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Drug–drug interactions (DDIs) involving hepatic organic anion transporting polypeptides 1B1/1B3 (OATP1B) can be substantial, however, challenges remain for predicting interaction risk. Emerging evidence suggests that endogenous biomarkers, particularly coproporphyrin‐I (CP‐I), can be used to assess in vivo OATP1B activity. The present work under the International Consortium for Innovation and Quality in Pharmaceutical Development was aimed primarily at assessing CP‐I as a biomarker for informing OATP1B DDI risk. Literature and unpublished CP‐I data along with pertinent in vitro and clinical DDI information were collected to identify DDIs primarily involving OATP1B inhibition and assess the relationship between OATP1B substrate drug and CP‐I exposure changes. Static models to predict changes in exposure of CP‐I, as a selective OATP1B substrate, were also evaluated. Significant correlations were observed between CP‐I area under the curve ratio (AUCR) or maximum concentration ratio (CmaxR) and AUCR of substrate drugs. In general, the CP‐I CmaxR was equal to or greater than the CP‐I AUCR. CP‐I CmaxR < 1.25 was associated with absence of OATP1B‐mediated DDIs (AUCR < 1.25) with no false negative predictions. CP‐I CmaxR < 2 was associated with weak OATP1B‐mediated DDIs (AUCR < 2). A correlation was identified between CP‐I exposure changes and OATP1B1 static DDI predictions. Recommendations for collecting and interpreting CP‐I data are discussed, including a decision tree for guiding DDI risk assessment. In conclusion, measurement of CP‐I is recommended to inform OATP1B inhibition potential. The current analysis identified changes in CP‐I exposure that may be used to prioritize, delay, or replace clinical DDI studies. [ABSTRACT FROM AUTHOR]

Introduction: Computed tomography is useful for the diagnosis of coronavirus disease (COVID‐19) pneumonia. However, many types of interstitial lung diseases and even bacterial pneumonia can show abnormal chest shadows that are indistinguishable from those observed in COVID‐19 pneumonia. Thus, it is necessary to identify useful biomarkers that can efficiently distinguish COVID‐19 pneumonia from COVID‐19 pneumonia‐like diseases. Herein, we investigated the usefulness of serum Krebs von den Lungen 6 (KL‐6) and surfactant protein D (SP‐D) for identifying patients with COVID‐19 pneumonia among patients with abnormal chest shadows consistent with COVID‐19 pneumonia. Method: This was a retrospective cohort study of consecutive patients who underwent evaluation of serum KL‐6 and SP‐D at a single center from February 2019 to December 2020. A total of 54 patients with COVID‐19 pneumonia and 65 patients with COVID‐19 pneumonia‐like diseases were enrolled in this study from the source population. Serum KL‐6 and SP‐D levels in both groups were analyzed. Result: The serum levels of KL‐6 and SP‐D in patients with COVID‐19 pneumonia were significantly lower than those in patients with COVID‐19 pneumonia‐like disease (median [interquartile range]: 208.5 [157.5–368.5] U/ml vs. 430 [284.5–768.5] U/ml, p < 0.0001 and 24.7 [8.6–51.0] ng/ml vs. 141 [63.7–243.5] ng/ml, p < 0.0001, respectively). According to receiver operating characteristic (ROC) analysis, the areas under the ROC curves (95% confidence intervals) of serum KL‐6 and SP‐D levels for distinguishing COVID‐19 pneumonia from COVID‐19 pneumonia‐like diseases were 0.761 (0.675–0.847) and 0.874 (0.812–0.936), respectively. The area under the ROC curve of serum SP‐D was significantly larger than that of serum KL‐6 (p = 0.0213), suggesting that serum SP‐D can more efficiently distinguish COVID‐19 pneumonia from COVID‐19 pneumonia‐like diseases. Conclusion: Serum SP‐D is a promising biomarker for distinguishing COVID‐19 pneumonia from COVID‐19 pneumonia‐like diseases. Serum SP‐D can be useful for the management of patients with abnormal chest shadow mimicking COVID‐19 pneumonia. [ABSTRACT FROM AUTHOR]

Fenofibrate (FF), a peroxisome proliferator‐activated receptor‐alpha (PPAR‐α) agonist and a lipid‐lowering agent, can decrease experimental pulmonary fibrosis. However, the mechanisms underlying the antifibrotic effect of FF remain unknown. Hence, this study was conducted to evaluate the effects of FF on transforming growth factor‐beta (TGF‐β)‐induced myofibroblast differentiation and activation in lung fibroblasts. The results showed that FF inhibited alpha‐smooth muscle actin (α‐SMA) and connective tissue growth factor expression, collagen production, cell motility, SMAD3 phosphorylation and nuclear translocation, and metabolic reprogramming in TGF‐β‐exposed cells. The inhibitory effect of FF did not decrease with the addition of a PPAR‐α antagonist. Moreover, the inhibitory effect given by FF could not be reproduced with the addition of an alternative PPAR‐α agonist. FF inhibited mitochondrial respiration. However, rotenone, a complex I inhibitor, did not suppress TGF‐β‐induced myofibroblast differentiation. Furthermore, the TGF‐β‐induced nuclear reduction of protein phosphatase, Mg2+/Mn2+‐dependent 1A (PPM1A), a SMAD phosphatase, was inhibited by FF. These results showed that FF suppressed TGF‐β‐induced myofibroblast differentiation and activation independent of PPAR‐α activation and impaired mitochondrial respiration. In conclusion, this study provides information on the effects of FF on anti‐TGF‐β mechanisms. [ABSTRACT FROM AUTHOR]

Background: Predicting the incidence of chemotherapy‐triggered acute exacerbation of interstitial lung disease (AE‐ILD) in patients with lung cancer is important because AE‐ILD confers a poor prognosis. The Glasgow prognostic score (GPS), which is an inflammation‐based index composed of serum levels of C‐reactive protein and albumin, predicts prognosis in patients with small cell lung cancer (SCLC) without ILD. In this study, we investigated AE‐ILD and survival outcome based on the GPS in patients with ILD associated with SCLC who were receiving chemotherapy. Methods: Medical records of patients who received platinum‐based first‐line chemotherapy between June 2010 and May 2019 were retrospectively reviewed to compare the incidence of AE‐ILD and overall survival (OS) between GPS 0, 1, and 2. Results: Among our cohort of 31 patients, six (19.3%) experienced chemotherapy‐triggered AE‐ILD. The AE‐ILD incidence increased from 9.5% to 25.0% and 50.0% with increase in GPS of 0, 1, and 2, respectively. Univariate and multivariate analyses revealed remarkable associations between GPS 2 and both AE‐ILD (odds ratio for GPS 2, 18.69; p = 0.046) and prognosis (hazard ratio of GPS 2, 13.52; p = 0.002). Furthermore, median OS in the GPS 0, 1, and 2 groups was 16.2, 9.8, and 7.1 months, respectively (p < 0.001). Conclusions: Our results suggest that GPS 2 is both a predictor of risk of chemotherapy‐triggered AE‐ILD and a prognostic indicator in patients with ILD associated with SCLC. We propose that GPS may be used as a guide to distinguish chemotherapy‐tolerant patients from those at high risk of AE‐ILD. [ABSTRACT FROM AUTHOR]

Aim: To verify the reliability and validity of a Japanese translation of the Satter eating competence Inventory‐2.0™ (ecSI‐2.0™) for parents of fifth and sixth grade elementary school students. Methods: Participants were parents who prepared meals for their children aged 10–12 years. A preliminary study was conducted with 11 parents using semi‐structured interviews and questionnaires, followed by a main study of 2,825 parents. Internal consistency and test–retest methods were used to verify reliability. Face and content validity were confirmed in the preliminary study, and feasibility was examined by the valid response rate and response time. Construct validity was verified using factor validity and known population validity. Results: Of the 2,825 persons surveyed, 626 returned valid responses, and among the 60 persons who received the re‐survey, 48 returned valid responses. The average score of the Japanese translation of the ecSI‐2.0™ was 33.1 (SD ± 7.8) points. Cronbach's alpha coefficient for the whole scale was.87 and ranged from.67–.79 for the four subscales. The test–retest method confirmed the scale's stability. Factor analysis confirmed that reproducibility of the four factors was similar to the original version. In the examination of known population validity, the same correlation as the original edition was confirmed. Conclusions: The Japanese translation of the ecSI‐2.0™ may be reliable and valid for understanding eating competence related to behavior of parents of school‐age children. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung disease (ILD) in patients with non‐small cell lung cancer (NSCLC) worsens the prognosis for overall survival (OS) due to chemotherapy‐triggered acute exacerbation (AE)‐ILD. The Glasgow Prognostic Score (GPS), which is based on serum C‐reactive protein and albumin levels, has been suggested as a reliable prognostic tool for mortality in cancer patients, including NSCLC. In this study, we investigated whether GPS is a predictor for chemotherapy‐triggered AE‐ILD and the prognosis in patients with NSCLC and pre‐existing ILD. Methods: We conducted a retrospective review on 56 NSCLC and ILD patients at our hospital who received platinum agent‐based treatment as first‐line chemotherapy between June 2010 and May 2019. We categorized these patients according to their GPS (0–2) and compared the incidence of chemotherapy‐triggered AE‐ILD and OS. Results: The GPS 0, 1, and 2 groups included 31, 16, and nine patients, respectively, out of 56. A total of 12 (21.4%) patients showed chemotherapy‐triggered AE‐ILD. The median OS was at 11.5 months (95% confidence interval: 8.0–15.1). The incidence of chemotherapy‐triggered AE‐ILD within the first year of chemotherapy in the GPS 0, 1, and 2 groups was three (9.6%), four (25.0%), and five (55.5%), and the median OS time was 16.9, 9.8 and 7.6 months, respectively. Univariate and multivariate analyses indicated that only GPS 2 could predict both chemotherapy‐triggered AE‐ILD and OS (P < 0.05). Conclusions: GPS assessment of patients with NSCLC and pre‐existing ILD is a valuable prognostic tool for predicting chemotherapy‐triggered AE‐ILD and OS. Key points: Significant findings of the study: We found that GPS 2 was an independent risk factor for chemotherapy‐triggered AE‐ILD and prognosis in patients with ILD associated with NSCLC. What this study adds: GPS may potentially enable the discrimination of patients tolerant of chemotherapy from those at an increased risk of AE‐ILD and predict the prognosis in patients with NSCLC and ILD receiving chemotherapy. [ABSTRACT FROM AUTHOR]

Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 are involved in the disposition of a variety of commonly prescribed drugs. The evaluation of OATP1B1/1B3 inhibition potential by investigational drugs is of interest during clinical drug development due to various adverse events associated with increased exposures of their substrates. Regulatory guidance documents on the in vitro assessment of OATP1B1/1B3 inhibition potential are conservative with up to a third of predictions resulting in false positives. This work investigated the utility of OATP1B1/1B3 endogenous biomarkers, coproporphyrin (CP)‐I and CP‐III, to assess clinical inhibition of OATP1B1/1B3 and potentially eliminate the need for prospective clinical drug‐drug interaction (DDI) studies. Correlations between CP‐I exposures and various OATP1B1 static DDI predictions were also evaluated. Glecaprevir/pibrentasvir (GLE/PIB) 300/120 mg fixed‐dose combination is known to cause clinical inhibition of OATP1B1/1B3. In a clinical study evaluating the relative bioavailability of various formulations of GLE/PIB regimen, CP‐I peak plasma concentration (Cmax) ratio and 0–16‐hour area under the concentration‐time curve (AUC0–16) ratio relative to baseline increased with increasing GLE exposures, whereas there was a modest correlation between GLE exposure and CP‐III Cmax ratio but no correlation with CP‐III AUC0–16 ratio. This suggests that CP‐I is superior to CP‐III as an endogenous biomarker for evaluation of OATP1B1 inhibition. There was a significant correlation between CP‐I and GLE Cmax (R2 = 0.65; P < 0.001) across individual subjects. Correlation analysis between GLE OATP1B1 R values and CP‐I exposures (Cmax ratio and AUC0–16 ratio) suggests that an R value of > 3 can predict a biologically meaningful inhibition of OATP1B1 when the inhibitor clinical pharmacokinetic parameters are available. [ABSTRACT FROM AUTHOR]

Aim: Nurses are expected to have a role in the transition of care from pediatric to adult medical practices for adolescents and young adults with childhood‐onset chronic diseases. This study compares the experience, knowledge, and perceptions regarding the ideal care among adult unit and pediatric nurses regarding the transition to adult care for those with childhood‐onset chronic diseases. Methods: A cross‐sectional study using self‐report questionnaires was conducted with nurses in a tertiary hospital in Tokyo. Questions were generated based on a literature review and expert discussion. Data from 1,064 participants were analyzed (adult unit nurses: n = 959, 90.1%; pediatric nurses: n = 105, 9.9%). Results: Among 623 adult unit nurses who had care experience for adult patients with a childhood‐onset chronic disease, 458 nurses (73.6%) were unaware of the concept of transitional care. As the obstructive factors for transition, pediatric nurses recognized problems in healthcare providers' attitudes and lack of transitional care coordinators, while the adult unit nurses emphasized the patients' wishes to continue to receive pediatric healthcare. Most adult unit nurses expected pediatric nurses to function as transitional care coordinators. Conclusion: Adult unit and pediatric nurses had different perceptions of the barriers in transitioning children with chronic diseases to adult care. It is important to have educational programs focusing on transitional care for all nurses, both to enable pediatric nurses to improve transition readiness of children with chronic diseases and to offer adult patients with a childhood‐onset chronic disease continuing support through adult unit nurses. [ABSTRACT FROM AUTHOR]

A 69‐year‐old man with a history of type 2 diabetes and high blood pressure was diagnosed with coronavirus disease 2019 (COVID‐19). He had hyperferritinaemia and respiratory failure. Despite the initiation of favipiravir and high‐dose corticosteroid and ceftriaxone, his respiratory failure progressed and serum ferritin levels increased. After polymyxin B‐immobilized fibre column direct haemoperfusion (PMX‐DHP) therapy, there was improvement of the respiratory failure and hyperferritinaemia. We report the first case of COVID‐19‐induced hyperferritinaemia and severe respiratory failure successfully treated by PMX‐DHP. [ABSTRACT FROM AUTHOR]

ABSTRACT: This study proposes an algorithm that combines ensemble numerical weather‐prediction model data and aircraft flight data in a wind nowcasting system for safe and efficient aircraft operation. It uses an ensemble‐weighted average method based on sequential importance sampling (SIS), which is a particle filter method for forecasting the wind field in real time. SIS is applied to the ensemble forecast data and control run data of the European Centre for Medium‐Range Weather Forecasts (ECMWF), Japan Meteorological Agency (JMA), Korea Meteorological Administration (KMA), National Centers for Environmental Prediction (NCEP) and United Kingdom Met Office (UKMO) for the two case studies that use flight data from 72 commercial aircraft flights. The results show that SIS can forecast better than the other four methods: direct ensemble average (DEA), elite strategy (ES), and selective ensemble average (SEAV) and weighted average (SEWE), with average improvements in forecast performance of about 10–15%, even at 300 min ahead. In addition, the overall forecast performance between the forecast wind and observation of the radiosonde of SIS was slightly better than DEA. In both cases, the forecast performance was significantly improved on points along the flight path of the aircraft used for this study. Case analyses and the impact of differences in the hyper‐parameters of SIS on forecast performance are also presented in this study. [ABSTRACT FROM AUTHOR]

Abstract: Background: Health‐related quality of life (HRQOL) is an important outcome in solid organ transplantation. This study evaluated and explored the factors of generic and transplant‐specific HRQOL in Japanese pediatric and adolescent patients with biliary atresia (BA) after living donor liver transplant (LDLT). Methods: A cross‐sectional survey using anonymous questionnaires was completed between April and July 2015. Patient medical records were accessed. The Japanese version of Pediatric Quality of Life InventoryTM Generic Core Scales and Transplant Modules (child self‐report and parent proxy‐report) was administered. Results: Participants consisted of 75 patients (mean age at survey, 9.6 years) and 74 parents. Japanese patients reported higher generic and transplant‐specific HRQOL (total score) than that reported by US patients with BA after LT (US I; age at survey, 7.2 years) and by US patients after solid organ transplant (US II; age at survey, 11.3 years; LT, 53.8%; effect size, 0.55–0.96). Japanese parents, however, rated their children's generic HRQOL (total score) similar to that rated by the US I and II parents (0.13 and 0.30, respectively) and reported lower transplant‐specific HRQOL (total score) than that reported by US II (0.26). Although the number of types of prescribed drugs was a common factor in HRQOL, most demographic and medical factors (e.g. child's age at survey and consultation frequency) varied with reporter (i.e. patients and parents). Conclusions: The levels and factors of generic and transplant‐specific HRQOL of Japanese pediatric and adolescent patients with BA after LDLT varied with reporter (i.e. patients or parents). [ABSTRACT FROM AUTHOR]

Key message: If a double‐ring sign is found in contrast‐enhanced computed tomography, this should raise concern not only for Takayasu arteritis, but also for granulocyte colony‐stimulating factor‐induced vasculitis. [ABSTRACT FROM AUTHOR]

Key message: In lung cancer patients, brain metastasis is often suspected when neurological symptoms appear; however, if ptosis, ocular motility disorder or optic nerve disorder is observed, it is important to identify and treat the orbital apex syndrome. [ABSTRACT FROM AUTHOR]

Background Health-related quality of life ( HRQOL) is an important outcome in pediatric solid organ transplantation. Considering the emerging problems after transplantation, an evaluation of transplant-specific aspects of HRQOL is essential, but no validated HRQOL measure is available in Japan. The aim of this study was therefore to develop the Japanese version of the Pediatric Quality of Life Inventory™ (Peds QL) Transplant Module Child Self-Report and to investigate its feasibility, reliability, and validity. Methods Based on the Peds QL linguistic validation process, the Japanese version of the Peds QL Transplant Module was developed through translation and cognitive interviews (patient testing). The scale's reliability and validity were investigated, using statistical analyses of field tests of the target population. Results Eighty-seven pairs of pediatric liver-transplant recipients and their parents participated in the field test. The pediatric patients completed the measure in 3-7 min, and the rate of missing items was low (0.27%). Excellent internal consistency and test-retest reliability were confirmed. Known-groups validity, concurrent validity, and convergent and discriminant validity also were confirmed. Conclusions Excellent feasibility, reliability, and validity of this Japanese self-report version of the Peds QL Transplant Module Child Self-Report were verified. As a measure of transplant-specific aspects of HRQOL in Japanese pediatric patients who have undergone organ transplants, the Japanese version of the Peds QL Transplant Module is appropriate for use in clinical and research settings. [ABSTRACT FROM AUTHOR]

Few studies have examined HRQOL in pediatric Tx recipients' parents. This study investigated HRQOL in these parents and relationships between HRQOL and perceived burden of nurturing, family functioning, and social support. Self-report anonymous questionnaires and a survey of medical records were completed between September and December 2013. The SF-36v2, which evaluates physical, psychological, and social health, was used to measure HRQOL. While values for physical and psychological health were higher than standard values (Cohen's d = 0.34 and 0.17, respectively), social health scores were lower ( d = 0.21). 'Parental consultation unrelated to donation' (standardized partial regression coefficient: β = −0.52) was associated with physical health. 'Family functioning' and 'Commuting time between home and primary follow-up hospital' (β = 0.57 and −0.31) were related to psychological health. 'Total score for perceived burden of nurturing' (β = −0.31) was related to social health. Regarding parental HRQOL, while physical and psychological health was favorable, social health was impaired. In clinical practice, interventions targeting parents' physical conditions and facilitation of community and family understanding and support to share recipients' nurturing are important in improving parental HRQOL. [ABSTRACT FROM AUTHOR]

Classification of the biological activities of chemical substances is important for developing new medicines efficiently. Various machine learning methods are often employed to screen large libraries of compounds and predict the activities of new substances by training the molecular structure‐activity relationships. One such method is graph classification, in which a molecular structure can be represented in terms of a labeled graph with nodes that correspond to atoms and edges that correspond to the bonds between these atoms. In a conventional graph definition, atomic symbols and bond orders are employed as node and edge labels, respectively. In this study, we developed new graph definitions using the assignment of atom and bond types in the force fields of molecular dynamics methods as node and edge labels, respectively. We found that these graph definitions improved the accuracies of activity classifications for chemical substances using graph kernels with support vector machines and deep neural networks. The higher accuracies obtained using our proposed definitions can enhance the development of the materials informatics using graph‐based machine learning methods. [ABSTRACT FROM AUTHOR]