated the relationship between at admission and at discharge diabetes treatment‐related quality of life scores and glycemic control after discharge. Results Data from 140 patients were analyzed in this study, which showed a significant improvement in the total, ‘Anxiety and dissatisfaction with treatment’, and ‘Satisfaction‐with‐treatment’ scores. A significant improvement was evident in HbA1c at 12 months after discharge. Multiple regression analysis showed that HbA1c after 12 months was independently associated with gender, duration of diabetes, and HbA1c at admission. Conclusions Our program effectively improves quality of life and post‐discharge glycemic control in patients with type 2 diabetes mellitus. It is particularly effective in patients of the male gender, with a shorter duration of diabetes mellitus and higher HbA1c at admission.

Abstract Background This study investigated the sex differences in the risk of end‐stage kidney disease (ESKD) and mortality, as well as the effect modification of sex on associated factors in patients with type 2 diabetes. Methods This multicenter observational cohort study included 4328 patients with type 2 diabetes. Hazard ratios (HRs) with 95% confidence intervals (CIs) of sex for ESKD and death were estimated using Cox proportional regression with adjustment for baseline covariates. For assessing risk modification, HRs and incidence rates for ESKD and death were compared between sexes across patient characteristics using Cox proportional and Poisson regression models. Results During a median follow‐up of 7 years, 276 patients (70% men) developed ESKD, and 241 patients (68% men) died. Men had higher risks of ESKD (HR 1.34; 95% CI 1.02–1.75; p = .034) and death (HR 1.64; 95% CI 1.24–2.16; p = .001) versus women after adjusting for multiple covariates. Among patients with microalbuminuria, men had a substantially higher risk of ESKD versus women, compared to those with normo‐ and macroalbuminuria (p for interaction .04). Incidence rates were also increased in men versus women with albuminuria of around 300 mg/g. No differences were detected in the association of sex and death across baseline patient subgroups. Conclusions In type 2 diabetes, men had an increased risk of ESKD and death versus women. Moderately increased albuminuria was strongly associated with sex difference in developing ESKD.

To improve the responsivity of terahertz (THz) antenna-coupled bolometer, heater (load) resistance has to be increased to suppress the thermal conduction and realize larger temperature rise of the thermistor. Proper design of antenna is therefore essential to assure the impedance matching between antenna and heater. From this viewpoint, a high-impedance folded-dipole antenna (FDA) has been studied numerically by the finite element simulation. The effect of FDA structural parameters such as number of arms, antenna width, and arm spacing are discussed with the lumped port and resistive heater coupled to the antenna gap for the cases of radiating and receiving modes, respectively. The product of resonant resistance and area efficiency is used to predict the improvement made by FDA as a figure of merit (FOM) correlated to the bolometer responsivity. This study revealed that the optimum FOM in FDA-coupled bolometer operating at 1 THz was obtained with three arms, 1- $\mu \text{m}$ antenna width and 4- $\mu \text{m}$ arm spacing. A comparison was made with the result from a half-wave dipole antenna and revealed that FDA could enhance the bolometer responsivity by a factor of 15. This research demonstrated the effectiveness of the FDA to improve the performance of THz antenna-coupled bolometer for applications such as imaging for non-destructive inspection.

Abstract Background The prognosis of lung cancer patients with interstitial lung disease (ILD) is poor, and acute exacerbation (AE) of ILD can occur during chemotherapy as a fatal adverse event. Although AE‐ILD development is correlated with various factors, no reports are investigating the disease activity of lung cancer at the time of AE‐ILD development. Methods All consecutive lung cancer patients with ILD who developed chemotherapy‐related AE‐ILD within 28 days after the last administration of cytotoxic chemotherapy between 2011 and 2020 were retrospectively reviewed. Results Among 206 lung cancer patients with ILD who were treated with cytotoxic chemotherapy, 30 patients were included. The median age was 72 years and all patients were men with smoking history. Usual interstitial pneumonia (UIP) and non‐UIP patterns of ILD was observed in 17 and 13 patients. Most of AE‐ILD occurred during second‐ or later‐line (22/30, 73.3%) and developed within first or second courses during chemotherapy (19/30, 63.3%). Regarding tumor response to chemotherapy at AE‐ILD development, majority of patients (18 patients, 60.0%) experienced progressive disease and only one patient (3.3%) experienced a partial response. Notably, 27 patients (90.0%) did not exhibit any tumor shrinkage of the thoracic lesions. Conclusion Lung cancer was uncontrolled with cytotoxic chemotherapy at the time of AE‐ILD development. Although AE‐ILD during chemotherapy has been generally discussed in terms of drug‐specific adverse effects, uncontrolled lung cancer may be also correlated with AE‐ILD development.

This study demonstrates the conversion of metallic titanium (Ti) to titanium oxide just by conducting electrical current through Ti thin film in vacuum and increasing the temperature by Joule heating. This led to the improvement of electrical and thermal properties of a microbolometer. A microbolometer with an integrated Ti thermistor and heater width of 2.7 µm and a length of 50 µm was fabricated for the current study. Constant-voltage stresses were applied to the thermistor wire to observe the effect of the Joule heating on its properties. Thermistor resistance ~14 times the initial resistance was observed owing to the heating. A negative large temperature coefficient of resistance (TCR) of −0.32%/K was also observed owing to the treatment, leading to an improved responsivity of ~4.5 times from devices with untreated Ti thermistors. However, this does not improve the noise equivalent power (NEP), due to the increased flicker noise. Microstructural analyses with transmission electron microscopy (TEM), transmission electron diffraction (TED) and energy dispersive X-ray (EDX) confirm the formation of a titanium oxide (TiOx) semiconducting phase on the Ti phase (~85% purity) deposited initially, further to the heating. Formation of TiOx during annealing could minimize the narrow width effect, which we reported previously in thin metal wires, leading to enhancement of responsivity.

Background: The Great East Japan Earthquake and the Fukushima Daiichi nuclear disaster forced the evacuation of residents and led to many changes in lifestyle for the evacuees. The Comprehensive Health Check was implemented to support the prevention of lifestyle-related disease and we analyzed the effect of prolonged evacuation (average of 3.0 years) on the new onset of hyper-LDL cholesterolemia. Methods: The study participants were Japanese adults living near the Fukushima Daiichi nuclear power plant in Fukushima Prefecture. Annual health checkups focusing on metabolic syndromes were conducted for persons ≥40 years by the Specific Health Checkup. Based on data from annual checkups from 2011 or 2012, we followed 18,670 participants without hyper-LDL cholesterolemia who underwent at least one other annual checkup during 2013–2015. Results: We found that the new onset of hyper-LDL cholesterolemia was 31% higher in evacuees than in non-evacuees. Evacuees had a significantly higher prevalence of obesity, hypertension, and diabetes, and higher frequency of weight change. Furthermore, logistic regression model analysis showed that the evacuation was significantly associated with the new onset of hyper-LDL cholesterolemia after adjusting age, gender, body mass index, smoking habit, alcohol consumption, diabetes, weight change, sleep deprivation, and exercise. Conclusion: The findings of the present study suggest that prolonged evacuation after a disaster is a risk factor for the new onset of hyper-LDL cholesterolemia, and lead to an increase in cardiovascular disease. It is therefore important to follow-up evacuees and recommend lifestyle changes where necessary.

Anti-melanoma differentiation-associated gene-5 (MDA-5) antibody is an autoantibody found in patients with dermatomyositis. These antibody-positive patients are clinically characterized by complications of rapidly progressive interstitial pneumonia resistant to treatment and with poor prognosis. We describe herein a patient with MDA-5 antibody-positive interstitial lung disease, which progressed rapidly to death after a period of slow progress. Recently, attention has been paid to the similarities in clinical courses and CT images between MDA-5 antibody-positive interstitial lung disease and coronavirus disease 2019 (COVID-19)-associated pneumonia. Patients with MDA-5 antibody do not always have diffuse and evenly distributed bilateral opacities at the time of first presentation. This patient had significant laterality of such opacities. It should be considered that MDA-5 antibody-positive patients with such laterality in opacities might progress rapidly. Chest physicians, dermatologists, and dermatologists need to be aware of the characteristics of the disease for optimal treatment choices.

Residents were forced to evacuate owing to the radiation released after the Fukushima Nuclear Power Plant (NPP) accident following the Great East Japan Earthquake on 11/03/2021; thus, their lifestyles drastically changed. The Comprehensive Health Check (CHC) of the Fukushima Health Management Survey (FHMS) was performed to evaluate health statuses and prevent lifestyle-related diseases in evacuation area residents. The first part of the CHC survey is a retrospective analysis of pre- and post-disaster data on health check-ups of evacuation area residents. The second part is a cross-sectional, prospective analysis of post-disaster (fiscal year (FY) 2011–2017) data on health check-ups. Subjects were men and women living in 13 municipalities in areas surrounding the NPP in Fukushima Prefecture. Post-disaster (FY 2011–2012) overweight, hypertension, dyslipidemia, diabetes mellitus, metabolic syndrome, liver dysfunction, hyperuricemia, polycythemia and atrial fibrillation cases increased from the pre-disaster (FY 2008–2010) levels. This tendency was strongest among residents who were forced to evacuate. Proportion of overweight people remained unchanged, the prevalence of liver dysfunction decreased and the proportion of people with treated hypertension and dyslipidemia increased during FY 2011–2017. Meanwhile, the prevalence of diabetes mellitus and mean levels of HbA1c increased. Furthermore, Evacuees showed higher risks of diabetes mellitus, dyslipidemia, chronic kidney diseases and liver dysfunction than non-evacuees. Therefore, residents in the evacuation area, especially evacuees, are at high risk of developing lifestyle-related diseases, especially cardiovascular diseases; therefore, it is necessary to observe health statuses and implement measures to prevent lifestyle-related diseases.

A Schottky barrier high-electron-mobility avalanche transit time (HEM-ATT) structure is proposed for terahertz (THz) wave generation. The structure is laterally oriented and based on AlGaN/GaN two-dimensional electron gas (2-DEG). Trenches are introduced at different positions of the top AlGaN barrier layer for realizing different sheet carrier density profiles at the 2-DEG channel; the resulting devices are equivalent to high–low, low–high and low-high–low quasi-Read structures. The DC, large-signal and noise simulations of the HEM-ATTs were carried out using the Silvaco ATLAS platform, non-sinusoidal-voltage-excited large-signal and double-iterative field-maximum small-signal simulation models, respectively. The breakdown voltages of the devices estimated via simulation were validated by using experimental measurements; they were found to be around 17–18 V. Under large-signal conditions, the series resistance of the device is estimated to be around 20 Ω. The large-signal simulation shows that the HEM-ATT source is capable of delivering nearly 300 mW of continuous-wave peak power with 11% conversion efficiency at 1.0 THz, which is a significant improvement over the achievable THz power output and efficiency from the conventional vertical GaN double-drift region (DDR) IMPATT THz source. The noise performance of the THz source was found to be significantly improved by using the quasi-Read HEM-ATT structures compared to the conventional vertical Schottky barrier IMPATT structure. These devices are compatible with the state-of-the-art medium-scale semiconductor device fabrication processes, with scope for further miniaturization, and may have significant potential for application in compact biomedical spectroscopy systems as THz solid-state sources.

Abstract Aims/Introduction As a low‐carbohydrate diet and the use of sodium–glucose transporter‐2 inhibitors are both known to increase D‐beta‐hydroxybutyrate levels, the effect of these levels on glucose metabolism has attracted attention. We investigated the acute effects of ketone monoester (KM) ingestion on blood glucose levels during the 75‐g oral glucose tolerance test (OGTT) in participants with impaired glucose tolerance. Materials and Methods Nine Japanese adults aged 48–62 years (4 men, 5 women) with impaired glucose tolerance participated in this study. After participants fasted overnight, we carried out OGTT for 180 min with and without KM ingestion on two separate days in a randomized cross‐over design. We compared the area under the curve (AUC) of D‐beta‐hydroxybutyrate, glucose, insulin, C‐peptide, glucagon and free fatty acids during OGTT. Results The AUC of D‐beta‐hydroxybutyrate during OGTT was significantly higher with KM than without KM (KM 5995.3 ± 1257.1 mmol/L·h; without KM 116.1 ± 33.9 mmol/L·h, P

Purpose: To investigate the long-term changes in body weight and serum albumin levels in patients with respiratory failure, and those with chronic heart failure, who were treated with home long-term oxygen therapy (LTOT) to understand the current status and contribute to future measures. Methods: Patients with chronic obstructive pulmonary disease (COPD), those with interstitial pneumonia (IP), and those with chronic heart failure (CHF) undergoing home LTOT for 6 months or more between January 2011 and January 2019 were included in the study. Body weight and serum albumin levels were assessed at the start of home LTOT and at the end of the observation period, a minimum of 6 months after commencing home LTOT. Results: Sixty-two patients (29 COPDs, 23 IPs, and 10 CHFs) were included. In COPD patients and IP patients, body weight decreased (P = 0.0017, P = 0.0018, respectively, Wilcoxon signed-rank test). Serum albumin levels decreased in IP patients (P = 0.0185) but not in COPD patients. There was neither significant decrease in body weight nor serum albumin levels in patients with CHF. Conclusion: Chronic respiratory failure patients who have home LTOT were likely to have a decreased nutritional status. In order to provide prolonged home LTOT, medical staff need to pay close attention to the nutritional status of patients receiving home LTOT.

Abstract Based on questionnaires from 197,825 non-diabetic participants in a large Japanese cohort, we determined impact of (1) habit of exercise, (2) habit of active physical activity (PA) and (3) walking pace on new-onset of type 2 diabetes mellitus. Unadjusted and multivariable-adjusted logistic regression models were used to determine the odds ratio of new-onset diabetes mellitus incidence in a 3-year follow-up. There were two major findings. First, habits of exercise and active PA were positively associated with incidence of diabetes mellitus. Second, fast walking, even after adjusting for multiple covariates, was associated with low incidence of diabetes mellitus. In the subgroup analysis, the association was also observed in participants aged ≥ 65 years, in men, and in those with a body mass index ≥ 25. Results suggest that fast walking is a simple and independent preventive factor for new-onset of diabetes mellitus in the health check-up and guidance system in Japan. Future studies may be warranted to verify whether interventions involving walking pace can reduce the onset of diabetes in a nation-wide scale.

Although advances have been made in the treatment and prevention of febrile neutropenia (FN) in cancer patients treated with chemotherapy, it is still a complication that requires clinical attention. Impaired nutritional status in patients who develop FN can affect the continuation of cancer treatment, but it has not been investigated. We conducted a retrospective longitudinal study in order to clarify (1) if body weight and serum albumin levels change in lung cancer patients who do and do not develop FN, and (2) if these indicators are more likely to worsen in patients with FN than in patients without FN. Patients undergoing cytotoxic chemotherapy between January 2011 and June 2020 were consecutively included in the study. Changes in body weight and serum albumin levels were investigated in a case–control study of patients with FN, and control patients without FN who were matched by age, gender, histopathology, and stage of lung cancer, at a ratio of 1:2. During the study period, 226 patients received cytotoxic chemotherapy. Among those, 33 (14.6%) patients developed FN during the first course of cytotoxic chemotherapy. We found a more pronounced decrease in both body weight and serum albumin level at four weeks after the initiation of chemotherapy in FN patients. In order to safely administer effective chemotherapy, medical staff need to pay close attention to the nutritional status of patients receiving chemotherapy.

Abstract Aims/Introduction In Japan, an insulin pump with predictive low‐glucose management (PLGM) was launched in 2018. It automatically suspends insulin delivery when the sensor detects or predicts low glucose values. The aim of this study was to analyze the safety and efficacy of PLGM in patients treated in a Japanese center. Materials and Methods We carried out a retrospective observational analysis of 16 patients with type 1 diabetes mellitus and one patient after pancreatectomy. They switched from the MiniMed 620G device to the 640G device with PLGM. The primary outcome was the change in the percentage of time in hypoglycemia. The secondary outcome was the change in HbA1c (%) over a period of 3 months. We also explored the presence of “post‐suspend hyperglycemia” with the 640G device. Results After changing to the 640G device, the percentage of time in hypoglycemia (glucose 180 mg/dL) significantly increased from 25.53% (15.78–44.14%) to 32.9% (24.71–45.49%; P = 0.0373). HbA1c significantly increased from 7.6 ± 1.0% to 7.8 ± 1.1% (P = 0.0161). From 1.5 to 4.5 h after the resumption of insulin delivery, the percentage of time in hyperglycemia was 32.23% (24.2–53.75%), but it was significantly lower, 2.78% (0–21.6%), when patients manually restarted the pump within 30 min compared with automatic resumption 31.2% (20–61.66%; P = 0.0063). Conclusions Predictive low‐glucose management is an effective tool for reducing hypoglycemia, but possibly elicits “post‐suspend hyperglycemia.” This information is useful for achieving better blood glucose control in the patients treated with PLGM.

Lung metastasis and metachronous double primary lung cancer are both common and often present diagnostic challenges. We present a case of metachronous isolated contralateral lung metastasis from pulmonary adenosquamous carcinoma with EGFR mutation. A 75-yearold woman presented with left lung nodule on a routine follow-up chest radiograph. She had had surgery for pulmonary adenocarcinoma with EGFR Ex21 L858R mutation 6 years ago. She underwent surgical resection, and histologic findings revealed adenosquamous carcinoma with the same EGFR mutation. Re-assessment of the resected specimen of the primary tumor resected 6 years ago revealed the morphologically similarity to the left lung tumor. Based on morphological and genetic identity, final diagnosis was adenosquamous cell carcinoma and metachronous isolated contralateral lung metastasis. The diagnosis of metachronous isolated metastasis is difficult but important for appropriate management and prediction of prognosis. A careful pathological examination and evaluation of genetic abnormality are needed to make the correct diagnosis.

In recent years, additional expressions such as ‘sensation of breathing discomfort’ and ‘discomfort of dyspnea’ are being used in daily nursing care in Japan. To better understand the current status of the use of these terms by nurses, and to ascertain what the term ‘dyspnea’ may not express, we designed an original questionnaire and conducted a study with all nurses at our hospital. The questionnaire included questions to determine if nurses used these terms, and in what context. Of the 279 nurses in our hospital, 225 (80.6%) responded. Three-quarters of nurses indicated that they use these terms in clinical nursing practice. There was no difference in the usage of these terms between nurses who had or had not worked in a respiratory outpatients/ward. However, the percentage of nurses using these terms was higher amongst those with 10 years or less nursing experience compared with those with more than 10 years’ experience. Open-ended questions revealed that these terms were used to communicate information between nurses and between nurses and patients’ families. Our observations need to be verified in large-scale studies to determine if these terms are meaningful for nursing practice in that they describe something not expressed with ‘dyspnea’. There is the possibility of confusion due to the use of inappropriate terms and a lack of education on the subject. Many nurses used these terms, and there may be things that the term ‘dyspnea’ could not express. The results of this study can be used to identify something that is lacking in communication about dyspnea between nurses, nurses and patients, and nurses and patients’ families.

Background and objectivesChronic inflammatory airway diseases, including asthma and chronic obstructive pulmonary disease (COPD), are complex syndromes with diverse clinical symptoms due to multiple pathophysiological conditions. In this study, using common and shared risk factors for the exacerbation of asthma and COPD, we sought to clarify the exacerbation-prone phenotypes beyond disease labels, and to specifically investigate the role of the IL4RA gene polymorphism, which is related to type 2 inflammation, in these exacerbation-prone phenotypes.MethodsThe study population comprised patients with asthma (n = 117), asthma-COPD overlap (ACO; n = 37) or COPD (n = 48) and a history of exacerbation within the previous year. Cluster analyses were performed using factors associated with both asthma and COPD exacerbation. The association of the IL4RA gene polymorphism rs8832 with each exacerbation-prone phenotype was evaluated by multinomial logistic analyses using non-asthma non-COPD healthy adults as controls (n = 1,529). In addition, the genetic influence of rs8832 was also examined in asthma patients with allergic rhinitis and no history of exacerbation (n = 130).ResultsTwo-step cluster analyses identified five clusters that did not necessarily correspond to the diagnostic disease labels. Cluster 1 was characterized by high eosinophil counts, cluster 2 was characterized by smokers with impaired lung function, cluster 3 was characterized by the presence of gastroesophageal reflux, cluster 4 was characterized by non-allergic females, and cluster 5 was characterized by allergic rhinitis and elevated total immunoglobulin E levels. A significant association with rs8832 was observed for cluster 5 (odds ratio, 3.88 (1.34-11.26), p = 0.013) and also for the type 2 exacerbation-prone phenotypes (clusters 1 and 5: odds ratio, 2.73 (1.45-5.15), p = 1.9 × 10-3).DiscussionOur results indicated that the clinical heterogeneity of disease exacerbation may reflect the presence of common exacerbation-prone endotypes across asthma and COPD, and may support the use of the treatable traits approach for the prevention of exacerbations in patients with chronic inflammatory airway diseases.

This paper proposes a new optical biosensor composed of a silicon-on-insulator (SOI) p–n junction photodiode (PD) with a surface plasmon (SP) antenna. When the phase-matching condition between two lateral wavelengths of the diffracted light from the SP antenna and the waveguiding mode in the SOI PD is satisfied, we observe sharp peaks in the spectroscopic light sensitivity. Since the peak wavelength depends on the RI change around the SP antenna corresponding to the phase-matching condition, the SOI PDs with an SP antenna can be applied to the optical biosensor. The RI detection limit is evaluated in the measurements with bulk solutions, and 1.11 × 10−5 RIU (refractive index unit) can be obtained, which is comparable to that of a surface plasmon resonance (SPR) sensor, which is well known as a representative optical biosensor. In addition, the response for intermolecular bonds is estimated by the electromagnetic simulations using the finite-difference time-domain (FDTD) method to clarify its ability to detect biomolecular interactions. The results of this paper will provide new ground for high-throughput label-free biosensing, since a large number of SOI PDs with an SP antenna can be easily integrated on a single chip via an SOI complementary metal-oxide-semiconductor (CMOS) fabrication process.

Dear Editor, We read with interest the article by Balis et al. on pulmonary tuberculosis and actinomyces co-infection as a lung mass....

Introduction Changes in albuminuria or estimated glomerular filtration rate (eGFR) can be used as a surrogate endpoint of end-stage kidney disease (ESKD) in people with type 2 diabetes. We investigated whether the combined changes in albuminuria and eGFR are more strongly associated with future risk of ESKD.Research design and methods Using data from a multicenter observational cohort study of people with type 2 diabetes, we evaluated the association of percentage change in urine albumin to creatinine ratio (UACR) and/or annual change in eGFR over 2 years with subsequent ESKD risk.Results Among 1417 patients with repeated albuminuria and eGFR over 2 years, 129 (9.1%) developed ESKD. Patients with >30% UACR decline had lower ESKD risk (HR 0.47; 95% CI 0.29 to 0.77), whereas those with >30% UACR increase had higher ESKD risk (HR 2.31; 95% CI 1.52 to 3.51), compared with those with minor UACR change. Patients with greater eGFR decline had an increased ESKD risk than those with minor eGFR change (a decline of 5 and 2.5–5 mL/min/1.73 m2/year, respectively. When the combined changes in UACR and eGFR were used, the highest ESKD risk (HR 5.60; 95% CI 2.08 to 15.09) was observed among patients with >30% UACR increase and an eGFR decline of >5 mL/min/1.73 m2/year compared with those with a minor change in UACR and eGFR.Conclusions Combined changes in albuminuria and eGFR over 2 years were strongly associated with future risk of kidney failure in patients with type 2 diabetes.

Based on the time-dependent master equation and taking the dynamic gate current into account, a new single-electron transistor (SET) model is proposed, which can represent intrinsic terminal capacitances and transcapacitances. By using this model, bias, frequency and temperature dependences of these capacitances are evaluated. Since the model is implemented in the SPICE circuit simulator, it can be used to analyze the high-frequency behavior of circuits, including SETs and is applied to the characterization of a SET-based inverting amplifier this time.

Abstract To ensure that experiences and lessons learned from the unprecedented 2011 Great East Japan Earthquake are used to improve future disaster planning, the Japan Diabetes Society (JDS) launched the “Research and Survey Committee for Establishing Disaster Diabetes Care Systems Based on Relevant Findings from the Great East Japan Earthquake” under the supervision of the Chairman of the JDS. The Committee conducted a questionnaire survey among patients with diabetes, physicians, disaster medical assistance teams (DMATs), nurses, pharmacists, and nutritionists in disaster areas about the events they saw happening, the situations they found difficult to handle, and the needs that they felt required to be met during the 2011 Great East Japan Earthquake. A total of 3,481 completed questionnaires were received. Based on these and other experiences and lessons reported following the 2011 Great East Japan Earthquake and the 2004 Niigata‐Chuetsu Earthquakes, the current “Manual for Disaster Diabetes Care” has been developed by the members of the Committee and other invited authors from relevant specialties. To our knowledge, the current Manual is the world's first to focus on emergency diabetes care, with this digest English version translated from the Japanese original. It is sincerely hoped that patients with diabetes and healthcare providers around the world will find this manual helpful in promoting disaster preparedness and implementing disaster relief.

The antenna-coupled microbolometer with suspended titanium heater and thermistor was attractive as a terahertz (THz) detector due to its structural simplicity and low noise levels. In this study, we attempted to improve the responsivity and noise-equivalent power (NEP) of the THz detector by using high-resistance heater stacked on the meander thermistor. A wide range of heater resistances were prepared by changing the heater width and thickness. It was revealed that the electrical responsivity and NEP could be improved by increasing the heater’s resistance. To make the best use of this improvement, a high-impedance folded dipole antenna was introduced, and the optical performance at 1 THz was found to be better than that of the conventional halfwave dipole antenna combined with a low-resistance heater. Both the electrical and optical measurement results indicated that the increase in heater resistance could reduce the thermal conductance in the detector, thus improved the responsivity and NEP even if the thermistor resistance was kept the same.

Background: Sensitive-relapsed small-cell lung cancer (SCLC) is thought to be sensitive to chemotherapy; therefore, second-line chemotherapy is recommended. Although platinum rechallenge is performed in the second-line chemotherapy for sensitive-relapsed SCLC, it remains unclear whether such a strategy is effective. Methods: We retrospectively analyzed the outcome of rechallenge chemotherapy for sensitive-relapsed SCLC. The endpoints of this study were progression-free survival from the time of relapse (PFS-Re) and overall survival from the time of relapse (OS-Re). We also compared the toxicity profile of rechallenge chemotherapy to that of first-line chemotherapy. Results: Of the 133 SCLC patients who received first-line treatment, 20 patients satisfied the definition of sensitive relapse and received rechallenge chemotherapy. Combined carboplatin and etoposide was the most commonly used rechallenge regimen, and 17 (85%) received it at a reduced dose due to hematological toxicity during the first-line treatment. Median PFS-Re and OS-Re were 4.5 months (95% CI: 3.5–5.4) and 10.5 months (95% CI: 7.9–13.0), respectively. There was no association between dose adjustment and survival. The frequency of hematologic toxicity tended to be lower with rechallenge than first-line treatment. The incidence of grade 3 febrile neutropenia decreased from 40% in first-line treatment to 15% in rechallenge. Conclusion: Platinum rechallenge could be a useful second-line option for sensitive-relapsed SCLC, having favorable efficacy and safety. Dose adjustment at rechallenge based on the toxicity profile during the first-line chemotherapy could reduce toxicity without weakening efficacy.

Background: Decreased insulin clearance could be a relatively upstream abnormality in obesity, metabolic syndrome, and nonalcoholic fatty liver disease. Previous studies have shown that sodium-glucose cotransporter 2 inhibitor (SGLT2i) increases insulin–C-peptide ratio, a marker of insulin clearance, and improves metabolic parameters. We evaluated the effects of the SGLT2i tofogliflozin on metabolic clearance rate of insulin (MCRI) with a hyperinsulinemic euglycemic clamp study, the gold standard for measuring systemic insulin clearance. Methods: Study participants were 12 Japanese men with type 2 diabetes. We evaluated MCRI and tissue-specific insulin sensitivity with a hyperinsulinemic euglycemic clamp (insulin infusion rate, 40 mU/m2·min) before and immediately after a single dose (n = 12) and 8 weeks (n = 9) of tofogliflozin. We also measured ectopic fat in muscle and liver and the abdominal fat area using 1H-magnetic resonance spectroscopy and magnetic resonance imaging, respectively, before and after 8 weeks of tofogliflozin. Results: MCRI did not change after a single dose of tofogliflozin (594.7 ± 67.7 mL/min·m2 and 608.3 ± 90.9 mL/min·m2, p = 0.61) or after 8 weeks (582.5 ± 67.3 mL/min·m2 and 602.3 ± 67.0 mL/min·m2, p = 0.41). The 8-week treatment significantly improved glycated hemoglobin and decreased body weight (1.7%) and the subcutaneous fat area (6.4%), whereas insulin sensitivity and ectopic fat in muscle and liver did not change significantly. Conclusions: MCRI did not change after a single dose or 8 weeks of tofogliflozin. Increased MCRI does not precede a decrease in body fat or improved glycemic control.

Abstract Although the incidence of hepatobiliary enzyme abnormality increased immediately after the Great East Japan Earthquake and subsequent Fukushima Daiichi Nuclear Power Plant accident, longer-term trends remain unclear. The aims of this study were to determine longer-term trends in hepatobiliary enzyme abnormality and to elucidate lifestyle factors associated with such changes among residents of a nuclear-disaster-affected area. This longitudinal survey enrolled 20,395 adults living in the vicinity of Fukushima Daiichi Nuclear Power Plant. Data were obtained from the records of annual health checkups of adults aged ≥40 years between 2011 and 2012. Follow-up examinations were conducted from June 2013 to March 2014. Associations were assessed between changes in hepatobiliary enzyme abnormality immediately and 3–4 years after the disaster and lifestyle factors. The overall prevalence of hepatobiliary enzyme abnormality significantly decreased over the study period, from 29.9% to 27.1%. Multivariate logistic regression analysis revealed significant associations between improved hepatobiliary enzyme abnormality and improvements in daily physical activity and frequency of breakfast consumption. The results suggest that improvements in daily physical activity and frequency of breakfast consumption significantly reduced the incidence of hepatobiliary enzyme abnormality 3–4 years after the Great East Japan Earthquake and Fukushima Daiichi Nuclear Power Plant accident.

We previously reported that the lifestyle of evacuees significantly increased the prevalence of polycythemia compared with non-evacuees at an average of 1.6 years (2011–2012) from the previous annual health checkup before the Great East Japan Earthquake (GEJE). Here we analyzed how the prolonged evacuation affected the prevalence of polycythemia an average of 2.5 years (2013–2014) after the previous data. Subjects were individuals aged 40–90 years living in the vicinity of the Fukushima Daiichi Nuclear Power Plant in Fukushima Prefecture who had attended the annual health checkups since 2008. The prevalence of polycythemia and changes in its defining factors of red blood cell count (RBC), hemoglobin (Hb) level, hematocrit (Ht) level were compared between before and after the GEJE in 7713 individuals (3349 men and 4364 women) receiving follow-up examinations both 2011–2012 and 2013–2014. RBC, Hb levels and Ht levels in 2011–2012 were higher among evacuees than non-evacuees in both men and women. However, all levels in 2013–2014 were on the decline from those in 2011–2012. On the other hand, among evacuees, Hb and Ht levels continued to be higher than before the GEJE in both men and women evacuees. The prevalence of polycythemia, which was diagnosed if one of the defining factors was beyond the standard value, was significantly higher among evacuees than non-evacuees regardless of the presence or the absence of overweight/obesity, smoking, and hypertension. Therefore, prolonged evacuation is a cause of polycythemia even 3 to 4 years after the GEJE and regular health management of evacuees is important.

Radiotherapy with systemic corticosteroid therapy has been used to treat intramedullary spinal cord metastasis (ISCM), but recovery of function and long-term survival of these patients has been rarely observed. We report herein a small cell lung cancer (SCLC) patient with recurrent thoracic ISCM, who was successfully treated with radiotherapy and systemic corticosteroid therapy. A 70-year-old man, who was diagnosed as having SCLC seven months previously, developed thoracic ISCM. Soon after the detection of the lesion, the patient received radiotherapy with systemic corticosteroid therapy. Sensory disturbance in both extremities and neurogenic bladder and bowel dysfunction was recovered. The patient could walk after irradiation again. The patient received additional chemotherapy and survived 20 months after the diagnosis of ISCM recurrence. Prompt diagnosis and appropriate treatment for ISCM and effective chemotherapy for recurrent SCLC might be the favorable factors for such patients. Further studies will be required to define a favorable subset of patients most likely to benefit from a conventional approach.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

We present a pixel-level angle sensitive detector composed of silicon-on-insulator (SOI) photodiode (PD) stacked with a gold surface plasmon (SP) antenna to affect the direction of the incoming light. The surface plasmons are excited in the grating-type SP antenna and enhance the diffraction efficiency of the grating. The diffracted light is coupled strongly with the propagation light in the SOI waveguide when the phase matching condition is satisfied. The phase matching takes place at a specific angle of light incidence, and the discrimination of the light based on the incident angle is achieved. As spatial patterns in the polar coordinate of the elevation-azimuth angles (θ, ϕ) of the incident light, we present the phase matching condition theoretically, the absorption efficiency in the SOI by simulation, and also the quantum efficiency of the SOI PD experimentally for different SP antennas of one-dimensional (1D) line-and-space (L/S) and two-dimensional (2D) hole array gratings under various polarization angles. 1D grating offers a polarization sensitive angle detection and 2D grating exhibits angle detection in two orthogonal directions, enabling a polarization independent angle sensitivity. A good agreement among the theory, simulation, and experiment are attained. The proposed device features relatively high quantum efficiency as an angle-sensitive pixel (ASP) and gives wider opportunities in applications such as three-dimensional (3D) imaging, depth-of-field extension, and lensless imaging.

Assuming that the 0.6-μm silicon-on-insulator (SOI) complementary metal–oxide–semiconductor (CMOS) technology, different Si-based temperature sensors such as metal-oxide-semiconductor field-effect transistor (MOSFET) (n-channel and p-channel), pn-junction diode (with p-body doping and without doping), and resistors (n+ or p+ single crystalline Si and n+ polycrystalline Si) were designed and characterized for its possible use in 1-THz antenna-coupled bolometers. The use of a half-wave dipole antenna connected to the heater end was assumed, which limited the integrated temperature sensor/heater area to be 15 × 15 µm. Our main focus was to evaluate the performances of the temperature sensor/heater part, and the optical coupling between the incident light and heater via an antenna was not included in the evaluation. The electrothermal feedback (ETF) effect due to the bias current was considered in the performance estimation. A comparative analysis of various SOI bolometers revealed the largest responsivity (Rv) of 5.16 kV/W for the n-channel MOSFET bolometer although the negative ETF in MOSFET reduced the Rv. The noise measurement of the n-channel MOSFET showed the NEP of 245 pW/Hz1/2, which was more than one order of magnitude smaller than that of the n+ polycrystalline Si resistive bolometer (6.59 nW/Hz1/2). The present result suggests that the n-channel MOSFET can be a promising detector for THz applications.

The cross talk between the adipose tissue and insulin target tissues is a key mechanism for obesity-associated insulin resistance. However, the precise role of the interaction between the skeletal muscle and adipose tissue for insulin signaling and glucose uptake is questionable. L6 myocytes were co-cultured with or without 3T3-L1 adipocytes (~5 × 103 cells/cm2) up to 24 h. Glucose uptake was evaluated by 2-[3H] deoxyglucose uptake assay. Levels of mRNA expression of Glut1 and Glut4 and mitochondrial enzymes were analyzed by quantitative real-time reverse transcription polymerase chain reaction. Levels of Glut1 and Glut4 protein and phosphorylation of Akt (Ser473 and Thr308) were analyzed by immunoblotting. Study 1: co-culture with 3T3-L1 adipocytes increased glucose uptake in dose- and time-dependent manner in L6 myocytes under insulin-untreated conditions. When co-cultured with 3T3-L1 cells, reactive oxygen species production and levels of Glut1 mRNA and protein were increased in L6 cells, while these changes were abrogated and the glucose uptake partially inhibited by antioxidant treatment. Study 2: co-culture with 3T3-L1 adipocytes suppressed insulin-stimulated glucose uptake in L6 myocytes. Insulin-induced Akt phosphorylation at Ser473 decreased, which was proportional to 3T3-L1 density. Antioxidant treatment partially reversed this effect. Interactions between skeletal muscle and adipose tissues are important for glucose uptake under insulin-untreated or -treated condition through oxygen stress mechanism.

BACKGROUND:According to studies by the National Kidney Foundation and Food and Drug Administration, 30% and 40% declines in estimated glomerular filtration rate (eGFR) could be used as surrogate endpoints of end-stage renal disease (ESRD). However, the benefits of using these endpoints in diabetic patients remain unclear. METHODS:This cohort study comprised Japanese patients with type 2 diabetes; those with repeated serum creatinine measurements during a baseline period of 2 years (n = 1868) or 3 years (n = 2001) were enrolled. Subsequent risks of ESRD following eGFR declines were assessed. RESULTS:In the 2-year baseline analysis, the cumulative prevalence of -20%, -30%, -40%, and -53% changes in eGFR were 23.9%, 11.1%, 6.8%, and 3.7%, respectively. There were 133 cases (7.1%) of subsequent ESRD during a median follow-up period of 6.5 years. In the 3-year baseline analysis, the corresponding proportions were 28.1%, 14.0%, 7.7%, and 3.9%, respectively, with 110 participants (5.5%) reaching ESRD during a median follow-up period of 5.5 years. The adjusted hazard ratios of subsequent ESRD following -53%, -40%, -30%, and -20% changes in eGFR during the 2-year baseline period were 22.9 (11.1-47.3), 12.8 (6.9-23.7), 8.2 (4.3-15.5), and 3.9 (2.2-7.0), respectively when compared with the no changes in eGFR. In the 3-year baseline analysis, the corresponding risks were 29.7 (10.8-81.9), 18.4 (7.6-44.7), 12.8 (5.2-32.2), and 5.4 (2.3-12.8), respectively. In the subgroup analysis, similar trends were observed in patients with macroalbuminuria at baseline. CONCLUSIONS:Declines in eGFR were strongly associated with subsequent risk of ESRD in Japanese type 2 diabetic patients. In addition to 30% and 40% declines, a 20% decline in eGFR over 2 years could be considered as a candidate surrogate endpoint of ESRD in diabetic kidney disease.

We investigated the effects of teneligliptin on uric acid metabolism in male Wistar rats and 3T3-L1 adipocytes. The rats were fed with a normal chow diet (NCD) or a 60% high-fat diet (HFD) with or without teneligliptin for 4 weeks. The plasma uric acid level was not significantly different between the control and teneligliptin groups under the NCD condition. However, the plasma uric acid level was significantly decreased in the HFD-fed teneligliptin treated rats compared to the HFD-fed control rats. The expression levels of xanthine dehydrogenase (Xdh) mRNA in liver and epididymal adipose tissue of NCD-fed rats were not altered by teneligliptin treatment. On the other hand, Xdh expression was reduced significantly in the epididymal adipose tissue of the HFD-fed teneligliptin treated rats compared with that of HFD-fed control rats, whereas Xdh expression in liver did not change significantly in either group. Furthermore, teneligliptin significantly decreased Xdh expression in 3T3-L1 adipocytes. DPP-4 treatment significantly increased Xdh expression in 3T3-L1 adipocytes. With DPP-4 pretreatment, teneligliptin significantly decreased Xdh mRNA expression compared to the DPP-4-treated 3T3-L1 adipocytes. In conclusion, our studies suggest that teneligliptin reduces uric acid levels by suppressing Xdh expression in epididymal adipose tissue of obese subjects.

We report a rare case of chronic eosinophilic pneumonia with subpleural curvilinear shadow. CT scan showed a patchy consolidation in the bilateral upper lungs. In addition, subpleural curvilinear shadow was found in the bilateral upper lungs. A bronchoalveolar lavage obtained from the right middle lobe showed 25 % eosinophils. Although very rare, we should therefore keep in mind that patients, who have patchy consolidation with areas of subpleural curvilinear shadow in the bilateral upper lungs, may have chronic eosinophilic pneumonia.

Background: Although sarcoidosis as well as lung cancer are frequently encountered common diseases, their metachronous or synchronous occurrence in the same patient is very rare. Methods: The charts of lung cancer patients, diagnosed between 1980 and 2007 in our hospital, were reviewed. Results: We found 3 cases with sarcoidosis and lung cancer. The first case had lung cancer 16 years after the diagnosis of sarcoidosis. The second case had two different metachronous lung cancers 18 and 10 years after the diagnosis of sarcoidosis. The third case detected these two diseases simultaneously. In simultaneously detected cases, it is difficult to determine whether noncaseating epithelioid cell granulomas coexisting with lung cancer represent sarcoid reaction or genuine systemic sarcoidosis. Conclusions: Either causality or coincidence, lung cancer, a condition that can be observed in patients with sarcoidosis, should be considered in the differential diagnosis when suspicious findings of it are discovered.

We report a case of liver metastasis of lung carcinoma with portal vein tumor thrombus (PVTT). Although the primary lesion of lung tumor remained unchanged, the patient rapidly developed wide-spread metastases and formed PVTT of liver metastasis. The primary lesion showed features of mixed Clara and bronchial surface epithelial cell component type adenocarcinoma with small foci of micropapillary pattern. Micropapillary pattern was observed in the metastatic lesions in the liver and PVTT. Micropapillary pattern lung adenocarcinoma may develop rapid metastases and cause PVTT associated with liver metastasis. We should perform a detailed examination to establish correct diagnosis.