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Abstract Indoxyl sulfate (IS), a uremic toxin, is a harmful factor that damages kidneys. Chronic heat stress in laying hens causes renal injury; however, whether IS accumulation is involved in this injury remains unknown. We selected 20 Boris brown laying hens (27 weeks old) and randomly assigned them to two groups (n = 10), one group was exposed to chronic heat stress (32 °C for 4 weeks), whereas the other was maintained at 24 °C. Chronic heat exposure significantly increased plasma and renal IS concentrations (P

Abstract Background Complete endoscopic resection of superficial non-ampullary duodenal epithelial tumors (SNADETs) is technically difficult, especially with an extremely high risk of adverse event (AE), although various endoscopic resection methods including endoscopic mucosal resection (EMR), underwater EMR (UEMR), and endoscopic submucosal dissection (ESD) have been tried for SNADETs. Accordingly, a novel simple resection method that can completely resect tumors with a low risk of AEs should be developed. Aims A resection method of Noninjecting Resection using Bipolar Soft coagulation mode (NIRBS) which has been reported to be effective and safe for colorectal lesions is adapted for SNADETs. In this study we evaluated its effectiveness, safety, and simplicity for SNADETs measuring ≤ 20 mm. Results This study included 13 patients with resected lesions with a mean size of 7.8 (range: 3–15) mm. The pathological distributions of the lesions were as follows: adenomas, 77% (n = 10) and benign and non-adenomatous lesions, 23% (n = 3). The en bloc and R0 resection rate was 100% (n = 13). The median procedure duration was 68 s (32–105). None of the patients presented with major AEs including bleeding and perforation. Conclusions Large studies such as prospective, randomized, and controlled trials should be conducted for the purpose of validating effectiveness, safety, and simplicity of the NIRBS for SNADETs measuring ≤ 20 mm suggested in this study.

ABSTRACT Aims The utilization of long‐term effect of internet of things (IoT) on glycemic control is controversial. This trial aimed to examine the effect of an IoT‐based approach for type 2 diabetes. Materials and Methods This randomized controlled trial enrolled 1,159 adults aged 20–74 years with type 2 diabetes with a HbA1c of 6.0–8.9% (42–74 mmol/mol), who were using a smartphone on a daily basis were randomly assigned to either the IoT‐based approach group (ITG) or the control group (CTG). The ITG were supervised to utilize an IoT automated system that demonstrates a summary of lifelogging data (weight, blood pressure, and physical activities) and provides feedback messages that promote behavioral changes in both diet and exercise. The primary end point was a HbA1c change over 52 weeks. Results Among the patients, 581 were assigned to the ITG and 578 were in the CTG. The changes in HbA1c from baseline to the final measurement at 52 weeks [mean (standard deviation)] were −0.000 (0.6225)% in ITG and − 0.006 (0.6449)% in CTG, respectively (P = 0.8766). In the per protocol set, including ITG using the IoT system almost daily and CTG, excluding those using the application almost daily, the difference in HbA1c from baseline to 52 weeks were −0.098 (0.579)% and 0.027 (0.571)%, respectively (P = 0.0201). We observed no significant difference in the adverse event profile between the groups. Conclusions The IoT‐based approach did not reduce HbA1c in patients with type 2 diabetes. IoT‐based intervention using data on the daily glycemic control and HbA1c level may be required to improve glycemic control.

Abstract Benralizumab, a monoclonal antibody targeting IL-5 receptors, reduces exacerbations and oral corticosteroid requirements for severe, uncontrolled eosinophilic asthma. In Japan, geographic disparities in asthma outcomes suggest differential prescribing and access. This study aimed to quantify regional prescribing variations for benralizumab nationwide. Using Japan’s National Database (NDB) of insurance claims (2009–2019), benralizumab standardized claim ratios (SCRs) were calculated for 47 prefectures. Correlations between SCRs and other biologics’ SCRs, economic variables like average income, and physician densities were evaluated through univariate analysis and multivariate regressions. Income-related barriers to optimal prescribing were examined. Wide variation emerged in benralizumab SCRs, from 40.1 to 184.2 across prefectures. SCRs strongly correlated with omalizumab (r = 0.61, p

Abstract This study integrated bacterial community and soil chemicals to characterize the soil ecosystem in an open upland field managed by six controlled fertilizer programs using the minimum amount of pesticides. Amplicon sequencing the 16S rRNA gene revealed that inorganic nitrogen fertilizer and compost altered the diversity and structure of the soil bacterial community throughout buckwheat (Fagopyrum esculentum Moench ‘Hitachiakisoba’) cultivation. The bacterial community comprised three clusters that contained bacteria that are prevalent in soils fertilized with nitrogen (cluster 1, 340 taxa), without nitrogen and compost (cluster 2, 234 taxa), and with compost-fertilized (cluster 3, 296 taxa). Cluster 2 contained more taxa in Actinobacteriota and less in Acidobacteriota, and cluster 3 contained more taxa in Gemmatimonadota compared with the other clusters. The most frequent taxa in cluster 1 were within the Chloroflexi phylum. The bacterial community structure correlated with soil chemical properties including pH, total organic carbon, SO4 2−, soluble Ca2+. A co-occurrence network of bacterial taxa and chemicals identified key bacterial groups comprising the center of a community network that determined topology and dynamics of the network. Temporal dynamics of the bacterial community structure indicated that Burkholderiales were associated with buckwheat ripening, indicating plant-bacteria interaction in the ecosystem.

In plants, plasmodesmata establish cytoplasmic continuity between cells to allow for communication and resource exchange across the cell wall. While plant pathogens use plasmodesmata as a pathway for both molecular and physical invasion, the benefits of molecular invasion (cell-to-cell movement of pathogen effectors) are poorly understood. To establish a methodology for identification and characterization of the cell-to-cell mobility of effectors, we performed a quantitative live imaging-based screen of candidate effectors of the fungal pathogen Colletotrichum higginsianum. We predicted C. higginsianum effectors by their expression profiles, the presence of a secretion signal, and their predicted and in planta localization when fused to green fluorescent protein. We assayed for cell-to-cell mobility of nucleocytosolic effectors and identified 14 that are cell-to-cell mobile. We identified that three of these effectors are “hypermobile,” showing cell-to-cell mobility greater than expected for a protein of that size. To explore the mechanism of hypermobility, we chose two hypermobile effectors and measured their impact on plasmodesmata function and found that even though they show no direct association with plasmodesmata, each increases the transport capacity of plasmodesmata. Thus, our methods for quantitative analysis of cell-to-cell mobility of candidate microbe-derived effectors, or any suite of host proteins, can identify cell-to-cell hypermobility and offer greater understanding of how proteins affect plasmodesmal function and intercellular connectivity. [Graphic: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Introduction The femoral head contralateral to the collapsed femoral head requiring total hip arthroplasty (THA) often manifests in the precollapse stage of osteonecrosis of the femoral head (ONFH). It is not yet demonstrated how autologous concentrated bone marrow injection may prevent collapse of the femoral head concurrent with contralateral THA. The primary objective is to evaluate the efficacy of autologous concentrated bone marrow injection for the contralateral, non-collapsed, femoral head in patients with bilateral ONFH, with the ipsilateral collapsed femoral head undergoing THA.Methods and analysis This is a multicentre, prospective, non-randomised, historical-data controlled study. We will recruit patients with ONFH who are scheduled for THA and possess a non-collapsed contralateral femoral head. Autologous bone marrow will be collected using a point-of-care device. After concentration, the bone marrow will be injected into the non-collapsed femoral head following the completion of THA in the contralateral hip. The primary outcome is the percentage of femoral head collapse evaluated by an independent data monitoring committee using plain X-rays in two directions 2 years after autologous concentrated bone marrow injection. Postinjection safety, adverse events, pain and hip function will also be assessed. The patients will be evaluated preoperatively, and at 6 months, 1 year and 2 years postoperatively.Ethics and dissemination This protocol has been approved by the Certified Committee for Regenerative Medicine of Tokyo Medical and Dental University and Japan’s Ministry of Healthy, Labour and Welfare and will be performed as a class III regenerative medicine protocol, in accordance with Japan’s Act on the Safety of Regenerative Medicine. The results of this study will be submitted to a peer-review journal for publication. The results of this study are expected to provide evidence to support the inclusion of autologous concentrated bone marrow injections in the non-collapsed femoral head in Japan’s national insurance coverage.Trial registration number jRCTc032200229.

Abstract We introduce a versatile metal-organic framework (MOF) for encapsulation and immobilization of various guests using highly ordered internal water network. The unique water-mediated entrapment mechanism is applied for structural elucidation of 14 bioactive compounds, including 3 natural product intermediates whose 3D structures are clarified. The single-crystal X-ray diffraction analysis reveals that incorporated guests are surrounded by hydrogen-bonded water networks inside the pores, which uniquely adapt to each molecule, providing clearly defined crystallographic sites. The calculations of host-solvent-guest structures show that the guests are primarily interacting with the MOF through weak dispersion forces. In contrast, the coordination and hydrogen bonds contribute less to the total stabilization energy, however, they provide highly directional point interactions, which help align the guests inside the pore.

Livestock production in Afghanistan highly relies on grazing and clover feed, which is a key component of pastures and forage crops. This study elucidated the genetic diversity of clover-nodulating rhizobia in different ecological regions and their effects on clover growth. A total of 57 rhizobia were isolated and their genetic diversities were studied through 16S rRNA and nifD genes. The isolates were inoculated to clover (Afghan local variety), to investigate the potential of nitrogen fixation and influences of clover growth. The 16S rRNA gene analysis showed two distinct groups of Rhizobium (94.7%) and Ensifer (5.3%) species. The nifD phylogenetic relationship revealed a high similarity to Rhizobium and a novel lineage group close to Rhizobium leguminosarum species. In the plant test, different genotypes significantly (p < 0.01) exhibited an increase in plant biomass production, compared to the un-inoculated plants. Among genotypes, the highest plant biomass was recorded in PC8 (1769.0 mg/plant) and PC9 (1409.2 mg/plant) isolates as compared to un-inoculated plants (144.0 mg/plant). Moreover, these isolates showed maximum nitrogen fixation rates of 8.2 and 6.5 µM/plant, respectively. These isolates were identified as the most promising rhizobial strains for developing biofertilizers in the context of Afghanistan.

Background/Aims Multiple white and flat elevated lesions (MWFL) that develop from the gastric corpus to the fornix may be strongly associated with oral antacid intake. Therefore, this study aimed to determine the association between the occurrence of MWFL and oral proton pump inhibitor (PPI) intake and clarify the endoscopic and clinicopathological characteristics of MWFL. Methods The study included 163 patients. The history of oral drug intake was collected, and serum gastrin levels and anti-Helicobacter pylori immunoglobulin G antibody titers were measured. Upper gastrointestinal endoscopy was performed. The primary study endpoint was the association between MWFL and oral PPI intake. Results In the univariate analyses, MWFL were observed in 35 (49.3%) of 71 patients who received oral PPIs and 10 (10.9%) of 92 patients who did not receive oral PPIs. The occurrence of MWFL was significantly higher among patients who received PPIs than in those who did not (p

Abstract Background Several methods have been reported for detecting resistance genes or phenotypic testing on the day of positive blood culture in Escherichia coli or Klebsiella pneumoniae bacteremia. However, some facilities have not introduced these methods because of costs or other reasons. Toyota Kosei Hospital introduced cefpodoxime (CPDX) rapid screening on May 7, 2018, to enable early detection of third-generation cephalosporin resistance. In this study, we aimed to evaluate the effects of intervention with an Antimicrobial Stewardship Team using CPDX rapid screening. Methods Cefotaxime (CTX)-resistant E. coli or K. pneumoniae bacteremia cases were selected retrospectively and divided into two groups: the pre-CPDX screening (June 1, 2015, to May 6, 2018) and CPDX screening groups (July 7, 2018, to August 31, 2021). The primary outcome was the proportion of cases in which modifications were made to the administration of susceptible antimicrobial agents within 24 h of blood culture-positive reports. Results Overall, 63 patients in the pre-CPDX screening group and 84 patients in the CPDX screening group were eligible for analysis. The proportion of patients who modified to susceptible antimicrobial agents within 24 h of blood culture-positive reports was significantly increased in the CPDX screening group compared to that in the pre-CPDX screening group (6.3% vs. 22.6%, p = 0.010). Conclusion The results demonstrated that in CTX-resistant E. coli or K. pneumoniae bacteremia, CPDX rapid screening increased the proportion of early initiation of appropriate antimicrobial agents.

Abstract Background Identifying the likelihood of life‐threatening recurrence after radical cystectomy by reliable and user‐friendly predictive models remains an unmet need in the clinical management of invasive bladder cancer. Methods A total of 204 consecutive patients undergoing open radical cystectomy (ORC) for bladder cancer were retrospectively enrolled between May 2005 and August 2020. Clinicopathological and peri‐ORC therapeutic data were extracted from clinical records. We explored predictive factors that significantly affected the primary endpoint of overall survival (OS) and secondary endpoints of cancer‐specific survival (CSS) and recurrence‐free survival (RFS). Results During a median follow‐up of 3.9 years, 42 (20.6%) and 10 (4.9%) patients died due to bladder cancer and other causes, respectively. Five‐year RFS, CSS, and OS were 66.5%, 77.6%, and 75.4%, respectively. Pathological T and N categories and lymphovascular invasion (LVI) significantly affected RFS by Cox regression analysis. Accordingly, clinical T and pathological N categories and LVI significantly affected CSS. Clinical T and pathological N categories, LVI, age, and ORC tumor grade significantly affected OS. Based on the assessment score for each independent risk factor, we developed the Gunma University Oncology Study Group (GUOSG) score, which predicts RFS, CSS, and OS. The GUOSG score classified four groups for RFS, three for CSS, and five for OS, with statistically significant distribution for nearly all comparisons. Conclusions The GUOSG model is helpful to show individualized prognosis and functions as a risk‐stratified historical cohort for assessing the lifelong efficacy of new salvage treatment regimens.

Abstract Background The severity of coronavirus disease 2019 (COVID-19) infections has led to the development of several therapeutic agents, with tocilizumab becoming increasingly used to treat patients with COVID-19-related pneumonia. This study compared the use of tocilizumab treatment with the standard of care (SOC) to determine its efficacy against severe COVID-19-related pneumonia in Japan. Methods This retrospective cohort study was designed to evaluate the efficacy of tocilizumab in two different databases: the JA42434 single-arm study and COVID-19 Registry Japan (COVIREGI-JP), with a synthetic control group from the COVIREGI-JP cohort as a benchmark for the tocilizumab group. The study’s primary objective was to evaluate the efficacy of tocilizumab in treating severe COVID-19-related pneumonia compared to the SOC among patients included in the above two databases. The SOC group was extracted as the synthetic control group using exact matching and a propensity score matching in sequence per subject. As a secondary objective, the efficacy of tocilizumab compared to the SOC was evaluated exclusively among patients included in the COVIREGI-JP database. In each objective, the primary endpoint was defined as the time to discharge or the status of awaiting discharge. Results For the primary endpoint, the hazard ratio (HR) of the tocilizumab group against the SOC group was 1.070 (95% confidence interval [CI]: 0.565–2.028). The median time from Study Day 1 to discharge or the state of awaiting discharge was 15 days in the tocilizumab group and 16 days in the SOC group. The HRs for the secondary endpoints, namely, time to improvement in the clinical state, time to clinical failure, and time to recovery, were 1.112 (95% CI: 0.596–2.075), 0.628 (95% CI: 0.202–1.953), and 1.019 (95% CI: 0.555–1.871), respectively. Similarly, the HR of the primary endpoint for the secondary objective was 0.846 (95% CI: 0.582–1.230). Conclusions Tocilizumab did not demonstrate a positive effect on time to discharge or the state of awaiting discharge. Furthermore, no statistically significant differences in other clinical outcomes, such as time to improvement in the clinical state, time to clinical failure, and time to recovery, were observed among the groups.

Abstract Photophysical properties of benzil (1,2-diphenylethane-1,2-dione) and its derivatives in the crystal state have recently attracted much attention. However, the study of substituted benzils has mostly been limited to para-substituted derivatives, which did not induce a significant effect on the emission wavelength compared to pristine benzil. The effects of ortho- and meta-substituents on the photophysical properties in the crystal state have not been investigated so far. Our recently developed organocatalytic pinacol coupling of substituted benzaldehydes allowed us to prepare various ortho-, meta-, and para-substituted benzil derivatives and to investigate their luminescence properties. Ortho- and meta-substituents affected the electronic states of benzils in the crystal state, resulting in differences in their luminescence properties. The luminescence wavelength and type, i.e., phosphorescence or fluorescence, were altered by these substituents. Fast self-recovering phosphorescence-to-phosphorescence mechanochromism by the para-CF3 substituent at room temperature was also discovered.

Introduction Venous hemorrhage from ectopic varices is potentially fatal. This report describes a rare case in which bleeding from mesenteric varices in an ileal conduit was treated successfully by embolization therapy. Case presentation The patient was an 82‐year‐old man who had previously undergone total pelvic exenteration for colon cancer with creation of an ileal conduit for urinary diversion. He subsequently developed liver cirrhosis and underwent partial hepatectomy for hepatocellular carcinoma. 9 years after his colon surgery, he was admitted with gross hematuria. Computed tomography revealed subcutaneous mesenteric varices in the ileal conduit and hemorrhage as a result of rupture of the varices. The bleeding continued despite repeated manual compression but was eventually stopped by embolization therapy. Conclusion Embolization therapy may be helpful for hemostasis in the event of intractable bleeding from mesenteric varices in an ileal conduit.

Abstract Background Among Japanese pharmacists, there is a gap in their commitment to self-improvement and a possible gap in their ability to identify and solve problems. However, the factors causing this situation have not yet been clarified. This study was conducted to identify factors that influence the abilities of Japanese pharmacists to identify and solve problems, which are skills considered essential for this profession. A prior history of presenting at academic conferences was set as a surrogate outcome to clarify whether having this experience affects the factors. Methods A nationwide internet-based survey was conducted among 300 participating hospitals and 300 community pharmacists. The survey was discontinued when the sample size of each group reached 300. The respondents were categorized into two groups on the basis of their experience of presenting at academic conferences in the survey item “status of self-improvement after employment.” Their association with other survey items was determined using univariate and multivariate logistic regression analyses. Results The multivariate analysis revealed that 152 (50.7%) hospital pharmacists and 41 (13.7%) community pharmacists had presented at academic conferences. Among the hospital pharmacists, the experience of presenting at academic conferences was significantly associated with the “age 30 s (*references 20 s),” “presence of pharmacists to consult,” “experience supervising interns,” and “number of types of self-improvement” factors. For the community pharmacists, prior conference presentation experience was significantly associated with “age over 70 s,” “highest educational background (doctoral or master’s degree),” and “number of types of self-improvement.” Conclusion This pioneering study suggests that having prior experience of presenting at academic conferences as a surrogate outcome of pharmacists' problem-finding and problem-solving skills may be related to the support provided by human environmental factors at the facility, the status of self-improvement, and the highest educational background.

Background/Aims Endoscopic resection of all colorectal adenomatous lesions with a low complication rate, simplicity, and negative residuals is challenging. Hence, we developed a new method called “non-injection resection using bipolar soft coagulation mode (NIRBS)” method, adapted for colorectal lesions. In addition, we evaluated the effectiveness of this method. Methods We performed NIRBS throughout a 12-month period for all colorectal lesions which snare resection was acceptable without cancerous lesions infiltrating deeper than the submucosal layer. Results A total of 746 resected lesions were included in the study, with a 4.5 mm mean size (range, 1–35 mm). The major pathological breakdowns were as follows: 64.3% (480/746) were adenomas, and 5.0% (37/746) were intraepithelial adenocarcinomas (Tis lesions). No residuals were observed in any of the 37 Tis lesions (mean size, 15.3 mm). Adverse events included bleeding (0.4%) but no perforation. Conclusions NIRBS allowed the resection of multiple lesions with simplicity because of the non-injection and without perforating due to the minimal burn effect of the bipolar snare set in the soft coagulation mode. Therefore, NIRBS can be used to resect adenomatous lesions easily, including Tis lesions, from small to large lesions without leaving residuals.

Abstract Excessive hip flexion torque to prioritize leg swings in the elderly is likely to be a factor that reduces their propulsive force and gait stability, but the mechanism is not clear. To understand the mechanism, we investigated how propulsive force, hip flexion torque, and margin of stability (MoS) change when only the hip spring stiffness is increased without changing the walking speed in the simple walking model, and verified whether the relationship holds in human walking. The results showed that at walking speeds between 0.50 and 1.75 m/s, increasing hip spring stiffness increased hip flexion torque and decreased the propulsive force and MoS in both the model and human walking. Furthermore, it was found that the increase in hip flexion torque was explained by the increase in spring stiffness, and the decreases in the propulsive force and MoS were explained by the increase in step frequency associated with the increase in spring stiffness. Therefore, the increase in hip flexion torque likely decreased the propulsive force and MoS, and this mechanism was explained by the intervening hip spring stiffness. Our findings may help in the control design of walking assistance devices, and in improving our understanding of elderly walking strategies.

Abstract Introduction Low phosphorus (P) use efficiency (PUE) of fertiliser is a critical problem in sustainable crop production, especially in strongly weathered tropical soils with a high P‐fixation capacity. Both intercropping and rhizobium inoculation have shown to improve the P availability of rhizosphere soil, but the effect of a combined approach of using both intercropping and rhizobium inoculation is still unclear. In this study, we aimed to evaluate the effect of rhizobium inoculation on the soil–plant P dynamics and fertilised PUE under the intercropping system in strongly weathered tropical soil. Materials and Methods We conducted an 85‐day cultivation pot experiment with pigeon pea (PP) and maize using highly weathered tropical soil under eight treatments: monocropping (CS) or intercropping, with or without rhizobium (Bradyrhizobium elkanii USDA61) inoculation (−I, +I) and with or without P fertilisation (0P, 50P) (2 × 2 × 2 = 8 treatments). We evaluated the effects of intercropping and rhizobium inoculation on plant growth parameters, P dynamics of the rhizosphere and bulk soil using the Hedley P fractionation method, the amount of organic acid from plant roots as a plant P‐mobilising capacity, and fertilised PUE. Results Total plant P uptake per pot was significantly increased by intercropping but not by combining intercropping and rhizobium inoculation, resulting in better fertilised PUE only in intercropping. The available inorganic P (Pi) and less labile Pi of the soil were higher in the rhizosphere than those in the bulk by intercropping under 50P and were similar in PP + I under 50 P. The amount of organic acid per pot under 50P increased with each treatment, that is, intercropping and rhizobium inoculation, but not with their combination. Conclusion The intercropping system has a strong potential to improve PUE by stimulating the P‐mobilising capacity of intercropping plant roots, whereas rhizobium inoculation of the intercropping system did not improve PUE in this study.

BackgroundPlatinum and fluoropyrimidine combinations typically comprise first-line (1L) therapy in advanced gastric cancer or gastroesophageal junction adenocarcinoma (G/GEA), although controversy exists regarding the use of 5doublet versus triplet cytotoxic regimens. Historically, second-line (2L) and third-line or later (3L+) therapy has been fragmented. Recent trials have increased the need for optimal treatment sequencing in advanced G/GEA.Materials and methodsWe conducted a systematic search of peer-reviewed manuscripts of randomized clinical trials examining 1L, 2L, and 3L+ therapy for advanced G/GEA published from 2009 through November 19, 2019. When available, overall survival, progression-free survival, time to progression, overall response rate, and toxicity were extracted from each and compared descriptively.ResultsIn 1L therapy, chemotherapy triplets demonstrated variable efficacy improvements with invariable increased toxicity compared with platinum/fluoropyrimidine doublets. Currently, the only published report of positive outcomes using biologics in 1L describes adding trastuzumab in HER2-overexpressing advanced G/GEA. In 2L, doublet chemotherapy regimens are not uniformly more efficacious than single-agent taxanes or irinotecan, and ramucirumab has demonstrated improved outcomes both as monotherapy and in combination.ConclusionFor advanced G/GEA, review of trial results from 2009-2019 support 1L therapy with platinum and fluoropyrimidine and sequencing with taxanes or irinotecan in combination with biologics as effective 2L options. Escalating to a triplet may add some efficacy at the expense of added toxicity.Implications for practiceThe rapidly changing treatment landscape for advanced gastric cancer includes increasing options for refractory disease. With multiple first-line platinum-based regimens, identification of those with the best benefit-to-risk ratio may provide guidance on treatment sequencing strategies. This article presents findings from the published literature of randomized controlled trials that included a first-line platinum/fluoropyrimidine combination and, for second-line trials, patients with platinum/fluoropyrimidine-refractory disease. This guiding summary could be a tool for clinicians to identify the optimal first-line regimen(s) followed by a strategy for subsequent regimens.