Trend in antibiotic prescription at pediatric primary emergency medical centers in Japan: A multi-center, cross-sectional study.

INTRODUCTION: Antimicrobial resistance is a global issue, and implementation of antimicrobial stewardship programs in outpatient settings is crucial. Japan has also focused on outpatient oral antimicrobial stewardship programs and difficulties in standardizing prescriptions have led to overprescription in primary emergency medical centers. There is a lack of research investigating the antibiotic prescription status of pediatric primary emergency medical centers and the benchmark prescription rates in pediatric outpatient settings. METHODS: We conducted a multi-center, cross-sectional study of seven pediatric primary emergency medical centers located in five prefectures of Japan. We retrospectively extracted data from health claims or directly obtained them from charts at each institution and evaluated trends in the antibiotic prescription rate based on the AWaRe classification between April 2016 and December 2019. RESULTS: Our study included 383,525 encounters, with the most common infectious disease diagnosis being acute upper respiratory tract infection in 93,449 cases (24.4 %). The antibiotic prescription rate during the study period was 7.4 %, representing a decrease of 46 %, from 10.2 % in 2016 to 5.5 % in 2019. The percentage of prescriptions in the Access group increased at all institutions; however, it exceeded 60 % in only three facilities in 2019. The percentage of third-generation cephalosporins varied among facilities, ranging from 1.7 % to 59.4 %, as of 2019. CONCLUSIONS: For pediatric primary emergency medical centers where antimicrobial stewardship programs are implemented, we suggest 5 % as a reasonable benchmark level for the antibiotic prescription rate. Prescribing the antibiotics in the Access groups less frequently remains a domestic challenge in Japan.

Routine assessment of cardiotoxicity in patients undergoing long-term immune checkpoint inhibitor therapy.

The indications for immune checkpoint inhibitors (ICIs) are expanding in cancer drug therapy, and while cardiac events associated with ICIs are often fatal, there are few reports regarding cardiac complications associated with long-term ICI therapy. We aimed to study cardiac complications in patients undergoing long-term ICI therapy. From the database of our local cardio-oncology unit, we enrolled patients with cancer undergoing ICI therapy for more than 6 months and for whom cardiologists continuously performed routine follow-ups. We defined the primary endpoint as discontinuation of ICI due to cardiac events. We also analyzed changes in cardiac biomarkers and echocardiographic parameters. We retrospectively analyzed 55 consecutive patients (43 males, mean age: 65 ± 11 years) treated with ICI therapy in our hospital between January 2017 and June 2021. None of the patients discontinued ICI therapy due to cardiac events more than 6 months after treatment was initiated. Among the participants, we observed four patients with elevated serum troponin I levels, seven patients with decreased global longitudinal strain values, and two patients with elevated plasma brain natriuretic peptide levels. No patient required drug intervention for these cardiac events; furthermore, there were no cases of clinically diagnosed myocarditis. In the present study, there were no cardiac events causing ICI discontinuation in patients undergo ICI therapy for more than 6 months.

Liver fibrosis index as a novel prognostic factor in patients with pulmonary arterial hypertension.

Liver dysfunction is an important determinant of the prognosis of left heart failure patients. However, few studies have reported on cardiohepatic interactions in right heart failure patients, a condition that is an important prognostic factor in pulmonary arterial hypertension (PAH). This study aimed to evaluate the existence and extent of hepatic fibrosis and its contribution as a prognostic factor in PAH. This prospective study enrolled 60 consecutive patients with PAH in the International University of Health and Welfare Mita Hospital from June 2016 to December 2017. After the application of the exclusion criteria, 35 patients were assessed for hepatic fibrosis, using real-time tissue elastography, and for clinical deterioration. Sixteen healthy controls were also assessed for comparison. The liver fibrosis index (LFI) was significantly higher in PAH patients than in healthy controls (1.214 ± 0.047 vs. 0.911 ± 0.059, P < 0.001), suggesting that PAH patients exhibited mild liver fibrosis. However, patients with deterioration (vs. no deterioration) had significantly higher LFI values (1.507 ± 0.078 vs. 1.080 ± 0.034, P < 0.001), independent from other established liver function parameters. A receiver operating characteristic curve analysis identified that an LFI ≥ 1.275 indicated a significant probability of clinical deterioration (hazard ratio: 8.4 (95% CI 1.5-45.4, P = 0.012), independent from other known PAH prognostic factors. PAH patients may exhibit subclinical liver fibrosis associated with chronic right heart failure. The LFI can serve as both a non-invasive evaluation of liver fibrosis and a predictive marker for the deterioration of PAH patients.

[A fatal case intra-abdominal hemorrhage following self-removal of a percutaneous transhepatic gallbladder drainage tube].

A 92-year-old woman with gallstone pancreatitis and acute cholangitis was admitted to our hospital where endoscopic retrograde cholangiopancreatography was performed for emergency biliary drainage. Biliary cannulation was unsuccessful. Consequently, percutaneous transhepatic gallbladder drainage (PTGBD) was performed, and her symptoms improved. The PTGBD tube was removed by the patient on the third day of admission resulting in cardiopulmonary arrest two hours later. Cardiopulmonary resuscitation restored spontaneous circulation. Contrast computed tomography revealed intra-abdominal hemorrhage from the right hepatic artery by the removed part of the PTGBD tube. The patient died despite hemostasis by transcatheter artery embolization. PTGBD is generally effective and safe;however, it can cause fatal hemorrhage, especially if PTGBD tubes are removed by the patient. Thus, self-removal should be strictly prevented.

[Leptomeningeal carcinomatosis from duodenal papillary carcinoma].

A woman in her 50s presented with ataxia and repeated falls during 2nd line S-1 therapy for duodenal papillary carcinoma with metastasis. She was diagnosed with leptomeningeal carcinomatosis based on gadolinium contrast-enhanced magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) examination, although plain computed tomography (CT) and MRI of the head showed no intracranial occupying lesions. This is a rare leptomeningeal carcinomatosis case with duodenal papillary carcinoma as the primary lesion, although aggressive treatment was not possible due to the decreased consciousness level.

An initial trial of quantitative evaluation of autoimmune pancreatitis using shear wave elastography and shear wave dispersion in transabdominal ultrasound.

BACKGROUND/OBJECTIVES: We aimed to examine therapeutic efficacy and prognosis prediction of autoimmune pancreatitis (AIP) using shear wave elastography (SWE) and shear wave dispersion (SWD) in transabdominal ultrasound (US). METHODS: The subjects were 23 patients with diffuse type 1 AIP who underwent SWE and SWD, and 34 controls with a normal pancreas. Elasticity and dispersion were defined as the pancreatic elastic modulus (PEM) and dispersion slope, respectively. PEM and dispersion slope were compared between AIP and control cases, and the short-term therapeutic effect and long-term prognosis were examined. RESULTS: PEM (30.9 vs. 6.6 kPa, P < 0.001) and dispersion slope (15.3 vs. 13.0 (m/sec)/kHz, P = 0.011) were significantly higher in AIP cases than in controls. Among the 17 AIP patients followed-up in two weeks after treatment, these parameters were 12.7 kPa and 10.5 (m/sec)/kHz with median decrease rate of 37.2% and 32.8%, respectively, which were significantly higher than the change in the size of pancreatic parenchyma (14.4%, P = 0.026). Fourteen of these subjects were followed up for >12 months, during which 2 had relapse; diabetes improved in 5 and worsened in 2; in 60% of cases, the pancreatic parenchyma was atrophied. The % change in PEM after two weeks was tended to be higher in non-atrophy cases. CONCLUSION: SWE and SWD measurement in US may be useful for quantitative assessment of AIP and evaluation of short-term treatment efficacy.

Utility of multiphase contrast enhancement patterns on CEH-EUS for the differential diagnosis of IPMN-derived and conventional pancreatic cancer.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is reported as a high-risk factor for pancreatic cancer (PC) that includes IPMN-derived cancers (IPMC) and the development of invasive pancreatic ductal adenocarcinoma (PDAC) concomitant with IPMN. Since invasive IPMC and PDAC exhibit different oncological behaviors, their differentiation is clinically important. We aimed to investigate the use of contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) for the differential diagnosis between invasive IPMC and PDAC. METHODS: This study involved 183 consecutive patients with PC (invasive IPMC: 42, PDAC concomitant with IPMN: 9, without IPMN: 132) who underwent CEH-EUS preoperatively. While investigating the patterns, enhanced effects in the solid part of the tumor were compared with those in the surrounding pancreatic parenchyma after administration of Sonazoid® and evaluated as hyperenhanced, isoenhanced, or hypoenhanced. We retrospectively compared the enhanced pattern of CEH-EUS by using multiphasic analysis and clinicopathological factors between invasive IPMC and PDAC. RESULTS: In multiphase evaluations at 20, 40 and 60 s in CEH-EUS, 75.2% (106/141) of PDACs were hypoenhanced (-) at ≥2 of the 3 time points, with significant differences from those of invasive IPMC (P < 0.001). The solid tumor diameter was significantly larger in PDAC than in invasive IPMC, and the tumor stage and preoperative serum carbohydrate antigen 19-9 level were higher. After propensity score matching of stage and solid tumor diameter, contrast enhancement patterns were significantly more persistent in invasive IPMC than in PDAC (P = 0.0013). CONCLUSIONS: Multiphase evaluation using CEH-EUS is a useful method for differentiating between invasive IPMC and PDAC.

Ambient Temperature and Cardiorenal Connection in Elderly Patients with Stable Heart Failure.

Heart failure increases among the elderly; however, the influence of ambient temperature on cardiorenal function has not been well investigated. Patients (n = 110, mean age 82.9 years, 43 males) with stable heart failure and creatinine < 3.0 mg/dl were studied. Medical records, such as ejection fraction, B-type natriuretic peptide (BNP), and estimated glomerular filtration rate (eGFR) at each visit every 1-3 months were collected by the end-point for death, additional prescription to treat heart failure, or heart failure hospitalization. The ambient temperatures at each visit were obtained from the Japan Meteorological Agency. During the follow-up period (median 399 days and 7 visits), follow-up BNP showed a trend toward a positive correlation with the diurnal temperature range. After dividing into two groups by median baseline eGFR, follow-up BNP was positively correlated with minimum temperature (p = 0.039) and the diurnal temperature range (p = 0.007) in the Low-eGFR group but not in the High-eGFR group. Follow-up eGFR was negatively correlated with the ambient day temperature in both groups (p ≤ 0.002). Follow-up BNP was positively correlated with follow-up eGFR (p < 0.0001) only in the Low-eGFR group and not in the High-eGFR group, suggesting that BNP and eGFR increase in winter and BNP and eGFR decrease in summer in the Low-eGFR group. In conclusions, heart failure may be worsened by larger diurnal temperature range or in winter in patients with renal impairment. This population should be carefully managed in the clinic according to the ambient temperature.

Diagnostic performance of endoscopic ultrasonography-guided elastography for solid pancreatic lesions: Shear-wave measurements versus strain elastography with histogram analysis.

BACKGROUND AND AIMS: Endoscopic ultrasound (EUS) elastography (EUS-EG) is a minimally invasive diagnostic method for evaluating tissue elasticity. The aim of this study was to evaluate the feasibility of newly developed EUS shear-wave measurement (EUS-SWM) and to compare diagnostic performance between EUS-SWM and the conventional strain elastography (SE) for the measurement of elasticity of solid pancreatic lesions (SPLs). METHODS: From December 2017 until August 2019, we retrospectively reviewed 64 consecutive cases with SPLs who underwent both EUS-SWM and SE. EUS-SWM was used to measure the shear-wave velocity, Vs (m/s), and the unique measurement reliability index, VsN (%), in the target lesion. SE images were assessed by strain histogram (SH) analysis, and the mean strain value of the elasticity index was measured. We evaluated the diagnostic performance of EUS-SWM and SE with SH to characterize the SPLs. RESULTS: The Vs (m/s) values of SPLs were 2.19 for pancreatic cancer (PC), 1.31 for pancreatic neuroendocrine neoplasm (PanNEN), 2.56 for mass-forming pancreatitis (MFP) and 1.58 for metastatic tumors. Vs showed no significant difference based on the disease. The mean strain values were 45.5 for PC, 47.3 for PanNEN, and 74.5 for MFP. In the comparison of tissue elasticity between PC and MFP, Vs showed no significant difference (P = 0.5687); however, the mean strain value was significantly lower in PC cases (45.4 vs 74.5: P = 0.0007). CONCLUSION: Endoscopic ultrasound SWM tended to be unstable for the measurement of elasticity of SPLs, and conventional SE with SH was superior for their characterization.

Phosphorylation of Gephyrin in Zebrafish Mauthner Cells Governs Glycine Receptor Clustering and Behavioral Desensitization to Sound.

The process by which future behavioral responses are shaped by past experiences is one of the central questions in neuroscience. To gain insight into this process at the molecular and cellular levels, we have applied zebrafish larvae to explore behavioral desensitization to sound. A sudden loud noise often evokes a defensive response known as the acoustic startle response (ASR), which is triggered by firing Mauthner cells in teleosts and amphibians. The probability of evoking ASR by suprathreshold sound is reduced after exposure to repetitive auditory stimuli insufficient in amplitude to evoke the ASR (subthreshold). Although it has been suggested that the potentiation of inhibitory glycinergic inputs into Mauthner cell is involved in this desensitization of the ASR, the molecular basis for the potentiation of glycinergic transmission has been unclear. Through the in vivo monitoring of fluorescently-tagged glycine receptors (GlyRs), we here showed that behavioral desensitization to sound in zebrafish is governed by GlyR clustering in Mauthner cells. We further revealed that CaMKII-dependent phosphorylation of the scaffolding protein gephyrin at serine 325 promoted the synaptic accumulation of GlyR on Mauthner neurons through the enhancement of the gephyrin-GlyR binding, which was indispensable for and could induce desensitization of the ASR. Our study demonstrates an essential molecular and cellular basis of sound-induced receptor dynamics and thus of behavioral desensitization to sound.SIGNIFICANCE STATEMENT Behavioral desensitization in the acoustic startle response of fish is known to involve the potentiation of inhibitory glycinergic input to the Mauthner cell, which is a command neuron for the acoustic startle response. However, the molecular and cellular basis for this potentiation has been unknown. Here we show that an increase in glycine receptor (GlyR) clustering at synaptic sites on zebrafish Mauthner cells is indispensable for and could induce desensitization. Furthermore, we demonstrate that CaMKII-mediated phosphorylation of the scaffolding protein gephyrin promotes GlyR clustering by increasing the binding between the ß-loop of GlyRs and gephyrin. Thus, the phosphorylation of gephyrin is a key event which accounts for the potentiation of inhibitory glycinergic inputs observed during sound-evoked behavioral desensitization.

The Arabidopsis CERK1-associated kinase PBL27 connects chitin perception to MAPK activation.

Perception of microbe-associated molecular patterns by host cell surface pattern recognition receptors (PRRs) triggers the intracellular activation of mitogen-activated protein kinase (MAPK) cascades. However, it is not known how PRRs transmit immune signals to MAPK cascades in plants. Here, we identify a complete phospho-signaling transduction pathway from PRR-mediated pathogen recognition to MAPK activation in plants. We found that the receptor-like cytoplasmic kinase PBL27 connects the chitin receptor complex CERK1-LYK5 and a MAPK cascade. PBL27 interacts with both CERK1 and the MAPK kinase kinase MAPKKK5 at the plasma membrane. Knockout mutants of MAPKKK5 compromise chitin-induced MAPK activation and disease resistance to Alternaria brassicicola PBL27 phosphorylates MAPKKK5 in vitro, which is enhanced by phosphorylation of PBL27 by CERK1. The chitin perception induces disassociation between PBL27 and MAPKKK5 in vivo Furthermore, genetic evidence suggests that phosphorylation of MAPKKK5 by PBL27 is essential for chitin-induced MAPK activation in plants. These data indicate that PBL27 is the MAPKKK kinase that provides the missing link between the cell surface chitin receptor and the intracellular MAPK cascade in plants.

Can contrast-enhanced harmonic endoscopic ultrasonography accurately diagnose main pancreatic duct involvement in intraductal papillary mucinous neoplasms?

BACKGROUND: Main pancreatic duct (MPD) involvement in branch duct-type intraductal papillary mucinous neoplasms (BD-IPMNs) is a high risk finding for malignant IPMNs. However, discrepancies exist in the identification of MPD involvement between imaging findings and pathological diagnosis. The purpose of this study was to evaluate the diagnostic accuracy of preoperative assessment of MPD involvement in IPMNs using contrast-enhanced harmonic endoscopic ultrasound (CH-EUS). METHODS: This study involved 166 consecutive patients with BD-IPMNs who underwent surgical resection. CH-EUS was used to evaluate the MPD involvement according to the presence of mural nodules (MN) that advanced into the MPD or involved the MPD. The CH-EUS findings were compared with the pathological findings. Additionally, we analyzed the risk factors for malignant BD-IPMNs using multivariate analysis. RESULTS: A total of 77, 51, and 38 patients were pathologically diagnosed with low-grade or intermediate-grade dysplasia, high-grade dysplasia and invasive IPMNs, respectively. MPD involvement was diagnosed using CH-EUS (MPD-inv.-EUS) in 90 (54.2%) patients with a sensitivity, specificity and accuracy of 83.5%, 87.0% and 84.9%, respectively. The malignancy rate in patients with MPD-inv.-EUS was 71.6% (63/90). Multivariate logistic regression analysis showed that MPD-inv.-EUS (OR, 3.61; 95% CI:1.45-8.98), age (OR, 5.70; 95% CI: 1.47-22.2), cyst size (OR, 2.45; 95% CI:1.04-5.78) and MN size (OR, 7.05; 95% CI:2.48-20.0) were significant for malignant BD-IPMNs. CONCLUSIONS: MPD-inv.-EUS accurately represents the pathological involvement of IPMN and may be a useful predictor of malignant BD-IPMNs.

Diagnosis of vascular invasion in pancreatic ductal adenocarcinoma using endoscopic ultrasound elastography.

BACKGROUND: Vascular invasion is an important criterion for resectability and deciding the therapeutic strategy for pancreatic ductal adenocarcinoma (PDAC), but imaging diagnosis is currently difficult. Endoscopic ultrasound (EUS) elastography (EG) images have band-like artifacts on the border between tumor and vessel due to different movement if the tumor is not connected to the vessel, i.e., no invasion. Based on this phenomenon, we assessed the usefulness of EUS-EG in the diagnosis of vascular invasion in PDAC. METHODS: The subjects were 44 out of 313 patients with PDAC who underwent EUS between January 2015 and November 2018, followed by surgery, no chemotherapy or radiotherapy, and pathological evaluation. Diagnostic accuracies of vascular invasion using dynamic computed tomography (CT), EUS B-mode and EUS-EG were compared with histopathological diagnosis. RESULTS: In 44 subjects (48 sites) who underwent both dynamic CT and EUS-B mode, the sensitivity, specificity and accuracy were 0.733, 0.697 and 0.708 on dynamic CT (48 sites); 0.733, 0.606 and 0.646 in EUS B-mode (48 sites); and 0.917, 0.900 and 0.906 in EUS-EG (32 sites). In 27 subjects (29 sites) with a tumor contacting a vessel with no vascular obstruction or stenosis on dynamic CT, the sensitivity, specificity and accuracy were 0.556, 0.750 and 0.690 on dynamic CT; 0.667, 0.700 and 0.690 in EUS B-mode; and 0.889, 0.850 and 0.862 in EUS-EG. CONCLUSIONS: These results suggest that EUS combined with EG improves diagnostic performance of vascular invasion in PDAC, especially in cases of which vascular invasion cannot be clearly assessed by dynamic CT.

Risks and characteristics of pancreatic cancer and pancreatic relapse in autoimmune pancreatitis patients.

BACKGROUND AND AIM: We examined the differences in the risks and characteristics of pancreatic relapse (PR) and pancreatic cancer (PC) in patients with autoimmune pancreatitis (AIP). METHODS: We retrospectively reviewed 123 type 1 AIP patients with a median follow-up of 55 months (interquartile range, 27-98). The following items were evaluated: (i) cumulative relapse rates and risk factors, (ii) the incidence of PC, (iii) PR versus PC, and (iv) outcomes after the appearance of morphological changes in the pancreas (focal enlargement, apparent mass lesions, or main pancreatic duct dilation). RESULTS: (i) The cumulative PR rates were 1.7% within 1 year, 11.5% within 3 years, and 22.6% within 5 years. Lack of maintenance therapy, IgG4-related sclerosing cholangitis, and IgG4-related kidney disease were identified as independent predictors of relapse. (ii) Two patients (1.6%) were diagnosed with PC at 17 and 22 months after initial AIP diagnosis. (iii) Thirteen (59.1%) and four (18.2%) patients with PR had focal enlargement and main pancreatic duct dilation, respectively. The median CA19-9 level at initial diagnosis was significantly higher in PC patients (21 vs 220.5 U/mL, P = 0.014). (iv) Eight PR patients underwent endoscopic ultrasound-guided fine-needle aspiration, none of whom had malignant findings. PC was diagnosed by ultrasound-guided fine-needle aspiration in both cancer patients. CONCLUSIONS: Although the incidence of PC is low, it may mimic PR in AIP patients. Surveillance is important, and when morphological changes occur, biopsy and evaluation of serum IgG4 and CA19-9 levels (particularly if the levels were high before) should be considered.

Dynamics of nitric oxide controlled by protein complex in bacterial system.

Nitric oxide (NO) plays diverse and significant roles in biological processes despite its cytotoxicity, raising the question of how biological systems control the action of NO to minimize its cytotoxicity in cells. As a great example of such a system, we found a possibility that NO-generating nitrite reductase (NiR) forms a complex with NO-decomposing membrane-integrated NO reductase (NOR) to efficiently capture NO immediately after its production by NiR in anaerobic nitrate respiration called denitrification. The 3.2-Å resolution structure of the complex of one NiR functional homodimer and two NOR molecules provides an idea of how these enzymes interact in cells, while the structure may not reflect the one in cells due to the membrane topology. Subsequent all-atom molecular dynamics (MD) simulations of the enzyme complex model in a membrane and structure-guided mutagenesis suggested that a few interenzyme salt bridges and coulombic interactions of NiR with the membrane could stabilize the complex of one NiR homodimer and one NOR molecule and contribute to rapid NO decomposition in cells. The MD trajectories of the NO diffusion in the NiR:NOR complex with the membrane showed that, as a plausible NO transfer mechanism, NO released from NiR rapidly migrates into the membrane, then binds to NOR. These results help us understand the mechanism of the cellular control of the action of cytotoxic NO.

Successful management of a Bacillus cereus catheter-related bloodstream infection outbreak in the pediatric ward of our facility.

Bacillus cereus can spread easily in various environments and can contaminate medical environments, such as ventilator equipment, intravascular catheters, and linen. B. cereus is known to infect immunocompromised patients. Although nosocomial B. cereus outbreaks are often reported, effective preventive measures are not clarified. We report an outbreak of B. cereus catheter-related bloodstream infection (CRBSI) in the pediatric ward and aim at identifying risk factors and effective infection control measures for the outbreak. The nurse station at the pediatric ward and blood cultures were assessed. Sterilization of devices has been ensured thereafter. We identified common risk factors including catheter placement for liquid nutrition, use of high-caloric amino-acid-containing infusion fluid, immunocompromised patients, and contact of the catheter route with the floor. Intervention by the Infection Control Team and educating the medical staff regarding methods of disinfection, including scrubbing the facility, helped terminate the outbreak. We discuss a pre-emptive intervention to terminate the outbreak of CRBSI.

RING finger protein 121 facilitates the degradation and membrane localization of voltage-gated sodium channels.

Following their synthesis in the endoplasmic reticulum (ER), voltage-gated sodium channels (NaV) are transported to the membranes of excitable cells, where they often cluster, such as at the axon initial segment of neurons. Although the mechanisms by which NaV channels form and maintain clusters have been extensively examined, the processes that govern their transport and degradation have received less attention. Our entry into the study of these processes began with the isolation of a new allele of the zebrafish mutant alligator, which we found to be caused by mutations in the gene encoding really interesting new gene (RING) finger protein 121 (RNF121), an E3-ubiquitin ligase present in the ER and cis-Golgi compartments. Here we demonstrate that RNF121 facilitates two opposing fates of NaV channels: (i) ubiquitin-mediated proteasome degradation and (ii) membrane localization when coexpressed with auxiliary NaVß subunits. Collectively, these results indicate that RNF121 participates in the quality control of NaV channels during their synthesis and subsequent transport to the membrane.

Estimation of Economic Indicator Announced by Government From Social Big Data.

We introduce a systematic method to estimate an economic indicator from the Japanese government by analyzing big Japanese blog data. Explanatory variables are monthly word frequencies. We adopt 1352 words in the section of economics and industry of the Nikkei thesaurus for each candidate word to illustrate the economic index. From this large volume of words, our method automatically selects the words which have strong correlation with the economic indicator and resolves some difficulties in statistics such as the spurious correlation and overfitting. As a result, our model reasonably illustrates the real economy index. The announcement of an economic index from government usually has a time lag, while our proposed method can be real time.

Conservation of Chitin-Induced MAPK Signaling Pathways in Rice and Arabidopsis.

Perception of microbe-associated molecular patterns (MAMPs) including chitin by pattern recognition receptors (PRRs) rapidly induces activation of mitogen-activated protein kinase (MAPK) cascades. However, how PRRs transmit immune signals to the MAPK cascade is largely unknown. Recently, Arabidopsis receptor-like cytoplasmic kinase PBL27 has been reported to activate MAPKs through phosphorylation of AtMAPKKK5 in the chitin signaling pathway. In this study, we found that OsRLCK185, a rice ortholog of PBL27, regulates chitin-induced MAPK activation in a similar fashion to PBL27 in rice. Upon chitin perception, OsRLCK185 is phosphorylated by OsCERK1, a component of the chitin receptor complex. OsRLCK185 interacted with OsMAPKKK11 and OsMAPKKK18, rice orthologs of AtMAPKKK5, in yeast two-hybrid assays. Silencing of both OsMAPKKK11 and OsMAPKKK18 significantly reduced chitin-induced activation of OsMPK3 and OsMPK6. Expression levels of OsMAPKKK18 were much higher than that of OsMAPKKK11 in rice cells, which was consistent with the fact that the Osmapkkk11 single mutation did not affect MAPK activation. This result suggested that OsMAPKKK18 plays a more important role than OsMAPKKK11 in the chitin-induced activation of OsMPK3 and OsMPK6. The bimolecular fluorescence complementation (BiFC) experiment indicated that OsRLCK185 interacted with OsMAPKKK18 at the plasma membrane in planta. In vitro phosphorylation experiments showed that OsRLCK185 directly phosphorylates OsMAPKKK18. Furthermore, OsMAPKKK18 interacted with the MAPKK OsMKK4, the upstream component of OsMPK3/6. These results suggested that OsRLCK185 connects the chitin receptor to the MAPK cascade consisting of OsMAPKKK18-OsMKK4-OsMPK3/6. Our data revealed that chitin-induced MAPK activation in rice and Arabidopsis is regulated by common homologous elements.