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Background Lower primary percutaneous coronary intervention (PCI) volume is known to be associated with worse outcomes in patients with acute myocardial infarction (MI) at hospital level. The present study aimed to evaluate the relations of primary, elective, and total PCI volume and primary/total PCI volume ratio per hospital to in‐hospital mortality in patients with acute MI undergoing primary PCI. Methods and Results Using a large nationwide administrative database, we included a total of 83 076 patients from 154 hospitals in Japan undergoing PCI for either acute MI or elective cases. Relations of annual procedural volumes for primary, elective, and total PCI to in‐hospital mortality after acute MI at hospital level were evaluated. The ratio of primary to total PCI volume per hospital was also assessed. The primary end point was the ratio of observed to predicted mortality. Of 83 076 patients, 26 913 (32.4%) underwent primary PCI for acute MI, among whom 1561 (5.8%) died during hospitalization. Overall, observed in‐hospital mortality after acute MI and observed/predicted mortality ratio were higher in hospitals with lower primary, elective, and total PCI volumes. Observed/predicted in‐hospital mortality ratio was higher in hospitals with low primary/total PCI volume ratio, even in those with high total PCI volume. Conclusions Primary, elective, and total PCI volume at hospitals were inversely associated with in‐hospital mortality in patients with acute MI undergoing primary PCI. Lower ratio of primary to total PCI volume were related to higher in‐hospital mortality, suggesting primary/total PCI volume ratio as an institutional indicator of quality of care for acute MI.

Background: Complementary and alternative medicine, including Japanese traditional medicine (JTM), has been used for various allergic diseases, but the evidence is limited. Shoseiryuto (Xiao-Qing-Long-Tang), one of the representative JTM drugs, is frequently used to treat allergic rhinitis (AR). However, its efficacy for seasonal AR has not been fully established. Using an Environmental challenge chamber (ECC), we evaluated the therapeutic effects of shoseiryuto on AR induced by Japanese cedar pollen (JCP). Methods: A placebo-controlled double-blind crossover study with shoseiryuto was conducted using the ECC. The shoseiryuto or placebo was orally administered from 2 weeks before the exposure test. The pollen exposure test was conducted for 3 h, and the pollen concentration was set at 8000 pollen/m3. The primary endpoint of the study was the total nasal symptom score (TNSS) during pollen exposure. A physician certified by the Japanese Society of Oriental Medicine as a specialist checked each participant's “pattern”, a comprehensive expression of signs obtained from individual patients' subjective symptoms and other personal findings. Blood samples collected just before the first pollen exposure were stimulated with cedar antigens and used for immunological studies. Results: The results of the 46 participants were analyzed, and no significant side effects were detected. There was no significant difference in TNSS during pollen exposure for 3 h in the ECC between the shoseiryuto and placebo groups. However, some symptoms were improved in the shoseiryuto group after leaving the ECC. There was no significant correlation between the “fluid retention pattern” and TNSS. In immunological studies, shoseiryuto did not inhibit Th2-type cytokine production and mRNA expression. Conclusions: Oral administration of shoseiryuto from 2 weeks before pollen exposure did not prevent or inhibit immediate symptoms of AR induced by JCP in the ECC. Further study is needed to reevaluate the shoseiryuto specific “pattern” in JTM.

BackgroundCytotoxic effects of radiation play an important role in the treatment of head and neck cancer. However, irradiation is known to lead to the migration of various cancer cells, including those of head and neck cancer. Recently, fibroblasts in the cancer microenvironment have been reported to be involved in this mechanism. Nevertheless, the mechanism underlying migration of head and neck cancer cells remains unclear. Herein, we aimed to elucidate this migration mechanism induced by irradiation in terms of the interaction of head and neck cancer cells with fibroblasts.MethodsWe used the head and neck squamous cell carcinoma (HNSCC) cell lines SAS and FaDu as well as fibroblast cell lines. These cells were irradiated and their viability was compared. In fibroblasts, changes in interleukin-6 (IL-6) secretion caused by irradiation were measured by enzyme-linked immunosorbent assay (ELISA). The cell migration ability of cancer cells was evaluated via a migration assay using a semipermeable membrane. HNSCC cells were cocultured with irradiated and nonirradiated fibroblasts, and their migration ability under each condition was compared. We also examined the effect of IL-6 on the migration of HNSCC cells. Furthermore, to investigate the effect of fibroblast-derived IL-6 on the migration ability of HNSCC cells, we conducted a coculture study using IL-6 neutralizing antibody.ResultsIrradiation reduced the survival of HNSCC cells, whereas fibroblasts were resistant to irradiation. Irradiation also increased IL-6 secretion by fibroblasts. Migration of HNSCC cells was enhanced by coculture with fibroblasts and further enhanced by coculture with irradiated fibroblasts. We also confirmed that the migration of HNSCC cells was induced by IL-6. The enhanced migration of cancer cells caused by coculturing with fibroblasts was canceled by the IL-6 neutralizing antibody.ConclusionThese results show that fibroblasts survive irradiation and induce the migration ability of HNSCC cells through increased secretion of IL-6.

Objective: To elucidate the possible role of MRI-detected osteophytes as a predictive imaging biomarker for knee osteoarthritis (KOA). Design: Subjects (n ​= ​303) were selected according to the following inclusion criteria from the Osteoarthritis Initiative (OAI) data set: (1) ​

Background:. Although the functional and anatomical differences between the left and right eyelids are important in the evaluation of age-related changes in the eyelids, they have not been described clearly as indications for surgical treatments. This study aimed to investigate how laterality of the eyelids affects evaluation of age-related changes. Methods:. Photographs of either one or both eyelids of 100 people were evaluated in four stages by 10 plastic surgeons. To investigate the consistency of the results between evaluations, surgeons evaluated the single-eyelid photographs (group U) or two-eyelid photographs (group B). It was investigated whether the difference in margin reflex distance 1, height of the upper eyelid crease, height of eyebrow, and levator contractile function were associated with mismatched evaluations. Results:. The weighted kappa coefficient for groups B and U was 0.77 (substantial agreement). One-point difference in scores was observed in 23 cases. In the multiple logistic regression analysis, only the laterality the height of the eyelid crease was significantly different between patients whose evaluations were matched and those whose evaluations were mismatched (0.9 ± 0.1 mm versus 1.7 ± 0.2 mm; OR = 1.06, 95%CI: 1.01–1.10; P = 0.01). Conclusions:. Besides the structure and function of each eyelid, the laterality of the height of the eyelid crease was important in the evaluation of the age-related changes in the eyelids. This factor may be important in evaluating the aesthetic and visual impressions of age-related changes in the eyelids.

In recent years, Child Death Review (CDR) has attracted attention in Japan. It is necessary to consider not only hospital deaths but also out-of-hospital deaths. However, recommending preventive measures may be difficult because statistics on Japanese child mortality are limited. We examined cause of death (COD) and its application in preventive medicine based on death certificates (DCs) in the Chiba Prefecture. Death documents (DDs) and death slips (DSs) were created for individuals aged under 20 years who died between January 2012 and December 2016. They were based on DCs submitted to the Chiba Prefecture. We examined the trend of COD, occurrence of extrinsic mortality, and characteristics of doctors and compared CODs mentioned in DCs with autopsy results. For 1149 cases, the descriptions of DSs and DDs matched. Half of the extrinsic and undetermined deaths, which were examined by police doctors, occurred out-of-hospital. The autopsy rate was 13.5%. The COD mentioned in DCs did not match the autopsy results for 26 out of 69 autopsies performed at our institute. Approximately 70% of sudden infant death syndromes were diagnosed without autopsy. Low autopsy rate, incorrect writings, and errors during the death diagnosis cannot be ignored while conducting CDR. As more than half of the preventable deaths occurred out-of-hospital and there is no system to collect detailed information on them, the Japanese CDR system may not be reliable. It is necessary to improve the death investigation system by promoting autopsies for children and constructing a comprehensive database.

Abstract Objective We aimed to test our hypothesis that traditional Japanese (Kampo) medicine, hochuekkito (Hochu-ekki-to: HET) has a preventive effect for the symptoms on COVID-19. Trial design The study is designed as a multi-center, interventional, parallel-group, randomized (1:1 ratio), investigator sponsored, two-arm study. Participants Six thousand participants will be recruited from healthy hospital workers in 7 Japanese University Hospitals. Inclusion criteria: 1. Age from 20 to 75 years old at the time of registration 2. Asymptomatic and body temperature below 37°C at the time of registration 3. Capable of eating orally Exclusion criteria: 1. Previous upper respiratory inflammation due to viral infection (including suspected COVID-19) 2. Taking immunosuppressants 3. Allergic to the Kampo medicines used in this study 4. History of hypokalaemia, severe hypertension, severe liver dysfunction, and interstitial pneumonia 5. Regularly taking other Kampo medicines 6. Pregnant or possibly pregnant 7. Participating in other research 8. Judged to be unsuitable for this study by the doctor in charge Intervention and comparator Kampo group: participants receive HET in 9 tablets 2 times per day for 8 weeks. Control group: participants receive placebo in the same dosage as the Intervention group - 9 tablets 2 times per day for 8 weeks. Placebo tablets are identical in appearance and package to HET. Taste of placebo is different from that of HET. The Ohsugi Pharmaceutical Co. Ltd, Osaka, Japan manufactured the placebo and HET. Main outcomes Primary outcome: Number of patients with a SARS-CoV-2 RNA by ploymerase chain reaction (PCR) positive result with at least one symptom (fever, cough, sputum, malaise, shortness of breath) during the 12-week study period (including the 4-week observation period after oral administration). Secondary outcomes: 1. Period from infection to onset 2. Period from the appearance of symptoms to the disappearance of PCR positive 3. Number of days until the appearance or improvement of symptoms 4. Severe stage: presence of hospitalization 5. Shock stage: ICU management required for mechanical ventilation, shock vitals or failure of organ(s) other than lungs Safety endpoints include numbness in the hands and/or feet, edema, skin rash or other allergic symptoms, and gastric discomfort. Randomisation Patients are randomized (1:1 ratio) to each group using minimization implemented with the Electric data capture system (DATATRAK Enterprise Cloud), with balancing of the arms with age range (under 50 years of age or not) and having a history of risk factors for COVID-19 (cardiovascular disease, hypertension, diabetes, respiratory diseases). Blinding (masking) Only participants will be randomized. Numbers to be randomised (sample size) The main research hypothesis of this study is that Kampo medicines significantly prevent the onset of COVID-19. It is assumed that the infection rate before the administration of the drug under consideration will be 0% and that the incidence of COVID-19 thereafter will be 2- 3%, of which 70%-80% will show symptoms of COVID-19. Assuming that the pharmaceutical effect of the drug will be effective in 50% of patients and that the incidence rates in the placebo and drug groups will be 1.4%-2.4% and 0.7%-1.2%, respectively, the placebo is calculated at 2%, and the study drug at 1%. Since the frequency of verification is low and the number of cases will be large, we set a total of 10 analyses (9 interim analyses and a final analysis). Since the number of cases at the time of the final analysis will be 4,986 under the conditions of α = 0.05 and a power of 80% by the Peto method. We set at 600 cases in each interim analysis with an estimated dropout rate of 16.9%. Finally, the total number of cases is set to 6,000 with 3,000 in the placebo group and 3,000 in the HET group. Trial status Protocol version 1.3 of October 23rd , 2020. Recruitment start (expected): December 1st, 2020. Recruitment finish (expected): December 31st, 2022. Trial registration This trial is registered in the Japan Registry of Clinical Trials (jRCT) ( jRCTs031200150 ) on 14 October 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

The balance between antioxidant capacity and oxidative stress-induced free radicals may be crucial in the pathophysiological development factor of autism spectrum disorder (ASD). We measured the following urinary and plasma biomarker levels of oxidative stress and antioxidants. As urinary biomarkers, (1) hexanoyl-lysine (HEL), which is a new biomarker of oxidative stress, (2) the total antioxidant capacity (TAC), and (3) 8-hydroxy-2′-deoxyguanosine (8-OHdG), as a product of oxidative modifications to DNA; and the plasma levels of (4) the antioxidant protein superoxide dismutase (SOD), which is the crucial defense again oxygen reactive species, and (5) transferrin and (6) ceruloplasmin, which are biomarkers of iron and copper neurotransmission and oxidant-antioxidant systems. We examined the relationship between these urinary and plasma biomarkers and behavioral symptoms in 19 individuals with ASD (mean age, 10.8 ± 5.2 years) and 10 age-matched healthy controls (mean age, 14.2 ± 7.0 years). Behavioral symptoms were estimated using the Aberrant Behavior Checklist (ABC). Urinary TAC levels were significantly lower, whereas urinary HEL levels were significantly increased in the ASD group as compared with the control group. The five ABC subscale and total scores were significantly raised in the autism group than in the control group. The results of a linear regression analysis revealed that plasma SOD levels may be a more accurate predictor of differences in ABC scores between individuals with ASD and control individuals. The present study firstly revealed the important findings that the cooperation between the urinary antioxidant TAC and plasma SOD levels may contribute to the ABC subscale scores of stereotypy. Urinary TAC activity and antioxidant protein SOD may be associated with incomplete mineral body store and antioxidant-related transcription factor and browning reactions. Consequently, a critical imbalance between TAC urinary levels and plasma SOD levels may be an important contributor to autistic behavioral symptoms.

Abstract Background Mobilising non-professional health workers has been successful in improving community health, but the effectiveness of an education program targeting youths in a community-based approach remains unclear. The objective of this study was to investigate the effect of an intervention with youth on cardiovascular disease risk factors of community adults. Methods A 12-month cluster randomised trial was conducted in a semi-urban area of Colombo in Sri Lanka. Facilitators trained youth club members aged 15–29 years to assess cardiovascular disease risk factors and take actions in the community to address relevant issues. The control group received no intervention. Body weight and blood pressure as primary outcomes and lifestyle of adults as secondary outcomes were measured pre- and post-intervention. Multilevel linear and logistic regressions were used to assess the effects of the intervention on changes in continuous and binary outcomes, respectively, from baseline to endpoint. Results Of 512 participants at baseline, 483 completed the final assessment after the intervention. Regarding primary outcomes, the intervention group showed a significantly greater decrease in body weight after intervention than the control group. The mean (95% confidence interval) difference of body weight change for intervention versus control group was − 2.83 kg (− 3.31, − 2.35). There was no statistically significant difference in blood pressure between the two groups. Turning to the secondary outcomes, in diet, the intervention group had a higher probability of consuming at least one serving/day of fruits (p = 0.02) and a lower probability of consuming snacks twice/day or more (p

Green stem disorder (GSD) in soybean (Glycine max (L.) Merrill) negatively affects harvest efficiency and seed appearances. Breeding GSD-insensitive cultivars is expected to be an effective countermeasure to GSD. However, it is difficult to stably detect cultivar differences in GSD under conventional field conditions because the occurrences of GSD largely vary by location and year. The thinning effect, which had been reported to promote GSD, may help accurate phenotyping for occurrences of GSD in breeding. To verify this possibility, the thinning treatment was applied to four cultivars, the GSD severity values of which were evaluated in an independent study by another group. As a result, the cultivar differences in GSD severity were generally comparable between the present and previous studies. However, the difference was more evident, with the thinning treatment exhibiting the GSD score of 2.8 of ‘Hatsusayaka’ compared with the GSD score of 3.6 of ‘Sachiyutaka’, while the scores of those cultivars were similar without the thinning treatment. A positive correlation between GSD severity and N concentration in the main stem could be seen but the increasing rate of GSD score with the N concentration in the main stem differed between cultivars. Thus, although more cultivars need to be tested to prove, the thinning treatment could be useful as a phenotyping technique in the breeding of GSD-insensitive cultivars.

Objective To compare the effects of remifentanil versus fentanyl during light sedation with dexmedetomidine in adults receiving mechanical ventilation (MV) in the intensive care unit. Methods In this retrospective cohort study, we compared the use of remifentanil versus fentanyl in adults receiving MV with dexmedetomidine sedation. The primary outcome was the proportion of time under light sedation (Richmond Agitation–Sedation Scale score between −1 and 0) during MV. Results We included 94 patients and classified 58 into the remifentanil group and 36 into the fentanyl group. The mean proportion of time under light sedation during MV was 66.6% ± 18.5% in the remifentanil group and 39.9% ± 27.3% in the fentanyl group. In the multivariate analysis with control for confounding factors, patients in the remifentanil group showed a significantly higher proportion of time under light sedation than patients in the fentanyl group (mean difference: 24.3 percentage points; 95% confidence interval: 12.9–35.8). Conclusions Remifentanil use might increase the proportion of time under light sedation in patients receiving MV compared with fentanyl administration.

Introduction: Secondary lymphoedema of the extremities is an important quality-of-life issue for patients who were treated for their malignancies. Indocyanine green (ICG) fluorescent lymphography may be helpful for assessing lymphoedema and for planning lymphaticovenular anastomosis (LVA). The objective of the present clinical trial is to confirm whether or not ICG fluorescent lymphography using the near-infrared monitoring camera is useful for assessing the indication for LVA, for the identification of the lymphatic vessels before the conduct of LVA, and for the confirmation of the patency of the anastomosis site during surgery. Methods and analysis: This trial is a phase III, multicentre, single-arm, open-label clinical trial to assess the efficacy and safety of ICG fluorescent lymphography when assessing and treating lymphoedema of patients with secondary lymphoedema who are under consideration for LVA. The primary endpoint is the identification rate of the lymphatic vessels at the incision site based on ICG fluorescent lymphograms obtained before surgery. The secondary endpoints are 1) the sensitivity and specificity of dermal back flow determined by ICG fluorescent lymphography as compared with 99mTc lymphoscintigraphy—one of the standard diagnostic methods and 2) the usefulness of ICG fluorescent lymphography when confirming the patency of the anastomosis site after LVA. Ethics and dissemination: The protocol for the study was approved by the Institutional Review Board of each institution. The trial was filed for and registered at the Pharmaceuticals and Medical Devices Agency in Japan. The trial is currently on-going and is scheduled to end in June 2020. Trial registration number: jRCT2031190064; Pre-results.

BackgroundEpidemiological studies have shown that total scores in depression screening scales change with age, but the mechanism underlying these age-related changes remains unclear. Previous research has indicated that item responses in depression screening scales exhibit characteristic distributions in the general population. We analyzed Patient Health Questionnaire-9 (PHQ-9) data from a representative survey conducted in the USA, to determine how the response pattern for each item changed with age and whether the pattern of responses contributed to age-related changes in total scores.MethodsWe analyzed PHQ-9 data for 17,274 participants in the 2011–2016 National Health and Nutrition Examination Survey. The PHQ-9 allows respondents to self-rate the frequency of depressive symptoms using a four-point scale ranging from “not at all” to “nearly every day”.ResultsThe lines for all nine item responses followed the same characteristic pattern across all age groups, which was marked by intersection at a single point between “not at all” and “several days” and parallel patterns between “several days” and “nearly every day” on a logarithmic scale. The probability of “nearly every day” showed a reverse U-shaped pattern, in that it was low from 12–29 years, increased during 30–50 years, and then decreased at ≥60 years. The age-related change in the probability of a response of “nearly every day” coincided with the trajectory of the PHQ-9 total scores.ConclusionsThis study demonstrated that item responses for the PHQ-9 followed a similar mathematical pattern across the adult lifespan. Moreover, our findings suggested that the probability of a response of “nearly every day” played an important role in age-related changes in PHQ-9 total scores across adulthood.

Background Invariant natural killer T (iNKT) cells produce copious amounts of cytokines in response to specific glycolipid antigens such as α-galactosylceramide (αGalCer) presented by CD1d-expressing antigen-presenting cells (APCs), thus orchestrating other immune cells to fight tumors. Because of their ability to induce strong antitumor responses activated by αGalCer, iNKT cells have been studied for their application in cancer immunotherapy. In our previous phase I/II trial in non-small cell lung cancer (NSCLC) patients who had completed the standard treatment, we showed a relatively long median survival time without severe treatment-related adverse events. Based on these results, we performed a phase II trial to evaluate clinical responses, safety profiles and immune responses as a second-line treatment for advanced NSCLC.Methods Patients with advanced or recurrent NSCLC refractory to first-line chemotherapy were eligible. αGalCer-pulsed APCs were intravenously administered four times. Overall survival time was evaluated as the primary endpoint. The safety profile and immune responses after APC injection were also monitored. This study was an open label, single-arm, phase II clinical trial performed at Chiba University Hospital, Japan.Results Thirty-five patients were enrolled in this study, of which 32 (91.4%) completed the trial. No severe adverse events related to the treatment were observed. The estimated median survival time of the 35 cases was 21.9 months (95% CI, 14.8 to 26.0). One case (2.9%) showed a partial response, 14 cases (40.0%) remained as stable disease, and 19 cases (54.3%) were evaluated as progressive disease. The geometric mean number of iNKT cells in all cases was significantly decreased and the mean numbers of natural killer (NK) cells, interferon-γ-producing cells in response to αGalCer, and effector CD8+ T cells were significantly increased after the administration of αGalCer-pulsed APCs.Conclusions The intravenous administration of αGalCer-pulsed APCs was well-tolerated and was accompanied by prolonged overall survival. These results are encouraging and warrant further evaluation in a randomized phase III trial to demonstrate the survival benefit of this immunotherapy.Trial registration number UMIN000007321.

IntroductionProgestin therapy is the only fertility-sparing treatment option for patients with atypical endometrial hyperplasia (AEH) and endometrial cancer (EC). However, the results of three meta-analyses revealed a high remission rate, as well as an association with a high rate of relapse. We previously conducted a phase II of medroxyprogesterone acetate (MPA) plus metformin as a fertility-sparing treatment for AEH and EC patients, and reported that metformin inhibited disease relapse after remission.Methods and analysisA randomised, open, blinded-endpoint design phase IIb dose response trial was planned to commence in July 2019. The trial aims to identify the appropriate dose of metformin to be combined with MPA therapy for fertility-sparing treatment of patients with AEH and EC. The primary endpoint of the trial is the 3-year relapse-free survival (RFS) rate. The secondary endpoints are RFS rate, the overall rate of response to MPA therapy, the conception rate after treatment, the outcome of pregnancy, toxicity evaluation and changes in insulin resistance and body mass index. A total of 120 patients will be enrolled from 15 Japanese institutions within a 2.5-year period and followed up for at least 3 years.Ethics and disseminationThe protocol was approved by the institutional review board at Chiba University Hospital and boards at 14 other institutions. The trial will be conducted according to the principles of the World Medical Association’s Declaration of Helsinki and in accordance with Good Clinical Practice (GCP) standards. The trial findings will be published in a peer-reviewed journal.Trial registration numberJapan Registry of Clinical Trials (jRCT2031190065).

BackgroundAlthough current guidelines recommend admission to the intensive/coronary care unit (ICU/CCU) for patients with ST-segment elevation myocardial infarction (MI), routine use of the CCU in uncomplicated patients with acute MI remains controversial. We aimed to evaluate the safety of management in the general ward (GW) of hemodynamically stable patients with acute MI after primary percutaneous coronary intervention (PCI).MethodsUsing a large nationwide administrative database, a cohort of 19426 patients diagnosed with acute MI in 52 hospitals where a CCU was available were retrospectively analyzed. Patients with mechanical cardiac support and Killip classification 4, and those without primary PCI on admission were excluded. A total of 5736 patients were included and divided into the CCU (n = 3488) and GW (n = 2248) groups according to the type of hospitalization room after primary PCI. Propensity score matching was performed, and 1644 pairs were matched. The primary endpoint was in-hospital mortality at 30 days.ResultsThe CCU group had a higher rate of Killip classification 3 and ambulance use than the GW group. There was no significant difference in the incidence of in-hospital mortality within 30 days among the matched subjects. Multivariable Cox proportional hazard model analysis among unmatched patients supported the findings (hazard ratio 1.12, 95% confidence interval 0.66-1.91, p = 0.67).ConclusionsThe use of the GW was not associated with higher in-hospital mortality in hemodynamically stable patients with acute MI after primary PCI. It may be feasible for the selected patients to be directly admitted to the GW after primary PCI.

Understanding how maturity genes affect soybean yield formation will provide important information for crop management decisions. This study aimed to reveal how maturity genes E2 and E3 in the soybean cultivar ‘Enrei’ affect yields and yield formation in warm regions of Japan. ‘Enrei’ (e2e3) and three near-isogenic lines of ‘Enrei’ (e2E3, E2e3, and E2E3) were cultivated in 2016 and 2017 in Fukuyama, Japan (34°30′N, 133°23′E). Two sowing dates were set in each year (June sowing and July sowing). E2 extended the period from emergence to R1 and also the period from R1 to R7, whereas E3 extended only the period from emergence to R1. Interaction between E2 and E3 did not affect duration of the period from emergence to R1, but did affect the period from R1 to R7. Although seed yield did not differ between genotypes in the June sowings, the effects of E2 and E3 on seed yield in July sowing were both significant and interaction between E2 and E3 also observed. The total number of nodes increased in E3 genotypes in both sowing dates, especially in E2E3. Pod-set ratio was lower in E2 and E3 genotypes than in e2 and e3 genotypes in the June sowings, but did not differ between genotypes in the July sowings. The high yield of E2E3 genotypes in the July sowings was attributed to increased number of nodes and flower production while maintaining pod-set ratio. Appropriate choice of sowing date is suggested to be essential when using E3 genotypes.Abbreviations: HI: harvest index; NIL: near-isogenic line; RUE: radiation use efficiency; TDM: total above-ground dry matter; TRI: total solar radiation intercepted

Soybean production in southwestern Japan tends to be unstable owing to wet soils during the rainy season. Although late sowing after the rainy season can avoid excess water, information on its yield potential is limited. The objective of this study was to reveal the effect of late sowing on yields and yield components of new soybean cultivars developed for warm regions. The experiment was conducted in 2016 and 2017 in Fukuyama, Hiroshima, Japan. Upland fields converted from paddy fields with a subirrigation system were planted in June (normal) or July (late sparse or late dense). Lodging was prevented with a net. The effects of late sowing and dense treatment were analyzed in relation to solar radiation use. In 2016, differences in yield among cultivars and among environments were not significant. In 2017, yield was significantly reduced following late sparse sowing. The total aboveground dry matter at maturity was correlated with total solar radiation intercepted (r = 0.76) but not with radiation use efficiency (r = 0.47). Late sowing increased harvest index (HI) significantly from 0.464 to 0.571 in 2016 and from 0.524 to 0.585 in 2017, but density had no significant effect. The changes in HI were correlated with stem dry weight (r = −0.80 in 2016 and r = −0.79 in 2017) rather than seed yield (r = 0.08, n.s. in 2016 and r = 0.19, n.s. in 2017). Thus, under irrigation, late dense sowing might stabilize yield in southwestern Japan because of higher HI. Abbreviations: DM: dry matter; FOEAS: farm-oriented enhancing aquatic system; HI: harvest index; RUE: radiation use efficiency

Recently, US soybean cultivars have exhibited higher yields than Japanese soybean cultivars. To identify the determinants for this yield difference in reference to dry matter dynamics, recently developed US cultivars and Japanese commercial cultivars were cultivated in drained paddy fields in 2012 and 2013. The total dry matter (TDM) of each cultivar was measured at the initial seed-filling stage (R5), at 30 d after R5, and at maturity (R8). From R5 to R8, the DM of abscised leaves and petioles were measured. The actual HI (with abscised leaves and petioles) and apparent HI (without abscised leaves and petioles) were determined at R8. US soybean cultivars showed higher yields and apparent TDM (without abscised leaves and petioles) than did Japanese cultivars at R8. However, the difference in actual TDM (with abscised leaves and petioles) production was not significant between US and Japanese cultivars at R8. On the other hand, the actual HI was higher in US cultivars than in Japanese cultivars. US cultivars exhibited a higher TDM distribution to the pod before R5 and a higher pod growth rate from R5 to 30 d after R5. US cultivars tended to show greater crop growth rates (CGRs) from R5 to 30 d after R5. The higher yield in US cultivars was associated with the higher actual HI, which was considered attributable to a greater TDM productivity during the seed-filling period and higher DM distribution in the pod before R5.

Abstract Background Recently, item responses and total scores on depression screening scales have been reported to have characteristic distributions in the general population. The distributional pattern of responses to the Patient Health Questionnaire-9 (PHQ-9) in the general population has not been well studied. Thus, we carried out a pattern analysis of the PHQ-9 item responses and total scores in US adults. Methods Data (5372 individuals) were drawn from the 2013–2014 National Health and Nutrition Examination Survey in the United States. The item responses and total score distributions of the PHQ-9 data were investigated with graphical analysis and exponential regression model. Results Lines of item responses showed the same pattern among the nine items, characterized by crossing at a single point between “not at all” and “several days” and a parallel pattern from “several days” to “nearly every day” on a log-normal scale. The total score distribution of the PHQ-9 exhibited an exponential pattern, except for at the lower end of the distribution. Conclusions The present results support that the item responses and total scores on the PHQ-9 in the general population show the same characteristic patterns, consistent with the previous studies using the Center for Epidemiologic Studies Depression Scale (CES-D) and Kessler Screening Scale for Psychological Distress (K6).

Background and Objectives: In recent years, the effectiveness of chemotherapy after immune checkpoint inhibitor administration has attracted attention in various cancers, including head and neck cancers. However, individual assessments of the administered chemotherapy regimens are insufficient. This study aimed to evaluate the efficacy and safety of chemotherapy after immune checkpoint inhibitor administration in recurrent metastatic head and neck cancer by focusing on a single regimen. Materials and Methods: We retrospectively reviewed clinical and radiological data from the medical records of 18 patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who received systemic chemotherapy with weekly cetuximab and paclitaxel (Cmab + PTX) after progression following immune checkpoint inhibitor (ICI) therapy. The objective response rate (ORR) and disease control rate (DCR) were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Adverse events (AEs) were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: In all patients, the ORR, DCR, median PFS, and median OS were 44.4%, 72.2%, 3.8 months, and 9.6 months, respectively. Regarding AEs, three patients developed grade 3 neutropenia. Grade 3 anemia, paronychia, asthenia, and peripheral neuropathy were observed in one patient each. There were no treatment-related deaths. Conclusions: Cmab + PTX was shown to maintain high efficacy and acceptable safety for R/M HNSCC that progressed after ICI therapy. Further research is needed to establish optimal treatment sequences and drug combinations for recurrent R/M HNSCC.

Abstract Objectives Total depressive symptom scores in the general population have been reported to follow an exponential distribution except at the lowest end of the range of scores. To verify the hypothesis that total depressive symptom scores follow the distribution of the latent trait, we performed a simulation study of depressive symptom scoring modeled after the Revised Clinical Interview Schedule (CIS-R). To simulate the scoring of ordinal scale items in CIS-R, two sets of random numbers were generated, one expressing the degree of the latent trait of depressive symptoms and another expressing the threshold for each item. Random latent trait numbers greater than those of item thresholds indicated the presence of specific symptoms. Results When exponential distribution was set to the latent trait’s random numbers and each item’s threshold had a certain degree of standard deviation, simulated total depressive symptom scores showed a linear pattern except at the lowest end of scores with a log-normal scale. Our results suggest that total depressive symptom scores follow the distribution of the latent trait of depressive symptoms due to the property of ordinal scales, which is characterized by individual differences in the threshold of each item.

Abstract Background The distributional pattern of total scores on depression screening scales in the general population has not been well studied. Recent studies suggest that the total scores on depression screening scales follow an exponential pattern, with the exception of the lower end of the distribution. To further investigate the findings, we determined the distributions of the total and individual item scores on the Kessler Screening Scale for Psychological Distress (K6). Methods Data were obtained from the National Survey of Midlife Development in the United States. Participants comprised 6,223 individuals between the ages of 25 and 74. The distributions of the total and individual item scores in various combinations were investigated with histograms and regression analysis. Results Irrespective of the combination of items, the total and individual item scores followed an exponential pattern except at the lower scores. The estimated rate parameters of regression analysis were similar among distributions with the same number of chosen items. At the lower scores, the distributional patterns of total scores varied according to the ratio of “a little” to “none” for each item response. Conclusions The present results have the potential to estimate the distribution of depressive symptoms in the general population. While the degree of depressive symptoms varies from individual to individual, an entire population may show a certain mathematical distribution.

Due to the synthetic utility of the products, stereoselective halogenation is a powerful method for the synthesis of chiral compounds. Here the authors report an enantioselective decarboxylative chlorination, giving access to a range of α-chloroketones.

Background: The prenatal maternal microbiome, including the gut microbiota, has been suggested to influence the incidence of allergies in offspring. Moreover, epidermal barrier dysfunction in early infancy has been attributed to the development of subsequent allergies. We hypothesized that the prenatal microbiome may affect the gut microbiota, acting as an initial trigger to alter immune development in the foetus. The maternal microbial composition may be linked to the prevalence of dermatitis in early infancy (DEI) of the offspring, leading to subsequent allergic symptoms. Methods: This study was conducted as part of the Chiba Study of Mother and Child Health (C-MACH) birth cohort that was initiated in 2013; 434 healthy pregnant women at

Background: Previous studies suggested that item responses on the 6-item Kessler Psychological Distress Scale (K6) exhibit characteristic distributions among the general population. To confirm the reproducibility of these findings, we conducted a pattern analysis of the K6 item responses using large-scale data from a US representative survey. Methods: Data were drawn from the 2016, and 2017 National Health Interview Survey in the United States (33,028, and 26,742 individuals, respectively). We analyzed the patterns of item responses for the six items using normal and logarithmic scales and proposed a model of item responses. Results: The lines for item responses showed the same pattern among the six items, characterized by crossing at a single point between “none” and “a little,” and parallel patterns from “a little” to “all of the time” on a logarithmic scale. The ratio of “some” to “a little,” “most” to “some,” and “most” to “all of the time” were similar across the six items. The model of item responses, which was based on the findings that the decreasing ratios of “some” to “a little,” “most” to “some,” and “all of the time” to “most” were similar across the six items, explained the characteristic patterns of item responses. Conclusion: These results provide further evidence that item responses on the K6 follow a particular distribution pattern among the general population.

Objective: Chronic rhinosinusitis with nasal polyps exhibits marked eosinophilic infiltration and its mucosal eosinophilia is associated with more severe symptoms. The Japanese epidemiological survey of refractory eosinophilic chronic rhinosinusitis found that patients with nasal polyps required multiple surgeries when there were higher infiltrating eosinophils in the mucosa. In order to identify plasma biomarkers for local eosinophil infiltration in rhinosinusitis for surgery, we examined the levels of molecules in the plasma of patients and compared the number of infiltrating eosinophils in the nasal mucosa.Materials and Methods: Mucosal tissues from 97 patients with chronic rhinosinusitis (CRS) were obtained from the nasal polyps during surgery. Tissues were immediately fixed and sections were stained with hematoxylin-eosin. The number of eosinophils in the mucosa was counted at HPF (x 400). Blood samples were obtained and the plasma was stored at −80°C. We measured the plasma cytokine and chemokine levels using multiple assay systems according to the manufacturers' protocols. The tissues were divided into high- and low-eosinophil mucosal infiltration group for recurrence after endoscopic sinus surgery (ESS). We also observed chemokine secretion from nasal fibroblasts.Results: The plasma level of eotaxin-3/ CC chemokine ligand 26 (CCL26) was significantly higher in the high-eosinophil mucosal infiltration group (p < 0.005). The number of infiltrating eosinophils in the mucosa was significantly higher in the group with the higher eotaxin-3 level (p < 0.001), but there was no significant difference in the blood eosinophil numbers among two groups. A significant positive correlation was found between the mucosal eosinophil count and the plasma levels of eotaxin-3 (p < 0.005). The levels of interleukin 33 (IL-33) (p < 0.001) and thymic stromal-derived lymphopoietin (TSLP) (p < 0.005) were significantly higher in the high-level eotaxin-3 group. IL-13 strongly induced the secretion of eotaxin-3 from human nasal fibroblasts (p < 0.05).Conclusion: This is the first report suggesting eotaxin-3 as a plasma biomarker for mucosal eosinophil infiltration. Furthermore, the level of eotaxin-3 was found to be closely related to IL-33 and TSLP levels which indicate respiratory diseases.

We investigated the effect of the mammalian target of rapamycin (mTOR) inhibitor everolimus on tuberous sclerosis complex- (TSC-) associated autistic symptoms and focal seizures with impaired awareness in a female child with TSC. We further evaluated the relationship between improved autistic symptoms and seizures and increased the serum levels of the antioxidant proteins, ceruloplasmin (Cp) and transferrin (Tf), and oxidant-antioxidant status indicated by the oxidant marker oxidized low-density lipoprotein (ox-LDL) and the antioxidant marker total antioxidant power (TAP). Everolimus treatment improved impaired social cognition and autistic behaviors; however, seizure and epileptic activity persisted. Serum Cp and Tf levels gradually increased in response to improved autistic symptoms. Serum TAP levels gradually decreased from baseline to the lowest value at 16 weeks and then increased at 24 weeks, showing a trend toward decreased total score of the Aberrant Behavior Checklist. This study revealed that everolimus treatment improved impaired social cognition with increased serum levels of the copper mediator (Cp) and iron mediator (Tf) via homeostatic control of mTOR activity accompanied by overlap of the oxidant-antioxidant system. Everolimus had no effect on TSC-related epileptiform discharges, and thus, the autistic symptoms and epileptic activity may be two independent end results of a common central nervous system disorder including mTOR hyperactivity. This trial is registered with JMAS-IIA00258.

Introduction: The prognosis of head and neck squamous cell carcinoma (HNSCC) is generally good in cases of high radiation sensitivity but poor in cases exhibiting radiation resistance; this resistance has been attributed to the presence of cancer stem cells. In recent years, CD98hc overexpression has been associated with poor prognosis in various types of cancers. CD98 is a heterodimer of heavy and light chains and is strongly involved in cell proliferation, survival, migration, and adhesion. We investigated whether CD98hc can be used as a cancer stem cell marker for HNSCC. Material and methods: We exposed five HNSCC cell lines to a total radiation dose of 60 Gy administered in 2 Gy fractions on consecutive days to investigate changes in CD98hc expression. Furthermore, we separated CD98-positive and CD98-negative cell populations to comparatively investigate the properties of each. Results: Radiation resistance was observed in all five cell lines, and resistant cells exhibited CD98hc overexpression, with enhanced spheroid formation, migratory, and invasive abilities. Radiation-resistant cell lines were separated into CD98-positive and CD98-negative populations. CD98hc-positive radiation-resistant cell lines exhibited enhanced spheroid formation, invasion, and plating efficiency as well as strong tumorigenicity in nude mice. Conclusions: CD98hc-positive cells exhibited cancer stem cell-like properties in all cell lines. Thus, CD98hc is a potential marker of radiation sensitivity as well as a potential therapeutic target for improved survival rates of patients with HNSCC. [ABSTRACT FROM AUTHOR]

Abstract Background Influenza viruses can spread easily from person to person, and annual influenza epidemics are serious public health issues worldwide. Non-pharmaceutical public health interventions could potentially be effective for combatting influenza epidemics, but combined interventions and/or interventions with greater effectiveness are needed. Experimental studies have reported that tea and its ingredients (especially catechins) have antiviral activities. Although several clinical studies have investigated the use of tea or its ingredients to prevent influenza infections, the effect of gargling these substances has remained uncertain. Methods We conducted a meta-analysis of randomized controlled studies and prospective cohort studies to assess the effect of gargling with tea and its ingredients on the prevention of influenza infection. The published literature was searched using the Cochrane Library, PubMed/MEDLINE (1966 to September 2015), Web of Science (1981 to September 2015), and Ichu-shi Web (1983 to September 2015). The extracted studies were read by two reviewers independently, and their overall scientific quality was evaluated. Studies meeting our inclusion criteria were pooled using the Mantel-Haenszel method in a fixed effects model and were also analyzed in a random effects model. The qualities of the model fits were assessed using the Akaike information criterion (AIC) and Bayesian information criterion (BIC). Results The literature search and review identified 5 studies that met the inclusion criteria for the meta-analysis (total number of participants, 1890; mean age range, 16–83 years). The participants who gargled with tea or its ingredients showed a lower risk of influenza infection than did participants who gargled with placebo/water or who did not gargle (fixed effects model, Mantel-Haenszel method: relative risk [RR] = 0.70, 95 % confidence interval [CI] = 0.54–0.89; random effects model: RR = 0.71, 95 % CI = 0.56–0.91). The fixed effects model had a better quality of fit than the random effects model (fixed effects model: AIC = 6.04, BIC = 5.65; random effects model: AIC = 8.74, BIC = 7.52). Conclusions Gargling with tea and its ingredients may have a preventative effect for influenza infection. However, additional large-scale studies in different populations and a pooled analysis of these studies are needed to confirm the effect.

The difference in yields of cultivars may be causing difference in soybean yield between Japan and the USA. The objective of this study was to identify the effect of the cultivar on dry matter production and to reveal the key factors causing the differences in yield by focusing utilization of solar radiation in recent Japanese and US soybean cultivars. Field experiments were conducted during two seasons in Takatsuki, Japan (34°50′), and in a single season in Fayetteville (36°04′), AR, USA. Five Japanese and 10 US cultivars were observed under near-optimal conditions in order to achieve yields as close to their physiological potential as possible. The seed yield and total aboveground dry matter (TDM) were measured at maturity as long as radiation was intercepted by the canopy. The seed yield ranged from 3.10t ha−1 to 5.91t ha−1. Throughout the three environments, the seed yield of US cultivars was significantly higher than that of Japanese cultivars. The seed yield correlated with the TDM rather than the HI with correlation coefficients from .519 to .928 for the TDM vs. .175 to .800 for the HI, for each of the three environments. The higher TDM of US cultivars was caused by a higher radiation use efficiency rather than higher total intercepted radiation throughout the three environments. The seasonal change in the TDM observed in four cultivars indicated that dry matter productivity was different between cultivars, specifically during the seed-filling period.