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New and simple crop yield prediction methods are expected to be developed owing to the increasing environmental stress caused by climate change. Algorithms of machine learning could be a powerful tool for predicting crop yield; however, the required feature variables and differences in their prediction accuracy are poorly addressed. The objectives of this study were to identify the best combination of feature variables to predict the yield of cowpea (Vigna unguiculata), which is widely grown in central Sudan Savanna under environmentally restricted conditions, and clarify the differences in the accuracy of major machine learning algorithms. The study also explored the environmental and plant factors affecting the prediction errors. Sample data were obtained from cowpea field experiments in central Sudan Savanna. The prediction was performed using 28 models, encompassing four machine learning algorithms and seven combinations of feature variables. Support Vector Regression and Neural Network algorithms effectively predicted cowpea yields using continuous leaf coverage rates as feature variables; however, some differences were observed in their prediction accuracy depending on the soil types and growth habits. The use of feature variables that are related to shoot growth and plant physiological status could minimize prediction errors., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Obesity indices reflect not only fat mass but also muscle mass and nutritional status in older people. Therefore, they may not accurately reflect prognosis. This study aimed to investigate associations between a body shape index (ABSI), body mass index (BMI), and mortality in the general older population., Methods: This nationwide observational longitudinal study included individuals aged between 65 and 74 years who underwent annual health checkups between 2008 and 2014. Exposures of interest were ABSI and BMI, and the primary outcome was all-cause mortality. Association between the ABSI and BMI quartile (Q1-4) and mortality was assessed using Cox regression analysis. A restricted cubic spline was also used to investigate nonlinear associations. The missing values were imputed using multiple imputation by chained equations., Results: Among 315,215 participants, 5074 died during a median follow-up period of 42.5 (interquartile range: 26.2-59.3) months. Compared with ABSI Q1, ABSI Q3 and Q4 were associated with increased risk of mortality, with the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 1.13 (1.05-1.22) and 1.23 (1.13-1.35), respectively. Compared with BMI Q3, BMI Q1 and Q2 were associated with an increased risk of mortality, with aHRs and 95% CIs of 1.51 (1.39-1.65) and 1.12 (1.03-1.22), respectively. The impacts of these indices were greater in male than in female. The heatmap of the aHR for mortality by continuous ABSI and BMI showed that higher ABSI was consistently associated with higher mortality risk regardless of BMI, and that the combination of low BMI and high ABSI was strongly associated with increased mortality risk., Conclusions: High ABSI and low BMI are additively associated with the risk of all-cause mortality in the general older population in Japan. Combination of ABSI and BMI is useful for evaluating mortality risk in older people., (© 2024 The American Geriatrics Society.)

Aims: Both low and high serum levels of high-density lipoprotein cholesterol (HDL-C) were reported to be associated with adverse kidney outcomes. However, this association has not been well investigated in the general Japanese population., Methods: This nationwide longitudinal study used data from the Japan Specific Health Checkups Study conducted between 2008-2014. The association between serum HDL-C levels and 40% decline in estimated glomerular filtration rate (eGFR) was analyzed using Cox regression analysis. Trajectories of eGFR were compared using mixed-effects model., Results: Among 768,495 participants, 6,249 developed 40% decline in eGFR during the median follow-up period of 34.6 (interquartile range: 14.8-48.4) months. Using serum HDL-C levels of 40-59 mg/dL as a reference, the adjusted hazard ratios (95% confidence intervals) for the kidney outcome of serum HDL-C levels of ＜40, 60-79 and ≥ 80 mg/dL were 1.26 (1.14-1.39), 0.91 (0.86-0.96), and 0.86 (0.78-0.93), respectively. Restricted cubic spline analysis showed that HDL-C levels of less than approximately 60 mg/dL were associated with an increased risk of kidney outcomes. Subgroup analysis showed that baseline eGFR and proteinuria modified the effects of serum HDL-C levels on kidney outcomes. The mixed-effects model showed that the lower category of HDL-C level was associated with a higher eGFR decline rate (p for interaction ＜0.001)., Conclusions: Low HDL-C levels were associated with kidney function decline; however, high HDL-C levels were not associated with adverse kidney outcomes in the general Japanese population.

Background: For the development of pharmaceutical products in kidney field, appropriate surrogate endpoints which can predict long-term prognosis are needed as an alternative to hard endpoints, such as end-stage kidney disease. Though international workshop has proposed estimated glomerular filtration rate (GFR) slope reduction of 0.5-1.0 mL/min/1.73 m /year and 30% decrease in albuminuria/proteinuria as surrogate endpoints in early and advanced chronic kidney disease (CKD), it was not clear whether these are applicable to Japanese patients., Methods: We analyzed J-CKD-DB and CKD-JAC, Japanese databases/cohorts of CKD patients, and J-DREAMS, a Japanese database of patients with diabetes mellitus to investigate the applicability of eGFR slope and albuminuria/proteinuria to the Japanese population. Systematic review on those endpoints was also conducted including the results of clinical trials published after the above proposal., Results: Our analysis showed an association between eGFR slope and the risk of end-stage kidney disease. A 30% decrease in albuminuria/proteinuria over 2 years corresponded to a 20% decrease in the risk of end-stage kidney disease patients with baseline UACR ≥ 30 mg/gCre or UPCR ≥ 0.15 g/gCre in the analysis of CKD-JAC, though this analysis was not performed on the other database/cohort. Those results suggested similar trends to those of the systematic review., Conclusion: The results suggested that eGFR slope and decreased albuminuria/proteinuria may be used as a surrogate endpoint in clinical trials for early CKD (including diabetic kidney disease) in Japanese population, though its validity and cutoff values must be carefully considered based on the latest evidence and other factors., (© 2024. The Author(s).)

Aim: Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH., Methods: This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality., Results: Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeutic-dose UFH was 9.2%. Logistic regression analysis showed that age ≥ 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; P＜.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; P＜.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test)., Conclusions: The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.

Introduction: Cigarette smoking is one of the most important life-modifiable risk factors for CVD events. The effect on CKD progression caused by smoking remained uncertain, while the effect on CVD had been established., Method: The study population included participants from the specific health check and specific health guidance, an annual health check-up for all inhabitants of Japan who were aged between 40 and 74 years. 149,260 subjects (male, 37.1%; female, 62.9%) were included in this analysis., Results: The relationship between smoking status along with new-onset proteinuria and eGFR deterioration more than 15 mL/min/1.73 m2 was examined. Median observation periods were 1427 days [738, 1813] in males and 1437 days [729, 1816] in females. In male participants, the strongest factor upon kidney dysfunction was new-onset proteinuria (1.41 [1.31 1.51], P < 0.001). The second strongest factor on kidney deterioration was smoking (1.24 [1.16 1.31], P < 0.001). In female participants, strongest factor upon kidney dysfunction was smoking (1.27 [1.16-1.39], P < 0.001). The second strongest factor on kidney deterioration was new-onset proteinuria (1.26 [1.17 1.36], P < 0.001). To reveal the relationship of effects from new-onset proteinuria and smoking on the kidney function, the participants were divided into four groups with and without new-onset proteinuria and smoking. The group with both proteinuria and smoking had significantly worst renal prognosis (P for trend < 0.001)., Conclusion: Large longitudinal observation study revealed smoking has an evil effect on the progression of CKD. This evil effect could be observed in CKD patients with proteinuria as well as in general population without new-onset proteinuria., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

DOATS score and DOAT score, COVID-19 progression prediction tools we have developed, utilize clinical information such as presence of diabetes/obesity (DO), age (A), body temperature (T), and oxygen saturation (S). They showed good predictive power, but their scoring calculation was slightly complex, leading us to develop simplified versions. This report discusses the ability of the simplified versions to assess deterioration risk in unvaccinated, mild/moderate COVID-19 patients aged <65 years. Logistic regression analysis identified independent risk factors for deterioration, to which points were assigned in order to derive overall prediction scores. The simplified versions showed high discriminating power, with the areas under the receiver operating characteristic curve for DOATS and DOAT being 0.79 and 0.77, respectively, indicating their clinical utility. Although the original versions have a slightly higher predictive power, the new versions are easier to use in emergency situations; thus, importantly, selecting the appropriate version depends on the situation., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Unlike systolic blood pressure (SBP), the prognostic value of diastolic blood pressure (DBP) in kidney function has not been established. We hypothesized that pulse pressure (PP), which is associated with arteriosclerosis, would affect the prognostic value of DBP., Methods: This longitudinal study used data from the Japan Specific Health Checkups Study was conducted between 2008 and 2014. The participants were stratified into three PP subgroups (low PP ≤39, normal PP 40-59 and high PP ≥60 mmHg). The exposures of interest were SBP and DBP, and the association between SBP/DBP and kidney outcomes (30% decline in the estimated glomerular filtration rate from baseline) was examined in each PP subgroup using a Cox proportional hazards model., Results: Among 725 022 participants, 20 414 (2.8%) developed kidney outcomes during a median follow-up period of 34.6 months. Higher SBP was consistently associated with a higher incidence of kidney outcome in all PP subgroups. Although DBP had a positive linear association with the incidence of kidney outcome in low- and normal-PP subgroups, both lower (≤60 mmHg) and higher (≥101 mmHg) DBP were associated with a higher incidence of kidney outcome in the high-PP subgroup, with a U-shaped curve. Hazard ratios (95% confidence intervals) of ≤60 mmHg (reference: 61-80 mmHg in normal-PP subgroup) and ≥101 mmHg were 1.26 (1.15-1.38) and 1.86 (1.62-2.14), respectively., Conclusions: In this large population-based cohort, DBP was differently associated with kidney outcome by PP level; lower DBP was significantly associated with a higher incidence of kidney outcome in the high-PP subgroup but not in the low- and normal-PP subgroups., Competing Interests: Nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

The antiviral drug acyclovir (ACV) may induce drug-induced neuropsychiatric symptoms as side effects. The detailed pathogenic mechanism remains unclear; however, it is hypothesized that 9-carboxymethoxymethylguanine (CMMG), a metabolite of ACV, is the causative compound. Therefore, the blood concentrations of ACV and CMMG should be analyzed in ACV toxicity studies. However, it is rare to find methods that can sufficiently separate the ACV and CMMG peaks during simultaneous analysis of both compounds. Therefore, we intended to develop a liquid chromatography-tandem mass spectrometry method with improved peak separation of analytes. Samples were deproteinized using methanol/acetonitrile solution (6:4, v/v). Analytes were separated on an InertSustain® Amide column (3 μm, 2.1 mm × 150 mm). The mobile phase consisted of acetonitrile/10 mM ammonium formate (5:95, v/v) (A) and acetonitrile/10 mM ammonium formate (95:5, v/v, pH 5.0) (B) and samples were eluted in the gradient mode. The separation of analytes was satisfactory and the peak shapes were good. Linear regression models weighted 1/x2 were obtained in the range of 0.25-10 μg/mL. The range of quality control (QC) bias was between 3.6% and 19.8%, and the within-run and between-run precisions of QC were within 13.5%. Recovery ranged from 83.6% to 103.7%, but ion suppression was observed. Samples from a patient with ACV encephalopathy were analyzed using this method. The resulting blood ACV and CMMG concentrations were 8.2 and 8.5 μg/mL, respectively. This method, with sufficient separation of ACV and CMMG, proved useful for use in ACV toxicity studies., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Rationale: Serotonin syndrome is a potentially life-threatening condition resulting from the use of antidepressants, their interactions with other serotonergic medications, or poisoning. It presents with a triad of psychiatric, dysautonomic, and neurological symptoms and is sometimes fatal. While cyproheptadine is a specific treatment option, the optimal duration of its administration remains unclear. The purpose of this report is to quantitatively assess the endpoints of serotonin syndrome treatment. Based on the hypothesis that neurological pupil index (NPi) on a digital pupil recorder would correlate with the severity of the serotonin syndrome, we administered cyproheptadine using NPi as an indicator., Patient Concerns: A patient with a history of depression was brought to our hospital after he overdosed on 251 tablets of serotonin and noradrenaline reuptake inhibitors., Diagnoses: On day 3, the patient was diagnosed with serotonin syndrome., Interventions: Cyproheptadine syrup was administered at 4 mg every 4 hours. The NPi of the automated pupillometer was simultaneously measured. On day 5, the NPi exceeded 3.0 cyproheptadine was discontinued., Outcomes: The patient was discharged on day 7., Lessons: The lack of considerable improvement during the treatment period suggests that the patient may have improved on his own. In this case, the relationship between NPi and the severity of serotonin syndrome could not be determined., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Expression of α-smooth muscle actin (αSMA) is constitutive in vascular smooth muscle cells, but is induced in nonmuscle cells such as hepatic stellate cells (HSCs). HSCs play important roles in both physiological homeostasis and pathological response. HSC activation is characterized by αSMA expression, which is regulated by the TGFβ-induced Smad pathway. Recently, protein kinase C (PKC) was identified to regulate αSMA expression. Diacylglycerol kinase (DGK) metabolizes a second-messenger DG, thereby controlling components of DG-mediated signaling, such as PKC. In the present study we aimed to investigate the putative role of DGKα in αSMA expression. Use of a cellular model indicated that the DGK inhibitor R59949 promotes αSMA expression and PKCδ phosphorylation. It also facilitates Smad2 phosphorylation after 30 min of TGFβ stimulation. Furthermore, immunocytochemical analysis revealed that DGK inhibitor pretreatment without TGFβ stimulation engenders αSMA expression in a granular pattern, whereas DGK inhibitor pretreatment plus TGFβ stimulation significantly induces αSMA incorporation in stress fibers. Through animal model experiments, we observed that DGKα-knockout mice exhibit increased expression of αSMA in the liver after 48 h of carbon tetrachloride injection, together with enhanced phosphorylation levels of Smad2 and PKCδ. Together, these findings suggest that DGKα negatively regulates αSMA expression by acting on the Smad and PKCδ signaling pathways, which differentially regulate stress fiber incorporation and protein expression of αSMA, respectively., (© 2023 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Polymicrobial sepsis is associated with a poor prognosis due to severe type-1 innate inflammation triggered by immune cells, such as dendritic cells and macrophages. This immune response frequently leads to damage in the heart. Although interleukin (IL)-13 is thought to play a protective role in organ inflammation, its function in polymicrobial sepsis remains unclear. We aimed to investigate the role of IL-13 in modulating myocardial injury during cecal ligation and puncture (CLP)-induced sepsis using a murine model. Cardiac troponin I (cTnI), a biomarker for myocardial damage, was measured in both IL-13-deficient (KO) and wild type (WT) mice subjected to CLP. Contrary to the conventional view of IL-13 as a protective cytokine, IL-13-competent mice exhibited significantly higher serum cTnI levels than IL-13-deficient mice, indicating exacerbated myocardial injury. Elevated cardiac tumor necrosis factor-alpha (TNF-α) levels and IL-1β in WT CLP mice corroborated this finding, suggesting IL-13's role in enhancing the inflammatory response. In vitro assays with bone marrow-derived dendritic cells (BMDCs) stimulated with lipopolysaccharide and Group A Streptococcus revealed a dose-dependent suppression of TNF-α and IL-6 production by recombinant IL-13. These findings indicate a complex role of IL-13 in sepsis, modulating inflammation but potentially increasing myocardial stress.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used to treat non-small cell lung cancer with EGFR mutations. However, first-generation erlotinib and second-generation afatinib often cause diarrhea, which may develop because of the association between EGFR-TKIs and the chloride channel or abnormalities in the intestinal microbiota due to disruption of the intestinal immune system. As reports on the effects of EGFR-TKIs on intestinal immunity are lacking, we aimed to determine whether the intestinal immune system is involved in the molecular effects of EGFR-TKIs on chloride channels using Caco-2 cells. Initially, we evaluated the association of chloride channels with α-defensin 5 (DEFA5), a marker of intestinal immunity. Erlotinib and afatinib significantly increased the extracellularly secreted DEFA5 level and autophagy-related 16-like 1 and X-box binding protein 1 transcript levels, indicative of enhanced granule exocytosis. Conversely, intracellular DEFA5 and Toll-like receptor 4 protein expression and tumor necrosis factor-α transcript levels decreased significantly, suggesting that Toll-like receptor 4 suppression repressed DEFA5 production. Furthermore, among the chloride channels, DEFA5 was found to significantly increase the transcript levels of cystic fibrosis transmembrane conductance regulators. These results indicate that DEFA5 plays a significant role in the mechanism of chloride channel-mediated diarrhea induced by EGFR-TKIs. Therefore, we successfully elucidated the potential host action of DEFA5 in cancer therapy for the first time.